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Biomedical subjects

P L McCarthy

Publications and source records attributed to P L McCarthy.

At least 19 recordsLinked to original sources

Cutaneous sarcoidosis in a patient with Philadelphia-positive chronic myelogenous leukemia treated with interferon-alpha.

A patient with Philadelphia-positive (Ph+) chronic myelogenous leukemia (CML) was diagnosed with cutaneous sarcoidosis after treatment with interferon-alpha (IFN-alpha). Following IFN-alpha dose reduction, the skin lesions disappeared. Few cases of sarcoidosis associated with IFN treatment have been reported, and only in one patient with pre-existing CML. Our patient was unique in that (1) the sarcoidosis was induced by the IFN-alpha treatment alone, (2) it developed de novo, and (3) it was confined to the skin.

Female

Fever without apparent source on clinical examination, infectious diseases, and lower respiratory infections in children.

This section focuses on issues in infectious diseases that are commonly encountered in pediatric office practice. Paul McCarthy discusses recent literature regarding the evaluation and management of acute fevers without apparent source on clinical examination in infants and children, and the evaluation of children with prolonged fevers of unknown origin. Jean Klig reviews recent literature about lower respiratory tract infection in children. Jeffrey Kahn and Eugene Shapiro discuss recent developments in pediatric infectious diseases concerning neonatal herpes infections, poliovirus immunization schedule, and group B streptococcus screening and treatment.

Child, Preschool

Design and analysis of epidemiological studies of excess cancer among children exposed to Chernobyl radionuclides.

Within the last decade, a substantial amount of attention has been devoted to etiological research on the association between exposure to fallout radionuclides from the Chernobyl accident and radiation-induced late effects (cancer) among children. A majority of the studies completed to date have been of the descriptive type, which only correlate average population exposure with average rate of cancer incidence as a function of calendar period. Since individual dosimetry is not performed in descriptive studies, it is unclear whether exposure precedes the development of cancer and a final decision cannot be made regarding the association between radiation exposure and cancer. This paper reviews the background epidemiology and outlines an analytical study design that is needed to clarify the unclear association between Chernobyl fallout exposure and childhood cancer. We discuss the essential elements of an analytical case-control design such as genetic predisposition, vital statistics, sample size and power determinations, ascertainment of cases and controls, and phenomenological dose modeling to establish individual doses. Examples such as cytogenetic biodosimetry, medical radiation dosimetry, and cytogenetic characterization of leukemia to minimize exposure and diagnostic misclassification are provided. We recommend the analytical methods described in this paper for studying the role of Chernobyl radionuclides and development of childhood cancer.

Adolescent

Fever without apparent source on clinical examination, lower respiratory infections in children, other infectious diseases, and acute gastroenteritis and diarrhea of infancy and early childhood.

This section focuses on issues in infectious disease that are commonly encountered in pediatric office practice. Paul McCarthy discusses recent literature regarding the evaluation and management of acute fevers without apparent source on clinical examination in infants and children and the evaluation of children with prolonged fevers of unknown origin. Jean Klig reviews recent literature about lower respiratory tract infection in children. Jeffrey Kahn and Eugene Shapiro discuss literature concerning several infectious diseases commonly seen in office settings and concerning which recent developments are of interest. Michael Baron reviews recent literature about gastroenteritis and diarrhea of infancy and early childhood.

Acute Disease

High-dose chemotherapy with autologous hematopoietic stem-cell support for breast cancer in North America.

