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Biomedical subjects

R Freeman

Publications and source records attributed to R Freeman.

At least 55 records · Page 3Linked to original sources
PubMed2001

Prevention of bone loss with tibolone in postmenopausal women: results of two randomized, double-blind, placebo-controlled, dose-finding studies.

Tibolone, a novel compound with tissue-specific effects, has been found to have antiresorptive properties in bone. To confirm the efficacy of tibolone and determine its minimum effective dose for prevention of bone loss in early postmenopausal women, two randomized, double-blind, placebo-controlled, dose-finding studies were performed. Seven hundred seventy healthy women postmenopausal within 1-4 yr, with normal bone density for their age, were treated for 2 yr with 0.3, 0.625, 1.25, or 2.5 mg tibolone daily or placebo. All subjects took supplemental calcium carbonate (500 mg daily). Bone mineral density (BMD) of the lumbar spine and right proximal femur was measured by dual-energy x-ray absorptiometry for up to 2 yr. At each dose level, except the lowest (0.3 mg), tibolone produced a progressive increase in lumbar spine and total hip BMD over the 2-yr treatment period; at 0.3 mg, total hip density was maintained. However, only the doses 1.25 mg and 2.5 mg produced a progressive increase in femoral neck BMD. The differences in mean percent change from baseline in spine and total hip density were significant (P < 0.05) for all tibolone dose groups compared with placebo at all time points. Tibolone was well tolerated, with a similar overall incidence of adverse events compared with placebo. Tibolone 1.25 mg per day is recommended because it shows a positive and statistically significant change in BMD of spine and femoral neck.

Aged↗
PubMed2001

Dental caries, age and anxiety: factors influencing sedation choice for children attending for emergency dental care.

OBJECTIVES: The aim of the study was to examine how physical (dental caries) and psychosocial (age, dental anxiety and dental health behaviour) factors, associated with child and parent, influenced dentists' sedation choice when a child presents in pain. METHODS: 600 parents whose children were aged between 5 and 11 years took part: 200 attended for routine dental care (RDC); the remaining 400 attended as emergency patients and were offered either dental general anaesthesia (DGA) or relative analgesia (RA). The subjects were approached and invited to take part. The researcher was blind as to the child's pattern of dental attendance and the type of sedation offered. All parents and children completed self-reported ratings of dental anxiety. The children's teeth were examined to determine past and present dental caries experience. RESULTS: The results showed that children who were offered DGA had greater experience of dentinal caries, were younger and dentally anxious. The children offered RA were older, had a higher frequency of brushing their teeth with fluoride toothpaste and were also dentally anxious. Discriminant analysis showed that 2 canonical functions provided clear categorisation of the three treatment groups. Function 1 was a physical (dental caries) factor, which was related to the child's experience of dentinal caries. Function 2 was a psychosocial factor, which was related to the child's age, dental anxiety and frequency of tooth brushing. A greater proportion of the variance in the treatment offered was explained by Function 1, suggesting that the most important factor in the decision to offer DGA was dentinal caries. Function 2 was of lesser importance. CONCLUSIONS: The findings have implications for the type of sedation offered to children presenting for emergency care. These children may not otherwise receive treatment and the need to provide less anxiety provoking forms of sedation must be promoted. By doing so, parents who have only brought their children when in pain may take advantage of RDC and the treatments offered to prevent and control dental caries and anxiety in their children.

Age Factors↗
PubMed2000

Abnormal baroreflex responses in patients with idiopathic orthostatic intolerance.

BACKGROUND: Patients diagnosed with idiopathic orthostatic intolerance report symptoms of lightheadedness, fatigue, and nausea accompanied by an exaggerated tachycardia when assuming the upright posture. Often, these symptoms are present in the absence of any decrease in arterial pressure. We hypothesized that patients with idiopathic orthostatic intolerance would have impaired cardiac vagal and integrated baroreflex function, lower blood volume, and increased venous compliance. METHODS AND RESULTS: Sixteen patients and 14 healthy control subjects underwent the modified Oxford technique to assess cardiac vagal baroreflex sensitivity. Progressive lower-body negative pressure (to -50 mm Hg; LBNP) was used to examine the integrated baroreflex response to progressive hypovolemic stimuli. Blood volume and venous compliance were also assessed. Patients with idiopathic orthostatic intolerance had lower cardiac vagal baroreflex sensitivity (12+/-1 versus 25+/-4 ms/mm Hg; P</=0.01). The integrated baroreflex response to low levels of LBNP was characterized by shorter R-R intervals and more symptoms such as lightheadedness, despite similar levels of blood pressure. There was a trend toward lower blood volume in the patient group (56+/-2 versus 63+/-3 mL/kg; P=0.054). CONCLUSIONS: Patients with idiopathic orthostatic intolerance have lower cardiac vagal baroreflex sensitivity and marginally lower blood volume and respond with faster heart rates despite similar levels of arterial pressure during LBNP. These findings may contribute to the exaggerated postural tachycardia and symptoms observed in patients with this disorder.

