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Biomedical subjects

Timothy Johnson

Publications and source records attributed to Timothy Johnson.

16 recordsLinked to original sources

A national survey of tobacco cessation programs for youths.

OBJECTIVES: We collected data on a national sample of existing community-based tobacco cessation programs for youths to understand their prevalence and overall characteristics. METHODS: We employed a 2-stage sampling design with US counties as the first-stage probability sampling units. We then used snowball sampling in selected counties to identify administrators of tobacco cessation programs for youths. We collected data on cessation programs when programs were identified. RESULTS: We profiled 591 programs in 408 counties. Programs were more numerous in urban counties; fewer programs were found in low-income counties. State-level measures of smoking prevalence and tobacco control expenditures were not associated with program availability. Most programs were multisession, school-based group programs serving 50 or fewer youths per year. Program content included cognitive-behavioral components found in adult programs along with content specific to adolescence. The median annual budget was 2000 dollars. Few programs (9%) reported only mandatory enrollment, 35% reported mixed mandatory and voluntary enrollment, and 56% reported only voluntary enrollment. CONCLUSIONS: There is considerable homogeneity among community-based tobacco cessation programs for youths. Programs are least prevalent in the types of communities for which national data show increases in youths' smoking prevalence.

Adolescent↗

Exploration of the diketoacid integrase inhibitor chemotype leading to the discovery of the anilide-ketoacids chemotype.

Integrase is one of three enzymes expressed by HIV and represents a validated target for therapy. A previous study of the diketoacid-based chemotype suggested that there are two aryl-binding domains on integrase. In this study, modifications to the indole-based diketoacid chemotype are explored. It is demonstrated that the indole group can be replaced with secondary but not tertiary (e.g., N-methyl) aniline-based amides without sacrificing in vitro inhibitory activity. The difference in activity between the secondary and tertiary amides is most likely due to the opposite conformational preferences of the amide bonds, s-trans for the secondary-amide and s-cis for the tertiary-amide. However, it was found that the conformational preference of the tertiary amide can be reversed by incorporating the amide nitrogen atom into an indoline heterocycle, resulting in very potent integrase inhibitors.

Amides↗

Triketoacid inhibitors of HIV-integrase: a new chemotype useful for probing the integrase pharmacophore.

Integrase is one of three enzymes expressed by HIV and represents a validated target for therapy. This study reports on the discovery of a new triketoacid-based chemotype that selectively inhibits the strand transfer reaction of HIV-integrase. SAR studies showed that the template binds to integrase in a manner similar to the diketoacid-based inhibitors. Moreover, comparison of the new chemotype to two different diketoacid templates led us to propose two aryl-binding domains in the inhibitor binding site. This information was used to design a new diketoacid template with improved activity against the enzyme.

HIV Integrase↗

What is the relation between cultural orientation and socially desirable responding?

Research suggests that collectivists are more likely to engage in deception and socially desirable responding to maintain good relationships with others. In contrast, individualists are portrayed as candid and sincere because individualism encourages people to "be yourself." The authors propose that people with both types of cultural orientations or backgrounds engage in desirable responding, albeit in distinct ways. In Study 1, respondents from the United States compared with those from Singapore, and European Americans compared with Asian Americans, scored higher on self-deceptive enhancement (SDE)-the tendency to see oneself in a positive light and to give inflated assessment of one's skills and abilities- but lower on impression management (IM) by misrepresenting their self-reported actions to appear more normatively appropriate. In Studies 2 to 4, horizontal individualism as a cultural orientation correlated with SDE but not with IM, whereas horizontal collectivism correlated with IM but not with SDE. Further analyses examining (a) individual differences in the tendency to answer deceptively and (b) responses to behavioral scenarios shed additional light on the culturally relevant goals served by these distinct types of socially desirable responding.

Adult↗

Age and racial/ethnic differences in drinking and drinking-related problems in a community sample of lesbians.

