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Biomedical subjects

E Gold

Publications and source records attributed to E Gold.

At least 19 recordsLinked to original sources

Abnormal anxiety-related behavior in serotonin transporter null mutant mice: the influence of genetic background.

Serotonin transporter (5-HTT) null mutant mice provide a model system to study the role genetic variation in the 5-HTT plays in the regulation of emotion. Anxiety-like behaviors were assessed in 5-HTT null mutants with the mutation placed on either a B6 congenic or a 129S6 congenic background. Replicating previous findings, B6 congenic 5-HTT null mutants exhibited increased anxiety-like behavior and reduced exploratory locomotion on the light <--> dark exploration and elevated plus-maze tests. In contrast, 129S6 congenic 5-HTT null mutant mice showed no phenotypic abnormalities on either test. 5-HTT null mutants on the 129S6 background showed reduced 5-HT(1A) receptor binding (as measured by quantitative autoradiography) and reduced 5-HT(1A) receptor function (as measured by 8-OH-DPAT-induced hypothermia). These data confirm that the 5-HTT null mutation produced alterations in brain 5-HT function in mice on the 129S6 background, thereby discounting the possibility that the absence of an abnormal anxiety-like phenotype in these mice was due to a suppression of the mutation by 129 modifier genes. Anxiety-like behaviors in the light <--> dark exploration and elevated plus-maze tests were significantly higher in 129S6 congenic +/+ mice as compared to B6 congenic +/+ mice. This suggests that high baseline anxiety-like behavior in the 129S6 strain might have precluded detection of the anxiety-like effects of the 5-HTT null mutation on this background. Present findings provide further evidence linking genetic variation in the 5-HTT to abnormalities in mood and anxiety. Furthermore, these data highlight the utility of conducting behavioral phenotyping of mutant mice on multiple genetic backgrounds.

Animals↗

Conceptualizing menopause and midlife: Chinese American and Chinese women in the US.

OBJECTIVES: The purpose of this qualitative project was to describe and examine expectations and experiences of menopause and midlife in pre- and postmenopausal Chinese American and Chinese women in the United States. METHODS: Four focus groups were formed from a total of 44 women: two groups of premenopausal Chinese/Chinese American women (one conducted in English and one in Cantonese) and two groups of postmenopausal Chinese/Chinese American women (one conducted in English and one in Cantonese). Qualitative data, in the form of transcripts, were interpreted using text-based content analysis. RESULTS: The major thematic findings were: meanings of menopause are inextricably bound with meanings of midlife; the borders and timing of the menopausal transition are ambiguous; the menopausal transition represents a natural progression through the life cycle; the expectations of the premenopausal women did not match the experiences of the postmenopausal women; menopause is viewed as a marker for aging; and the menopausal transition must be prepared for and managed. CONCLUSIONS: Study findings indicate that the participants did not share the strictly medicalized view of menopause as a discrete, biological entity. Menopause was typically described as a natural transition that was virtually interchangeable with midlife. While most of the participants characterized menopause as signaling the end of fertility and virtually synonymous with old age, some women described it as a new opportunity and a second chance at life. Participants felt a sense of their own agency in addressing what they viewed as a complex life stage, the experience of which could be manipulated.

Adult↗

High-dose chemotherapy and hematopoietic stem cell rescue for breast cancer: experience in California.

The role of high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell rescue in breast cancer is still controversial. We analyzed the outcomes of 1111 consecutive patients with histologically proven breast cancer who underwent HDCT at 5 major California medical centers. The overall treatment-related mortality (TRM) was 2.3%. TRM was not influenced by disease stage or the HDCT regimen delivered, but it was influenced by hematopoietic graft source. The TRM was 6.1% when bone marrow with or without blood stem cells was used, but only 1.4% when blood stem cells alone were used (P < .001). With a median follow-up of 2.8 years (range, 0.1-8.2 years) after HDCT and autologous hematopoietic stem cell rescue, the estimated 5-year event-free survival (EFS) and overall survival (OS) for stage II/IIIA patients with > or =10 involved axillary lymph nodes were 67% and 76%, respectively. Patients with metastatic breast cancer (MBC) (median follow-up, 1.9 years [range, 0.03-8.3 years]) achieving a complete response (CR) to conventional-dose chemotherapy or rendered to a "no evidence of disease" status before HDCT had significantly better estimated 5-year EFS and OS (28% and 57%, respectively) than those achieving a partial response before HDCT (19% and 27%, respectively; P < or = .0001). Our data suggest that HDCT with hematopoietic stem cell rescue is safe and can be beneficial to patients with high-risk primary breast cancer and for those with MBC achieving CR/no evidence of disease.

