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Biomedical subjects

B J Kennedy

Publications and source records attributed to B J Kennedy.

At least 19 recordsLinked to original sources
PubMed2000

Hodgkin's disease survival by stage and age.

OBJECTIVE: Prior reports on Hodgkin's disease have suggested a biologic behavior difference between young and old patients. A study of 35,033 patients could confirm that older patients do not do as well as young patients regardless of age. METHODS: The National Cancer Data Base provided data from U.S. tumor registries on 35,033 patients newly diagnosed with Hodgkin's disease from 1985 through 1994. For analysis the patients were divided into two time periods, 1985-1989 and 1990-1994. The earlier period provided survival data to assess the impact of age and stage. RESULTS: The overall disease-specific, 5-year survival rate for the 1985-1989 period was 84.9%. For stages I and II, it reached almost 90%. For both observed survival based on all deaths and disease-specific survival, the duration of survival decreased with increasing age. This decrease with age occurred for all stages of the disease. CONCLUSIONS: The data reflect the actual status of management of Hodgkin's disease in the United States rather than the best attainable results. The decreasing survival with increasing age and in all stages further supports the concept of a difference in biologic behavior of Hodgkin's disease associated with age.

Adolescent↗
PubMed2000

Passive transfer of antiserum specific for immunogens derived from a nontypeable Haemophilus influenzae adhesin and lipoprotein D prevents otitis media after heterologous challenge.

We recently determined that passive transfer of serum directed against a synthetic peptide called LB1 or a recombinant fusion protein immunogen [LPD-LB1(f)(2,1,3)] could prevent otitis media after challenge with a homologous nontypeable Haemophilus influenzae (NTHI) isolate. NTHI residing in the nasopharynx was rapidly cleared from this site, thus preventing it from ascending the eustachian tube and inducing otitis media in chinchillas compromised by an ongoing viral upper respiratory tract infection. While LB1 is based solely on one NTHI adhesin, the latter immunogen, LPD-LB1(f)(2,1,3), was designed to incorporate two NTHI antigens shown to play a role in the pathogenesis of otitis media; lipoprotein D (LPD) and the P5-homologous fimbrin adhesin. The design of LPD-LB1(f)(2,1,3) also accommodated for the recently demonstrated existence of three major groupings, based on amino acid sequence diversity, in the third surface-exposed region of P5-fimbrin. LPD-LB1(f)(2,1,3) was thus designed to potentially confer broader protection against challenge by diverse strains of NTHI. Chinchillas were passively immunized here with serum specific for either LB1 or for LPD-LB1(f)(2,1,3) prior to challenge with a member of all three groups of NTHI relative to diversity in region 3. The transferred serum pools were also analyzed for titer, specificity, and several functional activities. We found that both serum pools had equivalent ability to mediate C'-dependent killing and to inhibit adherence of NTHI strains to human oropharyngeal cells. When passively transferred, both serum pools significantly inhibited the signs and incidence of otitis media (P </= 0.01) induced by any of the three challenge isolates. Despite providing protection against disease, the ability of these antisera to induce total eradication of NTHI from the nasopharynx was not equivalent among NTHI groups. These data thus suggested that while early, complete eradication of NTHI from the nasopharynx was highly protective, reduction of the bacterial load to below a critical threshold level appeared to be similarly effective.

Adhesins, Bacterial↗
PubMed1999

Uracil mustard revisited.

BACKGROUND: A patient with diffuse large cell lymphoma who had a complete response lasting 35 years following a 3-day course of uracil mustard stimulated a recall review of patients treated with this oral alkylating agent. METHODS: Records of patients treated with uracil mustard between 1958 and 1970 were reviewed. A current histologic review according to the International Formulation was performed when possible. Total doses of uracil mustard were similar to those of mechlorethamine, although there were variations in the dose schedule. RESULTS: Employing criteria used over 25 years ago to evaluate patients' responses, the overall regression rate for 94 non-Hodgkin lymphoma patients was 69.2% (complete response [CR] 23.4%). Of 62 patients with Hodgkin disease, 69.4% responded (CR 9.7%). For 39 patients with chronic lymphatic leukemia, the combined complete and partial response rate was 74% (CR 7.7%). Thrombocytopenia was the primary toxicity. CONCLUSIONS: Uracil mustard is an unmarketed, inexpensive oral alkylating agent that has been effective in the treatment of patients with lymphoma, chronic lymphatic leukemia, and thrombocythemia. Perhaps it should be reevaluated.

