Document bOYdj8M2Dvy7dQQDX7OjJQYw0
Vo1- 291 No. 11
CORRESPONDENCE
583
Latin square. Since no effect attributable to order of administration
was evident, this was equivalent to a two-way ANOVA with subjects
aS blocks and drugs as the second factor When statistically signifi
cant drug effects were seen, a posteriori comparisons were made with
the Newman-Kculs method.
-
Three criteria were evaluated: the time required to achieve a max imum plasma level; and the areas under the plasma curve from base line to one hour and from base line to three hours, both estimated by the trapezoid rule. For each of the criteria three statistically signifi cantly different (p<0.05) groupings were demonstrated. The addi tion of sodium bicarbonate resulted in significantly earlier and higher plasma levels than were seen wi th naproxen alone or naprox en combined with magnesium carbonate. Magnesium oxide and aluminum hydroxide, on the other hand, delayed absorption and de creased the resultant plasma levels. In a similar study in which na proxen was administered alone or concurrently with 15 or 60 ml of commercial magnesium and aluminum hydroxides (Maalox), addi tion of the antacid tended to decrease the time required to achieve peak plasma levels and increased slightly the total area under the plasma level curve.
Our studies were designed to evaluate antacid effects on the rate of absorption. Sampling was not continued long enough to deter mine effects on total bioavailability, and it is possible that equilibri
um levels after long-term administration would not be affect ed. Nonetheless, striking differences in absorption rate were demonstrated, dissimilar for various antacids. Such effects might have real clinical implications for drugs with narrow therapeutic ratios. More systematic evaluation of antacid effects on bioavailabil ity is overdue.
Palo Alto, GA
Eugene J. Score, M.D, H. Sevelius, M.D. J. Varady, Pii.D. Syntcx Corporation
STUDIES OF PARENTS FOR CLUES TO THE ORIGINS OF CANCER IN THEIR OFFSPRING
To the Editor; By coincidence two recent reports in theJournal111 and a third published elsewhere3 have a thread in common: new under standing of the origins ofcancer was gleaned by study of the parents of the patients.
Meadows et al.1 observed a sibship in which three children had Wilms's tumor and a fourth had duplication of the left renal collect ing system. The mother limped, and was eventually noted to have congenital hemihypertrophy. This anomaly occurs in a syndrome with Wilms's tumor or genitourinary abnormalities, or bothri In this case the elements of the syndrome were distributed among close rela tives instead of being concentrated in one family member. From the family's experience it appears either that hemihypertrophy predis poses to Wilms's tumor and genitourinary abnormalities, or that the three disorders are different responses to the same cause (c.g., genetic pie iot ropis til).
A similar situation applies to a family in which three children had clinical neuroblastoma and a fourth had neuroblastoma in situ. A mediastinal tumor of at least 16 years' duration has just been recog nized in the mother.2 Until a year ago she had elevated urinary catecholamines, but no clinical disease. The lineal transmission of the neoplasm in the family is now apparent.
By special staining technics it is now possible in some cases of chronic myelogenous leukemia to identify markers that indicate if the Philadelphia (Ph') chromosome is derived from the maternal or the paternal line. Gahrton et al.3 used the quinacrine mustard fluo rescence technic to study chromosomes in the bone marrow and pe ripheral blood ofeight patients and their parents. Weak fluorescence was observed in a satellite of the Ph1 chromosome in the cells of one patient and the mother, and in another patient and the father. The other six patients had no such detectable marker. In the two cases with satellites, finding the marker in several metaphascs was in ac^ cord with the thesis that Ph'-positive chronic myelogenous leukemia is or clonal origin. One wonders whether a Philadelphia-like chromo some would be induced if the pat ent's satellited chromosomes were
subjected in vitro to x-rays, which arc known both to break chromo somes and to cause chronic myelogenous leukemia. - The study of chronic myelogenous leukemia depended on the de velopment of a new technic that was then applied to parent and child. The findings pertaining to Wilms's tumor and neuroblastoma were made by alert clinicians whose opportunities for contributing to etiologic knowledge were enhanced because the cancers invotved were familial.
Bethesda, MD
Robert W. Miller, M.D. National Cancer Institute
1. Meadows AT, Lichlenfeld JL, fCoop CE: Wilms's tumor in three children
of a woman with congenital hemihypertrophy. N Engl J Med 291:23-24,
1974
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2. Gcrson JM, Chatten J, Eisman S: Familial neuroblastoma -- a follow-up.
