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Biomedical subjects

D P Rice

Publications and source records attributed to D P Rice.

At least 19 recordsLinked to original sources
PubMed2000

Alcohol drinking patterns and medical care use in an HMO setting.

The objective of this study was to examine the association of medical care use (outpatient visits and hospitalization) with alcohol drinking patterns in a large health maintenance organization (HMO). Data were gathered from a random sample of 10,292 adult respondents through a telephone survey conducted between June 1994 and February 1996. Findings indicate that current nondrinkers with no past history of drinking had higher rates of outpatient visits and hospitalizations than current drinkers. Among current drinkers, medical care use declined slightly as drinking levels increased. Among nondrinkers, those with a drinking history exhibited significantly higher use of outpatient visits and hospital care than nondrinkers with no drinking history and current drinkers. Controlling for demographic and socioeconomic factors, health status, and common medical conditions in multivariate analyses suggests that nondrinkers with a drinking history use more services because they are sicker than other nondrinkers or current drinkers.

Adolescent↗
PubMed2000

Integration of FGF and TWIST in calvarial bone and suture development.

Mutations in the FGFR1-FGFR3 and TWIST genes are known to cause craniosynostosis, the former by constitutive activation and the latter by haploinsufficiency. Although clinically achieving the same end result, the premature fusion of the calvarial bones, it is not known whether these genes lie in the same or independent pathways during calvarial bone development and later in suture closure. We have previously shown that Fgfr2c is expressed at the osteogenic fronts of the developing calvarial bones and that, when FGF is applied via beads to the osteogenic fronts, suture closure is accelerated (Kim, H.-J., Rice, D. P. C., Kettunen, P. J. and Thesleff, I. (1998) Development 125, 1241-1251). In order to investigate further the role of FGF signalling during mouse calvarial bone and suture development, we have performed detailed expression analysis of the splicing variants of Fgfr1-Fgfr3 and Fgfr4, as well as their potential ligand Fgf2. The IIIc splice variants of Fgfr1-Fgfr3 as well as the IIIb variant of Fgfr2 being expressed by differentiating osteoblasts at the osteogenic fronts (E15). In comparison to Fgf9, Fgf2 showed a more restricted expression pattern being primarily expressed in the sutural mesenchyme between the osteogenic fronts. We also carried out a detailed expression analysis of the helix-loop-helix factors (HLH) Twist and Id1 during calvaria and suture development (E10-P6). Twist and Id1 were expressed by early preosteoblasts, in patterns that overlapped those of the FGF ligands, but as these cells differentiated their expression dramatically decreased. Signalling pathways were further studied in vitro, in E15 mouse calvarial explants. Beads soaked in FGF2 induced Twist and inhibited Bsp, a marker of functioning osteoblasts. Meanwhile, BMP2 upregulated Id1. Id1 is a dominant negative HLH thought to inhibit basic HLH such as Twist. In Drosophila, the FGF receptor FR1 is known to be downstream of Twist. We demonstrated that in Twist(+/)(-) mice, FGFR2 protein expression was altered. We propose a model of osteoblast differentiation integrating Twist and FGF in the same pathway, in which FGF acts both at early and late stages. Disruption of this pathway may lead to craniosynostosis.

Acrocephalosyndactylia↗
PubMed1999

Apoptosis in murine calvarial bone and suture development.

