Biomedical subjects

J Fox

Publications and source records attributed to J Fox.

At least 19 recordsLinked to original sources

PubMed2000

Computer support for interpreting family histories of breast and ovarian cancer in primary care: comparative study with simulated cases.

OBJECTIVES: To evaluate the potential effect of computer support on general practitioners' management of familial breast and ovarian cancer, and to compare the effectiveness of two different types of computer program. DESIGN: Crossover experiment with balanced block design. PARTICIPANTS: Of a random sample of 100 general practitioners from Buckinghamshire who were invited, 41 agreed to participate. From these, 36 were selected for a fully balanced study. INTERVENTIONS: Doctors managed 18 simulated cases: 6 with computerised decision support system Risk Assessment in Genetics (RAGs), 6 with Cyrillic (an established pedigree drawing program designed for clinical geneticists), and 6 with pen and paper. MAIN OUTCOME MEASURES: Number of appropriate management decisions made (maximum 6), mean time taken to reach a decision, number of pedigrees accurately drawn (maximum 6). Secondary measures were method of support preferred for particular aspects of managing family histories of cancer; importance of specific information on cancer genetics that might be provided by an "ideal computer program." RESULTS: RAGs resulted in significantly more appropriate management decisions (median 6) than either Cyrillic (median 3) or pen and paper (median 3); median difference between RAGs and Cyrillic 2.5 (95% confidence interval 2.0 to 3.0; P<0.0001). RAGs also resulted in significantly more accurate pedigrees (median 5) than both Cyrillic (median 3.5) and pen and paper (median 2); median difference between RAGs and Cyrillic 1.5 (1.0 to 2.0; P<0.0001). The time taken to use RAGs (median 178 seconds) was 51 seconds longer per case (95% confidence interval 36 to 65; P<0.0001) than pen and paper (median 124 seconds) but was less than Cyrillic (median 203 seconds; difference 23. (5 to 43; P=0.02)). 33 doctors (92% (78% to 98%)) preferred using RAGs overall. The most important elements of an "ideal computer program" for genetic advice in primary care were referral advice, the capacity to create pedigrees, and provision of evidence and explanations to support advice. CONCLUSIONS: RAGs could enable general practitioners to be more effective gatekeepers to genetics services, empowering them to reassure the majority of patients with a family history of breast and ovarian cancer who are not at increased genetic risk.

Breast Neoplasms↗

PubMed2000

Not just a pretty face: physical attractiveness and perfectionism in the risk for eating disorders.

OBJECTIVE: Considerable research has examined the correlates and consequences of both objective and subjective ratings of physical attractiveness. Numerous studies have found, for example, that subjective physical attractiveness is inversely related to weight and diet concerns. Surprisingly, however, no research has examined the relationship between objective physical beauty and eating pathologies, despite clinical and theoretical reasons to expect a positive relationship between the two. METHOD: We rated 203 young women on facial attractiveness and obtained self-report measures of perfectionism, neuroticism, and weight preoccupation. RESULTS: Attractiveness was positively related to weight preoccupation after controlling for body size and neurotic perfectionism. DISCUSSION: These findings provide the first evidence of physical beauty as a risk for disordered eating, and confirm earlier evidence that the relationship between general perfectionism and disordered eating only occurs when combined with a tendency to be anxious and hypercritical. Results are discussed in the context of identity formation and the attractiveness stereotype.

Adult↗

PubMed2000

Daily transient decreases in plasma parathyroid hormone levels induced by the calcimimetic NPS R-568 slows the rate of bone loss but does not increase bone mass in ovariectomized rats.

