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Biomedical subjects

L Marks

Publications and source records attributed to L Marks.

At least 19 recordsLinked to original sources
PubMed2000

The influence of mechanical stimulus on the pattern of tissue differentiation in a long bone fracture--an FEM study.

2D, coronal plane, finite elements models (FEMs) were developed from orthogonal radiographs of a diaphyseal tibial fracture and its reparative tissue at four different time points during healing. Each callus was separated into regions of common tissue histology by computerised radiographic analysis. Starting point values of tissue material properties from the literature were refined by the model to simulate exactly the mechanical behaviour of the subject's callus and bone during loading. This was achieved by matching measured inter-fragmentary displacements with calculated inter-fragmentary forces. Stress and strain distributions in the callus and bone were calculated from peak inter-fragmentary displacements measured during natural walking activity, and were correlated with the subsequently observed pattern of tissue differentiation and maturation of the callus. The growth and stiffening of the external callus progressively reduced the inter-fragmentary gap strain. Partial maturation of the gap tissue was apparent only one week before fixator removal. Principal stresses in the callus were compared with 'yield stresses' in corresponding tissue from the literature. This indicated the presence of stress concentrations medial and lateral to the fracture gap, which probably caused tissue damage during normal activity levels. Tissue damage may also have precipitated partial structural failure of the callus, both of which were believed to have delayed healing during the middle third of the fixation period. Had the fixation device provided greater inter-fragmentary support during early healing, this may have prevented callus failure and the consequent delay in healing. A further benefit of this would have been the reduction of the initially high intra-gap tissue strains to a magnitude more conducive to earlier maturation of the bridging tissue that united the bone.

Adult↗
PubMed2000

The Assaulted Staff Action Program (ASAP) and declines in rates of assault: mixed replicated findings.

The Assaulted Staff Action Program (ASAP) is a crisis intervention program that has been associated with providing both needed support for employee victims of patient assault and declines in rates of assaults in traditional state hospital and community mental health settings. This study examined the possible role of ASAP and declines in rates of assault in three community-based services impacted by privatization and managed care approaches: community residences, an acute care rural community mental health center, and an urban intermediate/extended care facility. ASAP was associated with a statistically significant decline in the rate of assault in the intermediate/extended care facility. The community residence program was not a true test because of structural issues associated with managed care. The community mental health center appeared to be a true failed replication. The extended care facility's decline in the rate of assault was interrupted by the aftermath of one serious clinical incident during one month and then continued to decline. The implications are discussed.

Adult↗
PubMed2000

Oral hygiene in 12-year-old disabled children in Flanders, Belgium, related to manual dexterity.

As part of a larger epidemiological survey of a stratified sample of 12-year-old handicapped children in Flanders, Belgium, the present study describes gingival health, gingival hypertrophy, oral cleanliness and the presence of calculus. Statistical analysis was performed with motor skills, brushing help, the use of chemical agents, the use of anti-epileptic drugs, the knowledge of parents and educators (or caregivers) and their opinion of the oral hygiene of their children/ pupils as response variables. From this study, it became clear that mildly mentally retarded and learning-impaired children had significantly better manual dexterity skills than moderately and severely mentally retarded and physically impaired children. However, this was not reflected in improved oral hygiene. The use of chemical plaque controlling agents was found to be extremely low and, with the exception of children with gingival hyperplasia, the users of these agents did not have better oral hygiene. No difference was found between subtypes in the opinion of parents and educators on oral status. There was, however, a difference between their assessment and the clinical picture. It was concluded that there was a need for in-service training programmes in oral health care for educators as well as for parents.

Analysis of Variance↗
PubMed2000

Antisense studies in PC12 cells suggest a role for H218, a sphingosine 1-phosphate receptor, in growth-factor-induced cell-cell interaction and neurite outgrowth.