Antineoplastic Combined Chemotherapy Protocols↗

High-dose chemotherapy (CTM) for breast cancer.

We designed and implemented a new mitoxantrone-based high-dose chemotherapy regimen to minimize pulmonary injury (seen in carmustine-based regimens) in patients with breast cancer. One hundred and ninety-one breast cancer patients (99 stage II/IIIA; 27 stage IIIB; 65 stage IV responsive to conventional-dose chemotherapy) were treated with high-dose chemotherapy (CTM) delivered over 4 days (cyclophosphamide (6 g/m2), thiotepa (600 mg/m2), and mitoxantrone (24-60 mg/m2)) followed by autologous hematopoietic stem cell rescue. Stage II/III patients received chest wall radiation and tamoxifen (if hormone-receptor positive) after CTM. The 5-year event-free survival (EFS) for stage II/IIIA patients with 10 or more involved axillary lymph nodes (n = 80) was 62 +/- 12%. Hormone receptor-positive patients with 10 or more nodes did significantly better than negative patients. The EFS for stage IIIB patients at 5 years was 44 +/- 19%; for stage IV patients at 5 years was 17 +/- 10%. Stage IV patients achieving complete response in viscera and/or soft tissue prior to CTM did significantly better than those achieving a partial response. There were six (3%) treatment-related deaths including two due to diffuse alveolar hemorrhage. There were no episodes of delayed interstitial pneumonitis. There were six severe cardiac events in 91 patients (6.6%) but none after instituting mitoxantrone dose-adjustment in the final 100 patients. We conclude that CTM is associated with a low treatment-related mortality and little pulmonary toxicity. CTM produces excellent outcomes in stage II/IIIA patients with 10 or more involved axillary lymph nodes.

Adult↗

The geoepidemiology of primary biliary cirrhosis: contrasts and comparisons with the spectrum of autoimmune diseases.

Recent data have suggested that the prevalence of many autoimmune diseases is higher than originally suspected. Indeed, the incidence of some autoimmune diseases may be increasing. Part of the problem in these latter two issues is that there is a dearth of well-designed and controlled epidemiologic studies, and often confounding variables in diverse populations and geographic areas that are not well controlled. Primary biliary cirrhosis (PBC) is a highly directed, organ-specific autoimmune disease that results in the destruction of intrahepatic bile ducts. It is primarily a disease of middle-aged women. Although there is no obvious association with MHC class I or class II alleles, the relative risk of a family member of a first-degree relative within a family having a member with PBC is a hundred-fold that of the general population. Unfortunately, most epidemiologic studies have been descriptive, providing incidence and prevalence rates with many methodologic problems, including lack of an appropriate case definition, varying criteria for inclusion of cases, and inaccurate estimate of the time period to which the rate applies. Because PBC is a very definable disease with significant clinical and serologic overlaps among patients throughout the world, we believe that a review of the geoepidemiology of PBC is not only specifically of value to workers interested in autoimmune liver disease, but also of generic interest in the study of autoimmune disease. In this review, we discuss the nature of the existing epidemiologic data and the possible roles of genetic and environmental factors in the etiology of the disease and compare such data to similar observations for multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis.

Autoimmune Diseases↗

Lactose malabsorption and rate of bone loss in older women.