Daily parathyroid hormone (PTH) injections that transiently increase plasma PTH levels within the physiological range increase bone mass in osteopenic, ovariectomized (ovx) rats. This study tested the hypothesis that repeated transient decreases in plasma PTH levels from normal, induced by the daily oral administration of the calcimimetic NPS R-568, would induce an anabolic effect in bone of ovx rats with established osteopenia and/or prevent the rapid bone loss that occurs following ovx. In the reversal study, NPS R-568 was administered orally (10 or 100 micromol/kg) for 30 days to 14-month-old retired breeder rats that were ovx 5 months earlier. NPS R-568 treatment did not increase bone formation rate (BFR) or cancellous bone area (B.Ar) in the proximal tibial metaphysis, or bone mineral density (BMD), at any femoral site. In the prevention study, 3-month-old virgin rats were ovx and given NPS R-568 for the following 28 days. The 10 micromol/kg dose prevented the increase in osteoclast number and 42% of the loss of B.Ar, without affecting the elevated osteoblast populations or BFR. Surprisingly, the 100 micromol/kg dose had fewer protective effects, despite preventing the increase in BFR in both cancellous and cortical bone. Detailed analysis of cancellous bone showed that tendency for a dose-related protection of true cancellous bone occurred, but, while the 10 micromol/kg dose prevented 88% of the loss of calcified cartilage seen in control ovx rats, the 100 micromol/kg dose increased that loss by a further 31%. The mechanism underlying these disparate effects of NPS R-568 on calcified cartilage accumulation in the tibial metaphysis is unclear, but may be related to the different effects that the two doses have on plasma Ca(2+) levels. In conclusion, transient increases in PTH levels above basal, and not simple oscillations in hormone levels below normal, appear necessary for the anabolic properties of endogenous PTH to be manifested in the bones of osteopenic ovx rats.

Aniline Compounds↗

PubMed2000

Daily intermittent decreases in serum levels of parathyroid hormone have an anabolic-like action on the bones of uremic rats with low-turnover bone and osteomalacia.

The calcium receptor agonist (calcimimetic) compound NPS R-568 causes rapid decreases in circulating levels of parathyroid hormone (PTH) in rats and humans. We hypothesized that daily intermittent decreases in serum PTH levels may have different effects on bone than do chronically sustained decreases. To test this hypothesis, we compared two NPS R-568 dosing regimens in rats with chronic renal insufficiency induced by two intravenous injections of adriamycin. Fourteen weeks after the second adriamycin injection, creatinine clearance was reduced by 52%, PTH levels were elevated approximately 2.5-fold, and serum 25(OH)D3 and 1,25(OH)2D3 levels were reduced substantially. Treatment by daily per os gavage, which decreased PTH levels intermittently, or continuous subcutaneous infusion, which resulted in a sustained suppression of serum PTH levels, then began for 8 weeks. Despite the hyperparathyroidism, the adriamycin-injected rats developed a low-turnover bone lesion with osteomalacia (fourfold increase in osteoid volume in the proximal tibial metaphysis) and osteopenia (67% decrease in cancellous bone volume and an 18% reduction in bone mineral density at the distal femur). Daily administered (but not infused) NPS R-568 significantly increased cancellous bone volume solely by normalizing trabecular thickness, and increased femoral bone mineral density by 14%. These results indicate that daily intermittent, but not sustained, decreases in PTH levels have an "anabolic-like" effect on bones with a low-turnover lesion in this animal model of chronic renal insufficiency.

Aniline Compounds↗

PubMed2000

Calcimimetic NPS R-568 prevents parathyroid hyperplasia in rats with severe secondary hyperparathyroidism.

