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Biomedical subjects

J F Hilton

Publications and source records attributed to J F Hilton.

At least 37 records · Page 2Linked to original sources

T-cell proliferative response to human papillomavirus type 16 peptides: relationship to cervical intraepithelial neoplasia.

The incidence of human papillomavirus (HPV)-related cervical intraepithelial neoplasia (CIN) and cervical cancer is increased with immunodeficiency, but the role of immune response, including cell-mediated immunity, in disease prevention is not well understood. In this study, T-cell proliferative responses to six synthetic peptides with predicted immunogenic determinants from the HPV-16 E4, E6, E7, and L1 open reading frames were analyzed in 22 sexually active women with new-onset CIN and 65 sexually active women without cervical disease, characterized by cytology, colposcopy, and HPV testing. T-cell proliferative responses were demonstrated to all six HPV-16 peptides. Although not statistically significant, rates of reactivity to E6 (24-45) were higher among sexually active women without disease (26%) than among women with current CIN (7%), as was the overall number of peptides stimulating a response. Women with CIN may not respond to selected HPV antigens as well as women without disease do.

Adult↗

Direct immunofluorescence vs. culture for detecting HSV in oral ulcers: a comparison.

Diagnostic tests may be necessary to determine the cause of oral ulcers. Direct immunofluorescence staining of oral smears supplies results much more quickly than viral culture, the "gold standard" for diagnosing HSV lesions. This study compares the sensitivity and specificity of direct immunofluorescence staining vs. viral culture and evaluates the usefulness of the two techniques for the general dental practitioner.

Adolescent↗

Time from HIV seroconversion to oral candidiasis or hairy leukoplakia among homosexual and bisexual men enrolled in three prospective cohorts.

OBJECTIVES: We evaluated time from HIV seroconversion to diagnosis of two common oral lesions associated with HIV infection and disease progression. DESIGN: Oral examinations were performed on homosexual and bisexual men enrolled in prospective cohorts. SETTING: Homosexual and bisexual men were followed in three epidemiologic cohort studies in San Francisco, California, USA. PARTICIPANTS: Data were evaluated from 80 men with well-defined dates of HIV seroconversion from 1984 through 1991. MAIN OUTCOME MEASURES: We determined the cumulative incidence of oral candidiasis and hairy leukoplakia after HIV seroconversion. RESULTS: Four per cent of men developed oral candidiasis within 1 year after HIV seroconversion, 8% within 2, 15% within 3, 18% within 4, and 26% within 5 years. Nine per cent developed hairy leukoplakia within 1 year, 16% within 2, 25% within 3, 35% within 4, and 42% within 5 years. The median CD4+ count was 391 x 10(6)/l when oral candidiasis was first reported and 468 x 10(6)/l when hairy leukoplakia was first reported. CONCLUSIONS: Oral candidiasis or hairy leukoplakia appeared in a significant proportion of HIV-infected homosexual and bisexual men. These lesions occurred relatively soon after HIV seroconversion, typically before AIDS. Evaluation of HIV-infected individuals for these lesions has many potential clinical and research benefits, including the possible use of oral lesions as primary end-points in clinical trials.

AIDS-Related Opportunistic Infections↗

The diagnosis of periodontal conditions associated with HIV infection.

Objective, reliable, and valid diagnostic criteria are required for studies of HIV-associated periodontal conditions. A set of diagnostic criteria were devised based on a literature review and the clinical experience of the authors. Validity was assessed by comparison with clinical photographs and the criteria were evaluated and refined for ease of use and objectivity. To assess the reliability of the criteria, 9 experienced examiners were shown 20 clinical photographs accompanied by brief vignettes of clinical information. Each examiner was asked to identify signs evident in a particular area of the photograph and to record a diagnosis. Five examiners were then trained and calibrated in the use of the criteria. Finally, all 9 examiners were shown the original 20 photographs and asked to identify signs and record diagnoses. The examiners showed only fair reliability in the recognition of clinical signs, made diagnoses intuitively, and had only fair agreement on the diagnosis of periodontal diseases. The inter-examiner reliability of examiners trained and calibrated in the use of the criteria increased and was greater than among untrained examiners. Rigid diagnostic criteria are essential in epidemiologic studies. Inter-examiner reliability will be increased if examiners are trained in their use and calibrated in the recognition of clinical signs. Diagnostic criteria should be modified as understanding of the diseases they classify increases. The proposed criteria will enhance the value of studies of HIV-associated periodontal changes and will contribute to that understanding.