To study the possible role of apoptosis in calvarial bone and suture development, terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) was performed on whole mount and sectioned calvariae from mice aged between E14 and P6. We also analyzed by in situ hybridization the expression of Msx2, Bmp4 and Bmp7 genes, which are known to act in conserved signaling pathways leading to apoptosis. We found TUNEL-positive cells from E16 onwards in the calvarial bones, intervening sutures and fontanelles. TUNEL-positive osteoblasts and preosteoblasts were identified at or close to the osteogenic fronts, areas of intense osteogenic activity, with TUNEL-positive mesenchymal cells located in the midsutural mesenchyme. TUNEL-positive osteoclasts and osteocytes were also observed in a sporadic fashion, as well as TUNEL-positive dural cells. Msx2 was expressed in the sutural mesenchyme and the dura mater. Bmp4 was expressed in the developing bone, underlying dura mater, the osteogenic fronts, and also weakly in the sutural mesenchyme. Bmp7 was detected at the same locations as Bmp4 but with noticeably stronger intensity in the meninges and overlying epidermis. We propose that this apoptosis is part of normal suture development, and is integral to the balance between bone formation and resorption, so that abnormal apoptosis may lead to premature (Craniosynostosis) or delayed (Cleidocranial dysplasia) suture closure.

Animals↗
PubMed1999

The economic impact of schizophrenia.

Although schizophrenia afflicts 1.1% of the U.S. population, it imposes a disproportionately large economic burden due to expenditures for hospitalization, treatment and rehabilitation, and lost productivity. Cost-of-illness studies, using a variety of methodologies to calculate direct and indirect costs, have estimated that in 1990 the total economic burden of schizophrenia was $32.5 billion. Of this total, $17.3 billion was attributable to direct medical costs. By comparison, in the same year the total and direct medical costs for anxiety disorders, which are more than 10 times more prevalent than schizophrenia, were $46.6 billion and $10.7 billion, respectively. For affective disorders, almost 10 times more prevalent than schizophrenia, the total and direct costs were $30.4 billion and $19.2 billion, respectively. Effective treatments used early in the course of schizophrenia can help reduce the costs associated with this illness.

Adolescent↗
PubMed1998

FGF-, BMP- and Shh-mediated signalling pathways in the regulation of cranial suture morphogenesis and calvarial bone development.

The development of calvarial bones is tightly co-ordinated with the growth of the brain and needs harmonious interactions between different tissues within the calvarial sutures. Premature fusion of cranial sutures, known as craniosynostosis, presumably involves disturbance of these interactions. Mutations in the homeobox gene Msx2 as well as the FGF receptors cause human craniosynostosis syndromes. Our histological analysis of mouse calvarial development demonstrated morphological differences in the sagittal suture between embryonic and postnatal stages. In vitro culture of mouse calvaria showed that embryonic, but not postnatal, dura mater regulated suture patency. We next analysed by in situ hybridisation the expression of several genes, which are known to act in conserved signalling pathways, in the sagittal suture during embryonic (E15-E18) and postnatal stages (P1-P6). Msx1 and Msx2 were expressed in the sutural mesenchyme and the dura mater. FGFR2(BEK), as well as Bmp2 and Bmp4, were intensely expressed in the osteogenic fronts and Bmp4 also in the mesenchyme of the sagittal suture and in the dura mater. Fgf9 was expressed throughout the calvarial mesenchyme, the dura mater, the developing bones and the overlying skin, but Fgf4 was not detected in these tissues. Interestingly, Shh and Ptc started to be expressed in patched pattern along the osteogenic fronts at the end of embryonic development and, at this time, the expression of Bmp4 and sequentially those of Msx2 and Bmp2 were reduced, and they also acquired patched expression patterns. The expression of Msx2 in the dura mater disappeared after birth. FGF and BMP signalling pathways were further examined in vitro, in E15 mouse calvarial explants. Interestingly, beads soaked in FGF4 accelerated sutural closure when placed on the osteogenic fronts, but had no such effect when placed on the mid-sutural mesenchyme. BMP4 beads caused an increase in tissue volume both when placed on the osteogenic fronts and on the mid-sutural area, but did not effect suture closure. BMP4 induced the expression of both Msx1 and Msx2 genes in sutural tissue, while FGF4 induced only Msx1. We suggest that the local application of FGF on the osteogenic fronts accelerating suture closure in vitro, mimics the pathogenesis of human craniosynostosis syndromes in which mutations in the FGF receptor genes apparently cause constitutive activation of the receptors. Taken together, our data suggest that conserved signalling pathways regulate tissue interactions during suture morphogenesis and intramembranous bone formation of the calvaria and that morphogenesis of mouse sagittal suture is controlled by different molecular mechanisms during the embryonic and postnatal stages. Signals from the dura mater may regulate the maintenance of sutural patency prenatally, whereas signals in the osteogenic fronts dominate after birth.

