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Biomedical subjects

J Albright

Publications and source records attributed to J Albright.

At least 19 recordsLinked to original sources

Degradative pathways in tissues of the temporomandibular joint. Use of in vitro and in vivo models to characterize matrix metalloproteinase and cytokine activity.

Identification of a small animal model that undergoes pathological temporomandibular joint (TMJ) degeneration would represent a significant research tool. To date however, no such model has been described. We therefore have investigated the pathological and immunohistochemical features of the TMJ of a transgenic mouse that over expresses the human form of TNFalpha. The TMJ of this animal appears to undergo changes that resemble arthriditics of temporomandibular dysfunction. Furthermore, the disc and articular cells express MMP9 and IL-1. Future work should validate this animal model as one that would have utility for the study of TMJ disorders. Maintenance of connective tissues in joints such as the TMJ is a normal process that allows for the reconstitution of important anatomic features. This maintenance involves both the removal and re-synthesis of structural proteins such as collagens, elastins and proteoglycans. An imbalance in the pathways for degradation and synthesis can lead to the degeneration of joint tissues. We describe the presence of a matrix metalloproteinase, MMP9 (92-kD gelatinase), in TMJ disc and articular cells that likely function in the degradative process. Additionally, we show that this enzyme is under the control of pro-inflammatory cytokines whereby TGFbeta and IL-1 stimulate and PGE(2) inhibits its activity.

Animals↗

Impact of zidovudine-based triple combination therapy on an AIDS drug assistance program.

A static deterministic model was used to estimate the effect of the shift to a triple combination therapeutic standard on the annual AIDS Drug Assistance Program (ADAP) budget, total medical care expenditures, and population health outcomes for New York (NY) state ADAP enrollees. The model used opportunistic disease incidence data from the Multicenter AIDS Cohort Study (MACS) and other studies. Costs of treating opportunistic infections (OIs) and other HIV complications with each type of therapy were derived from treatment algorithms and standard unit costs. CD4+ cell counts were used as an index of need for OI prophylaxis and for determining OI incidence. Treatment with zidovudine-based combination therapy has been shown to increase CD4+ cell counts and reduce OI incidence. The model estimated that a change from monotherapy to triple therapy would have increased NY ADAP budget expenditures per enrollee by 115%. However, total medical system costs per ADAP enrollee (including ADAP costs) would decrease by 0.4% in the base case as a result of reduction in OIs and other HIV sequelae and associated costs. Results are sensitive to the assumed percentage of people taking combination therapy as well as to the assumptions made about the impact of the combination therapy on CD4+ cell count. Total ADAP budget impacts will depend on the growth in ADAP enrollment as a result of the availability of more effective therapies. In conclusion, this model demonstrates how access to newer, more effective HIV drug treatments can reduce the costs of treating OIs and provide major health benefits for ADAP enrollees.

AIDS-Related Opportunistic Infections↗

Evaluation of a minimal self-help smoking cessation intervention following cervical cancer screening.

OBJECTIVE: This study was undertaken to evaluate a smoking cessation intervention provided to women smokers as follow-up to cervical cancer screening. METHODS: Women who had had a Pap test in the prior month (N = 4,053) were called to complete a survey that assessed smoking status; 580 identified smokers were randomized to receive Usual care (n = 292) or a Self-help intervention (n = 288) that included a self-help booklet, a smoking and reproductive health information card, and three telephone counseling calls. Women were followed up at 6 and 15 months post-base line. RESULTS: Cessation rates in the Usual care (UC) and Self-help (SH) groups did not differ at the 6-month (UC 10.5% vs SH 10.9%, P = 0.56) or 15-month follow-up (UC 15.5% vs SH 10.6%, P = 0.17). Among women with an abnormal Pap test result there were no differences by study group in cessation rates at 6-month (UC 9.8% vs SH 11.0%, P = 0.71) or 15-month follow-up (UC 14.6% vs SH 13.4%, P = 0.96). CONCLUSION: Integrating interventions into the clinical setting and involving providers at the point of care may have greater potential for capitalizing on this "teachable moment."

Adolescent↗

The association between cigarette smoking and low-grade cervical abnormalities in reproductive-age women.