Our previous studies of H218, a sphingosine 1-phosphate (S1P) receptor and a member of the G-protein-coupled receptor superfamily, suggest that it may participate in mammalian nervous system development. Thus, brain levels of H218 mRNA are higher during early neurogenesis than postnatally. In addition, embryonic H218 immunoreactivity is preferentially localized in young neuronal cell bodies during their early stages of differentiation and in axons during their extension. This report describes the morphological effects of reducing native H218 levels in PC12 cells. Western blot analyses demonstrated that PC12 cells stably transfected with an expression vector carrying an antisense-oriented H218 cDNA contain less H218 protein than vector-transfected control cells. When differentiated with growth factors, the antisense-H218 cells display more neurite production and form less cell-cell contacts than the control cells. Therefore, these data, along with our previous H218 expression studies and a recent, independent study of H218 overexpression, support the possibility that H218 contributes to developmental processes regulating neuronal interaction and axon growth. The data are also consistent with reports that H218 is a S1P receptor, that S1P is present in serum, like that used in our PC12 cell cultures, and that it causes PC12 cell neurite retraction. Finally, and in agreement with a S1P receptor role for H218, we find that the antisense-H218 cells display less S1P-induced neurite retraction than control cells.

Animals↗
PubMed1999

"Not just a statistic": the history of USA and UK policy over thrombotic disease and the oral contraceptive pill, 1960s-1970s.

Today it is estimated that over 100 million women worldwide have taken the oral contraceptive pill since 1956, when the first clinical trials were undertaken. Since its introduction on to the American market in 1960 and the British one in 1961, the pill has become one of the most popular contraceptives in both countries. Unlike other forms of drugs, which have primarily been formulated to prevent or cure illness, the oral contraceptive pill was designed to be given to healthy women over long periods of time, making the necessity for regulation and medical monitoring that much more pertinent. Focusing on the USA and Britain, this paper concentrates on the different ways in which each country has monitored and secured the safety of the pill between 1960 and 1970. While the British government decided to phase-out high dose oestrogen contraceptive pills associated with thrombotic disease in 1969, such pills continued to be available in the USA through to the 1980s, with measures instead being directed towards supplying better information to patients about the possible side-effects of the pill. The paper explores the reasons for this difference in policy, showing how it was shaped by the particular research orientation of each country as well as the specific legal, medical, social and political traditions within Britain and the USA.

Contraceptives, Oral↗
PubMed1999

Intravenous penciclovir for treatment of herpes simplex infections in immunocompromised patients: results of a multicenter, acyclovir-controlled trial. The Penciclovir Immunocompromised Study Group.

The efficacy and safety of penciclovir (PCV) for the treatment of herpes simplex virus (HSV) infections in immunocompromised (IC) patients were studied in a double-blind, acyclovir (ACV)-controlled, multicenter study. A total of 342 patients with mucocutaneous HSV infections received 5 mg of PCV per kg every 12 or 8 h (q12h or q8h) or 5 mg of ACV per kg q8h, beginning within 72 h of lesion onset and continuing for up to 7 days. The mean age of the patients was 49 years; 94% were white and 52% were female. The main reasons for their IC states were hematologic disorder (63%) and transplant plus hematologic disorder (16%). Clinical and virological assessments were performed daily during the 7-day treatment and then every other day until lesion healing. The primary efficacy parameter addressed new lesion formation. Secondary end points focused on viral shedding, healing, and pain. Approximately 20% of patients in each treatment group developed new lesions during therapy; thus, equivalence with ACV (defined prospectively) was demonstrated for both q12h and q8h PCV regimens. For all three treatment groups, the median time to the cessation of viral shedding was 4 days and the median time to complete healing was 8 days; there were no statistically significant differences in the rates of complete healing or the cessation of viral shedding when the results for PCV q12h and q8h were compared with those for ACV q8h. In addition, there was no statistically significant difference between PCV q12h or q8h, compared with ACV q8h, for the resolution of pain. PCV was well tolerated, with an adverse event profile comparable to that of ACV. In conclusion, PCV q12h is a well-tolerated and effective therapy for mucocutaneous HSV infection in IC patients and offers a reduced frequency of dosing compared with ACV q8h.

Acyclovir↗
PubMed1999

The "new team" triad.