Chi-Square Distribution↗

HIV-related oral manifestations in two cohorts of women in San Francisco.

The goals of this study were to compare the prevalence of oral lesions in women infected with human immunodeficiency virus (HIV) and HIV-negative women, and to determine the association of oral lesions with route of HIV transmission and with level of immunosuppression in infected women. As part of a prospective 4-year study, oral examinations and blood tests were performed, at 6-month intervals, on 176 HIV-infected women and on 117 HIV-negative women at risk for HIV infection. We evaluated participants for the following oral conditions: hairy leukoplakia, candidiasis, ulcers, warts, non-Hodgkin's lymphoma, Kaposi's sarcoma, and parotid enlargement. As previously reported in men, the prevalence of oral lesions was significantly higher among HIV-infected (22%) than HIV-negative women (3%) [odds ratio (OR) = 8.2; 95% confidence interval (CI) 2.8, 23.5], particularly candidiasis (14%) and hairy leukoplakia (10%). Among HIV-infected women with CD4 cell count nadir > or = 200 cells/microliters, the prevalence of hairy leukoplakia was higher among those infected heterosexually than among injection drug users (OR = 5.5; 95% CI: 1.5; 19). The OR for the association between oral lesions and CD4 cell count nadir (< 200 vs. > 500 cells/microliters) was 8.9 (95% CI: 2.6, 30), indicating a strong positive association with level of immunosuppression.

Adult↗

Power and sample size calculations for exact conditional tests with ordered categorical data.

We develop an algorithm for computing sample sizes, equal or unequal, for categorical data. We illustrate its use in the two-sample setting using the Wilcoxon rank-sum statistic, but the algorithm accommodates the entire class of linear rank statistics and can be extended to include nonlinear rank statistics as well. The sample size determinations can be based on either exact power or on a very precise Monte Carlo estimate of it. To reduce the computations further, power can be computed as a function of asymptotic critical values when the number of categories is not too small. For the Wilcoxon statistic we show that this approximation works well if there are more than five response categories.

Humans↗

Breast cancer incidence in women with abnormal cytology in nipple aspirates of breast fluid.

This is a prospective study of breast cancer risk in relation to nipple aspirate fluid cytology in 2,701 volunteer white women from the San Francisco Bay Area first enrolled between 1973 and 1980. The women were not pregnant or lactating and were free of breast cancer within 6 months of entry into the study. The breast cancer status of this cohort was determined between June 1988 and April 1991. Follow-up was complete for 87% (n = 2,343) of the cohort, representing 29,961 person-years and an average of 12.7 years of follow-up. The overall breast cancer incidence was 4.4% (104 of 2,343) and rose with fluid cytology findings as follows: no fluid obtained, 2.6% (9 of 352); unsatisfactory specimen, 4.8% (15 of 315); normal cytology, 4.3% (56 of 1,291); epithelial hyperplasia, 5.5% (18 of 327); and atypical hyperplasia, 10.3% (6 of 58). Relative risks for breast cancer and their 95% confidence intervals were estimated by Cox regression, adjusting for age and year of entry. Compared with the relative risk for women who yielded no fluid, relative risks were: unsatisfactory specimen, relative risk (RR) = 1.4 (95% confidence interval (CI) 0.6-3.3); normal cytology, RR = 1.8 (95% CI 0.9-3.6); epithelial hyperplasia, RR = 2.5 (95% CI 1.1-5.5); and atypical hyperplasia, RR = 4.9 (95% CI 1.7-13.9). These findings were strongest for and were mainly confined to women aged 25-54 years. Women with atypical hyperplasia and a first-degree family history of breast cancer were six times more likely to develop breast cancer than were women with atypical hyperplasia but without a family history of breast cancer (95% CI 1.0-30.2). These findings provide strong support for our hypothesis that hyperplasia and atypical hyperplasia diagnosed in nipple aspirates of breast fluid are associated with an increased risk of breast cancer.

Adolescent↗

Increased survival after massive thermal injuries in adults: preliminary report using artificial skin.