Adult↗
PubMed2000

Efficacy and safety of recombinant human nerve growth factor in patients with diabetic polyneuropathy: A randomized controlled trial. rhNGF Clinical Investigator Group.

CONTEXT: Nerve growth factor is a neurotrophic factor that promotes the survival of small fiber sensory neurons and sympathetic neurons in the peripheral nervous system. Recombinant human nerve growth factor (rhNGF) has demonstrated efficacy as treatment for peripheral neuropathy in experimental models and phase 2 clinical trials. OBJECTIVE: To evaluate the efficacy and safety of a 12-month regimen of rhNGF in patients with diabetic polyneuropathy. DESIGN: Randomized, double-blind, placebo-controlled phase 3 trial conducted from July 1997 through May 1999. SETTING: Eighty-four outpatient centers throughout the United States. PATIENTS: A total of 1019 men and women aged 18 to 74 years with either type 1 or type 2 diabetes and a sensory polyneuropathy attributable to diabetes. INTERVENTIONS: Patients were randomly assigned to receive either rhNGF, 0.1 microg/kg (n = 504), or placebo (n = 515) by subcutaneous injection 3 times per week for 48 weeks. Patients were assessed at baseline, 12 weeks, 24 weeks, and 48 weeks. MAIN OUTCOME MEASURES: The primary outcome measure was a change in neuropathy between baseline and week 48, demonstrated by the Neuropathy Impairment Score for the Lower Limbs, compared between the 2 groups. Secondary outcome measures included quantitative sensory tests using the CASE IV System, the Neuropathy Symptom and Change questionnaire, the Patient Benefit Questionnaire (PBQ), and a global symptom assessment, as well as nerve conduction studies and occurrence of new plantar foot ulcers. Patients also were evaluated for presence of adverse events. RESULTS: Among patients who received rhNGF, 418 (83%) completed the regimen compared with 461 (90%) who received placebo. Administration of rhNGF was safe, with few adverse events attributed to treatment apart from injection site pain/hyperalgesia and other pain syndromes. However, neither the primary end point (P =.25) nor most of the secondary end points demonstrated a significant benefit of rhNGF. Exceptions were the global symptom assessment (P =.03) and 2 of 32 comparisons within the PBQ, which showed a modest but significant benefit of rhNGF (P =.05 for severity of pain in the legs and P =.003 for 6-month symptoms in the feet and legs). CONCLUSION: Unlike previous phase 2 trials, this phase 3 clinical trial failed to demonstrate a significant beneficial effect of rhNGF on diabetic polyneuropathy. JAMA. 2000;284:2215-2221.

Activities of Daily Living↗
PubMed2000

Cyclooxygenase-2, a colorectal cancer nonsteroidal anti-inflammatory drug target, is regulated by c-MYB.

Cyclooxygenase-2 (COX-2) is an important pharmacological target with great promise in the prevention and treatment of colorectal cancer (CRC). The mechanism underlying COX-2 overexpression in CRC is unresolved. On the basis of the coincident high levels of the transcription factor c-MYB and COX-2 in CRC, we hypothesized that c-MYB is a candidate activator of COX-2 transcription. We identified 13 c-Myb binding sites in the human COX-2 promoter. Eight of these sites were moderate to high-affinity DNA binding targets. Promoter studies indicated that c-Myb can activate COX-2 transcription, whereas dominant-negative Myb mediated repression. These data provide the first rational basis for overexpression of COX-2 in CRC and offer an additional potential target for managing this disease.

Animals↗
PubMed2000

Neural and endothelial control of the microcirculation in diabetic peripheral neuropathy.

