Sarcomas in An
Etiologic
a
Consultation
We are pleased to present this unusual article by an author who is a leader in the field of childhood cancer, particularly those aspects having to do with epidemiology and associated malformation. This "etiologic consultation" by Robert W. Miller, MD, and his associates will whet your intellectual appetite, and thus possibly generate ideas for future "consultations" in this and other areas of pediatrics.\p=m-\Ed.
obtain con¬ sultations on and treat¬ but not for of an "idiopathic" disease such as cancer. When a peculiarity in occurrence is observed, etiologic consultation may generate
traditionally Physi c i a ns diagnosis ment, etiology
new
understanding
or
hypotheses
on
the basis of recent clinical and labora¬ tory studies. To illustrate this ap¬ proach, we present a consultation on a family in which dissimilar tumors in a child and her father could easily have been ignored as coincidence, but infor¬ mation from chart review and inter¬ views suggested studies that may indicate these tumors have origins in common.
CONSULTATION REQUEST A
Child and Her Father
4V2-year-old white girl
was
recently recognized as having em¬ bryonal rhabdomyosarcoma (RMS) of the right foot and popliteal space. During the past year, her 30-year-old father had been treated for osteosarcoma (OS). At the father's request, the attending physician consulted us for possible explanations for the familial occurrence of the sarcomas. CONSULTATION REPORT Personal History The Father.—His medical and social
history were unremarkable except for eight years of employment in a zinc smelter and his lifelong residency in an area of industrial pollution. He was admitted to the National Cancer Insti¬ tute (NCI) for treatment of OS of the left midhumerus, with numerous pulmonary métastases. After shoulder disarticulation, high doses of methotrexate resulted in complete regres¬ sion of all lung lesions. In addition to this therapeutic success, which sug¬ gested unusual drug sensitivity, the patient was remarkable because of his age at the occurrence of OS and of the tumor's atypical site. The Daughter.—The father men¬ tioned two unusual findings: she had
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 05/15/2015
poor hearing (perhaps related to recurrent ear infections) and at least
four large café au lait spots (CALS) on her trunk. The father had no CALS and reported none on his wife and two younger
daughters.
Family History The extended family history in¬ cluded only one additional case of
cancer: an unspecified malignant neo¬ plasm in a maternal first cousin of the
father who died at about age 27 years. Many relatives had lived to middle and old aere without evidence of Differential
Etiologic Diagnoses
The differential etiologic diagnoses consisted of the following: (1) Osteosarcoma in the father that was possi¬ bly related to occupational exposures. (2) Sporadic multiple neurofibromatosis (NF) in the daughter. (3) Heredita¬ ry NF. (4) Familial sarcoma-carcino¬ ma
syndrome.
Comments
on
the Differential
Diagnoses The Father's Tumor and the Environ¬
ment.—Osteosarcoma occurs primarily during the adolescent growth spurt in
sites of rapid bone growth, notably the distal femur and proximal tibia.1 It is infrequent in the third and fourth decades but its incidence increases after age 40 when the major sites of involvement are long and flat bones affected by Paget's disease. Besides occurring at an unusual age, the fa¬ ther's tumor developed at an atypical site, the midhumerus. We suggest that events of etiologic importance are most evident when tumors have some atypical features. In a series of 600 cases of OS from the Mayo Clinic, Rochester, Minn, only four occurred in the midhumerus.- The distal humérus was an equally rare site, occurring in only 0.8% (5/600) of cases. Interesting¬ ly, five of these nine tumors developed as complications of Paget's disease. Among 83 patients with OS seen at the NCI, only one other had a midhu¬ merus tumor. Twenty years before, this patient had undergone diagnostic carotid arteriography with thorium dioxide Th 232 (Thorotrast), now recognized to cause OS.3 The father had no obvious preexist¬ ing bone disease and denied medically or work-related exposures to radioac¬ tive substances. Extensive exposure to zinc is not known to be carcinogenic. Arsenic, a frequent zinc contaminant, causes skin and respiratory cancers but has not been associated with bone cancer.4 If any occupational exposure were found to be related to the fa¬ ther's cancer, it could also be asso¬ ciated with his daughter's tumor. Work dust brought home on a parent's clothes can cause cancer in exposed children decades later, as illustrated by mesothelioma due to asbestos.5 The county in which the family lived was noted for its industrial pollu¬ tion and had a significantly high risk of death from all cancers for white males and females." Even more perti¬ nent to the father's case is the fact that the area also had excessively high death rates in white males from cancers of bone and connective tis¬ sue.