Survival of major burn injuries has improved markedly from an expected survival of 10% to 20% in both children and adults to an expected survival of 60% in children with burns greater than 70% BSA. Increased survival for adults after similar burn injuries has been less dramatic than in children because of the profound influences of advancing age and the coexistent processes of aging upon survival after a major injury. Consecutive admissions of patients with massive burn injuries (greater than or equal to 70% BSA) to the Massachusetts General Hospital Adult Burn Unit from 1974 to 1986 were analyzed statistically using univariate and multiple logistic regression analysis to identify factors associated with survival and to identify patient characteristics associated with increases in expected survival. Survival of adults with massive burn injuries has improved markedly, from 24% of adults admitted to the Adult Burn Center in 1974-75 to 48% of adults admitted in 1984-86. An increased likelihood of survival was shown to be associated with the use of artificial skin. Improved survival rates in these massive burn injuries were attributed to multiple factors including wound management of prompt eschar excision and immediate wound closure.

Adolescent↗

Hepatoma in the noncirrhotic liver.

The pathologic features, clinical presentation and natural history of hepatocellular carcinoma (HCC) developing in the noncirrhotic liver were studied in 61 patients against a background of 63 patients seen concurrently with HCC complicating cirrhosis. Noncirrhotic HCC had a bimodal age distribution, with females predominating the first age-clustering (10-50 years) and males predominating the second age-clustering (50-90 years). Cirrhotic HCC had a unimodal age distribution (40-90 years) with male dominance throughout. Estrogen exposure was noted in 57% of the noncirrhotic HCC women overall and in 80% of those in the younger age-clustering. The majority of noncirrhotic HCC presented with a single hepatic mass or a dominant primary with satellite lesions in contrast to the usual multinodular or diffuse disease seen with cirrhosis. Twenty-nine noncirrhotic patients survived complete resection of disease limited to the liver and exhibited a median survival of 2.7 years with a 5-year survival of 25%. Low histologic grade, minimal necrosis, and the absence of hemoperitoneum, hepatomegaly, and adjacent organ involvement were all favorable prognostic variable. Patients with metastatic or locally unresectable noncirrhotic HCC had a median survival of 9 months, and 24% survived in excess of 2 years. This survival experience is significantly more favorable than cirrhotic HCC patients, who had only a 1.2-month median and a 3% 2-year survival. Low histologic grade, mild mitotic activity and the presence of some fibrosis within the specimen were associated with a favorable outcome in advanced noncirrhotic HCC. The favorable prognosis and heterogeneous composition of the noncirrhotic, when compared to the cirrhotic HCC cohort, may be important considerations in the design and evaluation of future clinical trials.

Actuarial Analysis↗

Significant reductions in mortality for children with burn injuries through the use of prompt eschar excision.

During the past 19 years, mortality due to burn injuries has markedly declined for children at the Boston Unit of the Shriners Burns Institute (SBI), dropping from an average of 9% of SBI admissions during 1968-1970 to an average of 1% during 1981-1986. Detailed statistical analysis using logistic regression was necessary for determining whether this decline in mortality was explained by changes in patient characteristics, such as age or burn size, which are known to strongly influence the outcome of burn injuries. This dramatic decline in mortality during the past 19 years was not the result of change in the age of the patients or their burn sizes; rather, it may be attributed to improvements in burn care. Results of this statistical analysis indicated that, for burn injury patients whose ages ranged from 11 days to 19 years, age had no demonstrable effect on survival from a burn injury. Children survived burn injuries at least as well if not better than the young adult (20-29 years of age). Also, infants (less than 1 year old) survived as well as other children (2-19 years old). Dramatic improvement in survival occurred in patients with burns covering more than 50% of the body surface area. Since 1979, mortality has been essentially eliminated for patients with burn sizes less than 70% of the total body surface area (of 296 patients with burns covering 15-69% of the total body surface area, only two patients died). During the period 1979-1986, 29 of 37 patients (78%) survived an 80% or greater total body surface area thermal injury.

Administration, Topical↗

Randomized phase II studies of cisplatin and a combination of cyclophosphamide-doxorubicin-cisplatin (CAP) in patients with progestin-refractory advanced endometrial carcinoma.