OBJECTIVE: To examine the role played by endothelium-dependent and endothelium-independent vasodilation of the cutaneous microcirculation and their relationship to neural microcirculatory control in type 1 and type 2 diabetic patients. METHODS: Acetylcholine and sodium nitroprusside were iontophoresed using a dose-response technique. Endothelium-dependent, endothelium-independent, and C-fiber-mediated vasodilation were measured with a laser Doppler device. RESULTS: Endothelium-dependent vasodilation of the forearm cutaneous microcirculation was attenuated in diabetic subjects. The response was less in type 2 diabetic subjects than in controls (p < 0.005). In contrast, there was no significant difference between type 1 diabetic subjects and controls. There was no significant abnormality in endothelium-independent vasodilation in either diabetic group. The C-fiber-mediated axon reflex in the forearm was impaired in both type 1 and type 2 diabetics, which is consistent with a small-fiber neuropathy (p < 0.005). The duration of diabetes in type 2 diabetics was a significant predictor of the maximum endothelium-mediated vasodilation. CONCLUSION: Changes in cutaneous blood flow are seen relatively early in the course of diabetic peripheral neuropathy and are characterized by endothelial and neural but not smooth muscle dysfunction. The presence of significant C-fiber impairment in both diabetic groups, together with significantly greater dysfunction in endothelium-dependent vasodilation in type 2 diabetics, suggests that the endothelial function and nitric oxide may play a greater role in the pathogenesis of diabetic peripheral neuropathy in type 2 diabetic patients.

Adult↗
PubMed2000

Strange effects of pulse shaping in water presaturation experiments

During the course of some water presaturation experiments with a shaped pulse envelope we observed inverted responses from certain signals flanking the water response. This phenomenon did not occur when a rectangular presaturation envelope was used. Apparently the leading and trailing edges of the shaped pulse act as adiabatic sweeps, causing the coupled magnetizations in question to be spin-locked. This gives rise to Hartmann-Hahn coherence transfer, and when the spin lock duration is equal to 1/(2J) the trajectories are such as to carry these magnetization vectors to the -z axis, leading to inverted signals in the final spectrum. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Determinants of cariogenic snacking in adolescents in Belfast and Helsinki.

The aim of the study was to investigate the determinants of reported snack consumption in adolescents residing in Belfast, Northern Ireland and Helsinki, Finland. Ten % random samples of 14-15 yr old Belfast (n = 628) and Helsinki (n = 600) adolescents were obtained. A questionnaire assessed their demography, oral health knowledge, attitudes and the consumption of cariogenic snacks containing non-milk extrinsic sugars (NMES). Five hundred and eighty-nine (94%) questionnaires were returned in Belfast and 441 (74%) questionnaires in Helsinki. Belfast adolescents had significantly higher levels of oral health knowledge and higher consumption rates for snacks containing NMES. The Helsinki adolescents had more positive attitudes towards their oral health. Multivariant analysis showed that demography was the most direct determinant of cariogenic snacking. The acquisition of oral health knowledge played a minor role. There is a need to develop tailored and focused programmes to promote healthier snacking regimes in adolescents.

Adolescent↗
PubMed2000

Hypnosis and distraction differ in their effects on cold pressor pain.

On the bases of Hilgard's neodissociation theory and Spano's (1982) sociocognitive theory, volunteers stringently selected for high (N = 10) and low (N = 10) hypnotizability were exposed to a cold pressor pain test during counterbalanced conditions of waking relaxation, distraction, and hypnosis. To better discriminate between hypnosis and distraction conditions, a new distraction procedure was developed involving the memorization of a sequence of colored lights. High hypnotizables showed significantly greater pain relief for hypnosis versus distraction or waking relaxation conditions. High hypnotizables also demonstrated significantly greater pain relief than low hypnotizables in response to hypnosis. Quantitative electroencephalographic (EEG) findings showed significantly greater high theta (5.5-7.5 Hz) activity for highs as compared to lows at parietal (P3) and occipital (01) sites during both hypnosis and waking relaxation conditions. The findings fail to support the socio-cognitive conceptualization of hypnotic behavior while providing additional evidence supporting the neo-dissociation theory and state based theories of hypnosis in general.

Cold Temperature↗
PubMed2000

Comparison of PCR detection of mecA with methicillin and oxacillin disc susceptibility testing in coagulase-negative staphylococci.

The provisional BSAC method for the detection of methicillin sensitivity in coagulase-negative staphylococci (CNS) requires incubation of isolates for 48 h and raises the problem of timely reporting of susceptibility data. The forthcoming withdrawal of methicillin raises another difficulty. We evaluated 42 clinically significant CNS blood culture isolates by PCR, methicillin and oxacillin disc testing and by using methicillin Etests. Our results suggest that, although oxacillin disc susceptibility testing is a reasonable first line step, optimal and timely detection of resistance or susceptibility may require a combination of phenotypic and genotypic methods.

