Biomedical subjects

S R Davis

Publications and source records attributed to S R Davis.

At least 19 recordsLinked to original sources

PubMed2006

Static knee alignment and its association with radiographic knee osteoarthritis.

OBJECTIVES: Although knee alignment is associated with the progression of knee osteoarthritis (OA), it is unclear which features that characterize radiographic OA are related to alignment. The aim of this study was to examine the relationship between static knee joint alignment (measured as a continuous variable) and the radiographic features of knee OA (joint space narrowing and osteophytes). METHODS: One hundred and twenty one adults with symptomatic knee OA were recruited using a combined strategy including referral from specialist centres, arthritis support groups and media advertising. X-rays were performed to classify the severity of disease and to determine static knee alignment. RESULTS: Increasing varus knee alignment was associated with increasing risk of medial compartment joint space narrowing (P < 0.001) and osteophytes (P = 0.005). Increasing valgus knee alignment was associated with an increased risk for lateral compartment joint space narrowing (P < 0.001) and osteophytes (P = 0.002). CONCLUSION: This study has demonstrated that the static knee angle, measured as a continuous variable, is an important determinant of the compartment-specific features of radiographic knee OA. Further work is required to determine whether interventions aimed at correcting these relatively minor levels of varus and valgus angulation will have an effect on the risk of tibiofemoral OA.

Aged↗

PubMed2006

Foot rotation--a potential target to modify the knee adduction moment.

Isolating the particular joints/limb segments associated with knee adductor moment variability may provide clinically important data that could help to identify strategies to reduce medial tibiofemoral joint load. The aim of this study was to examine whether or not foot and thigh rotation during human locomotion are significant determinants of knee adductor moment variability. Three-dimensional gait analyses were performed on 32 healthy adult women (mean age 54+/-12 years, mean BMI 25+/-4 kg m(-2)) with radiologically normal knees. The relationships between foot rotation, thigh rotation and the external knee adduction moment were examined during early and late-stance phases of the gait cycle. The degree of foot rotation correlated significantly with the magnitude of the peak knee adduction moment during late stance (r=0.40, p=0.024). No significant associations were apparent between thigh rotation and the peak knee adduction moment. The association between foot rotation and the knee adduction moment in this study suggests that women who walk with external rotation at the foot reduce their knee adduction moment during late stance. This result implies that changes in foot kinematics can modify the medial tibiofemoral load during gait, which may be important in the prevention and management of knee osteoarthritis.

Adult↗

PubMed2006

Sagittal plane movement at the tibiofemoral joint influences patellofemoral joint structure in healthy adult women.

OBJECTIVES: The influence exerted on cartilage and bone volumes by locomotor patterns is poorly understood, particularly at the patellofemoral joint. The aim of this study was to investigate the relationship between sagittal plane movement at the tibiofemoral joint and patella cartilage and bone volumes during the locomotion of healthy adult females. METHODS: Three-dimensional Vicon gait analyses and magnetic resonance imaging were performed on 20 healthy adult women. The relationships between the degree of tibiofemoral flexion and extension at varying stages of the gait cycle and the concomitant medial, lateral and total patella cartilage and total bone volumes were examined. RESULTS: For every degree the knee flexed during mid-stance, there was a 62.8 microL (95% confidence interval 3.7-122.0) increase in the medial patella facet cartilage volume after adjustment for age and the body mass index (BMI) (P = 0.04). A similar relationship that approached significance was observed for the lateral patella facet cartilage volume after adjustment for age and the BMI (P = 0.08). No association was observed between the sagittal plane tibiofemoral movements and the patella bone volume. CONCLUSIONS: The association between patella cartilage volume and tibiofemoral knee movement suggests that for every degree increase in knee flexion during mid-stance, there is an associated increase in patella cartilage volume. This may be the result of the geometry of the femoral condyle influencing patella tracking and or the retropatellar load exerted on the patella during walking. These results may have important implications for people who hyperextend their knee during gait and the pathogenesis of patellofemoral osteoarthritis.