Possible
Sporadic
NF in the
Daugh¬
ter.—Children younger than age 6 years, with five or more CALS greater than 0.5 cm in diameter are presumed to have F unless the spots can be otherwise explained.7 Such spots also
McCune-Albright syndrome (polyostotic fibrous dysplasia with precocious puberty), tuberous sclero¬ sis, nevoid basal cell carcinoma syn¬ drome, and multiple endocrine neopla¬ sia type III (multiple mucosal neuro¬ ma syndrome). They are occasionally seen in the syndromes of Turner, Bloom, Russell-Silver, Gaucher, ataxia telangiectasia, and multiple lentigines. Neurofibromatosis, with a fre¬ quency of 1/2,500 live births, is by far occur
in
the most common of these diseases. The presence of four CALS in this young girl in the absence of bony, metabolic, dysmorphic, or other cuta¬ neous lesions raises the possibility of NF. Rhabdomyosarcoma is a recently recognized malignant complication of this disease.8 Possible Familial NF.—Neurofibro¬ matosis is an autosomal dominant disorder. Since this diagnosis is being considered for the daughter, it must also be considered for other family members. The father had no apparent stigmata of NF; however, if he had subclinical disease, malignant trans¬ formation in preexisting fibroosseous dysplasia (a possible manifestation of NF) might explain his OS.
Familial Cancer Syndrome.—In 1969, Li and Fraumeni" described four families with soft-tissue sarcomas in sibs or cousins during childhood. Other malignant neoplasms present in ex¬ cess in these families included lung cancer and female breast cancer, often bilateral and of early onset (age 20 to 30 years). Familial cancer was seen to a lesser degree in a study of childhood OS; in addition to OS, tumors of the breast and CNS were preponderant.1" In one such family, OS and RMS developed in first cousins.11 With the exception of the youngest generations, the present family is relatively free of cancer; however, the tumors of father and daughter may still represent a malig¬ nant diathesis. In particular, the familial sarcoma-carcinoma syndrome could be diagnosed if carcinomas of the breast and other organs were to develop in young members of the
family.
Recommendations
With the
foregoing in mind,
the
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 05/15/2015
following
recommendations
were
made: (1) Relatives should be evalu¬ ated for NF. (2) In consideration of the familial sarcoma-carcinoma syn¬ drome, the child's mother and pater¬ nal aunt should have breast examina¬ tions, and records of the young cousin who died, of an unspecified malignant neoplasm should be reviewed. (3) Fibroblasts from father, daughter, and first-degree relatives should be obtained so that cell cultures can be evaluated for abnormalities indicative of increased cancer risk (for example, defects in the repair of radiationinduced DNA damage) and so that they can then be stored for appro¬ priate tests in the future. (4) Sera should be saved for special assays for NF as they are developed or improved (eg, nerve growth factor). (5) Micro¬ scope slides of the father's tumor should be studied autoradiographically for evidence of unknown exposure to radioisotopes, such as thorium diox¬ ide Th 232.
COMMENT
Peculiarities in the
occurrence
of
provide insights into its origin. Etiologic assessment can iden¬ tify such clues and enhance their pursuit. Through an etiologic consul¬ cancer can
tation, we have accumulated data on
a
family that may have an increased susceptibility to sarcomas. These data
have been used to outline several etio¬ logic possibilities to serve as the basis for future investigations. Profound insights into cancer cau¬ sation will likely result from knowl¬ edge of the molecular events asso¬ ciated with the commencement of tumor. These may be recognized in human syndromes that predispose to cancer and for which no animal models are yet known, eg, defective repair of DNA after damage by ultraviolet and gamma radiation in xeroderma pigmentosum and ataxia telangiectasia, respectively.12 Tissues from persons suspected to have an increased susceptibility to cancer may be particularly useful in the search for molecular abnormalities. To be of greatest value, specimens from such patients must be obtained prior to the administration of any therapy that may confound the findings. Timely
referrals to
"etiologists"
at
can
Pediatric Oncology Branch National Cancer Institute A521 Landow Bldg Bethesda, MD 20014
Hospital, permission to report his case, Safyer, MS, provided editorial
Michael R. Wollman, MD, Children's
Pittsburgh,
gave
and Andrew W. comments.