OBJECTIVE: Although research on alcohol use among women has increased dramatically during the past several decades, relatively few studies have focused on lesbians, and almost none have included sufficient numbers of older lesbians or lesbians of color to permit comparative analyses. Using data from the Chicago Health and Life Experiences of Women Study (CHLEW), we examined drinking patterns and problems in a large and diverse sample of lesbians. METHOD: Structured interviews were conducted with 447 community-residing adult women (ages 18-83) who self-identified as lesbians (48% non-Hispanic white, 28% non-Hispanic black, and 20% Hispanic/Latina; the remainder were in the "other" category). We used multivariate logistic regressions to examine and compare the prevalence of lifetime and 12-month problem-drinking indicators across four age and three racial/ethnic groups. RESULTS: Unlike findings from general population surveys, in which women's rates of drinking tend to decrease with age, we found relatively few differences across the four age groups of CHLEW respondents. We also found no significant differences between Hispanic and white lesbians on any of the lifetime or 12-month problem-drinking indicators and only a few significant differences between white and black lesbians. CONCLUSIONS: As with heterosexual women, patterns of drinking and drinking-related problems among lesbians vary by age and race/ ethnicity. However, given our findings of substantially smaller variations among lesbians than among women in the general population, research is needed that examines in greater depth the intersections between age, race/ethnicity, sexual orientation, and drinking. Understanding how these sociocultural factors interact with each other and with other known risk factors is important for identifying population groups at greatest risk for developing alcohol-related problems.

Adolescent↗

Modeling sources of self-report bias in a survey of drug use epidemiology.

PURPOSE: Well-documented errors in the reporting of drug-related behaviors have been attributed to several sources. These include: 1) respondent difficulties in understanding survey questions, 2) problems in recalling the information necessary to accurately answer these questions, and 3) social pressures that discourage accurate reporting. We report covariance structure models designed to simultaneously evaluate each of these potential sources of error. METHODS: Data examined are from a community survey of 627 Chicago adults which collected drug use self reports (via ACASI technology), multiple biological samples (including hair, urine, and saliva) that permit self-report validation, and a series of probes designed to collect systematic information regarding respondent comprehension and memory difficulties and social desirability concerns. These three sets of information were employed to construct latent variable covariance structure models that enabled an evaluation of the effects of each potential source of reporting error on the quality of drug use reporting. RESULTS: Social desirability concerns were predictive of discordant drug use reporting and drug use under-reporting. Memory difficulties were predictive of drug use over-reporting. Differences in the predictive power of these variables were found across race/ethnic groups. CONCLUSIONS: Both memory difficulties and social desirability concerns are independent sources of measurement error in surveys of drug use epidemiology.

Bias↗

Patterns of Internet use and impact on patients with melanoma.

BACKGROUND: Patients with cancer and their families frequently, and increasingly, turn to outside sources for information, particularly the World Wide Web. Our objective was to examine the use of the Internet and its impact among patients with melanoma. METHODS: A prospective survey was obtained from 1613 consecutive patients with cutaneous melanoma seen at our institution between August 2001 and February 2003. Main outcome measures included the ability to access the Internet, Internet use to search for melanoma information, and responses to such Internet searches. Further analysis of whether there were differences based on age, sex, or disease severity was performed. RESULTS: Of patients with melanoma, 39% indicated that they had used the Internet to research their disease, 30% themselves and 9% had someone else do it for them. Nearly half (47%) of patients younger than 40 years researched melanoma on the Internet compared with only 12% of patients 60 years or older. Neither sex nor disease severity impacted Internet use. The vast majority of patients (94%) thought the Internet was useful, 67% believed it helped them better understand their condition, and 45% said they would recommend using the Internet to others to find information about medical conditions. Roughly a third thought it decreased their anxiety, whereas a similar proportion believed the Internet made them more anxious. Increased anxiety correlated with decreasing age and increasing disease severity. CONCLUSIONS: The use of the Internet is common among patients with melanoma. Anxiety attributed to online information about their disease suggests that clinicians caring for patients with melanoma should familiarize themselves with online melanoma information, and be proactive in assisting their patients in using this resource.

Adolescent↗

Matrix metalloproteinase expression in basal cell carcinoma: relationship between enzyme profile and collagen fragmentation pattern.

Matrix metalloproteinases (MMPs) with collagenolytic and gelatinolytic activities are up-regulated in basal cell carcinoma. In the present study we demonstrate that the major collagenolytic enzyme detected is MMP-1 (interstitial collagenase) while gelatinolytic enzymes include both MMP-2 (72-kDa gelatinase A) and MMP-9 (92-kDa gelatinase B). Significant fractions of all three enzymes are present as active forms. In spite of the fact that high levels of gelatinolytic enzymes are present, the major fragmentation products resulting from digestion of intact type I collagen are the 1/4 and 3/4 fragments (products of MMP-1-mediated digestion). Thus, it appears that the gelatinolytic enzymes are not capable of degrading the collagen fragments as rapidly as they are produced. Since previous studies have demonstrated that interaction of interstitial fibroblasts with high molecular weight fragments of type I collagen leads to increased MMP production, the present results suggest a mechanism underlying altered function of stromal elements in the connective tissue adjacent to the growing neoplasm.

