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Biomedical subjects

L Marks

Publications and source records attributed to L Marks.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1995

[Oral hygiene of handicapped subjects in Flanders].

As part of an epidemiology survey within the population of handicapped 12-year old in Flanders this article describes several parameters related to oral health. On the average, it became obvious that oral hygiene had to be seriously increased. The presence of plaque and calculus is very typical for types 1, 2, 4 and 8. In addition, it is most striking to conclude that groups where a maximum of self-handiness is expected, do not score any better. The application of chemical controlling agents and the use of fluoride supplements is found extremely low. Finally, a lack was found, with respect to adequate oral hygiene instructions. There is a real need for in-service training programs for educators as well as for parents.

Belgium↗
PubMed1995

[Status of the teeth and degree of care in handicapped in Flanders].

In general, handicapped 12-year old do not show statistical relevant differences with non-handicapped age-matched children in Flanders regarding general caries prevalence, caries distribution and total caries experience. However, important differences were found for the restorative index showing a higher caries treatment need in handicapped children. When the results were analysed according to the type of handicapping condition, it was seen that children with borderline and mild mental handicap and children with speech-, language and/or learning difficulties show the most unfavorable picture. They have a high caries prevalence and caries experience and a low restorative index. Additional analysis of the results can throw some light on the presence of additional caries risk indicators and contributing caries risk factors.

Belgium↗
PubMed1994

Measurement of whole body acetate turnover in healthy subjects with stable isotopes.

Colonic fermentation of dietary fibres produces short-chain fatty acids (e.g. acetate, propionate). Measurements of whole body acetate turnover was used in order to estimate the production of colonic short-chain fatty acids in human subjects. However, higher flux rates for acetate have been reported in human studies with stable isotopes as compared to radioactive tracers. The reasons for this discrepancy are unclear. In this study, the stable isotope (1-13C)acetate was used and a method was developed to measure its enrichment in plasma. Variations between and within assays were less than 5%. The standard curve was linear from 0.5% to 10% enrichment. When this tracer was infused for 160 min in six healthy volunteers, acetate turnover was found to be 7.5 +/- 1 mumol kg-1 min-1, which is similar to data reported with radioactive tracers. We assumed that the higher flux rate previously observed with stable isotope tracers was related to differences in the physiological status of the subjects involved in these studies.

Acetates↗
PubMed1994

Rate of [15N]leucine incorporation and determination of nitrogenous fractions from gastro-jejunal secretion in fasting humans.

The aim of this study was to quantify the nitrogen fraction flow rates in gastro-jejunal secretions in fasting humans and to determine the [15N]leucine incorporation into the secreted proteins. A double lumen intestinal perfusion method was used in 5 healthy volunteers. Plasma and gastro-jejunal juices were collected during a 15-h intravenous [15N]leucine infusion. Total, soluble and insoluble nitrogen, amino acids and [15N]leucine enrichment were measured. The total nitrogen flow rate was 7.2 +/- 1.9 mmol.h-1 and 58% was ethanol soluble. The amino-acid composition remained constant and glycine was the most abundant. The plasma [15N]leucine enrichment at the isotopic plateau was 4.8 +/- 0.9 mol% excess. The [15N]leucine enrichment in the intestinal chyme increased asymptotically to reach a plateau after 5 h. The [15N]leucine enrichment at the plateau and the fractional synthesis rate of secreted proteins were 1.6 +/- 0.5 mol% excess and 21.5 +/- 3.3%.h-1, respectively. These results show that the composition of the basal gastro-jejunal secretion is very stable. A part of this secretion is composed of proteins with rapid synthesis rates.

Adult↗