Background Ingestion of a large dose of the milk sugar lactose-- for example, the 50-g load in 1 liter of milk -- causes symptomssuch as abdominal pain, diarrhea, bloating, and flatulence inthe majority of people with lactose malabsorption. It is uncertainwhether the ingestion of more common doses of lactose, suchas the amount in 240 ml (8 oz) of milk, causes symptoms. Somepeople insist that even smaller quantities of milk, such asthe amount used with cereal or coffee, cause severe gastrointestinaldistress.
Methods In a randomized, double-blind, crossover trial, we evaluatedgastrointestinal symptoms in 30 people (mean age, 29.4 years;range, 18 to 50) who reported severe lactose intolerance andsaid they consistently had symptoms after ingesting less than240 ml of milk. The ability to digest lactose was assessed bymeasuring the subjects' end-alveolar hydrogen concentrationafter they ingested 15 g of lactose in 250 ml of water. Subjectsthen received either 240 ml of lactose-hydrolyzed milk containing2 percent fat or 240 ml of milk containing 2 percent fat andsweetened with aspartame to approximate the taste of lactose-hydrolyzedmilk; each type of milk was administered daily with breakfastfor a one-week period. Using a standardized scale, subjectsrated the occurrence and severity of bloating, abdominal pain,diarrhea, and flatus and recorded each passage of flatus.
Results Twenty-one participants were classified as having lactosemalabsorption and nine as being able to absorb lactose. Duringthe study periods, gastrointestinal symptoms were minimal (meansymptom-severity scores for bloating, abdominal pain, diarrhea,and flatus between 0.1 and 1.2 [1 indicated trivial symptoms;and 2, mild symptoms]). When the periods were compared, therewere no statistically significant differences in the severityof these four gastrointestinal symptoms. For the lactose-malabsorptiongroup, the mean (±SEM) difference in episodes of flatusper day was 2.5 ±1.1 (95 percent confidence interval,0.2 to 4.8). Daily dietary records indicated a high degree ofcompliance, with no additional sources of lactose reported.
Conclusions People who identify themselves as severely lactose-intolerantmay mistakenly attribute a variety of abdominal symptoms tolactose intolerance. When lactose intake is limited to the equivalentof 240 ml of milk or less a day, symptoms are likely to be negligibleand the use of lactose-digestive aids unnecessary.
The milk sugar lactose must be hydrolyzed by a lactase at theintestinal brush border before it can be absorbed. After weaning,there is a genetically programmed reduction in lactase activityin many people that cannot be altered by the ingestion of milk.1,2,3Such people acquire what has been variously termed ``primaryacquired lactase deficiency,'' ``lactase nonpersistence'' or``lactose malabsorption.'' The ability to maintain throughoutadult life the levels of lactase characteristic of infancy isinherited through a single, highly penetrant autosomal dominantgene4,5 located on chromosome 2.6 People of northern Europeandescent generally have high lactase levels throughout adulthood.Most other people become lactase-nonpersistent.5,7 About 25percent of adults in the United States and 75 percent worldwidehave lactose malabsorption.7,8
Ingestion of a large dose of lactose, such as the 50-g loadin 1 liter (1.06 qt) of milk, causes diarrhea, bloating, andflatulence in the majority of people with lactose malabsorption.9There is controversy, however, about such people's toleranceof smaller doses of lactose, such as the amount found in 240ml (8 oz) of milk. One uncontrolled study suggested that themajority of people with lactose malabsorption have appreciablesymptoms after drinking 240 ml of milk.10 In contrast, a blindedstudy suggested that most of those with malabsorption tolerate240 ml of milk without recognizable symptoms.8 Nevertheless,it is extremely common for patients to insist that ingestingvery small quantities of milk, such as the amount used withcereal or coffee, causes severe gastrointestinal distress. Thisconcept of severe intolerance has been nurtured by innumerablearticles in the news media and advertisements for lactose-digestiveaids. People who believe that they are severely lactose-intoleranthave not been adequately represented in previous trials, whichhave evaluated people with lactose malabsorption independentlyof whether or not they considered themselves lactose-intolerant.11,12,13,14
In a self-selected group of people with severe lactose intolerance,we evaluated gastrointestinal symptoms after they drank 240ml of milk daily for one-week periods. Our findings suggestthat a variety of abdominal complaints are frequently misattributedto lactose intolerance.