OBJECTIVE: To evaluate the association between smoking and the occurrence of low-grade cervical cytological abnormalities. METHODS: We conducted a population-based cross-sectional study of smoking and other exposures in reproductive-age women with normal and abnormal cytology results (Class 1-4 Pap tests). Participants (n = 2,448) were enrollees of the Group Health Cooperative of Puget Sound, a health maintenance organization (HMO) in Washington state, USA. Non-pregnant women were selected monthly from the HMO's cytology database during 1995-6, with over-sampling of women with low-grade abnormalities. All participants completed a structured telephone-administered survey. RESULTS: Of the 2,448 participants, 19% (n = 465) had Class 2 Pap results, and 5% (n = 117) had Class 3-4 results. Forty percent of the sample (n = 975) reported ever smoking. Women reporting current/recent smoking (n = 514, 21%) had an increased likelihood of cervical abnormalities (adjusted odds ratio (OR) 1.4, 95% confidence interval (CI 1.1-1.8). Women who had never smoked but who reported recent passive smoking exposure also had a greater likelihood of abnormal test results (OR 1.4, 95% CI 1.0-2.0). Prior smoking was not associated with cytology status. CONCLUSIONS: Our results, examining low-grade cervical abnormalities, are compatible with those from studies of more severe cervical lesions, lending added support to the hypothesis that smoking predisposes to development of a spectrum of cervical abnormalities. Thus, even cytologic screening visits represent an opportunity to counsel women smokers about their health risks, particularly the more proximal risks of cervical abnormalities and cancer.

Adolescent↗

Promoting smoking cessation among women who seek cervical cancer screening.

OBJECTIVE: To determine whether 1) women smokers are aware that smoking increases their risk for cervical cancer; 2) awareness of risk factors and its impact on motivation to quit smoking vary by age; and 3) providers are advising smokers to quit smoking during routine gynecologic visits. METHODS: Women aged 18 years and older who had a Papanicolaou test in the prior month were identified from a managed care cytology database. Four weeks after receiving their test result, women were called to complete a health behavior survey in which their smoking status, sexual history, knowledge of risk factors for cervical cancer, and motivation to quit smoking were assessed. RESULTS: Only 49% of the 613 smokers surveyed were aware that smoking increased their risk of cervical cancer. Women aged 34 years and younger were significantly more likely to agree that smoking increased their risk for cervical cancer than women aged 45 years or older (54% versus 40%). Concern that smoking might cause cervical cancer or other cancers was endorsed highly by women as a motivator for cessation, particularly for women smokers aged 18-26 (mean 8.1 and 7.6 on 10-point scales, respectively). About 50% of the women reported that their provider had asked about smoking and had encouraged cessation. Only about 30% of smokers were aware of well-established risk factors for cervical cancer such as the number of lifetime sexual partners and not using a condom. CONCLUSION: Routine gynecologic screening visits represent an important and underutilized clinical opportunity to intervene with young women smokers.

Adolescent↗

The role of eosinophils and neutrophils in helminth-induced keratitis.

PURPOSE: Intrastromal injection of mice with antigens from the parasitic helminth that causes river blindness (Onchocerca volvulus) induces eosinophil recruitment to the corneal stroma at the time of maximum corneal opacification and neovascularization. The present study was conducted to examine the role of eosinophils and neutrophils in onchocercal keratitis in control C57Bl/6 mice and in interleukin-5 gene knockout (IL-5(-/-)) mice. METHODS: C57Bl/6 and IL-5(-/-) mice were immunized subcutaneously and injected intrastromally with soluble O. volvulus antigens. Mice were killed at various times thereafter. Development of keratitis was assessed by slit lamp examination, and inflammatory cells in the cornea were identified by immunohistochemistry. RESULTS: A biphasic recruitment of inflammatory cells was observed in C57Bl/6 mice; neutrophils predominated during the first 72 hours after intrastromal injection and subsequently declined, whereas eosinophil recruitment increased as time elapsed and comprised the majority (90%) of cells in the cornea by day 7. In contrast, neutrophils were the predominant inflammatory cells in IL-5(-/-) mice at early and late time points and were associated with extensive stromal damage and corneal opacification and neovascularization. Eosinophils were not detected in these mice at any time. CONCLUSIONS: In the absence of eosinophils, neutrophils can mediate keratitis induced by helminth antigens. Together with the early neutrophilic infiltrate in control animals, these observations indicate that neutrophils have an important role in onchocercal keratitis.

Animals↗

IL-12 exacerbates helminth-mediated corneal pathology by augmenting inflammatory cell recruitment and chemokine expression.