Coagulase↗
PubMed2000

Mycobacterium elephantis sp. nov., a rapidly growing non-chromogenic Mycobacterium isolated from an elephant.

A strain isolated from a lung abscess in an elephant that died from chronic respiratory disease was found to have properties consistent with its classification in the genus Mycobacterium. An almost complete sequence of the 165 rDNA of the strain was determined following the cloning and sequencing of the amplified gene. The sequence was aligned with those available on mycobacteria and phylogenetic trees inferred by using three tree-making algorithms. The organism, which formed a distinct phyletic line within the evolutionary radiation occupied by rapidly growing mycobacteria, was readily distinguished from members of validly described species of rapidly growing mycobacteria on the basis of its mycolic acid pattern and by a number of other phenotypic features, notably its ability to grow at higher temperatures. The type strain is Mycobacterium elephantis DSM 44368T.

Animals↗
PubMed2000

Hormone replacement therapy (estrogen and progesterone): is it necessary for heart disease prevention?

This is a brief review of the rationale for estrogen replacement as prevention of coronary artery disease. Epidemiological data suggest that Premarin (0.625 mg) together with medroxyprogesterone acetate (2.5 mg) can prevent or delay the onset of coronary artery disease in postmenopausal women. The major effects of estrogens are: improving the lipid profile by lowering low-density lipoprotein and raising high-density lipoprotein; acting on vessel walls to reduce intimal damage and plaque formation; dilating vessels by both an endothelial dependent and an independent pathway; and acting as an antioxidant, thereby reducing the oxidation of low density lipoprotein and increasing the production of nitric oxide locally in the blood vessel. Oral estrogens and transdermal estrogens may act differently on coagulation factors and lipids. The role of specific estrogen receptor modulators as possible treatment for postmenopausal women in part will depend on the effect of these drugs in preventing coronary artery disease. The specific estrogen receptor modulators decrease low-density lipoprotein and prevent triglyceride increases but it is unknown if they have estrogenic effects on blood vessel walls. Better compliance with estrogen replacement therapy will depend on educating women about their risk of getting coronary artery disease, and assisting them in decision making, as well as reducing side effects. The Heart and Estrogen/Progestin Replacement Study provides evidence that Prempro (Premarin/ medroxyprogesterone acetate) should not be given to someone who already has heart disease without careful monitoring. (c) 2000 by CHF, Inc.

Journal Article↗
PubMed2000

An exploratory qualitative study examining the social and psychological processes involved in regular dental attendance.

OBJECTIVE: This study aimed to provide a description of the psychosocial process involved in regular dental attendance. METHODS: The study design was a qualitative cross-sectional study using unstructured and semistructured interviews and observations of regular dental visits. The study participants included 12 men and 18 women attending general dental practices and six men and four women attending an emergency dental service. The data were systematically recorded and subjected to line-by-line grounded theory coding around the main concerns of those attending the dentist. RESULTS: The main concern of those attending for a regular dental visit was checking their oral health. The six-month recall was conceptualized as a checking cycle in six phases: recalling, responding, inducing (i), waiting, inducing (ii), and telling. The possible outcomes of the cycle were maintaining oral health, sustaining oral health, and a further checking cycle. Variations in checking cycles resulted from reordering and normalizing pressures within participants' lifestyles. CONCLUSIONS: The findings of this study suggest that people's patterns of dental attendance are similar to those of other chronic illnesses. An understanding of the dynamic psychosocial processes involved in frequent dental attendance may be achieved when further research into this phenomenon is conducted.

Appointments and Schedules↗
PubMed2000

Further evidence for the reliability and validity of the Modified Dental Anxiety Scale.

AIM: To gain further evidence of the psychometric properties of the Modified Dental Anxiety Scale. SETTING: Dental admission clinics. DESIGN: Consecutive sampling, cross-sectional survey. PARTICIPANTS: Patients (n = 800) in four cities (Belfast, Northern Ireland; Helsinki, Finland; Jyväskylä, Finland and Dubai, UAE). METHODS: Questionnaire booklet handed to patients, attending clinics, for completion following an invitation by the researcher to be included in the study. MEASURES: Modified Dental Anxiety Scale (MDAS), together with further questions concerning dental attendance and nervousness about dental procedures. RESULTS: Overall 9.3 per cent of patients indicated high dental anxiety. MDAS showed high levels of internal consistency, and good construct validity. The relationship of dental anxiety with age was similar to previous reports and showed lowered anxiety levels in older patients. CONCLUSION: Data from three countries has supported the psychometric properties of this modified and brief dental anxiety scale.

Adolescent↗