PURPOSE: To identify trends in high-dose therapy with autologous hematopoietic stem-cell support (autotransplants) for breast cancer (1989 to 1995). PATIENTS AND METHODS: Analysis of patients who received autotransplants and were reported to the Autologous Blood and Marrow Transplant Registry. Between January 1, 1989 and June 30, 1995, 19,291 autotransplants were reviewed; 5,886 were for breast cancer. Main outcomes were progression-free survival (PFS) and survival. RESULTS: Between 1989 and 1995, autotransplants for breast cancer increased sixfold. After 1992, breast cancer was the most common indication for autotransplant. Significant trends included increasing use for locally advanced rather than metastatic disease (P < .00001) and use of blood-derived rather than marrow-derived stem cells (P < .00001). One-hundred-day mortality decreased from 22% to 5% (P < .0001). Three-year PFS probabilities were 65% (95% confidence intervals [Cls], 59 to 71) for stage 2 disease, and 60% (95% Cl, 53 to 67) for stage 3 disease. In metastatic breast cancer, 3-year probabilities of PFS were 7% (95% Cl, 4 to 10) for women with no response to conventional dose chemotherapy; 13% (95% Cl, 9 to 17) for those with partial response; and 32% (95% Cl, 27 to 37) for those with complete response. Eleven percent of women with stage 2/3 disease and less than 1% of those with stage 4 disease participated in national cooperative group randomized trials. CONCLUSION: Autotransplants increasingly are used to treat breast cancer. One-hundred-day mortality has decreased substantially. Three-year survival is better in women with earlier stage disease and in those who respond to pretransplant chemotherapy.

Adult

A clinical phase I/II study of recombinant human interleukin-1 receptor in glucocorticoid-resistant graft-versus-host disease.

Graft-versus-host disease (GVHD) is the major complication of allogeneic bone marrow transplantation. GVHD is accompanied by the release of inflammatory cytokines, including interleukin (IL)-1, and previous work has demonstrated that IL-1 participates in the pathogenesis of GVHD. The recombinant human IL-1 receptor (rhuIL-1R) is the soluble form of the type I IL-1 receptor that can bind to IL-1 and prevent cellular activation. We report a phase I/II trial utilizing the rhuIL-1R in the treatment of allogeneic bone narrow transplant patients not improving with glucocorticoid therapy. RhuIL-R was given at four dose levels for 21 days to 14 patients with progressive or persistent acute GVHD. The study drug had no clinical or persistent hematopoiesis and the treatment was tolerated by patients without toxicity at all dose levels. Eight of 14 patients (57%) had an improvement of GVHD after rhuIL-1R therapy. Improvement in GVHD was noted at each dose level, although a dose-response effect for rhuIL-1R treatment was not observed. This work supports the concept that IL-1 plays a role in the inflammation associated with acute GVHD. A controlled study of the rhuIL-1R for treatment of prophylaxis of GVHD is warranted.

Adult

Improving participation and interrater agreement in scoring Ambulatory Pediatric Association abstracts. How well have we succeeded?

OBJECTIVE: To determine whether increasing the number and types of raters affected interrater agreement in scoring abstracts submitted to the Ambulatory Pediatric Association. METHODS: In 1990, all abstracts were rated by each of the 11 members of the board of directors of the Ambulatory Pediatric Association. In 1995, abstracts were reviewed by four to five raters, including eight members of the board of directors, two chairpersons of special interest groups, and 10 regional chairpersons, for a total of 20 potential reviewers. Submissions were divided into the following three categories for review: emergency medicine, behavioral pediatrics, and general pediatrics. Weighted percentage agreement and weighted kappa scores were computed for 1990 and 1995 abstract scores. RESULTS: Between 1990 and 1995, the number of abstracts submitted to the Ambulatory Pediatric Association increased from 246 to 407, the number of reviewers increased from 11 to 20, the weighted percentage agreement between raters remained approximately 79%, and weighted kappa scores remained less than 0.25. Agreement was not significantly better for the emergency medicine and behavioral pediatrics abstracts than for general pediatrics, nor was it better for the raters who reviewed fewer abstracts than those who reviewed many. CONCLUSIONS: The number and expertise of those rating abstracts increased from 1990 to 1995. However, interrater agreement did not change and remained low. Further efforts are needed to improve the interrater agreement.

Abstracting and Indexing

Allogeneic bone marrow transplantation for poor-prognosis lymphoma: response, toxicity and survival depend on disease histology.