References
cancer
facilitate the clinical and laboratory evaluation of unusual pa¬ tients. DILYS M. PARRY, PHD JOHN J. MULVIHILL, MD ROBERT W. MILLER, MD Clinical Epidemiology Branch ROBERT J. SPIEGEL, MD
centers
Etiology of childhood bone Epidemiologic observations. Recent Re-
1. Miller RW: cancer:
sults Cancer Res 54:50-62, 1976. 2. Dahlin DC, Coventry MB: Osteogenic sarcoma: A study of 600 cases. J Bone Joint Surg A 49:101-110, 1967. 3. Altner PC, Simmons DJ, Lucas HF, et al: Osteogenic sarcoma in a patient injected with Thorotrast. J Bone Joint Surg A 54:670-675, 1972. 4. Jackson R, Grainge JW: Arsenic and cancer. Can Med Assoc J 113:396-401, 1975. 5. Anderson HA, Lilis R, Daum SM, et al: Household-contact asbestos: Neoplastic risk. Ann N Y AcadSci 271:311-323, 1976. 6. Mason TJ, McKay FW, Hoover R, et al: Atlas of Cancer Mortality for US Counties: 1950-1969, Publication No. (NIH) 75-780. US Dept of Health, Education, and Welfare, 1975. 7. Whitehouse D: Diagnostic value of the caf\l=e'\au-lait spots in children. Arch Dis Child 41:316\x=req-\
319, 1966.
8. McKeen
EA, Bodurtha J, Meadows AT, et al:
Rhabdomyosarcoma complicating multiple
neu-
rofibromatosis. J Pediatr 93:992-993, 1978. 9. Li FP, Fraumeni JF Jr: Soft-tissue sarcomas, breast cancer, and other neoplasms: A familial syndrome? Ann Intern Med 71:747-752, 1969. 10. Miller RW: Deaths from childhood leukemia and solid tumors among twins and other sibs in the United States, 1960-67. J Natl Cancer Inst 46:203-209, 1971. 11. Fraumeni JF Jr: Clinical patterns of familial cancer, in Mulvihill JJ, Miller RW, Fraumeni JF Jr (eds): Genetics of Human Cancer. New York, Raven Press, 1977, pp 223-233. 12. Kraemer KH: Progressive degenerative diseases associated with defective DNA repair: Xeroderma pigmentosum and ataxia telangiectasia, in Nichols WW, Murphy DG (eds): DNA Repair Processes. Miami, Fla, Symposia Specialists, 1977, pp 37-71.
Priorities for Government-sponsored Research in Pediatric Infectious Diseases was held at a the National Institutes of Health on the medical of infections on care in impact the United States: Problems and priorities for future research." A more direct title might have been, "What kinds of research in infectious disNIH support?" eases should the because that was the thrust of the two-day meeting. It is no secret that, historically, the NIH has not supported so-called clinical research that often produces information of immediate, practical application. Should there be a balanced support of basic and clinical research by the federal government? Can the government justify spending tax dollars on clinical investigations that might lead to financial advantages for pharmaceutical companies? These are difficult
May 1978, meeting In (NIH) titled, "Symposium
questions I
was
to
answer.
asked to
speak on problems in
pediatric infectious diseases that deserve investigation. I not only realized that I was inadequate for the task, but I feared that I might present a distorted
constricted view based on and experiences. for help from I called Therefore, colleagues across the country with the question, What areas of research need emphasis and future development? The 28 respondents (see acknowl¬ edgments) represent all areas of pedi¬ atrie infectious diseases. I wrote to one person in each group of investiga¬ tors, but their responses summarized the opinions of co-workers. Thus, my survey should represent a fair summa¬ tion of the majority opinion in our field. The intensity of concern was expressed by the lengthy, detailed, objective responses from most investi¬ gators. Almost without exception, they emphasized the need for studies outside their own areas of primary my
own
or
prejudices
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 05/15/2015
interest. The most commonly men¬ tioned priorities can be grouped into the following seven broad categories: diagnostic methods, vaccines, diarrheal diseases, host and organism factors, studies of antimicrobials, co¬ operative studies of uncommon infec¬ tion, and miscellaneous. PRIORITIES
Diagnostic Methods Physicians who treat acutely ill chil¬ dren need help with the pragmatic
problem
of whether the child has
bacterial, viral, rickettsial, mycoplasmal or, chlamydial infection. Rapid identification of antigen by fluores¬ cent antibody, counterimmunoelectrophoresis, and latex agglutination tech¬ niques can sometimes provide an
immediate answer. Refinements and standardization of existing methods, which touch only a miniscule fraction of acute infectious diseases, are
Etiologic
a
Consultation
We are pleased to present this unusual article by an author who is a leader in the field of childhood cancer, particularly those aspects having to do with epidemiology and associated malformation. This "etiologic consultation" by Robert W. Miller, MD, and his associates will whet your intellectual appetite, and thus possibly generate ideas for future "consultations" in this and other areas of pediatrics.\p=m-\Ed.
