Acidentes Daying Light
Acidentes Daying Light
Acidentes Daying Light
load. Iron therapy can injure patients with thalassemia, who doctor–patient relationship that is rightly lauded at the con-
may already be overloaded with iron. clusion of the case. Trained interpreters make such commu-
The authors also state that the alpha-thalassemia trait was nication possible between people who speak different lan-
diagnosed by hemoglobin electrophoresis. Such a diagnosis is guages. As the number of persons with limited proficiency in
not usually possible except among newborns in whom Bart’s English grows in the United States, improving access to qual-
hemoglobin can be demonstrated. A defect in alpha-chain ified interpreters will become increasingly important to the
production has an equal effect on the synthesis of hemoglobin practice of good medicine.
A and A 2 and fetal hemoglobin. Therefore, the alpha-thalas-
semia trait is not associated with electrophoretic abnormali- STEVEN WOLOSHIN, M.D.
ties. Theoretically, you might predict the presence of a faint LISA M. SCHWARTZ, M.D.
hemoglobin H band in persons with the alpha-thalassemia Veterans Affairs
trait, but this is not encountered in actuality. Therefore, the White River Junction, VT 05009 Medical Center
questions to be answered are how the alpha-thalassemia trait 1. Woloshin S, Bickell NA, Schwartz LM, Gany F, Welch HG. Language barri-
was diagnosed in this patient, and whether the diagnosis was ers in medicine in the United States. JAMA 1995;273:724-8.
correct. 2. Putsch RW III. Cross-cultural communication: the special case of interpret-
ers in health care. JAMA 1985;254:3344-8.
RAYMOND GAMBINO, M.D. 3. Boston Area Center for Health Education. Bilingual medical interview. Bos-
Teterboro, NJ 07680 Corning Clinical Laboratories ton: Department of Health and Hospitals, 1987.
1. Pauker SG, Kassirer JP. The threshold approach to clinical decision making. larger concern, that physicians might become less careful giv-
N Engl J Med 1980;302:1109-17. en the pressures of cost containment and managed-care in-
2. van den Ende J, van Gompel A, van den Enden E, van Damme W, Janssen
P. Bridging the gap between clinicians and clinical epidemiologists: Bayes centives, is certainly appropriate, although not germane in
theorem on an ordinal scale. Theor Surg 1994;9:195. abstract. our largely fee-for-service setting. A chest x-ray film and tu-
berculin skin test should have been done far earlier in the pa-
tient’s clinical course.
To the Editor: I am the public health nurse coordinator who We agree with Drs. Gambino and Soloway that the labora-
monitored the patient in the Clinical Problem-Solving article tory diagnosis of iron deficiency would have greatly assisted the
during her treatment for tuberculosis. The organism isolated clinicians caring for the patient. They further question whether
from the patient was not resistant to any antituberculosis med- hemoglobin electrophoresis could have diagnosed both the he-
ication. Initially, a telephone report from the laboratory indi- moglobin E and alpha-thalassemia traits. In this case, electro-
cated resistance to isoniazid and ethambutol. At that time, phoretic quantification of hemoglobin E revealed a value of 27
these medications were dropped from the four-drug regimen percent, which is lower than is usually seen with the hemoglo-
and streptomycin and ciprofloxacin were added. When the fi- bin E trait and more suggestive of a mixed hemoglobinopathy
nal printed report came from the laboratory, it indicated sen- with alpha-thalassemia trait.1 Finally, Ms. Benoit has reported
sitivity of the organism to all medications. When the labora- that the patient’s strain of Mycobacterium tuberculosis was not
tory was asked to clarify these results, it noted that the initial drug-resistant. This information was known to her medical
telephone report incorrectly indicated resistance but that the team but absent from the records we reviewed.
finding was believed to be a result of antibiotic degradation.
All subsequent testing indicated 100 percent sensitivity to an- JONATHAN M. ROSS, M.D.
tibiotics. Rather than changing the drug regimen again, we HAROLD C. SOX, M.D.
continued to treat the patient with rifampin, pyrazinamide, Dartmouth–Hitchcock
streptomycin, and ciprofloxacin. Lebanon, NH 03756 Medical Center
VALERIE F. BENOIT, R.N., M.A. 1. Tuchinda S, Rucknagel DL, Minnich V, Boonyaprakob U, Balankura K, Su-
ratee V. The coexistence of the genes for hemoglobin E and a thalassemia in
Claremont, NH 03743-2280 Public Health District Office Thais, with resultant suppression of hemoglobin E synthesis. Am J Hum Ge-
net 1964;16:311-35.