Age Factors↗

PubMed2006

Homocysteine, estrogen and cognitive decline.

BACKGROUND: Factors that contribute to cognitive decline in women from midlife remain poorly understood. There are circumstantial data indicating a positive association between homocysteine and cognitive decline and that endogenous and exogenous estrogen may influence homocysteine levels. The aim of this review was to establish what is known of the relationships between cognitive change and homocysteine levels, and the impact of the menopause transition and exogenous estrogen on homocysteine levels. METHODS: We reviewed the recent published literature from 1993 to 2005 pertaining to the current understanding of the relationship(s) between plasma homocysteine levels and cognitive functioning and endogenous hormone levels and exogenous estrogen use in women. RESULTS: Hyperhomocysteinemia is consistently associated with cognitive decline. Dietary supplementation with vitamins may assist in normalizing homocysteine levels; however, there is no evidence that this results in favorable effects on cognition. Changes in endogenous estrogen levels are inversely associated with changes in serum homocysteine. Consistent with this, estrogen therapy is associated with reductions in plasma homocysteine, with the greatest effects reported in women with higher levels of homocysteine at baseline. Limited data indicate that tibolone is associated with little change in homocysteine. The use of raloxifene, the most studied selective estrogen receptor modulator, is associated with a modest reduction in homocysteine. CONCLUSIONS: There are data to suggest an underlying link between homocysteine levels and cognitive decline. There is also evidence for a link between both the menopause transition and use of exogenous estrogen therapy and homocysteine levels. Clinical data do not support a role for exogenous estrogen in the prevention of dementia in older women; however, the 'window of opportunity' theory suggests that there is a need for randomized controlled trials to evaluate the role of estrogen in the early postmenopausal years to protect against cognitive decline in later life.

Cognition↗

PubMed2005

Androgen levels in adult females: changes with age, menopause, and oophorectomy.

CONTEXT: Changes in androgen levels across the adult female life span and the effects of natural menopause and oophorectomy have not been clearly established. OBJECTIVE: The objective of this study was to document the effects of age on androgen levels in healthy women and to explore the effects of natural and surgical menopause. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study was conducted of 1423 non-healthcare-seeking women, aged 18-75 yr, randomly recruited from the community over 15 months. MAIN OUTCOME MEASURES: Serum levels by age of total testosterone (T), calculated free T, dehydroepiandrosterone sulfate, and androstenedione in a reference group of women free of confounding factors. Women in the reference group had no usage of exogenous steroid therapy; no history of tubal ligation, hysterectomy, or bilateral oophorectomy; and no hyperprolactinemia or polycystic ovarian syndrome. The effects of natural and surgical menopause on sex steroid levels were also examined. RESULTS: In the reference population (n = 595), total T, calculated free T, dehydroepiandrosterone sulfate, and androstenedione declined steeply with age (P < 0.001), with the decline of each being greater in the earlier than the later decades. Examination of serum androgen levels by year in women aged 45-54 yr showed no independent effect of menopausal status on androgen levels. In women aged 55 yr or older, those who reported bilateral oophorectomy and were not on exogenous steroids had significantly lower total T and free T levels than women 55 yr or older in the reference group. CONCLUSIONS: We report that serum androgen levels decline steeply in the early reproductive years and do not vary because a consequence of natural menopause and that the postmenopausal ovary appears to be an ongoing site of testosterone production. These significant variations in androgens with age must be taken into account when normal ranges are reported and in studies of the role of androgens in women.

Adolescent↗

PubMed2005

Lactational traits of importance in dairy cows and applications for emerging biotechnologies.

