Delay in diagnosis in breast cancer.
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Breast Neoplasms↗
Biomedical subjects
J Roberts
Publications and source records attributed to J Roberts.
Malaria surveillance--United States, 1995.
PROBLEM/CONDITION: Malaria is caused by four species of Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, or P. malariae), which are transmitted by the bite of an infective female Anopheles sp. mosquito. Most malaria infections in the United States occur among persons who have traveled to areas with ongoing transmission. Occasionally, cases occur in the United States through exposure to infected blood products, by congenital transmission, or by local mosquito-borne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. REPORTING PERIOD: Cases with onset of illness during 1995. DESCRIPTION OF SYSTEM: Malaria cases confirmed by blood smears are reported to local and/or state health departments by health-care providers and/or laboratory staff. Case investigations are conducted by local and/or state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS). Data from NMSS serve as the basis for this report. RESULTS: CDC received reports of 1,167 cases of malaria with onset of symptoms during 1995 among persons in the United States or one of its territories. This number represents an increase of 15% from the 1,014 cases reported for 1994. P. vivax, P. falciparum, P. malariae, and P. ovale were identified in 48.2%, 38.6%, 3.9%, and 2.2% of cases, respectively. More than one species was present in three patients (0.3% of total). The infecting species was not determined in 80 (6.9%) cases. The number of reported malaria cases acquired in Africa (n=519) remained approximately the same as in 1994 (n=517); cases acquired in Asia increased by 32.4% (n=335); and cases acquired in the Americas increased by 37.4 % (n=246). Of 591 U.S. civilians who acquired malaria abroad, 15.6% had followed a chemoprophylactic drug regimen recommended by CDC for the area where they had traveled. Nine patients became infected in the United States. Of these nine cases, five were congenitally acquired; one was acquired by organ transplantation; and one was acquired by a blood transfusion. For two of the nine cases, the source of infection was unknown. Six deaths were attributed to malaria. INTERPRETATION: The 15% increase in malaria cases in 1995 compared with 1994 resulted primarily from increases in cases acquired in Asia and the Americas, most notably a 100% increase in the number of cases reported from South America. This change could have resulted from local changes in disease transmission, travel patterns, reporting errors, or a decreased use of effective antimalarial chemoprophylaxis. In most reported cases, U.S. civilians who acquired infection abroad were not on an appropriate chemoprophylaxis regimen for the country where they acquired malaria. ACTIONS TAKEN: Additional information was obtained concerning the six fatal cases and the nine infections acquired in the United States. Malaria prevention guidelines were updated and distributed to health-care providers. Persons traveling to a malarious area should take the recommended chemoprophylaxis regimen and use personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently develops a fever or influenza-like symptoms should seek medical care; investigation should include a blood smear for malaria. Malaria infections can be fatal if not diagnosed and treated promptly. Recommendations concerning prevention and treatment of malaria can be obtained from CDC.
Humans↗
Evidence for a synergistic effect of the HIV-1 envelope protein gp120 and brain-derived neurotrophic factor (BDNF) leading to enhanced expression of somatostatin neurons in aggregate cultures derived from the human fetal cortex.
Changes in the expression of somatostatin (SRIF) have been observed in the brains of HIV encephalitis. Since gp120 is thought to play a major role in AIDS-associated abnormalities in the brain, we addressed the question: Does gp120 alter the functional expression of human fetal SRIF neurons in culture and if so, is this effect fetal-age dependent? Aggregate cultures, obtained from cortices of nine fetuses (14.9-20.7 weeks), were exposed for 7 days to BDNF or BDNF+gp120; BDNF induced production of SRIF during the subsequent 24-48 h was assessed. Similar effects of BDNF and gp120 were observed in the 9 brain-cultures. A 7-day exposure to BDNF alone led to a significant increase in SRIF production (p=0.014), whereas exposure to gp120 alone did not. Co-exposure to BDNF and gp120 led to an increase in BDNF-induced SRIF production which was significantly greater than that after BDNF alone (p=0.006). These effects were BDNF- and gp120-dose dependent and they were not accompanied by changes in DNA content of the aggregates nor in lactate dehydrogenase activity in the medium; indicating that gp120 did not lead to a major loss of cell integrity. These results are consistent with a synergistic effect of BDNF and gp120 leading to enhanced functional expression of the signalling pathway(s) mediating BDNF induction of SRIF production; an effect expressed by fetal brains throughout the 2nd trimester of gestation. Thus, this culture system can serve as a model to study the mechanism(s) underlying the early interactions between gp120 BDNF in the developing human brain.