N Engl J Med 290:14S7, 1974
3. Gahrton G, Lindsten J, Zech L: Clonal origin of the Philadelphia chro
mosome from either the paternal or the maternal chromosome number
22. Blood 43:837-840, 1974
4. Miller RW: Environmental agents in cancer. Yale J Biol Med 37:487-501,
1965
The above letter was referred to the authors of one of the letters in question, one of whom offers the following reply:
To the Editor; Studying parents for clues about the origins of cancer in their offspring is indeed valuable. Historical information and clin ical clues may be available, ifsought out by the concerned physician. However, in most cases the physician is preoccupied with the prob lems of treatment and complications, and has little time to devote to possible etiologic clues. Perhaps a standardized information sheet that can be filled in by the patient or His or her family with the assist ance of a paramedical person would be of value. Family histories should be available for cancer, paraneoplastic conditions, ectoder mal dysplasias, possible immunodeficiencies, and congenital abnor malities such as aniridia and hemi-hypertrophy. In neoplastic condi tions in which known biochemical aberrations can be measured, such as neuroblastoma, parents and siblings should also be evalu ated- Routine karyotypic analyses, immunoclcctrophoreses and evaluation of cellular immunity wrould also be of interest. . .
Philadelphia, PA
James M. Gerson, M.D. Children's Hospital of Philadelphia
Letters to the Editor should be typed double-spaced (includ ing references) with conventional margins. The length of the text is Limited to 1 Vi manuscript pages.
CONJUGAL MALIGNANT.MESOTHELIOMA
To the Editor; The relation between asbestos exposure and the de velopment of malignant mesothelioma is now well established. In addition to industrial exposures, 23 patients with mesothelioma have been described, almost all female, whose exposure to asbestos was domestic, apparently resulting from residence in the same house as an asbestos worker.'R We report on a case in which a malignant mesothelioma of the right pleural space developed in a man and his wife. His exposure to asbestos was industrial, and his wife's exposure was from washing his dusty clothes.
A 49-year-old man was seen in September, 1970, with a complaint of increasing pain in the right side of the chest for a year. He had had considerable industrial exposure to asbestos from 1941 to 1949- A large pleural effusion was present, and biopsies (needle and open surgical) of the pleura established a diagnosis ofmalignant mesothe lioma. Radiation therapy and chemotherapy had little beneficial ef fect, and he died in October, 1971,
His wife, 52 years of age, was seen in May, 1972, with complaints of dyspnea and pain in the right side of the chest for the preceding month. A large pleural effusion was present on the right, and needle biopsy of the pleura obtained tissue that was diagnosed as malignant mesothelioma. Slow progression occurred, and in July, 1973, there
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THE NEW ENGLAND JOURNAL OF MEDICINE
Sept. 12, l;i74 Vol. 291 Nc
was clinical and radiologic evidence of.mediastinal invasion with
esophageal compression. An enlarged right-axillary lymph node was
shown on biopsy to be infiltrated with malignant mesothelioma tis
sue. She died in December, 1973, and autopsy confirmed the diag
nosis.
.
Palo Alto, CA
G.A. Lillincton, M.D., F.R.C.P.(C) R.W. Jamplis, M.D.
J.R. Differding, M.D. Palo Alto Medical Clinic
1. McDonald AD, McDonald JC: Epidemiologic surveillance of mesothe lioma in Canada. Can Med Assoc J 109:359-362, 1973
2. Newhouse ML, Thompson Hi Mesothelioma of the pleura and peritone um following exposure to asbestos in the London area. Br J Ind Med 22:261-269, 1965
3. Lieben J, Pistawka H: Mesothelioma and asbestos exposure. Arch Envi ron Health 14:559-563, 1967
4. Ashcroft T, Heppleston AG: Mesothelioma and asbestos on Tyneside, Pneumoconiosis: Proceedings of the International Conference, Johannes burg, 1969. Edited by HA Shapiro. Capetown, Oxford University Press, 1970, pp 177-179
5. Rubino GF, Scansetti G, Donna A, et al: Epidemiology of pleural meso thelioma in North-Western Italy (Piedmont). Br J Ind Med 29:436-442 1972
6. Milne JL: Fifteen cases of pleural mesothelioma, associated with occupa tional exposure to asbestos in Victoria. Med J Aust 56:669-673, 1969
PARASITES THAT AVOID PULMONARY PASSAGE
To the Editor: In the weekly clinicopathological exercise that ap peared in the July 4 issue of the Journalsome fundamental errors in the discussion by Dr. George A. Jacoby, Jr., mar his otherwise excel lent presentation. In his reference to Locfflcr's syndrome, caused by parasites, he makes this statement: "The parasites usually pass through the lungs'as part of their life cycle in man." He then lists, among others, Trichuris irichiura, Enterobius ucrmicularis, Ancylostoma braeiliense, Taenia saginala, and Fasciola htpalica. In fact, none of these parasites pass through the human lung in their life cycles. T. Irichiura and E. vermicularis hatch from the swallowed eggs in the gut and ma ture there. A. bradltense causes "creeping eruption" and remains in the skin. T. saginala, ingested as an encysted scolex, attaches to the wall of the small intestine and begins to grow proglottids. F, hepalica larvae penetrate the small intestine and enter the biliary tract to take up residence in the liver. Finally, the dog tapeworm mentioned in a later paragraph ofDr. Jacoby's discussion is named Echinococcus gran ulosus, not E. granulosa.