New molecular and quantitative genetic technologies are the latest in a long list of technologies that have been introduced to dairy industries over many decades to improve the performance of cows. The catalysts for future advances will be sequencing of the bovine genome and development of high-throughput technologies to identify and exploit relevant variation in DNA sequences. The new technologies will allow the selection of animals based on specific genotypes that suit specific applications such as once-daily (OAD) milking or extended lactation. These technologies will also allow exploitation of between-cow variation in milk composition, which is currently hidden by bulking of milk on and between farms. Thus, there are opportunities to produce milk from herds of cows selected for specific milk composition that might be, for example, more suitable for cheese-making or have milkfat with specific properties to enhance human health. Identification of genes and gene polymorphisms associated with improved resistance to specific diseases in cows and other farm species also represents a real opportunity to improve animal health over the coming decade. New levels of genetic regulation have been identified, e.g. microRNA and epigenetics, the impacts of which on the performance of cows and humans are only just beginning to be understood. There is a potential role for veterinarians to provide or be the interface for provision of genetic advice to farmers in much the same way that nutritional advice is currently given.

Animals↗

PubMed2005

Postmenopausal hormone therapy: from monkey glands to transdermal patches.

The climacteric is not a condition of the modern age, although with increased life expectancy over the centuries, more women will experience this physiological transition. As women are living longer there is a greater expectation that good health will be maintained through to the late decade. Thus the potential long-term adverse health consequences of using hormonal therapies (HTs) to alleviate menopausal symptoms are of considerable concern for women and medical practitioners. This concern is often the basis for a decision whether or not to use HT. We have reviewed the history of knowledge of the menopause and the development of HT for the treatment of climacteric complaints. We have also summarised the current evidence for specific benefits and risks of HT. Data indicate that postmenopausal HT is appropriate for the management of vasomotor symptoms, but that HT should not be prescribed for the prevention of cardiovascular disease or dementia. HT does prevent bone loss and osteoporotic fracture; however, use for this purpose remains controversial. The risk of breast cancer with HT varies according to the preparation used, such that oestrogen without concurrent progestin appears to convey little, or possibly even no significant breast cancer risk. There is insufficient information regarding the long-term use of non-oral HT, low-dose HT or novel compounds such as tibolone or the selective oestrogen receptor modulators with respect to breast cancer and cardiovascular risk for specific recommendations to be made.

Administration, Cutaneous↗

PubMed2004

Tibial plateau size is related to grade of joint space narrowing and osteophytes in healthy women and in women with osteoarthritis.

OBJECTIVE: To determine the relation of bone size to radiographic severity in knee osteoarthritis. METHODS: 149 women (81 healthy and 68 with knee osteoarthritis) underwent knee radiography and magnetic resonance imaging on their symptomatic or dominant knee. Tibial plateau bone area was measured at baseline and at follow up. RESULTS: Women with osteoarthritis had larger medial and lateral tibial plateau bone area (mean (SD): 1850 (240) mm2 and 1279 (220) mm2, respectively) than healthy women (1670 (200) mm2 and 1050 (130) mm2) (p<0.001 for both differences). For each increase in grade of osteophyte, an increase in bone area was seen of 146 mm2 in the medial compartment and 102 mm2 in the lateral compartment. Similarly, for each increase in grade of joint space narrowing, tibial plateau bone area increased by 160 mm2 in the medial compartment and 131 mm2 in the lateral compartment (significance of regression coefficients all p<0.001). These relations persisted after adjusting for potential confounders, with the exception of the association between grade of medial osteophytes and medial plateau area. CONCLUSIONS: With increasing severity of radiographic knee osteoarthritis, tibial plateau size increases. Whether this bone increase plays a role in the pathogenesis of osteoarthritis remains to be determined.

Case-Control Studies↗

PubMed2004

Androgen insufficiency in women: diagnostic and therapeutic implications.