Brain-Derived Neurotrophic Factor↗
Sensitivity of elasticity estimates for OECD health care spending: analysis of a dynamic heterogeneous data field.
Current econometric research on the determinants of health care spending is characterized by three serious shortcomings: a lack of attention to dynamics, a failure to deal with heterogeneity and a neglect of sensitivity testing. The latter shortcoming is a particular problem in an area where there is little theoretical guidance with which to judge the validity of estimates. This paper deals with these three problems by adopting recently developed techniques for analysing dynamic heterogeneous data fields containing non-stationary variables. This method allows for parameter heterogeneity across countries and is preferred to pooling with country specific effects, since the latter does not yield consistent estimates in this context, despite its common use in studies of health care spending. Long-run and short-run elasticity estimates are found to be sensitive to both model specification and sample composition. An attempt is made to compensate for the weak theoretical base by increasing the emphasis on statistical and econometric criteria for model evaluation, and by subjecting the results to rigorous sensitivity testing.
Europe↗
The preterm prediction study: failure of midtrimester cervical sialidase level elevation to predict subsequent spontaneous preterm birth.
OBJECTIVE: Our objective was to determine any associations among midtrimester cervical fluid sialidase activity, bacterial vaginosis, and subsequent spontaneous preterm birth. STUDY DESIGN: In this nested case-control study all patients (n = 126) with spontaneous preterm birth at <35 weeks' gestation and selected control subjects delivered at >/=37 weeks' gestation (n = 126, matched for race, parity, and center) were derived from women enrolled in the multicenter National Institute of Child Health and Human Development Preterm Prediction Study. Sialidase activity and presence of bacterial vaginosis according to Gram stain were determined in cervical swabs and vaginal smears, respectively, obtained at 22 weeks' to 24 weeks 6 days' gestation. RESULTS: The mean +/- SD sialidase activities were similar in case patients and control subjects (0.64 +/- 1.60 vs 0.41 +/- 0.94 nmol. mL-1. min-1, P =.21). Neither sialidase activity above the 90th percentile (10.3% vs 9.5%, P =.8) nor sialidase activity above the 95th percentile (7.9% vs 4. 8%, P =.3) of control specimens (>1.43 and >2.23 nmol. mL-1. min-1, respectively) was associated with spontaneous preterm birth. The frequency of combinations of bacterial vaginosis and elevated sialidase activity was similar (P >/=.63 with either cutoff) in case patients and control subjects. Sialidase activity was significantly higher among women with bacterial vaginosis than among those without bacterial vaginosis (1.35 +/- 1.87 vs 0.03 +/- 0.14 nmol. mL-1. min-1, P <.0001). CONCLUSIONS: Elevated cervical fluid sialidase activity at 22 to 24 weeks' gestation did not distinguish women at increased risk for spontaneous preterm birth, nor did it discriminate a subgroup of patients who had bacterial vaginosis associated with spontaneous preterm birth.
Case-Control Studies↗
Do sick newborn infants benefit from participation in a randomized clinical trial?