PURPOSE: To evaluate outcomes and identify prognostic factors in allogeneic bone marrow transplantation in patients with end-stage lymphoma. PATIENTS AND METHODS: Data were retrospectively analyzed of 64 patients (42 men and 22 women) 18 to 48 years of age with recurrent or refractory lymphoma who underwent allogeneic bone marrow transplantation from matched sibling donors (or in 1 case from a one antigen-mismatched relative) between May 1981 and July 1994. RESULTS: Twelve patients survived free of disease. They were 8 of 15 with low-grade lymphoma (disease-free survival at 2 years 59% +/- 13%); 3 of 25 with lymphoblastic lymphoma (disease-free survival 17% +/- 8%); and 1 of 10 with diffuse small non-cleaved cell lymphoma (disease-free (10% +/- 9%). Survival and disease-free survival of patients with low-grade lymphoma were significantly superior compared to any other subgroup of patients (P <0.01). Only 2 patients with low-grade lymphoma had disease progression (9% +/- 9% actuarial risk at 2 years) as opposed to 5 of 15 with intermediate-grade lymphoma (39% +/- 14%), 9 of 25 with lymphoblastic lymphoma (28% +/- 9%), and 8 of 10 (80% +/- 13%) with diffuse small non-cleaved lymphoma. The actuarial risk for disease progression was significantly lower for patients with low-grade lymphoma than for any other histologic subgroup (P <0.02). It was significantly higher for those with diffuse small non-cleaved cell lymphoma than for other histologic subgroups (P < or = 0.003). CONCLUSIONS: Allogeneic bone marrow transplantation is an effective procedure in patients with refractory low-grade lymphoma. It results in long-term remissions and should be considered in younger patients with recurrent disease who have a matched sibling donor. The late recurrence in 1 patient indicates the necessity of continued follow-up. A small fraction of patients with end-stage intermediate- and high-grade lymphoma can obtain prolonged disease-free survival, but recurrence and regimen-related toxicity remain major problems. The results could be improved by the development of conditioning regimens with less toxicity and by the use of bone marrow transplantation earlier in the course of the disease.

Adolescent

Fever without apparent source on clinical examination, lower respiratory infections in children, other infectious diseases, and acute gastroenteritis and diarrhea of infancy and early childhood.

This section focuses on issues in infectious disease that are commonly encountered in pediatric office practice. Paul McCarthy discusses recent literature regarding the evaluation and management of acute fevers without apparent source on clinical examination in infants and children and the evaluation of children with prolonged fevers of unknown origin. Jean Klig reviews recent literature about lower respiratory tract infection in children. Eugene Shapiro discusses recent developments in the literature concerning several infectious diseases commonly facing practitioners in the office. Michael Baron reviews recent literature about gastroenteritis and diarrhea of infancy and early childhood.

Acute Disease

The pediatric clinical evaluation and pneumonia.

Pneumonia is a common serious illness in children with acute episodes of fever and in children with more prolonged episodes of fever, termed fevers of unknown origin. Recent studies have demonstrated that the clinical evaluation, including observation, history, and the physical examination, is highly sensitive in identifying children with acute episodes of fever who have pneumonia. The sensitivity of the clinical evaluation for pneumonia has been demonstrated for febrile infants younger than 90 days of age as well as older children. In children with fever of unknown origin, the chest roentgenogram is considered part of the diagnostic evaluation, but further research may define specific indications for its use based on observation, history, and physical examination.

Child, Preschool

Bone marrow transplants from HLA-identical siblings in advanced Hodgkin's disease.

PURPOSE: To determine the outcome of HLA-identical sibling bone marrow transplants in advanced Hodgkin's disease. PATIENTS AND METHODS: We reviewed the data on 100 consecutive patients with Hodgkin's disease who received HLA-identical sibling bone marrow transplants between April 1, 1982 and August 12, 1992, reported to the International Bone Marrow Transplant Registry (IBMTR). The median interval from diagnosis to transplant was 2.5 years (range, < 1 to 14). All had advanced disease. Eighty-nine of 100 patients were not in remission at the time of transplant. Fifty had pretransplant Karnofsky scores less than 90% and 27 had active infection in the week before transplant. Patients received a variety of conditioning regimens; 45 received total-body radiation. RESULTS: The 100-day probability of acute graft-versus-host disease (GVHD) was 35% (95% confidence interval [CI], 26% to 46%); the 3-year probability of chronic GVHD was 45% (95% CI, 31% to 59%). The 3-year probability of relapse was 65% (95% CI, 50% to 78%). The 3-year probability of survival was 21% (95% CI, 14% to 30%). The 3-year disease-free survival rate was 15% (95% CI, 9% to 24%). CONCLUSION: HLA-identical sibling bone marrow transplants have a limited role in advanced Hodgkin's disease.