UNLABELLED: Calcimimetic NPS R-568 prevents parathyroid hyperplasia in rats with severe secondary hyperparathyroidism. BACKGROUND: Secondary hyperparathyroidism (secondary HPT) in chronic renal insufficiency (CRI) is characterized by multiglandular hyperplasia. METHODS: In this study, we investigated the effects of the calcimimetic NPS R-568 on the parathyroid gland in rats with CRI induced by ligation of the renal arteries and severe secondary HPT induced by dietary phosphorus loading. Six days after surgery, high-phosphorus diet feeding was started, and NPS R-568 was administered to the rats for 56 days either by daily gavage (30 or 100 micromol/kg) or by continuous subcutaneous infusion (20 micromol/kg. day). RESULTS: After 54 days, serum PTH levels in vehicle-treated CRI rats were 1019 vs. 104 pg/mL in sham-operated controls. Infusion of NPS R-568 maintained serum PTH at levels comparable with those of sham-operated controls, whereas daily gavage also prevented much of the increase in CRI controls and decreased PTH levels intermittently in a dose-dependent fashion. Parathyroid gland enlargement was caused predominantly by hyperplasia. Total cell number per kg body wt was 3.5-fold higher in vehicle-treated CRI rats than in sham-operated controls. Both infusion and high-dose gavage of NPS R-568 completely prevented the increase in parathyroid cell number. CONCLUSION: These results demonstrate that the calcimimetic compound NPS R-568 can prevent both the increase in serum PTH levels and parathyroid hyperplasia in rats with CRI and severe secondary HPT. Moreover, these changes occurred despite decreases in serum 1, 25(OH)2D3 and increases in serum phosphate, suggesting a dominant role for the calcium receptor in regulating parathyroid cell proliferation.

Aniline Compounds↗

PubMed2000

Effect of carbohydrate ingestion on glycogen resynthesis in human liver and skeletal muscle, measured by (13)C MRS.

This study investigated the effect of carbohydrate (CHO) ingestion on postexercise glycogen resynthesis, measured simultaneously in liver and muscle (n = 6) by (13)C magnetic resonance spectroscopy, and subsequent exercise capacity (n = 10). Subjects cycled at 70% maximal oxygen uptake for 83 +/- 8 min on six separate occasions. At the end of exercise, subjects ingested 1 g/kg body mass (BM) glucose, sucrose, or placebo (control). Resynthesis of glycogen over a 4-h period after treatment ingestion was measured on the first three occasions, and subsequent exercise capacity was measured on occasions four through six. No glycogen was resynthesized during the control trial. Liver glycogen resynthesis was evident after glucose (13 +/- 8 g) and sucrose (25 +/- 5 g) ingestion, both of which were different from control (P < 0.01). No significant differences in muscle glycogen resynthesis were found among trials. A relationship between the CHO load (g) and change in liver glycogen content (g) was evident after 30, 90, 150, and 210 min of recovery (r = 0.59-0. 79, P < 0.05). Furthermore, a modest relationship existed between change in liver glycogen content (g) and subsequent exercise capacity (r = 0.53, P < 0.05). However, no significant difference in mean exercise time was found (control: 35 +/- 5, glucose: 40 +/- 5, and sucrose: 46 +/- 6 min). Therefore, 1 g/kg BM glucose or sucrose is sufficient to initiate postexercise liver glycogen resynthesis, which contributes to subsequent exercise capacity, but not muscle glycogen resynthesis.

Adult↗

PubMed2000

Skeletal muscle myosin heavy chain isoforms and energy metabolism after clenbuterol treatment in the rat.

Prolonged treatment with the beta(2)-adrenoceptor agonist clenbuterol (1-2 mg. kg body mass(-1). day (-1)) is known to induce the hypertrophy of fast-contracting fibers and the conversion of slow- to fast-contracting fibers. We investigated the effects of administering a lower dose of clenbuterol (250 microgram. kg body mass(-1). day (-1)) on skeletal muscle myosin heavy chain (MyHC) protein isoform content and adenine nucleotide (ATP, ADP, and AMP) concentrations. Male Wistar rats were administered clenbuterol (n = 8) or saline (n = 6) subcutaneously for 8 wk, after which the extensor digitorum longus (EDL) and soleus muscles were removed. We demonstrated an increase of type IIa MyHC protein content in the soleus from approximately 0.5% in controls to approximately 18% after clenbuterol treatment (P < 0.05), which was accompanied by an increase in the total adenine nucleotide pool (TAN; approximately 19%, P < 0.05) and energy charge [E-C = (ATP + 0.5 ADP)/(ATP + ADP + AMP); approximately 4%; P < 0.05]. In the EDL, a reduction in the content of the less prevalent type I MyHC protein from approximately 3% in controls to 0% after clenbuterol treatment (P < 0.05) occurred without any alterations in TAN and E-C. These findings demonstrate that the phenotypic changes previously observed in slow muscle after clenbuterol administration at 1-2 mg. kg body mass(-1). day(-1) are also observed at a substantially lower dose and are paralleled by concomitant changes in cellular energy metabolism.