Animals↗
PubMed1998

Health economics and cost implications of anxiety and other mental disorders in the United States.

BACKGROUND: Mental disorders impose a multi-billion dollar burden on the economy each year; translating the burden into economic terms is important to facilitate formulating policies about the use of resources. METHODS: For direct costs, data were obtained from national household interview and provider surveys; for morbidity costs, a timing model was used that measures the lifetime effect on current income of individuals with mental disorders, taking into account the timing of onset and the duration of these disorders, based on regression analysis of Epidemiologic Catchment Area study data. RESULTS: The total economic costs of mental disorders amounted to US$147.8 billion in 1990. Anxiety disorders are the most costly, amounting to $46.6 billion, or 31.5% of the total; schizophrenic disorders accounted for $32.5 billion, affective disorders for $30.4 billion, and other mental disorders for $38.4 billion. CONCLUSIONS: Mental illnesses, especially anxiety disorders, are costly to society. Although anxiety disorders have a higher prevalence than affective disorders and schizophrenia, use of medical care services is lowest for anxiety disorders. Anxiety disorders appear to be under-recognised and untreated even though treatment interventions have been shown to be effective and can be delivered in a cost-efficient manner.

Anxiety Disorders↗
PubMed1997

Detection of gelatinase B expression reveals osteoclastic bone resorption as a feature of early calvarial bone development.

Gelatinase B is a matrix metalloproteinase (MMP-9) produced by osteoclasts involved in bone resorption. Bone modeling, of which resorption is an integral part, is particularly evident in the intramembranous bones of the craniofacial region. To determine the role of osteoclasts in developing intramembranous bones we localized osteoclasts in calvariae from mice aged between embryonic day 16 and postnatal day 6, using gelatinase B and tartrate-resistant acid phosphatase activity (TRAP) as osteoclast markers. Through a combined approach of in situ hybridization and enzyme histochemistry, phenotypic differences between osteoclasts associated with calvarial bone were noted. Some cells expressed gelatinase B mRNA but were TRAP negative, whereas others demonstrated an overlap in enzyme profile exhibiting both TRAP activity and expressing gelatinase B mRNA. During more advanced development, most osteoclasts exhibited TRAP activity but did not express gelatinase B mRNA. The distribution of these cells differed, TRAP positive cells being detected in a widespread pattern at all ages, while gelatinase B transcripts were increasingly concentrated in areas of new and rapid bone growth, notably around the sutures. We propose the use of gelatinase B as an osteoclastic marker in the developing mouse. We conclude that gelatinase B may have a key role during early bone formation, the regulation of bone modeling, and perhaps in the maintenance of suture width.

Acid Phosphatase↗
PubMed1997

Catch-up growth induced by growth hormone in the craniofacial skeleton of the Snell strain of the hypopituitary dwarf mouse.

Immature Snell strain dwarf mice were treated with human growth hormone for 20 and 40 days, between the ages of 22 and 41 days and 22 and 61 days, respectively. Mature dwarfs were similarly treated for 20 and 40 days between the ages of 62 and 81 days and 62 and 101 days, respectively. These groups of treated mice were compared with untreated dwarfs and normal mice reared under the same conditions. The catch-up growth effected by human growth hormone on the craniofacial and somatic development of the Snell strain dwarf mouse at both immature and mature ages was considerable, overall being approximately 14 per cent. Neurocranial parameters tended toward the values of normal mice achieving 89-98 per cent of normal growth. Viscerocranial parameters showed greater catch-up, from a lower start point, reaching 81-93 per cent of the control. This catch-up in mature mice (aged 82-102 days) was at a time when any substantial growth in either dwarf or normal mice has usually ceased.