Blotting, Western↗

Perioperative morbidity in bilateral one-stage total knee replacements.

A retrospective review was done on 501 patients who had bilateral sequential one-stage total knee replacements from September 1995 to April 2000 to evaluate perioperative (inhospital) morbidity. One thousand two knee replacements were done with the patients receiving regional anesthesia, on 286 women and 215 men with an average age of 66 years. The average transfusion requirement was 2.8 units of blood per patient. There were no deaths, myocardial infarctions, or cerebrovascular accidents. The mean length of hospital stay was 7.2 days. One hundred forty-four perioperative complications were observed in 109 patients (21.8%). These complications included 27 arrhythmias (5%), one congestive heart failure (0.2%), 65 lower extremity deep venous thromboses (13%), 14 fat emboli (3%), and two pulmonary emboli (0.4%). Other major complications were pneumonia (1%), acute renal failure (0.4%), ileus (2%), and mental status changes (2%). Wound complications included two deep infections (0.4%), three hematomas (0.6%), and five delayed wound healings (0.9%). According to the current study the perioperative morbidity and mortality is acceptable if the procedure is used for selected patients. Patients with significant comorbidities should have a staged bilateral total knee replacement.

Adolescent↗

Ghana postgraduate obstetrics/gynecology collaborative residency training program: success story and model for Africa.

OBJECTIVE: We describe a residency program in Ghana that was developed to train obstetrics/gynecologist specialists for Ghana and the subregion to promote and manage the reproductive health of women and to reduce a high maternal mortality rate. STUDY DESIGN: The Carnegie-supported program, begun in 1989, is a 5-year residency in the two medical schools in Ghana, but with one central coordinating office. It has features that equip the graduate resident to practice in his/her environment. The fourth year of the program is unique: the resident attends a hospital management course for 3 months, goes for a clinical rotation in the United States or United Kingdom for 3 months, and moves to live and work in a rural district hospital for 6 months. RESULTS: The success rate of the Ghanaian residents in the examination of the West African College of Surgeons has been three to four times higher than the overall pass rate. As of October 2002, the program had produced 26 specialists, all of whom are practicing in Ghana. In contrast, of 30 specialists who were trained abroad between 1960 and 1980, only 3 specialist had returned home by the end of the 1980s. The current chairpersons of the two medical schools are graduates of the program. Carnegie financial support for the program came to an end in January 2000, but the Ghana Ministry of Health has increased its support enthusiastically. The program is being sustained. Maternal mortality and morbidity rates are falling slowly in the two teaching hospitals; case fatality rates have been reduced markedly. New residents are entering the program and are progressing to completion. CONCLUSION: The program has been an unqualified success and merits replication.

Education, Medical, Graduate↗

Blood management after bilateral total knee arthroplasty.

Four hundred sixty-one patients who had bilateral one-stage total knee replacements were reviewed to evaluate their blood management. Overall, patients received an average of 2.1 units of autologous blood and 0.9 units of allogenic blood. Seventy-six percent of the patients who preoperatively donated one unit of autologous blood required allogenic blood transfusions compared with 51% of patients who donated two units, 29% of patients who donated three units, and 27% of patients who donated four units of autologous blood. Ninety-eight percent of the patients who did not donate autologous blood required allogenic blood. Donating two units of autologous blood in combination with a perioperative cell saver reduced the incidence of allogenic blood transfusions to 8% but increased the amount of unused autologous blood to 54%. If the indication for wound drainage recovery is guided by the preoperative hematocrit (< or = 40%) or postoperative hemoglobin (> or = 11 mg/dL) the incidence of allogenic blood transfusions decreased to 17% and 13%, respectively and the amount of unused autologous blood decreased to 39% and 30%. There is no statistical difference among the three protocols regarding the need for allogenic blood transfusions and associated costs. Based on this retrospective evaluation the combination of preoperative donation of two units autologous blood and use of a postoperative cell salvage system in all patients is recommended.

Adult↗

The utility of sentinel lymph node biopsy in head and neck melanoma in the pediatric population.