Corneal inflammation (keratitis) is a major cause of visual impairment in Onchocerca volvulus infection. Previous studies showed that onchocercal keratitis can be induced in mice following s.c. immunization and intracorneal injection with soluble O. volvulus Ags (OvAg), and that the inflammatory response is dependent on T cells and IL-4. Since recombinant IL-12 impairs IL-4-dependent, Th2-mediated responses in other parasitic infections and in models of allergic asthma, the present study was undertaken to determine the effect of IL-12 on onchocercal keratitis. Mice were injected i.p. with IL-12 or saline at the time of initial sensitization to OvAg. Surprisingly, IL-12 treatment caused significant exacerbation of corneal pathology, which was associated with increased eosinophil and mononuclear cell infiltration into the corneal stroma. Consistent with the well-documented effect of IL-12 on Th1 cell development, corneas of IL-12-treated animals had elevated expression of the Th1 cytokine IFN-gamma and diminished expression of the Th2 cytokines IL-4, IL-5, IL-10, and IL-13. However, corneas from these animals also had marked elevation of alpha- and beta-chemokines known to be active on eosinophils and mononuclear cells, including IFN-gamma-inducible protein (IP)-10, macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, JE/monocyte chemotactic protein-1, RANTES (regulated upon activation, normal T expressed and secreted), and eotaxin. Together, these data indicate that IL-12 exacerbates OvAg-mediated corneal pathology by enhancing chemokine expression and recruitment of inflammatory cells.

Animals↗

Apoptosis is coordinately regulated with osteoblast formation during bone healing.

The ultimate fate of the expanded pool of osteoblasts formed following a typical bone injury is unclear. Since necrosis has not been described in the latter stages of bone healing, there must be some other mechanism by which obsolete osteoblasts are cleared from an injury site. We therefore evaluated the possibility that their removal is pre-programmed, by investigating the occurrence of apoptosis in rats that received a standardized bone injury. Histological evidence identical to that found in tissues known to exhibit apoptosis was obtained, thereby showing that programmed cell death was a normal concomitant of fracture healing. The concentration of apoptotic bodies reached its maximum after the differentiative response had peaked, suggesting that the two processes were coordinated. The same result was found in a second group of rats that received the same bone injury plus a simultaneous standardized soft-tissue injury. The combined injuries resulted in more osteoblasts and more apoptotic bodies, but an identical temporal relationship between the peak responses in the two parameters. The results suggested that osteoblasts were removed from the injury site via apoptosis, and that the process was coordinately regulated with differentiation. Since the number of apoptotic bodies per osteoblast varied during healing, it is likely that apoptosis was associated with healing and not merely with osteoblast concentration.

Animals↗

Onchocerca volvulus-mediated keratitis: cytokine production by IL-4-deficient mice.

Corneal inflammation similar to human onchocercal keratitis can be induced in mice by subcutaneous immunization of a soluble extract of Onchocerca volvulus (OvAg) followed by direct injection of OvAg into the corneal stroma. Previous studies have shown that corneal pathology is associated with increased systemic and corneal Th2 cytokine expression and that IL-4 gene knockout (IL-4-/-) mice develop less severe or no O. volvulus-mediated keratitis. The current study examined the contribution of Th2 cytokines to the diminished OvAg-induced corneal immunopathology observed in IL-4-/- mice. IL-4-/- mice (129Sv x C57B1/6), wild-type F2 littermates (IL-4+/+), and C57B1/6 mice were sensitized by repeated subcutaneous immunization with OvAg. Ten days after the final immunization, mice were sacrificed, spleens were removed, and cells were incubated with OvAg. Cells from immunocompetent C57B1/6 and IL-4+/+ mice produced IL-4 and IL-5, but no IFN-gamma, whereas cells from IL-4-/- mice had elevated IFN-gamma and no IL-4. Interestingly, cells from these animals produced levels of IL-5 protein equivalent to those of C57B1/6 and IL-4+/+ mice. To determine cytokine production in corneas during the onset of onchocercal keratitis, OvAg-immunized mice were injected intracorneally with OvAg, and cytokine gene expression in the cornea was determined by RT-PCR. Temporal analysis of cytokine gene expression in corneas of immunocompetent mice showed that the Th2-associated cytokines IL-4, IL-5, IL-10, and IL-13 were produced within 1 day of intrastromal injection, with sustained elevations for 10 days. Maximal IFN-gamma mRNA levels were not detected until Day 10. This was in contrast to IL-4-/- mice in which IFN-gamma appeared at Day 1 and remained elevated for at least 10 days. Moreover, in corneas from IL-4-/- mice, all Th2 cytokines with the exception of IL-4 were up-regulated and expressed with kinetics similar to that of IL-4+/+ littermates. Histologically, corneas from IL-4-/- mice were less edematous and contained fewer eosinophils and other inflammatory cells than those from immunocompetent controls. As there was no difference in peripheral eosinophil levels, these data indicate that the diminished severity of onchocercal keratitis in IL-4-/- mice is not due to failure to develop systemic or local Th2 cytokine responses or to produce eosinophils, but that IL-4 may be involved in recruitment of eosinophils and other inflammatory cells into the corneal stroma.