Age Factors↗
PubMed1997

The impact of aging and chronic disease on use of hospital and outpatient services in a large HMO: 1971-1991.

OBJECTIVES: To examine overall and diagnosis-specific trends in the use of inpatient and outpatient medical services (1970-1988) among older members of a large HMO. DESIGN: Two cohorts of approximately 3000 persons aged 65 or older in 1971 and 1980 were compared for hospital and outpatient utilization during 9-year follow-up periods (1971-79 and 1980-88). All subjects were evaluated for vital status throughout the follow-up period as well. PARTICIPANTS: All 6057 subjects were members of the Northern California Kaiser Permanente Medical Care Program in 1971 or 1980. The study sample was sex-age stratified (65-69,70-79,80+) at baseline. MEASUREMENTS: Data on demographics, outpatient health services utilization, categories of outpatient utilization and disease diagnoses were obtained from membership lists or medical chart review; inpatient utilization, including admitting and discharge diagnosis, length of stay, and number of hospital days was assessed from computerized hospitalization records. RESULTS: Hospital discharge rates (sex-age adjusted) increased by 12% between cohorts, with the largest increases at the oldest ages. There was a 25% increase among women and a 9% increase among men. Length of stay decreased by 20%. Hospitalization for ischemic heart disease decreased by 17%. Congestive heart failure (CHF) discharge rates (sex-age adjusted) were 92% higher in the 1980-88 cohort. For diagnoses related to nursing home institutionalization and frailty, discharge rates were significantly higher in the 1980-88 cohort: pneumonia (+34%), urinary tract infections (+104%), dehydration (+110%), osteoarthritis (+64%), syncope (+246%), leg cellulitis (+70%). In-hospital survival improved, but overall percent of readmissions also increased by 4%; readmissions for CHF increased by 13% and those for conditions of frailty by 120%. Overall outpatient visits increased by 17%. Use of laboratory tests (+57%) and outpatient surgeries (+99%) increased for all age strata in 1980-88 compared with 1971-79. CONCLUSIONS: While overall outpatient and inpatient utilization has largely decreased over the past 30 years, as a result of economic factors and improved treatments for some major diseases, there has been an increase in utilization among older people. Hospitalization for diagnoses associated with end-stage cardiovascular disease (CHF), musculoskeletal disease, frailty and iatrogenic aspects of institutionalization are clearly increasing substantially. The largest impact of aging on health care may be the result of institutionalization and its sequelae. Improved treatment for cardiovascular disease may also be leading to increased utilization at later stages in the disease process.

Aged↗
PubMed1996

Economic costs of anxiety disorders.

Anxiety disorders are estimated to affect 26.9 million individuals in the United States at some point during their lives. This study used the human capital approach to estimate the direct and indirect costs of these highly prevalent disorders. In 1990, costs associated with anxiety disorders were $46.6 billion, 31.5% of total expenditures for mental illness. Less than one-quarter of costs associated with anxiety disorders were for direct medical treatment; over three-quarters were attributable to lost or reduced productivity. Most of these indirect costs were associated with morbidity, as mortality accounted for just 2.7% of the total. Greater availability of effective, relatively low-cost outpatient treatment could substantially reduce the economic and social burden of these common and often crippling disorders.

Absenteeism↗
PubMed1996

Trends in cardiovascular disease incidence and survival in the elderly.