OBJECTIVES: to study the prevalence of lactose malabsorption with increasing age and to determine whether lactose malabsorbers consume less dietary calcium, have lower bone mineral density or display faster bone loss than lactose absorbers. DESIGN: 80 healthy Caucasian women aged 40-79 years (20 per decade) were studied for 1 year. METHODS: breath hydrogen exhalation was measured for 3 after a 50 g oral lactose challenge. Bone density was assessed in the radius, femoral neck, lumbar spine and total body by dual energy x-ray absorptiometry and dietary calcium intake was estimated by 4-day diet records and food-frequency questionnaires. RESULTS: lactose malabsorption rose with age (15% in those aged 40-59 years versus 50% in those aged 60-79; P < 0.01). Malabsorbers aged 70-79 years consumed significantly less calcium than lactose absorbers of this age (P < 0.05). Baseline total body calcium values were lower in lactose malabsorbers (n=26) than in lactose absorbers (n=54) but age-adjustment eliminated this difference. Bone change (% per year) was correlated with dietary calcium intake at the femoral neck and trochanter (P < 0.05) but was not statistically greater in malabsorbers than in absorbers. CONCLUSIONS: the ability to absorb lactose declines in the 7th decade. This may contribute to decreased dietary intakes of milk products and calcium in elderly women. However, lactose malabsorption without reduction in calcium intake has little effect on bone mineral density or the rate of bone loss.

Adult↗

Validity of DSM-IV attention-deficit/hyperactivity disorder for younger children.

OBJECTIVE: Little is known about the validity of the diagnosis of attention-deficit/hyperactivity disorder (ADHD) in young children. Moreover, the results of the DSM-IV field trials raised concerns that inclusion of the new predominantly hyperactive-impulsive type of ADHD in DSM-IV might increase the likelihood of the diagnosis being given to active but unimpaired preschool and primary school children. METHOD: The validity of DSM-IV criteria for each subtype of ADHD was evaluated in 126 children, aged 4 through 6 years, and 126 matched comparison children. Probands and controls were classified by using structured diagnostic interviews of the parent and a DSM-IV checklist completed by the teacher. RESULTS: Children who met DSM-IV criteria for each subtype of ADHD according to parent and teacher reports differed consistently from controls on a wide range of measures of social and academic impairment, even when other types of psychopathology and other potential confounds were controlled. CONCLUSIONS: When diagnosed by means of a structured diagnostic protocol, all three DSM-IV subtypes of ADHD are valid for 4- through 6-year-old children in the sense of identifying children with lower mean scores on measures of adaptive functioning that are independently associated with ADHD.

Attention Deficit Disorder with Hyperactivity↗

Women with past history of bone fracture have low spinal bone density before menopause.

AIMS: Recent work from our laboratory has demonstrated that young girls with bone fractures have low spinal bone density more often than girls who have never fractured. This study was undertaken to determine whether adult women approaching menopause who have any past history of fracture have lower spinal density than women who have never fractured. METHODS: A lifetime fracture history was taken from all premenopausal women (n = 59) enrolled in a clinical trial examining the effect of menopause on cardiac risk. Bone mineral density of the lumbar spine was measured at study entry by dual energy x-ray absorptiometry (Lunar DPX-L) and results from patients with and without fracture were compared. RESULTS: Women with a previous history of fracture (n = 23) had significantly lower bone density (6% less) than the women who had never broken a bone (n = 36). CONCLUSIONS: We conclude that women who report a previous history of fracture, either as young adults or in childhood, should be targeted for perimenopausal screening for osteoporosis since they are likely to have lower bone density and a greater risk of future fracture than women with no past history of fracture.

Absorptiometry, Photon↗

Gender differences in body fat content are present well before puberty.

To determine whether gender differences in body fat could be detected in prepubertal children using dual energy X-ray absorptiometry (DEXA), body composition was measured in 20 healthy boys aged 3-8 y matched for age, height and weight with 20 healthy girls. Although boys and girls did not differ in age, height, weight, body mass index (BMI) or bone mineral content, the boys had a lower percentage of body fat (13.5 +/- 5.1 vs 20.4 +/- 6.1%, P < 0.01), a lower fat mass (3.2 +/- 2.0 vs 4.9 +/- 3.1 kg, P < 0.01), and a higher bone-free lean tissue mass (18.6 +/- 4.3 vs 17.0 +/- 3.5 kg, P < 0.01) than the girls. Girls had approximately 50% more body fat than the boys. This is the first DEXA study to show that boys aged 3-8 y have less body fat than girls of similar age, height and weight. Thus, this technology demonstrates that significant gender differences in body composition are evident, well before the onset of puberty.