1. Folkman J. Clinical applications of research on angiogenesis. N Engl J Med sel density and evaluation of p53 can have synergistic prog-
1995;333:1757-63. nostic value in node-negative breast carcinoma.3
2. Costello P, McCann A, Carney DN, Dervan PA. Prognostic significance of
microvessel density in lymph node negative breast carcinoma. Hum Pathol FABIO PUGLISI, M.D.
1995;26:1181-4.
3. Hartveit F. Attenuated cells in breast stroma: the missing lymphatic system SIMONA SCALONE, M.D.
of the breast. Histopathology 1990;16:533-43. VINCENZO DILAURO, M.D.
4. Cann SA, van Netten JP, Ashby TL, Ashwood-Smith MJ, van der Westhuizen 33100 Udine, Italy University of Udine
NG. Role of lymphagenesis in neovascularisation. Lancet 1995;346:903.
5. Lauria R, Perrone F, Carlomagno C, et al. The prognostic value of lymphatic 1. Dameron KM, Volpert OV, Tainsky MA, Bouck N. Control of angiogenesis
and blood vessel invasion in operable breast cancer. Cancer 1995;76:1772-8. in fibroblasts by p53 regulation of thrombospondin-1. Science 1994;265:
1582-4.
2. Kieser A, Weich HA, Brandner G, Marme D, Kolch W. Mutant p53 potenti-
ates protein kinase C induction of vascular endothelial growth factor expres-
To the Editor: In his excellent overview of angiogenesis, sion. Oncogene 1994;9:963-9.
Folkman described the role of fibroblast growth factor in neo- 3. Gasparini G, Weidner N, Bevilacqua P, et al. Tumor microvessel density, p53
plastic and non-neoplastic diseases. There have been interest- expression, tumor size, and peritumoral lymphatic vessel invasion are rele-
ing reports on the role of somatostatin in the inhibition of vant prognostic markers in node-negative breast carcinoma. J Clin Oncol
1994;12:454-66.
angiogenesis.1,2 This effect is probably mediated by the soma-
tostatin receptor subtype 2, which has been shown to inhibit
the effect of the INT2 gene, which encodes fibroblast growth Dr. Folkman replies:
factor, in several tissues. Somatostatin and its analogues have
a potential role in treating some malignant conditions, either To the Editor: Van Netten et al. propose the term “vasogen-
through a direct antitumor effect or through potentiation of esis” for both angiogenesis and “lymphagenesis.” The pre-
the effect of other chemotherapies.3 This effect could be ex- ponderance of the experimental evidence is that tumors in-
plained by the inhibition of angiogenesis in tumors expressing duce new capillary blood vessels, but there is little evidence
the somatostatin receptor subtype 2. Tumors in different stag- that tumors induce new lymphatic vessels. Certain findings
es of differentiation vary in expression of the receptor, which argue against tumor-induced lymphangiogenesis. First, FLT4,
could explain the conflicting results of studies to date. a marker of lymphatic endothelium, was detected in melano-
New techniques for the selective detection of receptor sub- mas in the granulation tissue and dermis of the skin around
types call for new studies of the role of somatostatin and the tumor, but not in the tumor.1 Second, in a study of a vari-
receptor-specific analogues in oncology. The effect of these ety of tumors, no functional lymphatic vessels were found.2
agents in non-neoplastic conditions is also under investigation, Moreover, no lymphangiogenic factors have been isolated
and there are promising results in the treatment of ocular from tumors; microlymphangiographic and histologic studies
neovascularization.4 We are currently evaluating the possible of mice bearing a sarcoma in the tail reveal functional lym-
therapeutic effect of the somatostatin analogue octreotide in phatic vessels only outside the tumor, not within it; and tu-
rheumatologic diseases. mors implanted in the mouse or rabbit cornea induce blood-
vessel growth, but not lymphatic-vessel growth. Unless it can
HAIM PARAN, M.D. be demonstrated that tumors stimulate the growth of new
Kfar-Sava, Israel Meir Hospital lymphatic vessels, “vasogenesis” does not seem to be an im-
DAPHNA PARAN, M.D. provement over the currently accepted terms.