The proposed key symptoms of the female androgen insufficiency syndrome (FAIS) include reduced libido, diminished well being and lowered mood. The diagnosis of FAIS is made on the basis of these symptoms in the setting of a low serum free testosterone level. However, there is currently no readily available inexpensive assay which reliably measures free testosterone levels in the female range. The diagnosis of FAIS is further complicated by the lack of data demonstrating a minimum serum free testosterone level which, if below this, correlates with the symptoms of FAIS. Despite the complexities involved with defining FAIS, the symptoms have been reported to respond well to testosterone replacement. There is a need for formulations of testosterone therapy specifically designed for use in women, along with clear guidelines regarding optimal therapeutic doses and long-term safety data.

Androgens↗

PubMed2004

Relationship between the area of cartilage shown on the magnetic resonance imaging middle-slice image of the medial and lateral tibial cartilages with cartilage volume and grade of osteoarthritis over time.

OBJECTIVE: Knee cartilage volume measurement requires significant time and training. Simplifying the measurement may improve feasibility. We investigated whether the area of cartilage shown on the middle slice of the medial and lateral tibial cartilages on sagittal MRI correlates with radiological features of osteoarthritis (OA), cartilage volume, and longitudinal change in cartilage volume. METHODS: One hundred and seventy-three subjects (normal and osteoarthritic), who had serial magnetic resonance imaging (cartilage volume measured) and baseline weight-bearing antero-posterior radiographs of the same knee were examined. RESULTS: In the lateral compartment, with increasing grade of OA there was a significant reduction in cartilage area. In the medial compartment, this was true for medial joint-space narrowing (after adjusting for gender). There was a moderate to strong association between cartilage area and volume, especially in those with early or no OA. However, when change over time was examined, the strength of these relationships was weak. CONCLUSION: Our data suggests that cartilage area may provide a simple surrogate measure of cartilage volume, in cross-sectional studies, after adjustment for gender: especially in subjects with early disease. However, before it can be widely used, further investigation will be required.

Aged↗

PubMed2004

Postmenopausal hormone therapy: the pros and cons.

The use of postmenopausal hormone therapy (HT) has recently generated much debate following the results of various large randomised controlled trials. This has challenged physicians to reassess the use of HT in each individual woman within the realm of her symptomatology and risk profile for long-term illnesses. There are several areas of definite benefit or risk and many areas of uncertainty. The results of recent randomised controlled trials pertain to the specific HT regimens used and the characteristics of the study groups, such that the conclusions cannot be extrapolated to the use of HT in general.

Breast Neoplasms↗

PubMed2004

Tibial cartilage volume change in healthy postmenopausal women: a longitudinal study.

OBJECTIVE: To determine whether the amount of joint cartilage in healthy postmenopausal women is stable or changes over time, and whether oestrogen replacement therapy (ERT) influences this. DESIGN: A cohort study in healthy postmenopausal women without knee pain, initially selected on the basis of having either used ERT long term (more than five years) or never having used ERT. METHODS: 81 women (42 taking ERT and 39 non-users) had baseline knee radiographs and magnetic resonance imaging (MRI) on the dominant knee; 57 of these (70%) were followed with repeat MRI approximately 2.5 years later. Knee cartilage volume was measured at baseline and at follow up. Risk factors assessed at baseline, including ERT use, were tested for their association with change in knee cartilage volume over time. RESULTS: 29 subjects who were initially taking ERT and 28 non-users at baseline completed the study. Total tibial articular cartilage decreased, on average, by (mean (SD)) 2.4 (3.2)% per year (95% confidence interval for mean, 1.5% to 3.2%). Average annual reduction in medial and lateral tibial cartilage was 2.4 (3.6)% (1.4% to 3.3%) and 2.3 (4.2)% (1.2% to 3.4%), respectively. No association between ERT and the rate of reduction in cartilage volume was shown. CONCLUSIONS: Mean tibial cartilage volume loss in healthy postmenopausal women is between 1.5% and 3.2% a year. Whether this rate of change is similar throughout adult life or in men will require further investigation.

Cartilage, Articular↗

PubMed2004

Gamma-glutamyl transpeptidase inhibition suppresses milk protein synthesis in isolated ovine mammary cells.