Between May 1980 and September 1983, 30 progestin-refractory patients with metastatic endometrial carcinoma were assigned at random to treatment groups receiving either cisplatin (CDDP) 60 mg/m2 every 3 weeks or a combination of cyclophosphamide, doxorubicin, and cisplatin every 4 weeks in doses of 400, 40, and 40 mg/m2, respectively. Those who failed cisplatin were then offered cyclophosphamide 500 mg/m2 plus doxorubicin 40 mg/m2 every 3 weeks. Reduced doses were utilized in both of the combination regimens for patients who had received extensive pelvic radiation. Of the 14 patients initially receiving cisplatin alone, 3 experienced objective tumor regression. One of these three and one other who failed primary cisplatin therapy later responded favorably to cyclophosphamide plus doxorubicin as secondary treatment. Among the 16 patients who took all three drugs simultaneously (CAP) 5 experienced objective partial tumor regression. Survival experience for these relatively late-stage patients has been uniformly poor, with only 7 and 12% surviving at 2 years after beginning CDDP and CAP, respectively. Thus, while cisplatin is clearly an active agent against endometrial carcinoma, its therapeutic index as a single drug or in combination (CAP) is not adequate to preclude new-agent Phase II studies early in patients with advanced disease.

Antineoplastic Combined Chemotherapy Protocols↗

Ineffectiveness of tamoxifen in advanced endometrial carcinoma after failure of progestin treatment.

Between May 1980 and November 1983, 46 eligible patients with advanced, objectively evaluable endometrial carcinoma were treated with tamoxifen, 10 mg twice daily. Twenty-two of the patients had previously received progestational agents. None of the progestin-refractory patients experienced tumor regression on tamoxifen treatment, while five of the 24 previously untreated with progestins did experience tamoxifen-induced tumor regression. Of the five patients previously treated with cytotoxic drugs, only one experienced objective tumor regression on tamoxifen. Although 28 of these 46 patients were completely ambulatory at the beginning of tamoxifen treatment, only 26% were alive 1 year later; median survival for the entire group was only 120 days. Tamoxifen in this dose cannot be recommended routinely as effective secondary treatment for patients with progestin-refractory advanced endometrial carcinoma.

Aged↗

Development of experimental models for meningeal neoplasia using intrathecal injection of 9L gliosarcoma and Walker 256 carcinosarcoma in the rat.

Two models for meningeal neoplasia have been developed in rats using intrathecal injection of 9L gliosarcoma and Walker 256 carcinosarcoma cells. Tumor cells were injected in unanesthetized animals through an indwelling catheter inserted at the cisterna magna to the level of the lumbar enlargement of the spinal cord. Survival of rats was dependent on the number of tumor cells injected. Spread of tumor was quantified by histology using a grading scale, and functional and behavioral changes were measured. Rats injected with 10(6) 9L gliosarcoma cells showed progressive weight loss, flaccid paralysis, and neurogenic bladder dysfunction and had a median survival of 11 days. The tumor frequently grew as a mass compressing the spinal cord. The 9L gliosarcoma tumor cells markedly invaded the Virchow-Robin spaces but exhibited only minimal invasion of the central nervous system parenchyma. The tumor reached the brain by day 10. Rats injected with 2 X 10(5) Walker 256 carcinosarcoma cells showed progressive weight loss and weakness and had a median survival of 6 days. The tumor grew within the leptomeninges in a discontinuous multifocal fashion and reached the brain by day 4. There was extensive invasion of the central nervous system parenchyma by Walker 256 tumor cells along the Virchow-Robin spaces resulting in hemorrhage and necrosis of grey and white matter. Hot plate and tail flick response times were significantly delayed only in the days immediately preceding death of animals with either 9L or Walker 256 tumor and were not good indicators of tumor progression. Loss of motor coordination and failure of the stepping and placing reflex on the other hand showed good correlation with spread of tumor measured histologically. Control animals injected with 0.9% NaCl or with lethally irradiated tumor cells showed no significant weight loss or functional or behavioral changes. The intrathecal 9L gliosarcoma and Walker 256 carcinosarcoma models show different characteristics of human meningeal carcinomatosis and will be used for studies of experimental chemotherapy with intrathecally administered antitumor drugs.

Animals↗

Second-look laparotomy in ovarian cancer: evaluation of pathologic variables.

From 1977 through 1982, 135 patients with ovarian cancer, having a mean age of 53.7 years and no clinical evidence of disease after approximately 1 year of treatment, underwent a "second-look" laparotomy. Of the 135 patients, 58 (43%) had histologic confirmation of disease at the second-look procedure. Persistent disease was positively correlated with the original stage and negatively correlated with the extent of the original reductive surgery. The original histologic grade or cellular subtype did not significantly influence the findings at reexploration. Patient survival, as judged by percentage of patients alive 3 years after the second-look laparotomy, was dependent on the following surgical/pathologic parameters: tumor size at reexploration, peritoneal cytologic features, residual tumor after reexploration, and histologic grade.

