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Biomedical subjects

H Mitchell

Publications and source records attributed to H Mitchell.

At least 19 recordsLinked to original sources

Abnormal cervical cytology in bone marrow transplant recipients.

Particular human papillomavirus (HPV) subtypes are implicated in the genesis of abnormal cervical cytology and cervical cancer. While most immunocompetent hosts clear HPV infection with no sequelae, some develop premalignant cytological changes of whom a minority subsequently progress to overt carcinoma. Immunocompromised patients, such as renal allograft recipients and HIV-infected individuals, have a higher rate of cytological abnormalities. This is thought to be due to prolonged persistence of virus due to impaired clearance by the immune system. We undertook a retrospective review of the cervical cytology of all women who underwent BMT at two transplant centres and who had cervical smears performed between 1990 and 1998. The rate of cytological abnormalities was significantly higher than in the general population before BMT (age-adjusted odds ratio (OR) 2.2, P = 0.02) and after BMT (OR 7.0, P < 0.0001). After BMT, allogeneic recipients had a higher rate of abnormalities than did autologous patients (OR 2.6, P = 0.02) although only allogeneic recipients had a higher rate of abnormalities post-BMT compared to pre-BMT (allogeneic OR 6.8, P = 0.004). These observations suggest that pre-transplant disease and treatment factors increase the risk of cytologic abnormalities and that transplant-related factors such as conditioning therapy and immunosuppression further increase this risk. These data suggest that more frequent screening may be required in these at-risk groups, especially allogeneic recipients. Prospective studies are required to further evaluate cytological abnormalities and HPV shedding in these populations.

Adult↗

Helicobacter pylori--an African perspective.

Helicobacter pylori is ubiquitous in Africa, with acquisition in childhood the rule. Despite the prevalence of a virulent strain (in Soweto, most H. pylori organisms are cagA- and vacAS(1)-positive) H. pylori-associated pathology (duodenal ulcer, gastric ulcer and gastric cancer) has a variable, often low distribution in sub-Saharan Africa that does not parallel H. pylori prevalence in the population, suggesting a different natural history from that seen in developed countries. Progression to atrophic gastritis in Africans does not appear to differ from that reported in other regions, but as yet unidentified factors may play a role in inhibiting progression to gastric cancer. Studies have suggested that the specific IgG subclass response to H. pylori is predominately IgG1 (suggestive of a Th2 response), and the Th2 response may provide a protective effect against development of gastric cancer. Host immune mechanisms may be the key to different responses to H. pylori in the developed and developing worlds.

Africa↗

Predictors of early rescreening in the National Cervical Screening Program, Australia.

OBJECTIVE: To identify variables that predict early rescreening after a negative Pap smear report. METHODS: Cohort study using the records of a statewide Cervical Cytology Registry in Victoria, Australia. The cohort comprised 31,082 women who had a negative Pap smear report during the first half of 1996 and who were rescreened within the subsequent 36 months. Early rescreening was defined as a further Pap smear within 21 months. RESULTS: The strongest predictor of early rescreening was a recommendation at the time of issuing the negative Pap smear report by the laboratory for retesting before two years (adjusted odds ratio = 3.81, 95% confidence interval (CI) 3.58-4.05). Mention of reactive or inflammatory change as part of the negative Pap smear report was also a powerful predictor (adjusted odds ratio = 1.67, 95% CI 1.50-1.85). Significant predictors associated with the women were young age, high socio-economic status and residence in the capital city. Significant predictors associated with the practitioner were if either the index or subsequent smear was collected by an obstetrician/ gynaecologist or a hospital-based clinic, or if the practitioner collecting the index smear was a female. The population-attributable risk per cent associated with the laboratory recommendation was 27%. CONCLUSIONS: This data suggests that a multifaceted strategy targeting pathology laboratories, practitioners and women may be needed to reduce early rescreening. IMPLICATIONS: Early rescreening is wasteful of health resources. New screening programs should be designed to avoid this problem.

Adult↗

Effects of physical interventions on house dust mite allergen levels in carpet, bed, and upholstery dust in low-income, urban homes.