This study compared the age-specific incidence, postdiagnostic survival, and mortality for cardiovascular disease (CVD) in two cohorts of people aged 65 years and older. All subjects were members of a large prepaid health maintenance organization. The influence of changes in CVD risk factors on these rates also was evaluated. Trends in prevalence, incidence, postdiagnostic survival, and mortality for CVD were examined in both cohorts in 1971 and 1980. Myocardial infarction (MI), angina pectoris, stroke, and congestive heart failure (CHF) were included as CVD outcomes in this analysis. Nine-year prospective data on these diagnoses were abstracted from medical records and computerized hospitalization records for both cohorts. Age-sex-adjusted cardiovascular mortality was lower for both sexes by approximately 20% in the 1980 cohort. Overall survival did not change, whereas cancer mortality increased by 76% in women and 36% in men. With the exception of stroke, there was no increase in age-adjusted or age-specific prevalence. In men, the age-adjusted prevalence of stroke in men was 24% higher in the 1980 cohort. Age-adjusted 9-year incidence of MI, angina pectoris, stroke, and CHF did not change between cohorts in either sex Postdiagnostic, age-adjusted mortality for men with incident stroke was 24% lower in the 1980 cohort, and Postdiagnostic, age-adjusted mortality for men with incident angina was 35% lower in the 1980 cohort. Adjustment for risk factors measured at or before baseline had little influence on cohort differences in CVD incidence or duration of survival after CVD diagnosis. This study confirms other research showing a decline in CVD mortality over the past 20 years. These findings suggest that prevalent angina pectoris is increasing in men, and that survival with stroke and with angina is improving in men. Later diagnosis of incident CHF in men suggests that prevention and early detection may be postponing the development of more serious disease.

Age Distribution↗
PubMed1995

Economic costs of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD), classified as a severe mental illness by the National Advisory Mental Health Council, affects 2.1% of the population annually, as shown by the Epidemiological Catchment Area surveys. This study, using the human capital approach, estimated the direct and indirect costs of OCD. The total costs of OCD were estimated to be $8.4 billion in 1990, 5.7% of the estimated $147.8 billion cost of all mental illness, and 18.0% of the costs of all anxiety disorders, estimated to be $46.6 billion. The indirect costs of OCD, reflecting lost productivity of individuals suffering from or dying from the disorder, were estimated at $6.2 billion.

Cost of Illness↗
PubMed1995

The economic burden of affective disorders.

BACKGROUND: This paper summarises the methods and sources of data used to estimate costs of affective disorders and presents the results. METHOD: A timing model employing regression analysis was developed to estimate morbidity costs. This model measures the lifetime effect on current income of individuals with affective disorders, taking into account the timing of onset and the duration of these disorders. RESULTS: Affective disorders imposed an estimated US$ 20.8 billion burden in 1985 and US$ 30.4 billion in 1990 in the US. Affective disorders represent 21% of the costs of all mental illnesses. Direct treatment costs comprised 58.4% of the total in 1985; morbidity costs, 8.1%; mortality costs, the present value of future earnings lost due to premature mortality, 28.9%, based on a 6% discount rate; and other related costs, including the cost of crime, lost productivity due to incarceration, and caregiver services, 4.6%. Private sources account for 49% of the total direct expenditures for treatment of persons with affective disorders; state and local funds, 26%; and federal funds, 25%. CONCLUSION: In light of the high burden of affective disorders on societal resources, more attention should be directed at comprehensive, research-based strategies to reduce the prevalence of these disorders in the United States.

Adolescent↗
PubMed1993

The economic burden of Alzheimer's disease care.

This study examines total formal and informal care costs attributable to Alzheimer's disease for persons living in the community and in institutions. The total cost of caring for an Alzheimer's patient in northern California is approximately $47,000 per year whether the patient lives at home or in a nursing home, but the cost breakdown differs in the two settings. For community-resident patients, three-fourths of the total cost represents an imputed value for unpaid informal care compared with 12 percent for institutionalized patients. Formal services are financed primarily by individuals and their families. Over 60 percent of the services provided to patients in either care setting were paid out of pocket. With projected increases in the number of persons at risk of developing Alzheimer's disease, the economic impact of the disease on future long-term care costs will be significant.

Aged↗