Tel Aviv, Israel Tel Aviv Medical Center In the study cited by van Netten et al., Costello et al.3 do
not question whether tumor growth is dependent on angio-
1. Woltering EA, Barrie R, O’Dorisio TM, et al. Somatostatin analogues inhibit genesis, but whether tumor-microvessel density is a valid prog-
angiogenesis in the chick chorioallantoic membrane. J Surg Res 1991;50:
245-51. nostic marker. To date, the vast majority of reports show a
2. Patel PC, Barrie R, Hill N, Landeck S, Kurozawa D, Woltering EA. Postre- strong correlation between tumor-microvessel density and the
ceptor signal transduction mechanisms involved in octreotide-induced inhi- risk of metastasis.4
bition of angiogenesis. Surgery 1994;116:1148-52. Puglisi et al. emphasize the role of the p53 suppressor gene
3. Weckbecker G, Tolcsvai L, Stolz B, Pollak M, Bruns C. Somatostatin ana-
logue octreotide enhances the antineoplastic effects of tamoxifen and ovar- in the switch to the angiogenic phenotype. I agree. My review
iectomy on 7,12-dimethylbenz(a)anthracene-induced rat mammary carcino- cited the work of Dameron et al.5
mas. Cancer Res 1994;54:6334-7. Paran and Paran offer a possible mechanism for the anti-
4. Grant MB, Caballero S, Millard WJ. Inhibition of IGF-I and b-FGF stimulat- angiogenic activity of somatostatin and its analogues. Their
ed growth of human retinal endothelial cells by the somatostatin analogue,
octreotide: a potential treatment for ocular nonvascularization. Regul Pept suggestion that these molecules may be useful in the therapy
1993;48:267-78. of ocular neovascularization and rheumatologic disease is a
good one and merits further study.
To the Editor: Folkman addressed the “switch” of tumor cells JUDAH FOLKMAN, M.D.
to the angiogenic phenotype, but it is important to point out Boston, MA 02115 Children’s Hospital
that the p53 gene has an important role in controlling tumor 1. Kaipainen A, Korhonen J, Mustonen T, et al. Expression of fms-like tyrosine
angiogenesis. Dameron et al. have reported that the loss of kinase 4 gene becomes restricted to lymphatic endothelium during develop-
the wild-type p53 allele in cultured fibroblasts from patients ment. Proc Natl Acad Sci U S A 1995;92:3566-70.
2. Dumont RE. Factor VIII-related antigen. J Natl Cancer Inst 1993;85:674-6.
with the Li–Fraumeni syndrome results in a decrease in levels 3. Costello P, McCann A, Carney DN, Dervan PA. Prognostic significance of
of the endogenous negative regulator of neovascularization, microvessel density in lymph node negative breast carcinoma. Hum Pathol
thrombospondin-1.1 Other authors showed that a mutant p53 1995;26:1181-4.
gene determines neovascularization in some tumor cell lines 4. Weidner N. Intratumoral microvessel density as a prognostic factor in cancer.
Am J Pathol 1995;147:9-19.
by increasing the production of protein kinase C and enhanc- 5. Dameron KM, Volpert OV, Tainsky MA, Bouck N. Control of angiogenesis
ing the expression of the vascular endothelial growth factor.2 in fibroblasts by p53 regulation of thrombospondin-1. Science 1994;265:
A clinical implication of these findings is that tumor-microves- 1582-4.
No. of Accidents
ANSGAR W. LOHSE, M.D.
D-55101 Mainz, Germany Johannes Gutenberg University
4000
1. Czaja AJ, Carpenter HA, Santrach PJ, Moore SB, Homburger HA. The na- 2600
ture and prognosis of severe cryptogenic chronic active hepatitis. Gastroen-
terology 1993;104:1755-61.
2. Czaja AJ, Ludwig J, Baggenstoss AH, Wolf A. Corticosteroid-treated chronic 3800
active hepatitis in remission: uncertain prognosis of chronic persistent hepa- 2500
titis. N Engl J Med 1981;304:5-9.
3. Thaler H. The natural history of chronic hepatitis. In: Schaffner F, Sherlock
S, Leevy CM, eds. The liver and its diseases. New York: Stratton Interconti-
nental Medical, 1974:207-15. 2400 3600
re
e
ly
ly
r
r
te
te
4. Kirk AP, Jain S, Pocock S, Thomas HC, Sherlock S. Late results of the Royal
Im efor
r te
r te
fo
af
af
te ia
te ia
Be
Free Hospital prospective controlled trial of prednisolone therapy in hepatitis
B
af ed
k
af ed
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B surface antigen negative chronic active hepatitis. Gut 1980;21:78-83.