Nurse managers develop new staffing patterns to increase the quality and cost-effectiveness of care. Ongoing evaluation and adjustments to the new patient-care delivery system are key.

Hospitals, Community↗
PubMed1997

Immunohistochemical localization of netrin-1 in the embryonic chick nervous system.

Netrin-1 has profound in vitro effects on the growth properties of vertebrate embryonic axons. In addition, netrin-1 mRNA is found in the floor plate of the embryonic nervous system, an intermediate target of many axons, including commissural axons that are affected by netrin-1 in vitro. Moreover, genetic studies of netrin-1 homologs in Caenorhabditis elegans and Drosophila implicate these proteins in commissure formation. We raised polyclonal antisera that recognize chick netrin-1 in fixed tissue sections. The antisera were used to immunohistochemically map netrin-1 in the embryonic spinal cord, brain, and retina. The relationship between netrin-1 localization and the growth of pioneering axons suggests roles for netrin-1 in the regulation of circumferential, commissural, and longitudinal axon growth in the spinal cord and brain. The data also suggest that the primary or sole effect of netrin-1 on pioneering spinal cord commissural axons is haptotactic. Furthermore, the pattern of netrin-1 localization raises the possibility that this protein helps mediate neuronal migration in the spinal cord, brain, and retina.

Animals↗
PubMed1997

Embryonic expression pattern of H218, a G-protein coupled receptor homolog, suggests roles in early mammalian nervous system development.

Heterologous expression studies employing mammalian cell tissue culture techniques and in vivo studies of lower eukaryotes suggest that G-protein coupled receptors may play critical roles in regulating early stages of vertebrate nervous system development. Previous work suggests that H218, a rat G-protein coupled receptor homolog, could serve such a role. Most importantly, northern blot data indicate that whole brain H218 mRNA levels are highest during embryogenesis. In the present studies we raised, affinity-purified and characterized several anti-H218, polyclonal antisera and immunohistochemically mapped the expression of H218 during the early stages of rat embryonic nervous system development. The resulting data indicate that H218 is preferentially expressed in young, differentiating neuronal cell bodies and axons. Moreover, the expression is temporally regulated such that highest H218 levels are found in neuronal cell bodies during their early stages of differentiation and in axons during their outgrowth. Therefore, we propose that H218 signal transduction may widely participate in the regulation of some of the first steps in neuronal differentiation including axon outgrowth.

Amino Acid Sequence↗
PubMed1997

Oral health condition of 12-year-old handicapped children in Flanders (Belgium).

The dental condition of 626 12-year-old handicapped children with mild mental or moderate to severe mental retardation or learning impairment, being 25% of the population of each of these groups, was examined in Flanders. An evaluation of oral cleanliness showed poor oral hygiene in 31.8% of the children. No significant differences were found in oral cleanliness among types of handicapping conditions. The mean DMFT score was 2.9 (s: 2.6) and DMFS score was 5.4 (s: 5.6). Almost 21% of the children were free of caries or fillings. No significant differences were found among groups of handicapped children. Handicapped children presented a low level of restorative care (restorative index score: 48.7%). Mildly mentally retarded children demonstrated the lowest restorative index (43.9%). The caries experience of first permanent molars represented the largest part of the DMFT score (64.1%). Sealants were present in 7.9% of children examined. A considerable percentage of mildly mentally retarded children and learning impaired children did not brush daily (22.1% and 20.9%) and did not receive help with toothbrushing from their parents or carers (91.0% and 94.7%, respectively).

Belgium↗
PubMed1997

Reaction strains on the condylar neck during mastication and maximum muscle stimulation in different condylar positions: an experimental study in the miniature pig.