BACKGROUND: Adult participants in randomized controlled trials often have better outcomes than patients who are eligible but not enrolled. OBJECTIVE: To examine whether newborn infants who were allocated to placebo in an investigational drug trial had better outcomes than infants who were eligible but not randomized (eligible NR). STUDY DESIGN: During a randomized controlled trial of antithrombin therapy in premature infants with respiratory distress syndrome, data were collected prospectively on all 76 infants in the eligible NR group. Study outcomes were compared with those of all 61 infants who were randomized to placebo. The same exogenous surfactant was used in all patients. RESULTS: In the placebo group the mean (SD) birth weight was 1201 (314) g, mean (SD) gestational age was 28.8 (2.3) weeks, and 51% were male. In infants in the eligible NR group, mean (SD) birth weight was 1141 (262) g, mean (SD) gestational age was 28.3 (2. 3) weeks, and 58% were male; 57% of infants in both groups had been exposed to steroids before birth. The median duration of mechanical ventilation was reduced from 6.2 days in the eligible NR group to 4. 8 days in the placebo group (P =.008). There was also a trend toward less frequent and less severe intraventricular hemorrhage in trial participants. CONCLUSIONS: These data are consistent with the hypothesis that sick newborn infants may benefit from participation in a randomized controlled trial.
Antithrombins↗
Prevalence of dysthymic disorder in primary care.
BACKGROUND: Dysthymic disorder is characterised as a chronic state of depressed mood which is not otherwise attributable to physical, psychological or social events. While it can occur alone, there is increasing evidence that the majority of individuals who meet criteria for dysthymic disorder also experience more severe episodic mood disorders throughout their lifetime, and there is also an aggregation of mood disorders within their family members. Patients with dysthymic disorder are most often seen in primary care. Some researchers suggest that the majority of these individuals are never diagnosed or are not diagnosed until a more severe episodic mood disorder develops. The objective of this study was to determine the 12-month prevalence of Axis I psychiatric disorders, and in particular dysthymic disorder, in a primary care Health Service Organization in Ontario, Canada. METHODS: Eligible and consenting adults registered with a primary care Health Service Organization were screened using the modified form of the University of Michigan Composite International Diagnostic Interview. RESULTS: Of the 6280 eligible subjects, 4327 (69%) consented to screening. Two hundred and twenty-two (5.1%) subjects screened positive for dysthymic disorder. In addition, 90% of those who screened positive for dysthymic disorder also screened positive for other Axis I disorders including major depressive disorder, panic, simple phobia, and generalized anxiety disorder. CONCLUSIONS: There is much potential for the primary care physician to play a pivotal role in the recognition and treatment of dysthymic disorder and associated Axis I disorders. A focus on the family as a unit for care may be especially important given the reported aggregation of dysthymic disorder within families.
Adolescent↗
Alopecia areata investigational assessment guidelines. National Alopecia Areata Foundation.
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Alopecia Areata↗
The cost of implementing the Dialysis Outcomes Quality Initiative Clinical Practice Guidelines.
For a clinical practice guideline to be accepted by the end-user, the system of reimbursement for the targeted service must be favorable. The National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) Guideline recommendations were developed without primary concern for the costs of their execution. Arguably, an unfavorable financial environment and excessive mercantile behavior by providers and payers would offer a considerable hindrance to their implementation. Toward addressing these concerns, three leaders in the development of the DOQI Guidelines for the Treatment of Anemia of Chronic Renal Failure, Hemodialysis Adequacy, and Vascular Access, have evaluated the hypothesis that implementing the recommendations of the DOQI Guidelines will increase the treatment costs for dialysis providers but will effect savings in the entire end-stage renal disease (ESRD) program. Their analyses suggest that under the current reimbursement system, this assumption may be true. However, restructured global reimbursement in the ESRD program will permit financial incentives for dialysis providers and the payer to coincide.
Anemia↗
An improved method for dissociation and aggregate culture of human fetal brain cells in serum-free medium.