The membrane spanning enzyme gamma-glutamyl transpeptidase (gamma-GT; EC 2.3.2.2) catalyses the breakdown of the tripeptide glutathione and uses free amino acids (AA) to form gamma-glutamyl transpeptidase (GT) AA that become transported into cells and converted back into free AA. gamma-Glutamyl transpeptidase activity has been shown to be important for mammary AA uptake in rodent systems, and while gamma-GT activity is high in lactating bovine mammary tissue, the role of this enzyme in milk protein synthesis of the ruminant has not been defined. The present study shows that gamma-GT activity in the ovine mammary gland, like that of rodents, increases during pregnancy and peaks early in lactation. Acivicin, a well-known inhibitor of gamma-GT, decreased gamma-GT activity in acini isolated from the ovine mammary gland and did not have secondary toxicity effects on cell viability or the uptake of radiolabeled amino-isobutyric acid. Isolated ovine acini were incubated in the presence of radiolabeled leucine, and incorporation of label into secreted protein increased during incubation. Incubation of acini with acivicin decreased milk protein secretion by 75%, indicating that gamma-GT plays an important role in milk protein production in the ruminant. Acivicin did not inhibit secretion of specific caseins but caused a global decrease in individual proteins suggesting that gamma-GT may be responsible for providing a complement of AA for milk protein synthesis.

Animals↗

PubMed2003

The effect of the knee adduction moment on tibial cartilage volume and bone size in healthy women.

OBJECTIVES: There is considerable evidence that an abnormally high knee adductor moment is a characteristic of the gait patterns in people with knee osteoarthritis (OA). The aim of this study was to examine the relationship between the peak knee adduction moment during the early and late stance phases of gait, and medial and lateral tibial bone size and cartilage volume in healthy women. METHODS: Three-dimensional Vicon gait analyses and magnetic resonance imaging (MRI) were performed on 20 healthy women without knee OA. The external knee adduction moment was correlated with medial and lateral tibial bone size and cartilage volume for the dominant leg. RESULTS: The knee adduction moment significantly correlated with the bone size of the medial tibial plateau (r = 0.63, P < 0.005), but was not related to the bone size of the lateral plateau. No relationship was observed between the knee adduction moment and medial or lateral tibial cartilage volume. CONCLUSIONS: Although the knee adduction moment was positively associated with the bone size of the medial tibial plateau, it appeared to have little effect on cartilage volume in that compartment in healthy women. It may be that the effect of the knee adduction moment differs in healthy subjects compared with those with established knee OA.

Aged↗

PubMed2003

Modeling the interaction of milking frequency and nutrition on mammary gland growth and lactation.

A mathematical model of biological mechanisms regulating lactation is constructed. In particular, the model allows prediction of the effect of milking frequency on milk yield and mammary regression, and the interaction of nutrition and milking frequency in determining yield. Possible interactions of nutrition with milking frequency on alveolar dynamics are highlighted. The model is based upon the association of prolonged engorgement (as a consequence of milk accumulation) of active secretory alveoli with changes in gene expression that result in impairment and, ultimately, cessation of milk secretion. The emptying of alveoli at milking, following alveolar contraction induced by oxytocin, prevents this process and also allows quiescent alveoli to reactivate. Prolonged engorgement results in apoptosis of the secretory cells and, hence, regression of the mammary gland. Milk yield is linked to alveolar populations, with secretion rates being modulated by nutrition and udder fill effects. The model was used to investigate different management scenarios, and is in agreement with experimental results. The model shows that while milking frequency drives alveolar population, and therefore potential milk production, actual production varies considerably with nutrition. A significant portion of the loss associated with once-daily milking was due to udder fill rather than loss of secretory tissue. The model showed qualitative agreement with experimental data, on the acute and chronic effects of temporary once-daily milking.

Animal Nutritional Physiological Phenomena↗

PubMed2003

Modeling the effect of energy status on mammary gland growth and lactation.