Most researchers agree that the primate temporomandibular joint (TMJ) is loaded compressively during function and that condylar position must play a role in mediating such loads. However, the precise nature of that role remains unclear. Using a pig model in this study, we attempted to analyze strain on the neck of the condyle during normal mastication and during simulated function in different condylar positions. Miniature three-element rosette strain gauges were bonded to the lateral surface of the condylar neck in 4 female miniature pigs (one per condyle). Measurements of strain were made during normal mastication and with the pigs under general anesthesia during maximum stimulation of the masseter and temporalis muscles in each of five condylar positions--centric occlusion, centric relation, anterior, relaxed and wide open--established through use of acrylic splints. Condylar position was evaluated by superimposition of lateral and dorsoventral cephalograms, with measurement of horizontal and vertical changes in location of implants placed on the zygomatic arch. As in primates, the TMJ was found to be load-bearing during mastication, with compressive strain oriented approximately perpendicular to the occlusal plane. In 3 pigs, strain was higher during balancing than during working function. During stimulation, the TMJ reaction strains were significantly lower with the condyles in the anterior position compared with the other positions, and the compressive strain was directed more anteriorly along the neck of the condyle in that position.

Analysis of Variance↗
PubMed1997

[The use of chlorhexidine as a preventive and therapeutic means of plaque control in the handicapped. Review of the literature and definitive advise for application].

With respect to oral hygiene, most of the handicapped are very dependent. Moreover, it is shown that the higher the dexterity level, the poorer the oral hygiene. It's well documented that the use of Chlorhexidine (CHX) is an essential tool in oral care for the handicapped. The efficacy however, only becomes optimal after thorough plaque and calculus removal. From the literature, it becomes clear that the application of a 1% gel in prefabricated trays is the most efficient. Regarding mouthrinses, it's important to use big volumes in order to reach optimal contact with tooth surfaces. The use of a spray seems very handy but is quiet inefficient; no homogeneous diffusion of CHX can be obtained. The choice of any device for CHX application depends on the handicapping condition and on the knowledge and motivation of educators, and medical care takers. The present article summarizes the dental literature on the use of CHX in handicapped. An advice for well indicated use of CHX is proposed.

Aerosols↗
PubMed1996

Radiosurgery for the treatment of previously irradiated recurrent primary brain tumors and brain metastases: initial report of radiation therapy oncology group protocol (90-05).

PURPOSE: To determine the maximum acutely tolerable dose of single fraction radiosurgery in patients with recurrent previously irradiated primary brain tumors or brain metastases. METHODS AND MATERIALS: Between August 1990 and September 1993, 102 analyzable patients were entered on Radiation Therapy Oncology Group (RTOG) protocol 90-05, 38 of whom had recurrent primary brain tumors (median prior dose 60 Gy), and 64 of whom had recurrent brain metastases (median prior dose 30 Gy) < or = 40 mm in maximum diameter. Unacceptable toxicity was defined as irreversible Grade 3, any Grade 4, or Grade 5 central nervous system (CNS) toxicity according to the RTOG CNS criteria, occurring in > 20% of patients per treatment arm within 3 months of radiosurgery. RESULTS: Patients were initially entered onto one of three treatment arms according to the maximum diameter of the recurrent lesion. Twelve to 22 patients were entered on each arm. The dose levels were: arm 1, < or = 20 mm, 18 Gy; arm 2, 21-30 mm, 15 Gy; and arm 3, 31-40 mm, 12 Gy. Subsequently, doses were escalated as follows: arm 4, < or = 20mm, 21 Gy; arm 5, 21-30 mm 18 Gy; and arm 6, 31-40 mm, 15 Gy. Unacceptable acute toxicity secondary to cerebral edema occurred in 0, 7 and 5% of patients on Arms 1, 2 and 3, respectively, and in no patients on arms 4, 5, or 6. Multivariate analysis revealed that tumor volume > or = 8200 mm(3) and a ratio of maximum dose to prescription dose (MD/PD) > or = 2 were significantly associated unacceptable toxicity. Of 15 patients with both tumor volume > or = 8200 mm(3) and MD/PD > or = 2, unacceptable toxicity occurred in 2 of 4 treated with a single isocenter and 1 of 11 treated with multiple isocenters. Subsequently, operation for symptomatic radionecrosis was required in 6% of patients. CONCLUSION: We found that the incidence of acute toxicity was acceptable at 0-7% in patients with recurrent, previously irradiated primary brain tumors or brain metastases < or = 40 mm in maximum diameter treated according to the protocol described.