Adenosine Diphosphate↗

PubMed2000

Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats.

Parathyroid hormone (PTH) is an effective bone anabolic agent, but it must be administered parenterally. An orally active anabolic agent would provide a valuable alternative for treating osteoporosis. NPS 2143 is a novel, selective antagonist (a "calcilytic") of the parathyroid cell Ca(2+) receptor. Daily oral administration of NPS 2143 to osteopenic ovariectomized (OVX) rats caused a sustained increase in plasma PTH levels, provoking a dramatic increase in bone turnover but no net change in bone mineral density. Concurrent oral administration of NPS 2143 and subcutaneous infusion of 17beta-estradiol also resulted in increased bone turnover. However, the antiresorptive action of estrogen decreased the extent of bone resorption stimulated by the elevated PTH levels, leading to an increase in bone mass compared with OVX controls or to either treatment alone. Despite the sustained stimulation to the parathyroid gland, parathyroid cells did not undergo hyperplasia. These data demonstrate that an increase in endogenous PTH secretion, induced by antagonism of the parathyroid cell Ca(2+) receptor with a small molecule, leads to a dramatic increase in bone turnover, and they suggest a novel approach to the treatment of osteoporosis.

Animals↗

PubMed2000

Dynamic changes in the intrafollicular inhibin/activin/follistatin axis during human follicular development: relationship to circulating hormone concentrations.

Previous studies of normal human ovaries suggest that inhibins, activins, and follistatin (FS) are produced in a stage-specific pattern indicative of intraovarian, autocrine/paracrine roles in regulating follicle development. However, these studies relied largely on surgical specimens and thus include little information about the menstrual cycle stage or dominant follicle status at the time follicles or ovaries were obtained. The purpose of this study was to 1) determine the pattern of intrafollicular hormone biosynthesis across antral follicle development in normal women, 2) compare hormone concentrations in dominant and nondominant follicles from the same ovary, and 3) examine the relationship between dominant follicle hormone content and circulating hormone levels. Intrafollicular estradiol, progesterone, and inhibin A concentrations increased significantly with follicle size or maturity, whereas significant inverse relationships were observed for androstenedione and the androstenedione/estradiol (A:E) ratio. In contrast, neither inhibin B, activin A, nor free FS varied consistently with size or maturity. Estradiol, progesterone, and inhibin A levels and A:E ratio were significantly lower in nondominant follicles compared to the dominant follicle aspirated from the same ovary. Although intrafollicular and serum concentrations of each hormone followed the same general pattern as follicles develop, the human follicular fluid/serum gradients changed during the follicular phase and were different for estradiol and inhibin A, suggesting the presence of stage-specific differences in pharmacodynamics. These results are consistent with the hypothesis that the orderly transition from an activin-dominant to an inhibin A/FS-dominant microenvironment is critical for dominant follicle development.

Activins↗

PubMed2000

Cerebello-olivary and lateral (accessory) cuneate degeneration in a juvenile American Miniature horse.

A 12-month-old American Miniature horse colt was presented to the Virginia Tech Veterinary Teaching Hospital with a 7-month history of progressive ataxia. Physical examination revealed a head intention tremor, base-wide stance, and ataxia. Necropsy findings were confined to the brain. There were bilateral areas of liquefactive necrosis and cavitation corresponding to the dorsal accessory olivary and lateral (accessory) cuneate nuclei. Cerebellar folia of the dorsal vermis were thin. Microscopically, the cerebellar cortex was characterized by patchy areas of Purkinje cell loss with associated variable thinning of the molecular and granule cell layers and astrogliosis. Dorsal accessory olivary and lateral cuneate nuclei were cavitated and had mild glial response around their periphery. Additionally, a focus of necrosis and neuropil vacuolization was found in the right putamen. These findings indicate the presence of a neurodegenerative disorder centered, but not confined to, the cerebellum and its connections in this American Miniature horse colt.