The impact of nutrition on lactation can be separated into acute effects, affecting day-to-day yield, and chronic effects, which govern the persistency of lactation and rate of decline of the lactation curve. A mathematical model of the mammary gland was constructed to investigate both acute and chronic effects. Mammary growth is expressed in terms of the dynamics of populations of active (secreting) and quiescent (engorged) alveoli. The secretion rate of active alveoli is expressed in terms of the energy status of the dam. The model was fitted to data from a 2 x 2 factorial trial in which lactation curves were measured for heifers of two different genotypes (North American and New Zealand Holstein-Friesians) fed two different diets [grass and total mixed rations (TMR)]. Total formation of alveoli during pregnancy and lactation was statistically the same across all groups despite differences between diets, in the rate of formation of alveoli at parturition. The senescence rate of alveoli was significantly higher for heifers fed grass compared with heifers fed TMR, which corresponds to better persistency for heifers fed TMR. Heifers fed TMR had a higher rate of reactivation of quiescent alveoli than heifers fed grass, which also contributes to increased persistence for heifers fed TMR. There was a genotype x diet interaction in the rate of quiescence of active alveoli: the North American-Grass group had a higher rate of quiescence than the other three groups, perhaps reflecting differences in selection pressures between the New Zealand and North American genotypes.

Animal Nutritional Physiological Phenomena↗

PubMed2003

Transition to raloxifene with and without low-dose estrogen therapy in postmenopausal women: effects on serum lipids and fibrinogen - a pilot study.

OBJECTIVE: To compare the effects of transferring from low-dose transdermal estrogen to raloxifene (RLX), with a phase of alternate-day RLX therapy with or without low-dose transdermal estrogen, on serum lipids and fibrinogen in postmenopausal women previously administered estrogen plus progestogen therapy. METHODS: Sixty postmenopausal women (mean age 55 years) were randomized to one of two treatment groups: RLX + low-dose transdermal estrogen (RLX + E) or RLX + placebo. The study consisted of four 8-week phases: phase I (all subjects low-dose transdermal estrogen 25 microg/day), phase II (double-blind RLX 60 mg every 2nd day in combination with either low-dose transdermal estrogen or placebo), phase III (all subjects RLX 60 mg every 2nd day + placebo) and phase IV (all subjects RLX 60 mg/day + placebo). RESULTS: No significant differences existed between groups for baseline measurements prior to phase I. In phase I, for all subjects combined, total cholesterol and low-density lipoprotein cholesterol both showed a significant increase (median increase of 0.2 mmol/l, p = 0.008 and 0.4 mmol/l, p< 0.001, respectively), while triglycerides decreased significantly (median decrease of 0.2 mmol/l, p< 0.001). For the primary analysis (phase II to phase IV), the mean change from baseline observations showed no significant differences between the therapy groups for serum lipids, fibrinogen, vital signs or weight. In the comparison phase (phase II), changes in serum lipids, fibrinogen, vital signs and weight were not significantly different between groups. CONCLUSION: Gradual conversion to RLX from low-dose transdermal estrogen, with a phase of alternate-day RLX therapy with or without low-dose transdermal estrogen, does not have any effect on the serum lipid profile or fibrinogen level.

Administration, Cutaneous↗

PubMed2002

Influence of milking frequency on mammary gland dynamics.

The effects of milking frequency on milk production is a key question for the dairy industry. Milk production is related to the number of active alveoli in the mammary gland and movement between active and quiescent alveolar pools is influenced by the milking frequency. In this paper, we analyse a mechanistic model based on known biological inputs that describes the effect of milking frequency on the alveolar composition of the mammary gland. It is shown that the model can qualitatively reproduce the correct alveolar dynamics. We also investigate the model robustness and parameter sensitivity. Additionally, by making the plausible assumption that the senescence rate of alveoli is proportional to the number of quiescent alveoli present, we obtain an analytical solution requiring periodic resetting.

Animals↗