Moscona, in the early sixties [A.A. Moscona, Recombination of dissociated cells and the development of cell aggregates, in: B.M. Willmer (Ed.), Cells and Tissues in Culture, Academic Press, New York, 1965, pp. 489-529.] [16], discovered that aggregation of dissociated cells is a property of embryonal cells. Several features of the aggregate culture system are particularly attractive for the conduct of biochemical and molecular studies on the human fetal brain. (i) All the pertinent procedural parameters can be readily controlled and standardized, resulting in a consistently reproducible system suitable for quantitative analyses. (ii) Neuronal enriched aggregates can be readily obtained, with minimal neurotoxicity. (iii) Aggregates can be easily harvested for biochemical and molecular studies. Aggregate cultures, generated from rodent fetal brains, have been extensively utilized as a tool to study regulation of aminergic neurons [P. Honegger, E. Richelson, Biochemical differentiation of mechanically dissociated brain in aggregating cell culture, Brain Res. 109 (1976) 335-354; P. Honegger, E. Richelson, Biochemical differentiation of aggregating cell cultures of different fetal rat brain regions, Brain Res. 133 (1977) 329-339.] [11,12] and peptidergic neurons (neuropeptide Y (NPY) and somatostatin (SRIF) [A. Barnea, E. Anthony, G. Lu, G. Cho, Morphological differentiation of neuropeptide Y neurons in aggregate cultures of dissociated fetal cortical cells: a model system for glia-neuron paracrine interactions, Brain Res. 625 (1993) 313-322; A. Barnea, G. Cho, G. Lu, M. Mathis, Brain-derived neurotrophic factor induces functional expression and phenotypic differentiation of cultured fetal neuropeptide Y producing neurons, J. Neurosci. Res. 42 (1995) 638-647; A. Barnea, A. Hajibeigi, G. Cho, P. Magni, Regulated production and secretion of immunoreactive neuropeptide Y by aggregating fetal brain cells in culture, Neuroendocrinology 54 (1991) 7-13; P. Magni, A. Barnea, Forskolin and phorbol ester stimulation of neuropeptide Y (NPY) production and secretion by aggregating fetal brain cells in culture: evidence for regulation of NPY biosynthesis at transcriptional and posttranscriptional levels, Endocrinology 130 (1992) 976-984.]) [4-6,14]. However, very few studies have utilized this system to study regulatory processes of human fetal neurons/glia [M. McCarthy, L. Resnik, F. Taub, R.V. Stewart, R.D. Dix, Infection of human neural cell aggregate cultures with a clinical isolate of cytomegalovirus, J. Neuropathol. Exp. Neurol. 50 (1991) 441-450; L. Pulliam, M.E. Berens, M.L. Rosenblum, A normal human brain cell aggregate model for neurobiological studies, J. Neurosci. Res. 21 (1988) 521-530.] [15,17]. In a series of studies in our laboratory [N. Aguila-Mansilla, A. Barnea, Human fetal brain cells in aggregate culture: a model system to study regulatory processes of the developing human neuropeptide Y (NPY) producing neuron, Int. J. Dev. Neurosci. 14 (1996) 531-539; A. Barnea, N. Aguila-Mansilla, H.T. Chute, A.A. Welcher, Comparison of neurotrophin regulation of human and rat neuropeptide Y (NPY) neurons: induction of NPY production in aggregate cultures derived from rat but not from human fetal brains, Brain Res. 732 (1996) 52-60; A. Barnea, N. Aguila-Mansilla, G. Lu, R.H. Ho, Opposite effects of astrocyte-derived soluble factor(s) on the functional expression of fetal peptidergic neurons in aggregate cultures: enhancement of neuropeptide Y and suppression of somatostatin, J. Neurosci. Res. 50 (1997) 605-617; A. Barnea, J. Roberts, R.H. Ho, Evidence for a synergistic effect of the HIV-1 envelope protein gp120 and brain-derived neurotrophic factor (BDNF) leading to enhanced expression of somatostatin neurons in aggregate cultures derived from the human fetal cortex, Brain Res. 815 (1999) 349-357.] [1-3,7], we have established a human-derived aggregate culture system, maintained in serum-free medium for up to 28 days, in which expression
Brain↗
Leucovorin, 5-fluorouracil, and gemcitabine: a phase I study.