Animals↗

PubMed2000

Paranormal belief, experience, and the Keirsey Temperament Sorter.

121 college students completed the Anomalous Experience Inventory and the Keirsey Temperament Sorter. Multiple regression analyses provided significant models predicting both Paranormal Experience and Belief; the main predictors were the other subscales of the Anomalous Experience Inventory with the Keirsey variables playing only a minor role.

Adult↗

PubMed2000

25 years of Population Trends.

This article monitors some of the more significant demographic changes over the last twenty-five years, depicted in various issues of Population Trends. It is, of necessity, selective in coverage in terms of quotes, figures and topics. Other articles in this issue go into more depth on specific topics, such as families, ethnic minority groups, marriage and divorce, health inequalities and fertility and family planning. Consequently, there is some overlap and the articles could usefully be cross-referenced. Some coverage is also given to the development of sources, international events and selected partnerships outside the Office. Relevant legislation enacted over the period is also mentioned.

Demography↗

PubMed1999

FGF receptor availability regulates skeletal myogenesis.

Fibroblast growth factors (FGFs) and their receptors are critical participants in embryonic development, including the genesis of skeletal, cardiac, and smooth muscle. FGF signaling is mediated through interactions between multiple FGF ligands and transmembrane tyrosine kinase receptors, resulting in activation of a number of signal transduction pathways. Skeletal myocytes express FGF ligands and receptors in a coordinated fashion, suggesting that these molecules participate in autocrine signaling in the myocyte. Endogenously produced FGF has been shown to inhibit myogenesis, but the role of FGF receptor availability in directing myocyte proliferation and differentiation has not been established. To determine the contribution of receptor availability to the regulation of myogenesis, receptor availability was either increased by expressing a full-length FGF receptor-1 or decreased by expressing a truncated FGF receptor-1 in cultured skeletal myocytes. Constitutive expression of a full-length FGF receptor-1 increased myocyte proliferation and delayed differentiation. Conversely, a reduction in functional FGF receptor signaling by expression of a truncated FGF receptor-1 decreased proliferation and enhanced differentiation of myocytes. These data demonstrate that FGF receptor availability plays a critical regulatory role in skeletal myogenesis.

Animals↗

PubMed1999

Computer support for recording and interpreting family histories of breast and ovarian cancer in primary care (RAGs): qualitative evaluation with simulated patients.

OBJECTIVES: To explore general practitioners' attitudes towards and use of a computer program for assessing genetic risk of cancer in primary care. DESIGN: Qualitative analysis of semistructured interviews and video recordings of simulated consultations. PARTICIPANTS: Purposive sample of 15 general practitioners covering a range of computer literacy, interest in genetics, age, and sex. INTERVENTIONS: Each doctor used the program in two consultations in which an actor played a woman concerned about her family history of cancer. Consultations were videotaped and followed by interviews with the video as a prompt to questioning. MAIN OUTCOME MESURESs: Use of computer program in the Consultation. RESULTS: The program was viewed as an appropriate application of information technology because of the complexity of cancer genetics and a sense of "guideline chaos" in primary care. Doctors found the program easy to use, but it often affected their control of the consultation. They needed to balance their desire to share the computer screen with the patient, driven by their concerns about the effect of the computer on doctor-patient communication, against the risk of premature disclosure of bad news. CONCLUSIONS: This computer program could provide the necessary support to assist assessment of genetic risk of cancer in primary care. The potential impact of computer software on the consultation should not be underestimated. This study highlights the need for careful evaluation when developing medical information systems.

Adult↗

PubMed1999

Mosaicism with a normal cell line and an unbalanced structural rearrangement.

Mosaicism with a normal cell line (N) and an unbalanced autosomal structural rearrangement (UASR) is rare. This report describes a case of a newborn female with a karyotype of 46,XX,der(4)t(4;15)(q35;q22)/46,XX. Molecular cytogenetic analysis confirmed the origin of the derivative chromosome 4. Here we discuss this case as well as other cases of mosaic karyotypes involving N/UASR.