House dust mite allergen exposure is a postulated risk factor for allergic sensitization, asthma development, and asthma morbidity; however, practical and effective methods to mitigate these allergens from low-income, urban home environments remain elusive. The purpose of this study was to assess the feasibility and effectiveness of physical interventions to mitigate house dust mite allergens in this setting. Homes with high levels of house dust mite allergen (Der f 1 + Der p 1 > or = 10 microg/g dust by enzyme-linked immunosorbent assay) in the bed, bedroom carpet, and/or upholstered furniture were enrolled in the study. Carpets and upholstered furniture were subjected to a single treatment of either dry steam cleaning plus vacuuming (carpet only) or intensive vacuuming alone. Bed interventions consisted of complete encasement of the mattress, box spring, and pillows plus either weekly professional or in-home laundering of nonencased bedding. Dust samples were collected at baseline and again at 3 days (carpet and upholstery only) and 2, 4, and 8 weeks posttreatment. We compared pretreatment mean allergen concentrations and loads to posttreatment values and performed between-group analyses after adjusting for differences in the pretreatment means. Both dry steam cleaning plus vacuuming and vacuuming alone resulted in a significant reduction in carpet house dust mite allergen concentration and load (p < 0.05). Levels approached pretreatment values by 4 weeks posttreatment in the intensive vacuuming group, whereas steam cleaning plus vacuuming effected a decrease that persisted for up to 8 weeks. Significant decreases in bed house dust mite allergen concentration and load were obtained in response to encasement and either professional or in-home laundering (p < 0.001). Between-group analysis revealed significantly less postintervention house dust mite allergen load in professionally laundered compared to home-laundered beds (p < 0.05). Intensive vacuuming and dry steam cleaning both caused a significant reduction in allergen concentration and load in upholstered furniture samples (p < 0.005). Based on these data, we conclude that physical interventions offer practical, effective means of reducing house dust mite allergen levels in low-income, urban home environments.

Allergens↗

Utility of commonly used commercial human chorionic gonadotropin immunoassays in the diagnosis and management of trophoblastic diseases.

BACKGROUND: Patients with trophoblastic diseases produce ordinary and irregular forms of human chorionic gonadotropin (hCG; e.g., nicked hCG, hCG missing the beta-subunit C-terminal segment, hyperglycosylated hCG, and free beta subunit) that are recognized to differing extents by automated immunometric hCG (or hCG beta) assays. This has led to low or false-negative results and misdiagnosis of persistent disease. False-positive hCG immunoreactivity has also been detected, leading to needless therapy for trophoblastic diseases. Here we compare seven commonly used hCG assays. METHODS: Standards for five irregular forms hCG produced in trophoblastic diseases, serum samples from 59 patients with confirmed trophoblastic diseases, and serum samples from 12 women with previous false-positive hCG results (primarily in the Abbott AxSYM assay) were blindly tested by commercial laboratories in the Beckman Access hCG beta, the Abbott AxSYM hCG beta, the Chiron ACS:180 hCG beta, the Baxter Stratus hCG test, the DPC Immulite hCG test, the Serono MAIAclone hCG beta tests, and in the hCG beta RIA. RESULTS: Only the RIA and the DPC appropriately detected the five irregular hCG standards. Only the Beckman, DPC, and Abbott assays gave results similar to the RIA in the patients with confirmed trophoblastic diseases (values within 25% of RIA in 49, 49, and 54 of 59 patients, respectively). For samples that were previously found to produce false-positive hCG results, no false-positive results were detected with the DPC and Chiron tests (5 samples, median <2 IU/L), but up to one-third of samples were false positive (>10 IU/L) in the Beckman (1 of 5), Serono (2 of 9), and Baxter assays (1 of 5), and the hCG beta RIA (3 of 9; median for all assays, <5 IU/L). These samples, which produced false-positive results earlier in the Abbott AxSYM assay, continued to produce high values upon reassessment (median, 81 IU/L). CONCLUSIONS: Of six frequently used hCG immunometric assays, only the DPC detected the five irregular forms of beta hCG, agreed with the RIA, and avoided false-positive results in the samples tested. This assay, and similarly designed assays not tested here, seem appropriate for hCG testing in the diagnosis and management of trophoblastic diseases.

Choriocarcinoma↗

Hormone replacement therapy and accuracy of mammographic screening.