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Spring Shift Fall Shift
DAYLIGHT SAVINGS TIME AND TRAFFIC
ACCIDENTS Figure 1. Numbers of Traffic Accidents on the Mondays before
and after the Shifts to and from Daylight Savings Time for the
To the Editor: It has become increasingly clear that insuffi- Years 1991 and 1992.
cient sleep and disrupted circadian rhythms are a major pub- There is an increase in accidents after the spring shift (when an
lic health problem. For instance, in 1988 the cost of sleep- hour of sleep is lost) and a decrease in the fall (when an hour
related accidents exceeded $56 billion and included 24,318 of sleep is gained).
deaths and 2,474,430 disabling injuries.1 Major disasters, in-
cluding the nuclear accident at Chernobyl, the Exxon Valdez oil
spill, and the destruction of the space shuttle Challenger, have to daylight savings time increased the risk of accidents. The
been linked to insufficient sleep, disrupted circadian rhythms, Monday immediately after the shift showed a relative risk of
or both on the part of involved supervisors and staff.2,3 It has 1.086 (95 percent confidence interval, 1.029 to 1.145; x 2 9.01,
been suggested that as a society we are chronically sleep- 1 df; P0.01). As compared with the accident rate a week later,
deprived4 and that small additional losses of sleep may have the relative risk for the Monday immediately after the shift was
consequences for public and individual safety.2 1.070 (95 percent confidence interval, 1.015 to 1.129; x 2 6.19,
We can use noninvasive techniques to examine the effects 1 df; P0.05). Conversely, there was a reduction in the risk of
of minor disruptions of circadian rhythms on normal activi- traffic accidents after the fall shift from daylight savings time
ties if we take advantage of annual shifts in time keeping. when an hour of sleep was gained. In the fall, the relative risk
More than 25 countries shift to daylight savings time each on the Monday of the change was 0.937 (95 percent confidence
spring and return to standard time in the fall. The spring shift interval, 0.897 to 0.980; x 2 8.07, 1 df; P0.01) when com-
results in the loss of one hour of sleep time (the equivalent in pared with the preceding Monday and 0.896 (95 percent con-
terms of jet lag of traveling one time zone to the east), where- fidence interval, 0.858 to 0.937; x 2 23.69; P0.001) when
as the fall shift permits an additional hour of sleep (the equiv- compared with the Monday one week later. Thus, the spring
alent of traveling one time zone to the west). Although one shift to daylight savings time, and the concomitant loss of one
hour’s change may seem like a minor disruption in the cycle hour of sleep, resulted in an average increase in traffic acci-
of sleep and wakefulness, measurable changes in sleep pattern dents of approximately 8 percent, whereas the fall shift result-
persist for up to five days after each time shift.5 This leads to ed in a decrease in accidents of approximately the same mag-
the prediction that the spring shift, involving a loss of an nitude immediately after the time shift.
hour’s sleep, might lead to an increased number of “micro- These data show that small changes in the amount of sleep
sleeps,” or lapses of attention, during daily activities and thus that people get can have major consequences in everyday ac-
might cause an increase in the probability of accidents, espe- tivities. The loss of merely one hour of sleep can increase the
cially in traffic. The additional hour of sleep gained in the fall risk of traffic accidents. It is likely that the effects are due to
might then lead conversely to a reduction in accident rates. sleep loss rather than a nonspecific disruption in circadian
We used data from a tabulation of all traffic accidents in rhythm, since gaining an additional hour of sleep at the fall
Canada as they were reported to the Canadian Ministry of time shift seems to decrease the risk of accidents.
Transport for the years 1991 and 1992 by all 10 provinces. A Vancouver, BC V6T 1Z4, STANLEY COREN, PH.D.
total of 1,398,784 accidents were coded according to the date Canada University of British Columbia
of occurrence. Data for analysis were restricted to the Mon-
day preceding the week of the change due to daylight savings 1. Leger D. The cost of sleep-related accidents: a report for the National Com-
mission on Sleep Disorders Research. Sleep 1994;17:84-93.
time, the Monday immediately after, and the Monday one 2. Coren S. Sleep thieves. New York: Free Press, 1996.
week after the change, for both spring and fall time shifts. 3. Mitler MM, Carskadon MA, Czeisler CA, Dement WC, Dinges DF, Graeber
Data from the province of Saskatchewan were excluded be- RC. Catastrophes, sleep, and public policy: consensus report. Sleep 1988;11:
cause it does not observe daylight savings time. The analysis 100-9.
4. Webb WB, Agnew HW Jr. Are we chronically sleep deprived? Bull Psycho-
of the spring shift included 9593 accidents and that of the fall nom Soc 1975;6:47-8.
shift 12,010. The resulting data are shown in Figure 1. 5. Monk TH, Folkard S. Adjusting to the changes to and from daylight saving
The loss of one hour’s sleep associated with the spring shift time. Science 1976;261:688-9.