Chromosome Aberrations↗

PubMed1999

Metal working fluid-associated hypersensitivity pneumonitis: an outbreak investigation and case-control study.

Occupational exposure to bacterial or fungal antigens has been associated with hypersensivity pneumonitis (HP), an immunologically-mediated pulmonary disease. Between August 1995 and April 1996, 34 employees working in machining and assembly areas of an engine manufacturing plant were clinically diagnosed with HP. Of these, 20 employees met an epidemiologic case definition. In a case-control study, no exposure variables, including duration and intensity of metal working fluid (MWF) exposure, were statistically associated with an increased risk of disease. Neither cases nor controls demonstrated precipitin reactivity against unused samples of the seven MWF and two biocides used in the plant. HP cases had a significantly higher prevalence of positive precipitin reactions to used oil soluble and synthetic MWFs. Reactivity to used but not unused MWF suggests a biocontaminant, probably bacteria or fungi, is the causative antigen in the development of HP in this setting.

Alveolitis, Extrinsic Allergic↗

PubMed1999

Mechanisms and impact of enteric infections.

The increased recognition of both old and new enteric pathogens and their potential impact requires an improved understanding of pathogenesis and effective interventions. While the overwhelming mortality (> 3 million children per year) due to diarrheal diseases is well-recognized, the potential long-term impacts of enteric infections and early childhood diarrhea morbidity are just beginning to be appreciated. Furthermore, several enteric infections are now being recognized as causes of growth shortfalls with or without diarrhea; i.e., malnutrition may be one of the greatest yet of the "emerging infectious diseases." The increased appreciation of this extended impact calls for further quantification and improved understanding of the deranged physiology. In particular, persistent diarrheal illnesses exhibit common themes of blunted villi, disruption of intestinal barrier function and varying degrees of sub-mucosal inflammation for which lactulose/mannitol permeability and fecal lactoferrin provide respective quantification. Finally, such improved understanding will allow targeted interventions among those most vulnerable, which will enable further documentation of cost effectiveness and the potential for improved human development which is critical to reducing the widening disparity and population overgrowth which increasingly threaten our global security.

Animals↗

PubMed1999

Naturally occurring GM2 gangliosidosis in two Muntjak deer with pathological and biochemical features of human classical Tay-Sachs disease (type B GM2 gangliosidosis).

Two juvenile sibling male Muntjak deer (Muntiacus muntjak) with histories of depression, ataxia, circling and visual deficits were studied. Cerebrospinal fluid analyses revealed vacuolated macrophages that contained long parallel needle-like intracytoplasmic inclusions. Light microscopically, nerve cell bodies throughout the brain, ganglion cells within the retina and neurons in the myenteric plexuses were variably swollen and had pale granular to finely vacuolated eosinophilic cytoplasm. Neuronal cytoplasm stained specifically with sudan black and Luxolfast blue stains. Within the brain there were occasional axonal spheroids, foci of astrogliosis and scattered microglial cells with abundant pale foamy cytoplasm. Electron microscopy of the brain and retina revealed numerous neurons and ganglion cells, respectively, with multiple membrane-bound structures that contained compact electron-dense membranous whorls and fewer parallel membranous stacks. Thin layer chromatography of total lipid extracts of the cerebral cortex of both cases revealed massive accumulation of G(M2) ganglioside. Crude kidney extracts of the two affected deer were able to hydrolyze 4-methylumbelliferyl beta-GlcNAc, but not 4-methylumbelliferyl beta-GlcNAc-6-sulfate, indicating the defect of beta-hexosaminidase A. Cellogel electrophoresis of the kidney extracts also revealed the deficiency of beta-hexosaminidase A in the two deer. It is concluded that these two deer had the biochemical lesion identical to that of human type B G(M2) gangliosidosis (classical Tay-Sachs disease).

Animals↗