BACKGROUND: Hormone replacement therapy (HRT) is commonly used and may affect the accuracy of mammographic screening. METHODS: We examined the sensitivity, specificity, and small-cancer detection rate according to HRT use in 103,770 women in Victoria, Australia, who attended first-round screening in 1994 and who did not have a personal history of breast cancer or a breast lump or a bloodstained or watery nipple discharge at the time of screening. BreastScreen Victoria provides mammography to women aged 40 years and older every 2 years. Unconditional logistic modelling was used to adjust for age, family history, and symptom status. FINDINGS: The sensitivity of screening mammography for a 2-year screening interval was lower in HRT users (64.8% [95% CI 58-72]) than non-users (77.3% [74-81]). In the target group (50-69 years), the sensitivity was 64.3% (57-72) in HRT users and 79.8% (76-84) in non-users. Among women who were diagnosed with cancer during the 2-year screening interval, HRT users were more likely to have a false negative result than non-users (odds ratio 1.60 [1.04-2.21]) after adjusting for potential confounding factors. Specificity was 0.6% lower in HRT users compared with non-users. Among women who did not have cancer diagnosed in the interval, HRT users were more likely to have a false positive result (adjusted odds ratio 1.12 [1.05-1.19]). INTERPRETATION: We show that HRT use reduces the sensitivity of mammographic screening. In countries where HRT use is widespread, the reduction in sensitivity with HRT use may undermine the capacity of population-based mammographic-screening programmes to realise their potential mortality benefit.

Adult↗

Undetectable ultrasensitive PSA after radical prostatectomy for prostate cancer predicts relapse-free survival.

Radical retropubic prostatectomy is considered by many centres to be the treatment of choice for men aged less than 70 years with localized prostate cancer. A rise in serum prostate-specific antigen after radical prostatectomy occurs in 10-40% of cases. This study evaluates the usefulness of novel ultrasensitive PSA assays in the early detection of biochemical relapse. 200 patients of mean age 61. 2 years underwent radical retropubic prostatectomy. Levels < or = 0.01 ng ml-1 were considered undetectable. Mean pre-operative prostate-specific antigen was 13.3 ng ml-1. Biochemical relapse was defined as 3 consecutive rises. The 2-year biochemical disease-free survival for the 134 patients with evaluable prostate-specific antigen nadir data was 61.1% (95% CI: 51.6-70.6%). Only 2 patients with an undetectable prostate-specific antigen after radical retropubic prostatectomy biochemically relapsed (3%), compared to 47 relapses out of 61 patients (75%) who did not reach this level. Cox multivariate analysis confirms prostate-specific antigen nadir < or = 0.01 ng ml-1 to be a superb independent variable predicting a favourable biochemical disease-free survival (P < 0.0001). Early diagnosis of biochemical relapse is feasible with sensitive prostate-specific antigen assays. These assays more accurately measure the prostate-specific antigen nadir, which is an excellent predictor of biochemical disease-free survival. Thus, sensitive prostate-specific antigen assays offer accurate prognostic information and expedite decision-making regarding the use of salvage prostate-bed radiotherapy or hormone therapy.

Adult↗

Cognitive-behavioral predictors of asthma morbidity in inner-city children.

Asthma is a growing health problem among children in the United States, particularly in urban, inner-city areas. This article examines the relationship between cognitive-behavioral aspects of asthma management (caretaker asthma knowledge, expectations, and problem-solving) and asthma morbidity in a sample of 1,376 inner-city children with physician-diagnosed asthma. In the analyses, baseline symptom severity served as a covariate, and the average of the 3-, 6-, and 9-month follow-up data served as the outcome measure. Children of caregivers with ineffective problem-solving strategies had significantly more days of wheezing over a 14-day period. Ineffective problem-solving capabilities were also associated with poorer functional status; however, positive caregiver expectations were associated with better functional status. Of the cognitive-behavioral factors studied in a high-risk urban population, caregiver problem-solving skills and expectations emerged as meriting further investigation and possible intervention.

Asthma↗

The sensitivity, specificity, and positive predictive value of screening mammography and symptomatic status.

OBJECTIVE: To examine whether the accuracy of screening mammography varies according to symptomatic status reported at the time of screening. SETTING: Victoria, Australia, where free biennial screening is provided to women aged 40 and older. METHODS: We examined the sensitivity, specificity, and the positive predictive value of screening mammography by symptom status in 106,826 women from Victoria, who attended for first round mammography in 1994 and who did not have a personal history of breast cancer. Symptomatic status was divided into the following categories: asymptomatic; significant symptoms, if the woman reported a breast lump and/or blood stained or watery nipple discharge; and other symptoms, if reported. Unconditional logistic regression modelling was used to adjust for age, use of hormone replacement therapy (HRT), and family history. RESULTS: Sensitivity was lower for women with other symptoms (60.0%) than asymptomatic women (75.6%), or women with significant symptoms (80.8%). Specificity was lower for women with significant symptoms (73.7%) than asymptomatic women (94.9%), or women with other symptoms (95.4%). Among women who had invasive cancer detected during screening interval, women with other symptoms were more likely to get a false negative result (odds ratio 1.79, 95% confidence interval 1.03 to 3.04) than asymptomatic women, after adjusting for age, use of HRT, and family history. CONCLUSION: The lower sensitivity in women with other symptoms requires further investigation. Possible explanations include increased breast density and poor image quality. The high sensitivity in women with significant symptoms is probably due to more cautious radiological practice, which has also resulted in low specificity in this group.