Adolescent

Caring for survivors of the Chernobyl disaster. What the clinician should know.

The health status of approximately 1 million immigrants in the United States and Israel may have been adversely affected by radiation exposure as a result of the Chernobyl nuclear power plant disaster and cleanup efforts. Many of these immigrants suffer from significant psychological distress, fearing that they have a radiation-induced illness. Based on a review of the literature and our experience from the US National Chernobyl Registry Coordinating Center, we recommend that medical management of these immigrants include routine physical examination, with particular attention to the thyroid gland. Adults should receive regular cancer screening as well as routine blood chemistry tests, thyroid function tests, complete blood cell count, and urinalysis. Children should be examined regularly, with attention to the thyroid and overall body growth. It is reasonable for children to undergo thyroid studies, a complete blood cell count, or neuropsychiatric testing if there is clinical suspicion of a disorder. Given the long latency period for disease induction by radiation exposure, it is still too early to fully assess and draw conclusions concerning the possible health effects of the Chernobyl disaster, and long-term follow-up of all potentially affected individuals is important.

Adult

Fever without apparent source on clinical examination, lower respiratory infections in children, bacterial infections, and acute gastroenteritis and diarrhea of infancy and early childhood.

This section focuses on issues in infectious disease that are commonly encountered in pediatric office practice. Paul McCarthy discusses recent literature regarding the evaluation and management of acute fevers without apparent source on clinical examination in infants and children and the evaluation of children with prolonged fevers of unknown origin. David Bachman reviews recent literature about lower respiratory tract infection in children and focuses on community-acquired lower respiratory infections and respiratory syncytial virus. Eugene Shapiro discusses literature concerning several infectious diseases commonly seen in office settings and concerning which recent developments are of interest: the hemolytic-uremic syndrome and enterohemorrhagic Escherichia coli. Streptococcus pneumoniae resistant to penicillin, infections in day care centers, and new antimicrobial drugs. Michael Baron reviews recent literature about gastroenteritis and diarrhea of infancy and early childhood and discusses diagnosis, complications, pathogenesis and physiology, epidemiology, and treatment.

Bacterial Infections

Down-regulation of cytokine action.

The study of cytokines that regulate all areas of cellular communication has expanded over the past few years. The control and modulation of the complex network of cytokine action remains an area of intense interest. Agents that will modulate cytokine signal transduction at the cellular level will assist in the understanding of the molecular basis of cytokine cellular activation and in the design of drugs for the management of clinical disease. Recent work has demonstrated the existence of complex mechanisms of negative regulation of cytokine action. New methods utilizing isolated protein products that participate in immunomodulation may prove useful for clinical regulation of the host response to cytokine up-regulation. Currently, most interest in soluble cytokine receptors, natural cytokine inhibitors, genetically engineered cytokine antagonists and single or combinations of anti-inflammatory cytokines has focused on the possibility that they may become standard pharmacological agents for the treatment of inflammatory complications of clinical disease. Specifically, TNF and IL-1 inhibitors and the cytokines IL-10 and TGF-beta, alone or in combination may be effective for the inhibition of severe clinical inflammation. Soluble receptors for other cytokines such as IL-6 may prove to be carrier proteins that enhance cytokine action and will require cautious investigation. Because most cytokines are pleiomorphic in their activities, down-regulation through the utilization of direct inhibitors or anti-inflammatory cytokines may cause immunosuppression, making the host susceptible to opportunistic infection. Selective and short-term inhibition of inflammatory cytokine action may be necessary to prevent unwanted clinical side-effects.

Animals

The febrile infant.

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Anti-Bacterial Agents