, New York, NY
Michael Katz, M.D. Columbia University School of
Public Health
The above letter was referred to the discusser of the CPC in ques tion, who offers the following reply:
To the Editor: Dr. Katz is correct, and his clarification is welcome for those misled by "usually" in the phrase quoted since, as he points out, only a majority of the 13 parasites listed thereafter traverse the lungs as part of their life cycles in man.
Boston, MA
George A. Jagoby, Jr., M.D. Massachusetts General Hospital
BOOK REVIEWS
Atlas of Microscopic Anatomy: A companion, to histology and ncuroanatomy. By Ronald A. Bergman, Ph.D.; and Adel K. Afifi, M.D., M.Sc. 426 pp*, illustrated. Philadelphia: W.B. Saunders Company, 1974* S18.50.
This attractively designed atlas of 300 plates with photomicro graphs in color ofhistologic preparation of cells, tissues and organs is
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intended primarily for the students of histology. Although it will not
replace the usefulness of a good collection of histologic "class-slides,"
it should definitely be useful to students as a source of reference to
the differential tinctorial images of the human and animal tissues
and organs as they arc seen under the light microscope. The authors
indicate that the atlas was prepared with the material from a large
collection ofhistologic preparations, some photomicrographs having
been made from preparations 80 years old. Most of the histologic
staining technics introduced since then are represented in the atlas.
It is a pleasure to see the undeservedly neglected Gerlach carmine
(cochineal) method of staining chromated material.
The division of the atlas into 17 sections follows the conventional
classification of cells and tissues by derivation and of organs by sys
tems. Each such section of the atlas is preceded by a concise and ex
cellent text summarizing essential histologic features, origin and
functional attributes of different cells, tissues and organs. The color
microphotographs are economically but clearly labeled on the mar
gins of plates and provided with legends describing the source of tis
sue, the fixative used, the staining method and the histoarchiteciurc
shown at specified magnifications. The color reproductions of the
differential stains are somewhat uneven. Some plates arc excellent.
Some, however, especially hematoxylin and cosin stained prepara*
tions, give a blurred effect, and the tissue elements staining naturally
red or blue have anr unnatural purplish tinge.
'
The section on the central nervous system hardly justifies the sub
title of the atlas as a companion of "ncuroiinatomy." The atlas con
tains all the material for an excellent textbook of histology. It makes
one hope that the writers will apply their scholarly competence and
technical skill for such a book. The atlas will be useful to a beginner.
It is regrettable that the technical and histologic information re
ferred to in the introductory text to sections and in the five appen
dixes to the atlas in section 18 is not provided with a more exten
sive reference to at least the original publications. A subject index uf
12 pages concludes the book.
Paul I. Yakovlev, M.D,
Growth and Development of Children* Sixth edition. By George H, Lowrey, M.D. 446 pp., illustrated. Chicago: Year Book Medical Publishers, Incorporated, 1973.
Much fascinating literature on the topics of growth and develop ment is available from the late 1930's, the I940fs and the 1950's. A summary of this information is presented by Lowrey, presumably most of it being merely carried over from the first three editions (published in 1951, 1954 and 1958). One would have hoped that a new edition, published in 1973, would present the older data in the light of the enormous progress in growth and development that has occurred during the past decade. Little such reinterpretation is in cluded.
In the preface the author states that "an attempt has again been made to select references of a review nature whenever possible . . [and] to keep them up to date," I must conclude that this goal has not been attained. Of the roughly 750 to 800 references, there are perhaps 15 percent from the period 1967 through 1973. The preface indicates that the fifth chapter has been completely rewritten. One may note that about one third of the references in that chapter are from the years 1967 through 1973. It is reasonable to ask, why were not all the chapters rewritten?
In Chapter 2 it is stated, "In the United States one study showed mcnarchc took place at 14.5 years in 1900 but in the same area now occurs at an average age of 13 years." In checking the reference one finds that "now" is 1956. In Chapter 3 it is stated that "it is well es tablished that maternal nutrition influences the nutrition and conse quently the growth of the child." Of the three references given in support of the statement, two were published in 1943 and one m 1948, The ensuing discussion omits reference to additional data pub lished in the past 25 years. In the fifth chapter the author refers to "A recent study ofchildren from Scandinavia," and the reference to this "recent" study is a report published in 1952. A few pages later, in relation to survival of premature infants, the author mentions im provement in survival rate "in the past 20 years," but the table sup^ porting the statement provides data only for the years 1945 and
i960. Many o* extent of revii
A chapter Growth," pro various purpo sen ted in figiu gvin agreement ^protein, calcii Sy inates of requi culations.
Pathologic Ph by William A. man, M.D,, :. Saunders Goi
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