Adult↗

Do obese inner-city children with asthma have more symptoms than nonobese children with asthma?

OBJECTIVE: To test whether obesity is associated with decreased peak expiratory flow rates (PEFR), increased asthma symptoms, and increased health service use. DESIGN/METHODS: Secondary analysis of data from a cross-sectional convenience sample. SETTING: Emergency departments (EDs) and primary care clinics in 8 inner-city areas in 7 cities. PARTICIPANTS: One thousand three hundred twenty-two children aged 4 to 9 years with asthma. MEASURES: Obesity was defined as a body mass index (BMI, weight/height(2)) >95th percentile. Nonobese children were those with a BMI between the 5th and 95th percentile. Underweight children with a BMI <5th percentile were eliminated from the study. Demographic and anthropometric data were obtained during a baseline interview with the primary caretaker and the child. Symptoms, health service use data and measurements of PEFR were obtained by parental report during the baseline interview and at 3-month intervals by telephone interview over the following 9-month period. RESULTS: Obese (n = 249) and nonobese (n = 1073) children did not differ in terms of age, gender, family income, passive smoke exposure, caretaker's mental health, and skin test reactivity to indoor allergens. Obese children were more often Latino (28% vs 17%) and, in the 3 months before the baseline interview, were more likely to have used oral steroids (30% vs 24%). There were no differences between groups in terms of baseline PEFR scores. During the 9 months after baseline assessment, the obese group had a higher mean number of days of wheeze per 2-week period (4.0 vs 3.4), and a greater proportion of obese individuals had unscheduled ED visits (39% vs 31%). There were no differences between the groups in terms of frequency of hospitalization, or in nocturnal awakening. CONCLUSIONS: In our sample of inner-city children with asthma, obese children used more medicine, wheezed more, and a greater proportion had unscheduled ED visits than the nonobese children.

Asthma↗

Inverse relation between prostate-specific antigen and insulin-like growth factor-binding protein 3 in bone metastases and serum of patients with prostate cancer.

The usual osteoblastic phenotype of metastatic prostate cancer is unexplained. Here we show that tissue and serum concentrations of prostate-specific antigen (PSA)-vary inversely with a substrate protein that binds a growth factor known to activate osteoblasts. These findings suggest that PSA may contribute to the osteoblastic phenotype, and could thus represent a new drug target devoid of antiandrogenic toxicity.

Biomarkers, Tumor↗

Guidelines for development and application of aquatic animal health regulations and control programs. AVMA Aquaculture and Seafood Advisory Committee.

The creation of sound health regulations or disease control programs for any animal species is a complex endeavor. When the diverse stakeholder interests related to aquaculture are considered, this endeavor becomes daunting. The AVMA Aquaculture and Seafood Advisory Committee designed the following guidelines as a tool to assist aquatic animal health professionals who discuss potential regulations or control programs with government and industry entities. The guide focuses on determining whether a regulation or program is appropriate and, if so, developing a suitable and effective aquatic animal health plan. The Aquaculture and Seafood Advisory Committee was established in 1992 as an ad hoc committee of the AVMA Executive Board. The committee is composed of 9 veterinarians with diverse interests in aquaculture and seafood, and one non-veterinarian who represents the aquaculture industry. Participants from the USDA/APHIS and FDA serve as consultants to the Committee.

Animals↗

A randomized clinical trial to reduce asthma morbidity among inner-city children: results of the National Cooperative Inner-City Asthma Study.

OBJECTIVE: To evaluate a family-focused asthma intervention designed for inner-city children 5 to 11 years old with moderate to severe asthma. STUDY DESIGN: Randomized, multisite, controlled trial to minimize symptom days (wheeze, loss of sleep, reduction in play activity) measured by a 2-week recall assessed at 2-month intervals over a 2-year follow-up period. The intervention was tailored to each family's individual asthma risk profile assessed at baseline. RESULTS: Averaged over the first 12 months, participants in the intervention group (n = 515) reported 3.51 symptom days in the 2 weeks before each follow-up interview compared with 4.06 symptom days for the control group (n = 518), a difference of 0.55 (95% CI, 0.18 to 0.92, P =.004). The reduction among children with severe asthma was approximately 3 times greater (1.54 d/2 wk). More children in the control group (18.9%) were hospitalized during the intervention compared with children in the intervention group (14. 8%), a decrease of 4.19% (CI, -8.75 to 0.36, P =.071). These improvements were maintained in the intervention group during the second year of follow-up, during which they did not have access to the asthma counselor. CONCLUSIONS: We demonstrated that an individually tailored, multifaceted intervention carried out by Masters-level social workers trained in asthma management can reduce asthma symptoms among children in the inner city.