Adult↗
PubMed1996

Immunohistochemical localization of ciliary neurotrophic factor receptor alpha expression in the rat nervous system.

Ciliary neurotrophic factor receptor alpha (CNTFR alpha) is essential for normal embryonic development and may be involved in postnatal and adult neuronal maintenance. In addition, a rapidly growing body of evidence suggests that CNTFR alpha serves as a site of action for future growth factor therapeutics capable of treating a wide variety of disorders resulting from neuronal loss. We raised two polyclonal, anti-CNTFR alpha antisera against synthetic peptides corresponding to independent regions of rat CNTFR alpha. Western blot and immunohistochemical analyses indicated that affinity-purified preparations of both antisera specifically recognize CNTFR alpha. In the adult brain, the highest levels of CNTFR alpha immunoreactivity were found in the perikarya, dendrites and, occasionally, the axons of several distinct classes of neurons including hippocampal formation neurons, some sensory neurons, and many neurons involved in motor control. CNTFR alpha immunoreactivity also was concentrated in the following: perikarya, dendrites, and axons of ventral horn motor neurons in adult spinal cord; perikarya and axons of adult dorsal root ganglion neurons; and axons in adult peripheral nerve. In embryonic tissue, the highest levels of CNTFR alpha immunoreactivity were observed in differentiating neurons and their processes. Therefore, the present data suggest that CNTFR alpha serves several diverse functions in adulthood and during development.

Amino Acid Sequence↗
PubMed1995

Measurement of mevalonic acid in human urine by bench top gas chromatography-mass spectrometry.

Urinary excretion of mevalonate was reported to be correlated with endogenous cholesterol biosynthesis. A method is described whereby mevalonate (MVA) concentration in urine is determined by bench top gas chromatography-mass spectrometry after extraction as mevalonalactone (MVL) and conversion to mevalonolactone mono-TMS derivative. Within- and between-assay coefficients of variation were 4.02% and 8%, respectively. The mean concentration of MVA in 24-h urine collections from ten normolipidemic urinary subjects was 203 +/- 49.6 ng/ml (range: 44-576 ng/ml). Administration of 40 mg of Pravastatin (an HMG-CoA reductase inhibitor) significantly decreased (approximately 50%) the night concentration of MVA in five healthy volunteers. This assay could be useful for investigation of endogenous cholesterol synthesis rate in various dyslipidemias and in response to drug treatment.

Adult↗
PubMed1995

Effect of acetate and propionate on fasting hepatic glucose production in humans.

OBJECTIVE: Short chain fatty acids (SCFA, e.g. acetate and propionate) produced from bacterial colonic fermentation may be involved in the improvement of fasting glucose concentration observed with high dietary fibre diets. Because fasting blood glucose is related to hepatic glucose production, we have tested the effect of propionate and acetate on hepatic glucose production. SETTING: The study was carried out in the Clinical Research Center for Human Nutrition. SUBJECTS: Six healthy young volunteers. INTERVENTIONS: The subjects received, in a random order: acetate (12 mmol/h), or propionate (4 mmol/h), or acetate+propionate (12 mmol/h + 4 mmol/h), or an isotonic sodium salt solution (saline) in 3 h gastric infusions. Blood glucose and plasma insulin was monitored. Hepatic glucose production was measured with an isotopic method using [6,6-2H2] glucose. RESULTS: No changes were observed in blood glucose, plasma insulin concentrations or hepatic glucose production with any of the infused solutions. An increase in free fatty acid (FFA) plasma concentration related to the fasting state was observed with the saline solution, but not with the SCFA infusions (P < 0.05). There was also an increase in beta-hydroxybutyrate concentration with the saline and the acetate solutions, but not with the propionate or acetate+propionate solutions. CONCLUSIONS: SCFA, administered at a rate calculated on the basis of a continuous daily fermentation of 30 g dietary fibres, do not change hepatic glucose production or fasting blood glucose. Propionate and acetate decrease plasma FFA, and further studies are needed to explore this effect on glucose tolerance and insulin sensitivity.

Acetates↗