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Biomedical subjects

J R Harris

Publications and source records attributed to J R Harris.

At least 361 records · Page 20Linked to original sources

Identification of patients at high risk for local recurrence after conservative surgery and radiation therapy for stage I or II breast cancer.

The extent of excision prior to radiation for breast cancer is controversial. Three hundred evaluable patients with invasive ductal carcinoma received radiation therapy after gross tumor excision. The median follow-up was 70 months. Local recurrence was related to the presence of an extensive intraductal component (EIC) in addition to the invasive ductal carcinoma. From operative notes and pathology reports, patients with an EIC were categorized as having discrete masses with the extent of disease confirmed histologically or as having one of five criteria in which the final pathologic findings revealed more intraductal disease than was evident grossly or by frozen section. After ten years of follow-up, the local failure rate of patients without an EIC (193) was 3% compared with 35% for those with an EIC (107). Eight-year recurrence rates were 18% for clearly defined tumors and 71% for tumors in which the intraductal component was detectable only histologically.

Breast Neoplasms↗

B subunit-whole cell and whole cell-only oral vaccines against cholera: studies on reactogenicity and immunogenicity.

We conducted a randomized trial among persons in rural Bangladesh to evaluate the side effects and immunogenicity of orally administered B subunit-killed whole cell (BS-WC) and killed whole cell-only (WC) cholera vaccines and a killed Escherichia coli strain K12 placebo proposed for field testing. Three doses of BS-WC, WC, E. coli, or a control agent were given with antacid to 1,257 women (aged greater than 15 years) and children (aged to to 15 years). The four groups exhibited no statistically significant differences in occurrence of symptoms after each dose, and rises in titers of vibriocidal (VC) antibodies to Inaba and Ogawa were twofold higher for vaccinees than for controls (P less than .001). Half of the persons with fourfold or greater VC responses to WC responded after the first dose; many additional patients, particularly young children, responded after subsequent doses. In contrast, 89% of persons who responded to BS-WC with twofold or greater rises in titer of IgG antibodies to cholera toxin did so after the first dose. After the third dose, vaccinees exhibited a fivefold higher rise in titer than did controls (P less than .001); a dose-to-dose booster effect was most evident in young children.

Administration, Oral↗

The 5-year results of a randomized trial of adjuvant radiation therapy after chemotherapy in breast cancer patients treated with mastectomy.

The use of adjuvant radiation therapy in breast cancer patients treated with mastectomy and adjuvant chemotherapy has been controversial. In order to assess the necessity and effectiveness of adjuvant radiation therapy in this setting, we reviewed the results in 510 patients with T1-T3 tumors and pathologically positive nodes or tumors larger than 5 cm and negative nodes who were treated with adjuvant chemotherapy. Patients with four or more positive nodes or at least one positive apical node were randomized to receive either five or ten cycles of cyclophosphamide/Adriamycin (Adria Laboratories, Columbus, OH) (CA) and patients with one to three positive nodes or operable tumors larger than 5 cm and pathologically negative nodes were randomized to receive eight cycles of either cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF) or methotrexate and 5-FU (MF) chemotherapy. Two hundred six of these patients were subsequently rerandomized to receive either no further treatment or adjuvant radiotherapy. Thirty-five patients withdrew after randomization, including 34 who declined to receive radiotherapy. Radiation therapy consisted of 4,500 cGy in 5 weeks to the chest wall and appropriate draining lymph nodes. Median follow-up from chemotherapy randomization is 45 months for patients in the CA arm and 53 months for those in the CMF/MF arm. The crude rate of local failure (chest wall or draining lymph node areas) as first site of failure for patients randomized to receive chemotherapy only was 14%; for those randomized to receive both chemotherapy and radiotherapy it was 5% (P = .03). For patients in the CMF/MF arm, the rate of local failure as the first site of failure was nearly the same for patients randomized to chemotherapy only as for those randomized to adjuvant radiotherapy as well (5% v 2%). For patients in the CA arm, the crude rate of local failure was 20% for patients randomized to receive chemotherapy only, and 6% for those randomized to both types of adjuvant treatment (P = .03). Among the 43 patients treated with CA who actually received radiotherapy, there was only one local failure, compared with 12 local failures among the 59 patients (20%) who actually did not receive radiotherapy (P = .007). No significant difference was seen in disease-free survival or overall survival in either the CA or the CMF/MF arm between patients randomized to receive radiation therapy and those randomized to no further treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Mammographic detection of recurrent cancer in the irradiated breast.

Recurrence of cancer in the irradiated breast is an uncommon but potentially curable problem. Posttreatment mammograms were studied in 45 patients who had biopsies of an irradiated breast for suspected local recurrence to evaluate the usefulness of mammography in detecting such recurrences. Of 23 biopsy-proven recurrences, eight (35%) were detected by mammography only, nine (39%) were detected by physical examination only, and six (26%) were detected by both. Mammographic findings in recurrent malignancy included microcalcifications in six, microcalcifications associated with a mass in four, soft-tissue masses in three, and inflammatory changes in one. The results show that mammographic follow-up is complementary to physical examination in the detection of local recurrence in women who have undergone radiation therapy for early breast cancer.

Adult↗

Decline of anti-p24 antibody precedes antigenaemia as correlate of prognosis in HIV-1 infection.