Carcinoma↗

Intravesical thiotepa and mitomycin C treatment immediately after transurethral resection and later for superficial (stages Ta and Tis) bladder cancer: a prospective, randomized, stratified study with crossover design.

In a prospective, randomized, stratified study with crossover design the effect of thiotepa was compared to that of mitomycin C when each was instilled intravesically immediately at the end of complete removal of superficial bladder cancer (stages Ta and Tis) and later on tumor recurrence. The 3-month and 1-year rates free of recurrence were 93 and 78 per cent, respectively, for thiotepa (41 patients), and 97.6 and 67.1 per cent, respectively, for mitomycin C (42 patients) (p equals 0.6). On crossover (5 patients to thiotepa and 9 to mitomycin C) at 1 year 60 per cent of the patients receiving thiotepa secondarily and 51.9 per cent of those receiving mitomycin C secondarily were free of recurrence (p equals 0.52). Therefore, both drugs are equally effective in reducing bladder tumor recurrence. Future comparative studies should continue to include thiotepa as a standard by which the efficacies of other agents are judged.

Adult↗

Planning a spit tobacco cessation intervention: identification of beliefs associated with addiction.

We examine the relationship between beliefs regarding spit tobacco (ST) use and addiction among 473 male college athletes who currently use ST. Beliefs were assessed using methods prescribed by the Theory of Reasoned Action. Independent associations between beliefs and addiction, defined by self-reported amount of ST used per week, were found via multivariate polychotomous regression modeling. We found that with increasing addiction level, athletes were significantly more likely to believe that "ST helps me relax," "ST keeps me alert," "ST tastes good," and "ST is addicting." All athletes believed that clinicians, parents, and girlfriends do not approve of their ST use, but that male peers, coaches, and professional athletes are fairly indifferent about it. To increase quit rates, highly addicted ST users may require an intensive cessation program including nicotine replacement to overcome symptoms of withdrawal, oral substitutes for the enjoyable taste of ST, and the support of male peers and athletes who influence their social norms.

Adolescent↗

Prevalence, patterns, and correlates of spit tobacco use in a college athlete population.

We surveyed varsity athletes (N = 1,328) in 16 California colleges about their patterns of spit (smokeless) tobacco (ST) use, related habits, reasons for use, and preferred methods for quitting. Prevalence of use was analyzed by sport and demographic characteristics, and patterns of use in players using snuff exclusively, using chewing tobacco exclusively, and those using both were compared. Odds ratios and 95% confidence intervals were calculated, adjusting for ethnic group. Prevalence was highest in Whites (44%) and Native Americans (48%) and lowest in African Americans (11%), and higher in varsity baseball (52%) than varsity football players (26%), in players attending rural colleges, and among those who ever smoked cigarettes or used alcohol. Forty-one percent of ST users initiated regular use during their high school years. Athletes who used snuff exclusively used it more intensively and for more years than those who used chewing tobacco exclusively. Snuff users indicated a greater perceived need for ST, but also were more ready to quit. These data suggest ST programs with prevention and cessation components are appropriate for high school as well as college athletes. Such interventions should focus on baseball players, distinguish snuff from chewing tobacco users in planning quit strategies, integrate intervention programs for cigarette smoking and alcohol consumption, provide training in refusal skills, and attempt to change social norms in support of ST use by integrating popular peers and significant others (e.g., wives/girlfriends) to endorse nonuse of ST.

Adolescent↗

Clinical trial of a plant-derived antibody on recolonization of mutans streptococci.

OBJECTIVE: This double-blinded, placebo-controlled clinical trial tested the safety and efficacy of a topical secretory IgA antibody manufactured in tobacco plants (plantibody) in preventing recolonization of mutans streptococci (MS) in human plaque as measured by whole stimulated saliva samples. METHODS: Following a 9-day antimicrobial treatment with chlorhexidine (CHX), 56 eligible adults (enrollment salivary MS > or = 10(4) CFU/ml; no current caries) were randomized equally to a group receiving 0, 2, 4, or 6 topical applications of plantibody followed by 6, 4, 2, or 0 applications of placebo, respectively, over a 3-week period. RESULTS: Among the 54 subjects who completed the trial, the CHX regimen eliminated salivary MS in 69%. After 6 months, there were no significant differences in MS levels by number of applications, relative to placebo (p > 0.43). No adverse effects were observed. CONCLUSION: Plantibody is safe but not effective at the frequency, concentration, and number of applications used in this study.

Adult↗