Absorptiometry, Photon↗

Effects of hysterectomy on bone in intact rats, ovariectomized rats, and ovariectomized rats treated with estrogen.

To determine whether the uterus plays any role in mediating the ability of estrogen to conserve bone in the rat, eight groups of animals (n = 8) with their skeletons labeled with 45Ca were studied. Rats were ovariectomized (OVX), hysterectomized (Hyst), or given sham operations (Sham) and then pair-fed a low-hydroxyproline casein diet for 4 weeks. The groups were treated orally with 17 beta-estradiol (E2) or vehicle, and serial measurements of biochemical markers of bone breakdown were made in weeks 1, 2, and 4. The femur density was measured by dual-energy X-ray absorptiometry (DXA), and skeletal calcium and 45Ca content were determined chemically. Final total body calcium values (mg) in the eight treatment groups were (means +/- SD): Sham, 2573 +/- 179; Sham + E2, 2635 +/- 159; Hyst, 2537 +/- 151; Hyst + E2, 2410 +/- 151; OVX, 2189 +/- 146; OVX + E2, 2559 +/- 172; OVX/Hyst, 2138 +/- 132; and OVX/Hyst + E2, 2460 +/- 140. Ovariectomy raised biochemical markers of bone resorption (urinary 45Ca, hydroxyproline, and deoxypyridinoline), lowered DXA bone mineral density, and reduced total body calcium and 45Ca content in both Hyst and Sham-Hyst animals (p < 0.001), whereas E2 treatment prevented these changes. Hysterectomy did not impair the ability of E2 to conserve bone in OVX rats. Thus, we conclude that estrogen-mediated induction of growth factors from uterine tissue does not play an essential role in mediating the bone-conserving actions of estrogen in the rat.

Animals↗

Changing femoral geometry in growing girls: a cross-sectional DEXA study.

In elderly women, a long hip axis length has been shown to increase the risk of hip fracture. However, to date, few measurements of hip geometry have been reported in children and adolescents. The present cross-sectional dual-energy X-ray absorptiometry (DEXA) study of 200 girls aged 3-16 years was undertaken to determine at what age adult hip geometry is achieved and to examine possible influences of anthropometry and body composition on the development of femur axis length (FAL) and femur width (FW) during growth. Adult values for FAL and FW were achieved by age 15 years. Age, height, lean tissue mass, total body bone mineral content (BMC), weight, FW, neck of femur bone mineral density (BMD), and fat were each strongly associated with FAL (p < 0.001), the highest correlations being with age (r = 0.917) and height (r = 0.906). However, after adjusting for age and height, only lean tissue mass, weight, and fat mass remained significantly associated with FAL, suggesting that bone mineral accrual does not influence variance in FAL. Our results also suggested that fat mass and weight per se tended to have greater influence on FW than on FAL in age- and height-adjusted data. Twin studies indicate that 20% of adult hip axis length is associated with environmental factors. We therefore conclude that any environmental effects of physical activity or nutrition on hip geometry must occur before early teen-age years.

Absorptiometry, Photon↗

Regional body fat distribution in relation to pubertal stage: a dual-energy X-ray absorptiometry study of New Zealand girls and young women.

A cross-sectional study of 140 healthy, non-obese women and growing girls aged 8-27 y was undertaken to examine changes in total-body and regional fat and fat-free lean tissue mass by Tanner stage of pubertal development with dual-energy X-ray absorptiometry. Absolute fat mass and absolute fat-free lean tissue mass were higher at successive Tanner stages (1 through 5) but the proportional increase was greater for fat: total fat mass (kg) was about threefold higher in Tanner stage 5 than in stage 1 (P < 0.001), whereas lean tissue mass (kg) in Tanner stage 5 was about double that in stage 1 (P < 0.001). Furthermore, although the regional distribution of lean tissue mass in the trunk and legs remained fairly constant at different pubertal stages, the regional distribution of fat was altered significantly, becoming more central and less peripheral. Trunk fat (as a percentage of total body fat) was significantly higher at stage 5 than at stage 1 (P < 0.001). In the whole population, body mass index was positively correlated with trunk fat (r = 0.662, P < 0.0001) and negatively with leg fat (r = -0.457, P < 0.0001). We conclude that girls accumulate a higher proportion of their total adult fat mass than of their total adult lean tissue mass during puberty, and that regional fat patterns become more android and less gynoid with maturity.