A cohort of 84 homosexual men presenting with persistent generalized lymphadenopathy (PGL) was studied between March 1982 and March 1987. A progression rate to AIDS of 5% per year was seen in those who were infected with HIV. Certain clinical features and routine laboratory investigations were significantly associated with an increased risk of disease progression, but had only limited predictive value. Two hundred and fifty-two serial sera from 57 patients were analysed for the p24 antigen (Abbott), the principal core protein of HIV and antibody against p24 by direct enzyme-linked immunosorbent assay (ELISA). Patients who remained well retained a high titre of anti-p24 antibody compared with those who progressed to AIDS-related complex (ARC) or AIDS. HIV antigen was detectable in 40% of AIDS patients 2 years before diagnosis, but antigenaemia was preceded by loss of anti-p24 antibody by up to 18 months and preceded AIDS by up to 40 months. ARC patients tended to be negative when tested for both alpha-p24 antibody and antigen, suggesting a transitional state. Analysis of the humoral response against gag proteins appears to correlate closely with clinical status and may be an earlier and more consistent way of predicting disease progression than p24 antigenaemia, or clinical and routine laboratory investigations.

AIDS-Related Complex↗

Female prostitutes and sexually transmitted diseases.

The epidemiology of HIV infection emphasizes the need to be able to identify and communicate with female prostitutes as a group. Health education, screening and the prevention of STD in female prostitutes remains an essential priority for the well-being of the prostitutes, their clients and the health of society. However, these goals will not be achieved by compulsory screening, as this will miss the highest risk group. Instead, increased official recognition and measures to encourage female prostitutes to participate in and communicate with the health care system may result in an improvement in our management of these women.

Acquired Immunodeficiency Syndrome↗

The use of radiotherapy for treatment of isolated locoregional recurrence of breast carcinoma after mastectomy.

The role of radiotherapy in the treatment of isolated local recurrence of breast cancer after mastectomy is controversial. In an attempt to define this role, the results of moderate-dose radiotherapy in 90 such patients were reviewed. The median follow-up time for these patients was 81 months. The actuarial probability of local control after treatment was 42% at 5 years and 35% at 10 years. Freedom from distant failure was 30% at 5 years and only 7% at 10 years. The rate of appearance of distant metastasis was fairly constant at approximately 20% of patients per year. Overall survival was 50% at 5 years and 26% at 10 years. Overall survival and relapse-free survival were both chiefly influenced by the disease-free interval (DFI). Patients who presented with a DFI of greater than or equal to 2 years had a 5-year actuarial overall survival rate of 58% compared to 33% for patients with a DFI of less than 2 years (P = 0.04). Subsequent local failures after radiotherapy were principally seen at the initial site of recurrence, but also at other sites in or at the edge of the radiation fields. These results strongly suggest that patients with apparently isolated local recurrence after mastectomy are incurable by further local treatment. Effective systemic therapy is required to improve the results in these patients. Radiotherapy is a useful palliative procedure in patients with long disease-free intervals. The role of radiotherapy in conjunction with systemic therapy is, as yet, undefined.

Breast Neoplasms↗

Field trial of oral cholera vaccines in Bangladesh.

The protective efficacy of oral B subunit killed whole-cell (BS-WC) and killed whole-cell (WC) cholera vaccines was assessed in 63 498 Bangladeshi children aged 2-15 years and women aged over 15 years. Each received three doses of BS-WC, WC, or placebo in a randomised, double-blinded fashion. Surveillance for cases seeking medical care up to six months after the third dose revealed 26 cases of confirmed cholera in the placebo group, 4 cases in the BS-WC group (protective efficacy 85%; p less than 0.0001), and 11 cases in the WC group (protective efficacy 58%; p less than 0.01). For each vaccine protective efficacy was consistent in different age-groups (2-10 years versus greater than 10 years) and for different severities of cholera.

Administration, Oral↗

Three-year prospective study of HTLV-III/LAV infection in homosexual men.

170 symptom-free homosexual men were recruited in London in 1982-83 and 133 were evaluable in 1983-85. Of the 33 who were seropositive to HTLV-III/LAV at entry, 4 (12%) progressed to AIDS, 16 (48%) progressed to persistent generalised lymphadenopathy (PGL), and 13 (40%) remained symptom-free. A further 15 men seroconverted during the study (7% per annum), of whom 8 progressed to PGL. Serial estimations of T lymphocyte subsets showed progressive reduction in T4 numbers in the seropositive groups, but these indices also varied widely in the seronegative group. Counts of T4 and T8 cells or T4/T8 ratio at entry were not of prognostic value. Seronegative subjects were as likely as seropositives to have abnormal immunological tests. Serial measurement of T lymphocyte subsets seems to be of little prognostic or clinical value in the monitoring of populations infected with the HTLV-III/LAV virus. The strongest association with prognosis was an episode of sexually transmitted disease in the six months before entry to the study. This supports the hypothesis that intercurrent infection may be an important co-factor in the acquisition of HTLV-III/LAV infection, and in subsequent disease progression.

Acquired Immunodeficiency Syndrome↗

Observations on survival curve analysis with particular reference to breast cancer treatment.

The proper analysis of survival curves of patients treated for cancer is critical to advances in clinical investigation. In this article, the presentation of such survival curves is reviewed and the various possible effects of treatment on these curves are discussed. The results of breast cancer treatment are used as examples. It is argued that the use of a semilogarithmic presentation is preferred in displaying the long-term force of mortality of the disease. In many human cancers, such as carcinoma of the breast, the demonstration of a "cured" subgroup requires follow-up of greater than 10 years and cannot be inferred from data evaluated earlier. Beneficial effects noted on the initial portion of the survival curve are not necessarily associated with an improvement in the likelihood of long-term survival, but are rather a reflection of delay or reduction on the initial force of mortality. Since both hosts and tumors are heterogeneous, it is also possible that there are different effects on various subgroups, making curve interpretation complex. In some cases, an early detrimental effect may obscure a benefit in the long-term outcome. These considerations emphasize that effects seen on the early portion of survival curves may not only be premature, but may also be misleading.

Actuarial Analysis↗