obtain con¬ sultations on and treat¬ but not for of an "idiopathic" disease such as cancer. When a peculiarity in occurrence is observed, etiologic consultation may generate
traditionally Physi c i a ns diagnosis ment, etiology
new
understanding
or
hypotheses
on
the basis of recent clinical and labora¬ tory studies. To illustrate this ap¬ proach, we present a consultation on a family in which dissimilar tumors in a child and her father could easily have been ignored as coincidence, but infor¬ mation from chart review and inter¬ views suggested studies that may indicate these tumors have origins in common.
CONSULTATION REQUEST A
Child and Her Father
4V2-year-old white girl
was
recently recognized as having em¬ bryonal rhabdomyosarcoma (RMS) of the right foot and popliteal space. During the past year, her 30-year-old father had been treated for osteosarcoma (OS). At the father's request, the attending physician consulted us for possible explanations for the familial occurrence of the sarcomas. CONSULTATION REPORT Personal History The Father.—His medical and social
history were unremarkable except for eight years of employment in a zinc smelter and his lifelong residency in an area of industrial pollution. He was admitted to the National Cancer Insti¬ tute (NCI) for treatment of OS of the left midhumerus, with numerous pulmonary métastases. After shoulder disarticulation, high doses of methotrexate resulted in complete regres¬ sion of all lung lesions. In addition to this therapeutic success, which sug¬ gested unusual drug sensitivity, the patient was remarkable because of his age at the occurrence of OS and of the tumor's atypical site. The Daughter.—The father men¬ tioned two unusual findings: she had
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 05/15/2015
poor hearing (perhaps related to recurrent ear infections) and at least
four large café au lait spots (CALS) on her trunk. The father had no CALS and reported none on his wife and two younger
daughters.
Family History The extended family history in¬ cluded only one additional case of
cancer: an unspecified malignant neo¬ plasm in a maternal first cousin of the
father who died at about age 27 years. Many relatives had lived to middle and old aere without evidence of Differential
Etiologic Diagnoses
The differential etiologic diagnoses consisted of the following: (1) Osteosarcoma in the father that was possi¬ bly related to occupational exposures. (2) Sporadic multiple neurofibromatosis (NF) in the daughter. (3) Heredita¬ ry NF. (4) Familial sarcoma-carcino¬ ma
syndrome.
Comments
on
the Differential
Diagnoses The Father's Tumor and the Environ¬
ment.—Osteosarcoma occurs primarily during the adolescent growth spurt in
sites of rapid bone growth, notably the distal femur and proximal tibia.1 It is infrequent in the third and fourth decades but its incidence increases after age 40 when the major sites of involvement are long and flat bones affected by Paget's disease. Besides occurring at an unusual age, the fa¬ ther's tumor developed at an atypical site, the midhumerus. We suggest that events of etiologic importance are most evident when tumors have some atypical features. In a series of 600 cases of OS from the Mayo Clinic, Rochester, Minn, only four occurred in the midhumerus.- The distal humérus was an equally rare site, occurring in only 0.8% (5/600) of cases. Interesting¬ ly, five of these nine tumors developed as complications of Paget's disease. Among 83 patients with OS seen at the NCI, only one other had a midhu¬ merus tumor. Twenty years before, this patient had undergone diagnostic carotid arteriography with thorium dioxide Th 232 (Thorotrast), now recognized to cause OS.3 The father had no obvious preexist¬ ing bone disease and denied medically or work-related exposures to radioac¬ tive substances. Extensive exposure to zinc is not known to be carcinogenic. Arsenic, a frequent zinc contaminant, causes skin and respiratory cancers but has not been associated with bone cancer.4 If any occupational exposure were found to be related to the fa¬ ther's cancer, it could also be asso¬ ciated with his daughter's tumor. Work dust brought home on a parent's clothes can cause cancer in exposed children decades later, as illustrated by mesothelioma due to asbestos.5 The county in which the family lived was noted for its industrial pollu¬ tion and had a significantly high risk of death from all cancers for white males and females." Even more perti¬ nent to the father's case is the fact that the area also had excessively high death rates in white males from cancers of bone and connective tis¬ sue.