Asthma↗

Results of the National Cooperative Inner-City Asthma Study (NCICAS) environmental intervention to reduce cockroach allergen exposure in inner-city homes.

BACKGROUND: Cockroach allergen is important in asthma. Practical methods to reduce exposure are needed. OBJECTIVE: We sought to evaluate the effectiveness of house cleaning and professional extermination on lowering cockroach antigen levels in inner-city dwellings. METHODS: As part of the National Cooperative Inner-City Asthma Study intervention, 265 of 331 families with asthmatic children who had positive skin test responses to cockroach allergen consented to a professional home extermination with 2 applications of a cockroach insecticide (Abamectin, Avert) combined with directed education on cockroach allergen removal. On a random subset of 48 homes undergoing cockroach extermination in the intervention group, Bla g 1 was measured in settled dust from the kitchen, bedroom, and TV/living room. The first sample was collected 1 week before extermination, with additional samples after the exterminations at approximately 2, 6, and 12 months after the first sample. Self-reported problems with cockroaches were collected at baseline and after 12 months of follow-up in both the intervention and control group. RESULTS: The geometric mean kitchen level of Bla g 1 decreased at 2 months (33.6 U/g) relative to preextermination levels (68.7 U/g, P <.05). The percent of kitchens with over 8 U/g of Bla g 1 followed a similar pattern, but only the decrease from preextermination to 6-month levels was significant (86.8% vs 64.3%, P <.05). By the 12-month visit, the allergen burden had returned to or exceeded baseline levels. Except for an increase in the bedroom at 2 months (8.9 U/g vs 11.1 U/g, P <.05), no other significant change was seen. Only about 50% of the families followed the cleaning instructions; no greater effect was found in these homes. Self-reported problems with cockroaches showed no difference between the intervention and control group after 1 year of follow-up. CONCLUSIONS: Despite a significant, but short-lived, decrease the cockroach allergen burden remained well above levels previously found to be clinically significant.

Allergens↗

Effect of antenatal dexamethasone therapy on maternal plasma human chorionic gonadotrophin, oestradiol and progesterone.

The aim of this study was to determine whether the current regimen of dexamethasone administration to induce fetal lung maturation affected the circulating concentrations of placental hormone. A standard regimen of dexamethasone that comprised two doses of 12-mg intramuscular injections, 12 h apart was administered to 12 pregnant women to promote fetal lung maturation in anticipation of premature delivery before 34 completed weeks of gestation. Blood samples were collected before starting the dexamethasone therapy, 24 h, and 48 h after completing therapy for the measurement of the plasma concentrations of human chorionic gonadotrophin (HCG), oestradiol and progesterone. There was a progressive fall in the plasma concentrations of HCG following dexamethasone therapy (P = 0.049 and P = 0.034, 24-h and 48-h post therapy respectively). There was an initial fall in the plasma concentrations of oestradiol after dexamethasone therapy (z = 3.059; P = 0.002, 24-h post therapy), which recovered by 48 h (P = 0.239). There was no difference between the plasma concentrations of progesterone at the three time points. The effect of dexamethasone on HCG concentrations suggests that it has a direct inhibitory effect on placental hormone synthesis or secretion. Further studies are needed to define the mechanism of action of dexamethasone on placental HCG production.

Adult↗

Division of responsibility for asthma management tasks between caregivers and children in the inner city.

This investigation examined caregiver and child perceptions of the division of responsibility for asthma management tasks in families. The study sample included 789 children with asthma, aged 6 to 9 years, who lived in the inner city. These children and their primary caregivers completed the Asthma Responsibility Interview. The correlation between the caregiver's and child's ratings of the child's responsibility was low (.19), with children rating themselves as more responsible than their caregivers rated them. Caregiver and child ratings of the child's responsibility increased with the child's age; however, caregivers' ratings of their own responsibility remained constant over the age range studied. Kappa statistics ranged from -.03 to .12, with up to 16% of children reporting less responsibility for self-care than was indicated by the caregiver. More than one third of families reported four or more asthma caregivers. The discrepancy between the caregiver's and child's perceptions and the involvement of multiple caregivers raise the possibility of unintentional nonadherence.

Asthma↗