Animals↗

Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest.

OBJECTIVE: To assess whether the dietary intake of long-chain n-3 polyunsaturated fatty acids from seafood, assessed both directly and indirectly through a biomarker, is associated with a reduced risk of primary cardiac arrest. DESIGN: Population-based case-control study. SETTING: Seattle and suburban King County, Washington. PARTICIPANTS: A total of 334 case patients with primary cardiac arrest, aged 25 to 74 years, attended by paramedics during 1988 to 1994 and 493 population-based control cases and controls, matched for age and sex, randomly identified from the community. All cases and controls were free of prior clinical heart disease, major comorbidity, and use of fish oil supplements. MEASURES OF EXPOSURE: Spouses of case patients and control subjects were interviewed to quantify dietary n-3 polyunsaturated fatty acid intake from seafood during the prior month and other clinical characteristics. Blood specimens from 82 cases (collected in the field) and 108 controls were analyzed to determine red blood cell membrane fatty acid composition, a biomarker of dietary n-3 polyunsaturated fatty acid intake. RESULTS: Compared with no dietary intake of eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3), an intake of 5.5 g of n-3 fatty acids per month (the mean of the third quartile and the equivalent of one fatty fish meal per week) was associated with a 50% reduction in the risk of primary cardiac arrest (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.4 to 0.8), after adjustment for potential confounding factors. Compared with a red blood cell membrane n-3 polyunsaturated fatty acid level of 3.3% of total fatty acids (the mean of the lowest quartile), a red blood cell n-3 polyunsaturated fatty acid level of 5.0% of total fatty acids (the mean of the third quartile) was associated with a 70% reduction in the risk of primary cardiac arrest (OR, 0.3; 95% CI, 0.2 to 0.6). CONCLUSION: Dietary intake of n-3 polyunsaturated fatty acids from seafood is associated with a reduced risk of primary cardiac arrest.

Adult↗

Confirmation of the association of human papillomavirus with human colon cancer.

The human papillomavirus (HPV) has been shown to be associated with neoplasms of the human colon using immunohistochemistry and in situ hybridization. We now report our use of the polymerase chain reaction and Southern blotting to investigate that same association. We selected 38 carcinomas, 21 adenomas, and 24 normal mucosal samples for the current study. Tissue sections were prepared, and then DNA was extracted and subjected to 40 cycles of amplification using Thermus aquaticus DNA polymerase and a set of degenerate primers. Amplified products were analyzed by agarose gel electrophoresis and Southern blotting. The L1 region of the HPV genome was identified in 13 of 38 carcinomas (32%), 8 of 21 adenomas (38%), and 2 of 24 normal biopsy specimens (8%). These observations validate our previous results and confirm the presence of HPV in human colon mucosa and tumors of that mucosa.

Adenoma↗

Validity and reliability issues in alternative patient classification systems.

The validity and reliability issues involved in using alternative patient classification systems were reviewed. Disease Staging and Patient Management Categories (PMCs) were applied separately and in conjunction with DRGs to three populations of patients drawn from a nine-hospital community data base. Data were examined with analyses that were as consistent as possible with hospital-based reviews of resource utilization. Questions focused on content and context validity (partially assessable by homogeneity), general and statistical reliability (measured by variance reduction), gaming, and cost. Ordinal stratifications were inconsistently produced, and improvement to DRGs' homogeneity was generally negligible. When used alone, staging produced only half the variance reduction of DRGs. PMCs, when used alone, appeared to produce sizeable variance reductions that may have been due to the large number of one- and two-case categories produced. Staging had category overlap, was expensive, and was unidimensional and subject to manipulation. PMCs had potentially serious logic problems, and both were inadequately documented. Neither system was considered appropriate for all needs, but each might work adequately under well-defined and limited conditions.

Diagnosis-Related Groups↗