Possible
Sporadic
NF in the
Daugh¬
ter.—Children younger than age 6 years, with five or more CALS greater than 0.5 cm in diameter are presumed to have F unless the spots can be otherwise explained.7 Such spots also
McCune-Albright syndrome (polyostotic fibrous dysplasia with precocious puberty), tuberous sclero¬ sis, nevoid basal cell carcinoma syn¬ drome, and multiple endocrine neopla¬ sia type III (multiple mucosal neuro¬ ma syndrome). They are occasionally seen in the syndromes of Turner, Bloom, Russell-Silver, Gaucher, ataxia telangiectasia, and multiple lentigines. Neurofibromatosis, with a fre¬ quency of 1/2,500 live births, is by far occur
in
the most common of these diseases. The presence of four CALS in this young girl in the absence of bony, metabolic, dysmorphic, or other cuta¬ neous lesions raises the possibility of NF. Rhabdomyosarcoma is a recently recognized malignant complication of this disease.8 Possible Familial NF.—Neurofibro¬ matosis is an autosomal dominant disorder. Since this diagnosis is being considered for the daughter, it must also be considered for other family members. The father had no apparent stigmata of NF; however, if he had subclinical disease, malignant trans¬ formation in preexisting fibroosseous dysplasia (a possible manifestation of NF) might explain his OS.
Familial Cancer Syndrome.—In 1969, Li and Fraumeni" described four families with soft-tissue sarcomas in sibs or cousins during childhood. Other malignant neoplasms present in ex¬ cess in these families included lung cancer and female breast cancer, often bilateral and of early onset (age 20 to 30 years). Familial cancer was seen to a lesser degree in a study of childhood OS; in addition to OS, tumors of the breast and CNS were preponderant.1" In one such family, OS and RMS developed in first cousins.11 With the exception of the youngest generations, the present family is relatively free of cancer; however, the tumors of father and daughter may still represent a malig¬ nant diathesis. In particular, the familial sarcoma-carcinoma syndrome could be diagnosed if carcinomas of the breast and other organs were to develop in young members of the
family.
Recommendations
With the
foregoing in mind,
the
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 05/15/2015
following
recommendations
were
made: (1) Relatives should be evalu¬ ated for NF. (2) In consideration of the familial sarcoma-carcinoma syn¬ drome, the child's mother and pater¬ nal aunt should have breast examina¬ tions, and records of the young cousin who died, of an unspecified malignant neoplasm should be reviewed. (3) Fibroblasts from father, daughter, and first-degree relatives should be obtained so that cell cultures can be evaluated for abnormalities indicative of increased cancer risk (for example, defects in the repair of radiationinduced DNA damage) and so that they can then be stored for appro¬ priate tests in the future. (4) Sera should be saved for special assays for NF as they are developed or improved (eg, nerve growth factor). (5) Micro¬ scope slides of the father's tumor should be studied autoradiographically for evidence of unknown exposure to radioisotopes, such as thorium diox¬ ide Th 232.
COMMENT
Peculiarities in the
occurrence
of
provide insights into its origin. Etiologic assessment can iden¬ tify such clues and enhance their pursuit. Through an etiologic consul¬ cancer can
tation, we have accumulated data on
a
family that may have an increased susceptibility to sarcomas. These data
have been used to outline several etio¬ logic possibilities to serve as the basis for future investigations. Profound insights into cancer cau¬ sation will likely result from knowl¬ edge of the molecular events asso¬ ciated with the commencement of tumor. These may be recognized in human syndromes that predispose to cancer and for which no animal models are yet known, eg, defective repair of DNA after damage by ultraviolet and gamma radiation in xeroderma pigmentosum and ataxia telangiectasia, respectively.12 Tissues from persons suspected to have an increased susceptibility to cancer may be particularly useful in the search for molecular abnormalities. To be of greatest value, specimens from such patients must be obtained prior to the administration of any therapy that may confound the findings. Timely
referrals to
"etiologists"
at
can
Pediatric Oncology Branch National Cancer Institute A521 Landow Bldg Bethesda, MD 20014
Hospital, permission to report his case, Safyer, MS, provided editorial
Michael R. Wollman, MD, Children's
Pittsburgh,
gave
and Andrew W. comments.