Absorptiometry, Photon↗

Regional body fat distribution in New Zealand girls aged 4-16 years: a cross-sectional study by dual energy X-ray absorptiometry.

OBJECTIVE: To measure total body fat content and its regional distribution within the body (head, arms, legs and trunk) in young girls and adolescents in relation to age and body mass index (BMI). DESIGN: Cross-sectional observational study. SUBJECTS: 196 healthy Caucasian girls aged 4-16 years living in an urban town in the South Island of New Zealand. MEASUREMENTS: Body weight, height and BMI. Total body fat mass (kg) and the regional distribution of this fat (measured by dual energy X-ray absorptiometry). RESULTS: All the measured variables, including total and % fat mass were higher in older age groups. Regional distribution of fat differed, with older girls having a higher proportion of their body fat in the trunk and a smaller proportion of their body fat in the heat than younger girls. BMI was positively correlated with % trunk fat (r = 0.700) and negatively correlated with % leg fat (r = -0.465). Girls with higher levels of adiposity (> 75th percentile for BMI) stored more fat in the trunk and correspondingly less in the legs than girls with lower adiposity (< or = 75th percentile for BMI) at five of the six age groups (P < 0.05). CONCLUSION: It is concluded that body fat mass increases and shows a more central distribution in young girls as they grow older. Increasing adiposity as determined by BMI is associated with an increase in fat deposition in the trunk and a decrease in the legs.

Absorptiometry, Photon↗

DEXA supports the use of BMI as a measure of fatness in young girls.

OBJECTIVE: To examine the relationship of body fat mass measured by dual energy X-ray absorptiometry (DEXA) to BMI in young girls, according to age and normative BMI percentile groupings. DESIGN: Cross-sectional observation study. SETTING: Dunedin, an urban town in the South Island of New Zealand. SUBJECTS: 196 healthy Caucasian girls aged 4-16 y. MEASUREMENTS: Body weight, height and BMI, total fat mass and % body fat (by DEXA). RESULTS: Our BMI percentile standard groupings were < 5 centile (n = 7); 5-50 centile (n = 71); 51-75 centile (n = 50); 76-90 centile (n = 42); 91-95 centile (n = 12); > 95 centile (n = 14). In this whole population sample DEXA-derived fat mass correlates well with BMI (n = 0.934) indicating that BMI accounts for 87.2% of the variance in body fat mass. However, at the extremes of BMI the association is weaker. A nomogram for predicting DEXA fat mass from BMI in girls is presented. CONCLUSION: Because DEXA-derived fat mass correlates well with BMI throughout the 'normal' range of BMI (5-95th centiles) our study supports the usefulness of BMI as a simple measure of fatness in girls. Children with BMI values outside the normal BMI range may benefit from more exact body composition assessment using DEXA.

Absorptiometry, Photon↗

Tamoxifen and norethisterone: effects on plasma cholesterol and total body calcium content in the estrogen-deficient rat.

It is important that drugs which are used to protect bone from the osteoporotic effects of estrogen deficiency should not affect plasma lipids adversely. Effects of a) norethisterone acetate and b) tamoxifen citrate on plasma cholesterol and on bone conservation in rats with normal plasma 17B-estradiol and in rats made estrogen-deficient with the LHRH agonist, buserelin are reported. Tamoxifen halved total plasma cholesterol (p < 0.01), whereas norethisterone did not lower plasma cholesterol. Furthermore tamoxifen fully protected bone from estrogen-deficiency osteopenia whereas norethisterone conserved bone less well. Reductions in cholesterol elicited by tamoxifen were similar in estrogen-deficient rats and in rats with normal ovarian function. This is the first report in the rat that tamoxifen has lipid-lowering actions. It is suggested the rat may be useful for future investigations of the lipid-lowering mechanisms of tamoxifen.

Animals↗