Adolescent↗
PubMed1999

Medical oncology: its origin, evolution, current status, and future.

BACKGROUND: Over the last 26 years, the subspecialty of medical oncology has been evolving, and in the process bringing to the community improved oncologic management. During this evolution, guidelines for training new members of the subspecialty have been developed, and these have been heralded as important strides forward in medical education. Continual adjustment to new technology and changing population needs represent challenges for the future. METHODS: The steps in the development of this subspecialty, which are documented in educational publications, are reviewed in this article. RESULTS: Medical oncology evolved because of the introduction of multiple new cancer therapies and an awareness of the need of patients with cancer for continual care, from diagnosis to the end-of-life phase. Together, certified medical oncologists represent the third largest of the current subspecialties of internal medicine. Training guidelines and the needs of the work force are being continually assessed in an effort to maintain an important future for these specialists. CONCLUSIONS: Medical oncologists are cancer specialists who are not in competition with primary care physicians, but are instead supportive. By serving as principal caregivers (those subspecialists who provide most of a patient's health care needs), and by paying increasing attention to older patients with cancer, medical oncologists will remain in demand.

Education, Medical, Graduate↗
PubMed1999

Protection against development of otitis media induced by nontypeable Haemophilus influenzae by both active and passive immunization in a chinchilla model of virus-bacterium superinfection.

Three separate studies, two involving active-immunization regimens and one involving a passive-transfer protocol, were conducted to initially screen and ultimately more fully assess several nontypeable Haemophilus influenzae outer membrane proteins or their derivatives for their relative protective efficacy in chinchilla models of otitis media. Initial screening of these antigens (P5-fimbrin, lipoprotein D, and P6), delivered singly or in combination with either Freund's adjuvant or alum, indicated that augmented bacterial clearance from the nasopharynx, the middle ears, or both anatomical sites could be induced by parenteral immunization with P5-fimbrin combined with lipoprotein D, lipoprotein D alone, or the synthetic chimeric peptide LB1 (derived from P5-fimbrin), respectively. Data from a second study, wherein chinchillas were immunized with LB1 or lipoprotein D, each delivered with alum, again indicated that clearance of nontypeable H. influenzae could be augmented by immunization with either of these immunogens; however, when this adjuvant was used, both antibody titers in serum and efficacy were reduced. A third study was performed to investigate passive delivery of antisera directed against either LB1, lipoprotein D, nonacylated lipoprotein D, or a unique recombinant peptide designated LPD-LB1(f)2,1,3. The last three antiserum pools were generated by using the combined adjuvant of alum plus monophosphoryl lipid A. Passive transfer of sera specific for LB1 or LPD-LB1(f)2,1,3 to adenovirus-compromised chinchillas, prior to intranasal challenge with nontypeable H. influenzae, significantly reduced the severity of signs and incidence of otitis media which developed (P </= 0.001). Collectively, these data indicate the continued merit of further developing LB1 and LPD-LB1(f)2,1,3 as components of vaccines for otitis media.

Amino Acid Sequence↗
PubMed1998

The National Cancer Data Base report on Hodgkin's disease for 1985-1989 and 1990-1994.