References
cancer
facilitate the clinical and laboratory evaluation of unusual pa¬ tients. DILYS M. PARRY, PHD JOHN J. MULVIHILL, MD ROBERT W. MILLER, MD Clinical Epidemiology Branch ROBERT J. SPIEGEL, MD
centers
Etiology of childhood bone Epidemiologic observations. Recent Re-
1. Miller RW: cancer:
sults Cancer Res 54:50-62, 1976. 2. Dahlin DC, Coventry MB: Osteogenic sarcoma: A study of 600 cases. J Bone Joint Surg A 49:101-110, 1967. 3. Altner PC, Simmons DJ, Lucas HF, et al: Osteogenic sarcoma in a patient injected with Thorotrast. J Bone Joint Surg A 54:670-675, 1972. 4. Jackson R, Grainge JW: Arsenic and cancer. Can Med Assoc J 113:396-401, 1975. 5. Anderson HA, Lilis R, Daum SM, et al: Household-contact asbestos: Neoplastic risk. Ann N Y AcadSci 271:311-323, 1976. 6. Mason TJ, McKay FW, Hoover R, et al: Atlas of Cancer Mortality for US Counties: 1950-1969, Publication No. (NIH) 75-780. US Dept of Health, Education, and Welfare, 1975. 7. Whitehouse D: Diagnostic value of the caf\l=e'\au-lait spots in children. Arch Dis Child 41:316\x=req-\
319, 1966.
8. McKeen
EA, Bodurtha J, Meadows AT, et al:
Rhabdomyosarcoma complicating multiple
neu-
rofibromatosis. J Pediatr 93:992-993, 1978. 9. Li FP, Fraumeni JF Jr: Soft-tissue sarcomas, breast cancer, and other neoplasms: A familial syndrome? Ann Intern Med 71:747-752, 1969. 10. Miller RW: Deaths from childhood leukemia and solid tumors among twins and other sibs in the United States, 1960-67. J Natl Cancer Inst 46:203-209, 1971. 11. Fraumeni JF Jr: Clinical patterns of familial cancer, in Mulvihill JJ, Miller RW, Fraumeni JF Jr (eds): Genetics of Human Cancer. New York, Raven Press, 1977, pp 223-233. 12. Kraemer KH: Progressive degenerative diseases associated with defective DNA repair: Xeroderma pigmentosum and ataxia telangiectasia, in Nichols WW, Murphy DG (eds): DNA Repair Processes. Miami, Fla, Symposia Specialists, 1977, pp 37-71.
Priorities for Government-sponsored Research in Pediatric Infectious Diseases was held at a the National Institutes of Health on the medical of infections on care in impact the United States: Problems and priorities for future research." A more direct title might have been, "What kinds of research in infectious disNIH support?" eases should the because that was the thrust of the two-day meeting. It is no secret that, historically, the NIH has not supported so-called clinical research that often produces information of immediate, practical application. Should there be a balanced support of basic and clinical research by the federal government? Can the government justify spending tax dollars on clinical investigations that might lead to financial advantages for pharmaceutical companies? These are difficult
May 1978, meeting In (NIH) titled, "Symposium
questions I
was
to
answer.
asked to
speak on problems in
pediatric infectious diseases that deserve investigation. I not only realized that I was inadequate for the task, but I feared that I might present a distorted
constricted view based on and experiences. for help from I called Therefore, colleagues across the country with the question, What areas of research need emphasis and future development? The 28 respondents (see acknowl¬ edgments) represent all areas of pedi¬ atrie infectious diseases. I wrote to one person in each group of investiga¬ tors, but their responses summarized the opinions of co-workers. Thus, my survey should represent a fair summa¬ tion of the majority opinion in our field. The intensity of concern was expressed by the lengthy, detailed, objective responses from most investi¬ gators. Almost without exception, they emphasized the need for studies outside their own areas of primary my
own
or
prejudices
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 05/15/2015
interest. The most commonly men¬ tioned priorities can be grouped into the following seven broad categories: diagnostic methods, vaccines, diarrheal diseases, host and organism factors, studies of antimicrobials, co¬ operative studies of uncommon infec¬ tion, and miscellaneous. PRIORITIES
Diagnostic Methods Physicians who treat acutely ill chil¬ dren need help with the pragmatic
problem
of whether the child has
bacterial, viral, rickettsial, mycoplasmal or, chlamydial infection. Rapid identification of antigen by fluores¬ cent antibody, counterimmunoelectrophoresis, and latex agglutination tech¬ niques can sometimes provide an
immediate answer. Refinements and standardization of existing methods, which touch only a miniscule fraction of acute infectious diseases, are