Gemcitabine is a chemotherapy agent with efficacy in the treatment of lung, pancreas, bladder and breast cancer. It inhibits DNA synthesis by interfering with cytidine triphosphate production and also inhibits the activity of ribonucleotide reductase. Gemcitabine may potentiate fluorouracil's inhibition of thymidylate synthase. This inhibition would be expected to be sequence dependent, occurring only if gemcitabine were administered following fluorouracil (5FU). The combination of leucovorin, 5-FU, and gemcitabine was assessed in this phase I trial. Eligibility requirements included refractory solid tumor malignancy; adequate hematologic, renal and hepatic reserve; no prior therapy with the combination of leucovorin and 5FU, or with gemcitabine; ECOG performance status 0-2, and signed informed consent. Eleven men and nine women were eligible. The median age was 52.5 years and the median performance status was 1. All but three patients had prior chemotherapy. The starting doses were leucovorin 20 mg/m2, 5FU 255 mg/m2 and gemcitabine 600 mg/m2. 5FU and gemcitabine were escalated in tandem to 340 mg/m2 and 800 mg/m2 and thereafter to 425 mg/m2 and 1000 mg/m2, respectively. Gemcitabine administration always followed that of 5FU by 30 minutes. The median number of cycles was 2 (range 1-32). Two patients at the starting dose had disease progression within the first cycle with one death on day 28. One patient with cholangiocarcinoma had a partial response and remained on study for 40 months. There were no other responses. The maximum tolerated dose is leucovorin 20 mg/m2, 5FU 340 mg/m2, and gemcitabine 800 mg/m2. The impact of drug sequence remains undetermined.
Adult↗
The quick response initiative in the emergency department: who benefits?
OBJECTIVES: This collaborative project between two community hospitals, a Metropolitan Home Care Program and the University, was designed to quantify the applicability (who is eligible for) and acceptability (who will likely comply with) Home Care services, provided through a Quick Response Program (QRP) initiative as compared to usual hospital care services, to patients, families and physicians. METHODS: During a 6 week period of sampling (5 days per week, 8 hours per day) in two Emergency Departments (ED) in moderately sized community hospitals in a major metropolitan city, all patients triaged to the urgent category were assessed for eligibility for QRP services by on-site Home Care Coordinators using specific criteria. Patients meeting the criteria initially were reviewed by the ED physician for approval for QRP services and then randomized to experimental and control conditions. Patients not meeting the eligibility criteria were managed by the usual ED services procedures. Demographic and clinical data were obtained on all urgent category patients at presentation to the ED. Additionally, the nature and cost of all health care services used by the ED patients during the ED event and 10 days follow up, were obtained through hospital and Home Care record abstraction and compared among the different sample groups. RESULTS: The QRP Initiative was applicable to 2% of the total ED patient population and 5% of the urgent category of patients triaged in the ED. It was acceptable to 97% of this eligible group. One hundred and fifty-five patients who initially qualified for QRP were excluded from eligibility at a subsequent assessment. Ninety of these patients were admitted to hospital and 65 were discharged home. In the total "exclusion" group, 37 refused Home Care services including the QRP. HEALTH CARE PRACTICE IMPLICATIONS: The sampling results raise important questions about broader system issues concerning the role of the hospital and community in providing health care services and the social value or utility that guides the allocation of health care funds. What level of applicability and acceptability would justify priority services for certain target groups. In the future, policy makers will need to be able to show that it is in the best interest of patients and society to prioritize mixtures of services to certain target groups.
Adult↗
Economic aspects of haemophilia care.
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Blood Coagulation Factors↗
Economic evaluations of community-based care: lessons from twelve studies in Ontario.
A series of 12 studies (five historic cohort and seven randomized trials) examined clients in community settings in Southern Ontario suffering from a variety of chronic physical and mental health conditions. These studies are appraised using a framework for evaluating possible outcomes of economic evaluation. In the 12 studies, sample composition and size varied. Each study was designed to quantify the well-being outcomes and expenditures associated with different community-based approaches to care provided in the context of a system of national health insurance. As a collective, these studies represent increasing methodological rigour. Multiple-perspective client well-being outcome measures were used. In two studies, caregiver burden also was analysed. A common approach to quantification and evaluation of expenditures for service consumption was used in all 12 studies. The nature of community-based health services (health vs. disease care orientation) was found to have direct and measurable impact on total expenditures for health service utilization and client well-being outcomes. In most cases, a recurring pattern of equal or better client outcomes, yet lower expenditures for use of community based health services, was associated with well-integrated health oriented services. Integrated services aimed at factors which determine health are superior when compared to individual, fragmented, disease oriented, and focused approaches to care. The main lessons from the 12 studies are that it is as or more effective and as or less expensive to offer complete, proactive, community health services to persons living with chronic circumstance than to provide focused, on-demand, piecemeal services. Complete services would have a psychosocial and mental health focus included with the physical care approach. Furthermore, people with coexisting risk factors (age, living arrangements, mental distress and problem-solving ability) are the ones who most benefit at lower expense from health oriented, proactive interventions.