BACKGROUND: A national survey of the management of Hodgkin's disease patients based on cases in the National Cancer Data Base (NCDB) provides a basis for evaluating the results of educational and therapeutic programs. These patients are believed to have been drawn from all nationalities, native and migrant, and were reported by hospital cancer registries throughout the United States, including large and small community hospitals, university and other teaching hospitals, military and Veterans Administration (VA) hospitals, and National Cancer Institute (NCI)-Designated Centers. METHODS: Data submitted voluntarily to the NCDB were used to determine trends in patterns of patient care across time. For the period 1985-1994, data from 35,033 patients with newly diagnosed Hodgkin's disease were analyzed and separated into two time periods, 1985-1989 and 1990-1994. RESULTS: Data were analyzed with respect to age, race, histology, stage, treatment, and survival. The majority of patients (83.6%) were white, the age group with the highest incidence was 20-29 years, and nodular sclerosis was the most common histologic type. Staging was reported as a combination of clinical and pathologic stage ("combined stage"). The number of cases of reported stage increased from 51.7% for the years 1985-1989 to 75.7% for the years 1990-1994. Radiation therapy was used primarily to treat patients in Stages I and II, although the overall use of radiotherapy declined by 10% in the later period. The overall observed 5-year survival rate was 83.2%, and the disease specific observed survival rate was 84.9%. Stage for stage, survival was better for younger patients and poorer for older patients. CONCLUSIONS: The survey reflects the actual management of Hodgkin's patients disease. The reported cases for 1994 represent 60.6% of the estimated occurrences for that year in the U.S. There has been a significant improvement in the frequency of use of the staging system. A continuing increase in survival for patients with Hodgkin's disease is occurring. This method of studying disease management provides a measure of educational efforts and guides to developmental research.

Adolescent↗
PubMed1998

Adjuvant therapy of breast cancer--an overview.

Adjuvant therapy in the treatment of breast cancer commonly refers to therapies that supplement primary treatment, traditionally mastectomy and, more recently, breast-conserving surgery. The present paper examines the evolution of systemic therapies and radiotherapy in their role as adjuvants to mastectomy, and offers a brief description of current treatment regimens for early and locally advanced disease.

Antineoplastic Agents↗
PubMed1998

Familial hearing loss and cisplatin therapy.

Familial high-tone hearing loss in males is a recessive trait often unrecognized. Cisplatin chemotherapy may be associated with hearing loss. A review was made of audiograms in 85 patients with testicular carcinoma prior to cisplatin chemotherapy to determine the extent of preexisting familial hearing loss. Clinical histories defined patients exposed to high noise levels and other common causes of hearing loss. Audiometric findings were classified according to normal hearing or mild, moderate, and severe hearing impairment. Pretreatment audiograms were normal in 51 patients and abnormal in 19 patients with histories of high-level noise exposure, and in 15 patients with high-frequency hearing loss there was no history of noise exposure, ear infection, or other potential causes of hearing loss. These last 15 patients were judged to have recessive familial hearing loss. Awareness of familial hearing loss is important in male patients in whom cisplatin chemotherapy is planned. Pretreatment hearing assessment, including audiograms, is recommended for such male patients.

Antineoplastic Agents↗
PubMed1997

Serial in vivo passage of HIV-1 infection in Macaca nemestrina.

In an earlier study we found that pigtailed macaques (Macaca nemestrina) that were experimentally infected with human immunodeficiency virus type 1 (HIV-1) initially became viremic and seroconverted, but HIV-1 replication diminished markedly over time. In an attempt to develop a longer term pathogenic model, blood from HIV-1-infected macaques was serially transfused into three groups of naive macaques. Transfer was successful through two transfusions as shown by repeated virus isolations and confirmed by the development of cell-free plasma viremia and by seroconversion. Three to five weeks after transfusion, plasma levels of HIV-1 RNA from several macaques in the first two groups exceeded those of the initially inoculated macaques. However, animals in the third group had diminished RNA levels, were virus culture negative, and did not seroconvert. Sequence analyses of env-region clones from infected animals revealed only minimal changes over the course of the passages. These results confirm HIV-1 replication in M. nemestrina during the acute phase of infection. However, adaptation of HIV-1 to a macaque-pathogenic variant did not occur during serial passage, possibly because the animals were able to restrict HIV-1 replication below a level required for a pathogenic variant to emerge. Whether such containment is a function of the host's immune response or a virus cell incompatibility remains to be determined.

Adaptation, Physiological↗