Intraoperative lymph node mapping and sentinel lymph node biopsy have proven beneficial techniques in staging adult patients with melanoma of the head and neck, where there is great variability in lymphatic drainage. This technique has also been applied to pediatric patients with truncal cutaneous melanomas in an effort to determine nodal status without the morbidity associated with complete lymph node dissection. Nevertheless, the utility of sentinel lymph node biopsy in head and neck melanoma in the pediatric population has not been established. The objective of the authors' study was to determine the clinical utility of intraoperative lymph node mapping and sentinel lymph node biopsy of head and neck melanoma in the pediatric population. The authors reviewed the records of seven pediatric patients with head and neck melanoma or borderline melanocytic proliferations of unknown biologic potential who underwent intraoperative lymph node mapping and sentinel lymph node biopsy between 1998 and 2001. All sentinel lymph node specimens were examined by a melanoma dermatopathologist for the presence of metastatic melanoma. The mean operative time for each case was 3 hours, 8 minutes (range, 2 hours, 15 minutes to 3 hours, 50 minutes). All seven pediatric patients who underwent extirpation of a primary head and neck melanoma and preoperative lymphoscintigraphy had unique and identifiable basins of drainage to regional nodal groups. Four of seven patients had at least one positive sentinel lymph node. Overall, five of 19 sentinel nodes (26 percent) resected had evidence of metastatic melanoma. Of the patients with positive sentinel lymph nodes, two of the primary lesions were diagnosed as melanoma while two were initially considered atypical melanocytic proliferations of uncertain biologic potential with melanoma in the differential diagnosis. Sentinel lymph nodes in pediatric patients with melanoma of the head and neck can be successfully mapped and biopsied, as in adult patients. In addition, this procedure can provide critical diagnostic information for those pediatric patients with diagnostically challenging, controversial, or borderline melanocytic lesions.

Child, Preschool↗

Insulin-like growth factor I is a comitogen for hepatocyte growth factor in a rat model of hepatocellular carcinoma.

Hepatocyte growth factor-scatter factor (HGF-SF) is a potent hepatic mitogen yet inhibits hepatocellular carcinoma (HCC) cell growth in vitro. Insulin-like growth factor I (IGF-I) is a pleiotropic growth factor shown to be important in cell growth and differentiation in other tumors. We hypothesized that IGF-I may play a role in regulating HGF-SF activity and HCC progression. Using an in vivo model of HCC, we showed elevated IGF-I messenger RNA (mRNA) expression in normal liver from tumor-burdened animals in the absence of changes in circulating IGF-I levels. Analysis of IGF-I receptor (IGF-IR) and HGF-SF (c-met) receptor expression showed significantly higher expression of both receptors in normal liver compared with an HCC specimen. Using cultured HCC cells from this model, we next showed that treatment with IGF-I led to significant increases in mitogen-activated protein kinase (MAPK) activity. Furthermore, we observed significant time-dependent increases in the expression of the c-fos and c-jun proto-oncogenes after addition of IGF-I (n = 5 per group, P <.05). Despite activation of a MAPK pathway and increased proto-oncogene expression, IGF-I failed to significantly affect cell mitogenesis. In contrast, HGF significantly inhibited cell mitogenesis in HCC lines (68.4% +/- 9.4% vs. control, n = 4, P <.05). Pretreatment of HCC cells with IGF-I (60 minutes) led to significant HGF-SF stimulation of total cell mitogenesis dependent on both IGF-I and HGF-SF dose (194% +/- 8% increase vs. control, n = 4, P <.05). In conclusion, tumor burden is important in altering intrahepatic growth factor synthesis. Signal cooperation between multiple cytokine pathways is an important factor in the progression of HCC.

Animals↗

Prediction of depressive distress in a community sample of women: the role of sexual orientation.

OBJECTIVES: This study compared factors known or hypothesized to influence depressive symptomatology in a community sample of lesbians and heterosexual women. METHODS: Data were collected in a multisite survey of lesbians' physical and mental health. RESULTS: Findings confirmed earlier reports suggesting that traumatic life events such as physical and sexual abuse, and individual traits and coping styles are risk factors for depressive distress. However, findings of higher rates of suicidal behavior and of several risk factors for depressive distress among lesbians suggest that risk for depression may differ among lesbians and heterosexual women. CONCLUSIONS: Sexual orientation may represent an important but poorly understood risk factor for depressive distress as well as suicidal ideation and behavior.

Adaptation, Psychological↗

Current melanoma staging.

American Joint Committee on Cancer (AJCC), TNM staging, represents the cornerstone of management for cutaneous melanoma. This staging system groups patients with similar prognoses and has important implications in optimizing management and treatment and conducting better clinical trials. T describes the extent of the primary tumor, N the extent of regional lymph node metastases, and M the extent of distant metastases. The AJCC staging system for cutaneous melanoma underwent significant revision in 2002. The revised, current AJCC staging system and the TNM classification are detailed in this review.

Humans↗