Cohort Studies↗
Serum androgens and genetic linkage analysis in early onset androgenetic alopecia.
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Alopecia↗
Cold storage induces time-dependent F2-isoprostane formation in renal tubular cells and rat kidneys.
BACKGROUND: Previous findings suggest a possible role for free radicals in cold-storage-associated tissue injury. Because free radical-induced lipid peroxidation catalyzes the cyclooxygenase-independent formation of vasoconstrictive F2-isoprostanes, the hypothesis that isoprostanes are produced during cold storage was tested in this study. METHODS: Total isoprostanes (free and esterified) in renal tubular epithelial (LLC-PK1) cells or whole kidneys, subjected to cold storage, were quantitated employing the gas chromatographic-mass spectroscopic method. LLC-PK1 cells were stored at 4 degrees C in a University of Wisconsin (UW) solution for 0, 24, 48, and 72 hours or 48 hours with desferrioxamine (DFO) or the lazaroid compound 2-methyl aminochroman (2-MAC). In the rat model, kidneys were perfused and stored for 48 hours in the UW solution with or without added DFO or 2-MAC. RESULTS: Isoprostanes in LLC-PK1 cells increased by fivefold following 24 hours of cold storage (36 +/- 2 pg/well to 185 +/- 6, mean +/- SE, following 24 hours of cold storage, P < 0.0001), and the levels continued to increase significantly at 48 and 72 hours. DFO and 2-MAC caused significant suppression of isoprostane formation. Cold storage of the kidneys in UW solution for 48 hours was accompanied by an eightfold increase in isoprostanes compared with control kidneys not subjected to cold storage (25.0 +/- 3.0 vs. 2.9 +/- 0.1 ng/g, P < 0.0001). The addition of 2-MAC or DFO to the UW solution was associated with a near complete suppression of 48-hour cold-induced isoprostane formation. CONCLUSION: Our findings provide evidence for the formation of large quantities of antioxidant-suppressible isoprostanes in kidney cells and whole kidney during cold-preservation. Based on this, it is hypothesized that (a) isoprostanes, which are potent renal vasoconstrictors, may contribute to immediate post-transplant vasoconstriction and dysfunction in kidneys subjected to extended cold storage, and that (b) the addition of 2-MAC or DFO to a UW solution in such circumstances may attenuate these alterations partly by suppressing isoprostane formation.
Animals↗
Patient-perceived importance of negative effects of androgenetic alopecia in women.
Despite the prevalence of androgenetic alopecia (AGA) and the acceptance of its associated psychological factors in women, few studies have directly queried women about which specific aspects of their lives are affected by hair thinning and the relative importance of such effects. Perceptions of such negative effects can influence patient satisfaction, health-related quality of life (HRQL) and the impetus to seek medical attention for hair loss. Women (n = 120) aged 22-66 years with at least mild (Ludwig I) AGA were recruited from two dermatology clinics and from a large worksite and asked to complete a questionnaire. The questionnaire solicited information about specific aspects of their lives potentially affected by AGA and the relative importance of those aspects. Inability to style their hair, dissatisfaction with their appearance, concern about hair loss continuing, and concern about others noticing their hair loss were most important to women. Emotional aspects also ranked high, including self-consciousness, jealousy, embarrassment, and feeling powerless to stop their hair loss. In summary, women with AGA report numerous ways in which their hair thinning affects their lives. Knowledge of these effects may be beneficial in counseling such patients and in designing clinical trials or epidemiological studies to evaluate hair loss in women.
Adaptation, Psychological↗