Methods
Subjects
People who believed they were severely lactose-intolerant wererecruited through advertisements posted at the Minneapolis VeteransAffairs Medical Center and the University of Minnesota campus.Seventy-eight initial respondents were screened through a telephonequestionnaire. Subjects were excluded if they did not reportconsistently having symptoms (abdominal pain, bloating, flatulence,or diarrhea) after drinking less than 240 ml of milk; if theyhad undergone gastrointestinal surgery, had other major illnesses,or received antibiotic therapy within the previous two months;or if they indicated that they could not consume aspartame.Of the 30 people selected for further study, 10 avoided milkin any form and 20 consistently used a commercial lactose-digestiveaid (lactose-hydrolyzed milk or a lactase preparation).
Lactose Absorption
The ability of the 30 subjects to digest lactose was determinedby measuring their end-alveolar hydrogen concentrations hourlyfor five hours after they ingested 15 g of lactose in 250 mlof water (0.18 mol per liter). Subjects were classified as havinglactose malabsorption if their breath hydrogen concentrationsincreased by more than 10 parts per million (ppm) (0.9x10-6g of hydrogen per liter of air or 0.45 micromol per liter).15The ability of the colonic flora to produce hydrogen throughfermentation in response to carbohydrate malabsorption was testedin seven of the nine subjects who were able to absorb lactoseafter they ingested 10 g of lactulose (Xactdose, South Beloit,Ill.) in 250 ml of water (0.12 mol per liter). Lactulose isa nonabsorbable disaccharide that is fermented by the same enzymaticpathway as lactose.
The protocol was approved by the Human Subjects Committee ofthe institutional review board at the Minneapolis Veterans AffairsMedical Center. All subjects gave written informed consent.
Regimens
In a randomized, double-blind, crossover trial, each subjectreceived 240 ml of milk daily with his or her usual breakfastfor two one-week periods. The milk preparation was either a2-percent-fat lactose-hydrolyzed milk or a 2-percent-fat milk(containing a mean of 12.1 g of lactose [0.14 mol per liter;range, 11.8 to 12.5 g]) plus an artificial sweetener (Equal;NutraSweet, Deerfield, Ill.). Subjects were instructed to avoidconsuming additional dairy products and other lactose-containingfoods. Daily dietary records were kept by the subjects duringeach experimental period.
Milk Preparation
The lactose in fresh low-fat milk was hydrolyzed by adding 1.07g of lactase from Kluyveromyces lactis (Lactaid, Pleasantville,N.Y.) to 1 liter of milk (7.9 micromol per liter). Treated milkwas incubated for 48 hours at 4 °C. No measurable residuallactose remained in the lactose-hydrolyzed milk (<0.05 gper liter [<0.14 mmol per liter]), as determined by an enzymaticassay (Lactose/d-galactose test kit; Boehringer-Mannheim Biochemical,Indianapolis).
The hydrolysis of lactose increases the sweetness of milk. Therefore,the nonhydrolyzed milk was sweetened with aspartame (Equal,0.82 g per liter [2.8 mmol per liter]). A panel of 30 untrainedsubjects, not otherwise participating in this study, could notdistinguish between the two products in a sensory triangle test(three samples, two of which contained the same product, werepresented, and the subject was required to identify the oddsample).16 Of the total of 90 observations, 41 were correctand 49 were incorrect (P = 0.25).
Hydrogen and Carbon Dioxide Analysis
The concentrations of carbon dioxide and hydrogen in breathsamples were analyzed by gas chromatography17 (Microlyzer GasAnalyzer, model DP; Quintron Instruments, Milwaukee). The observedhydrogen values were corrected for atmospheric contaminationof alveolar air by normalizing the concentrations of observedcarbon dioxide to 45 mm Hg, the partial pressure of carbon dioxidein alveolar air. Changes in hydrogen concentrations were calculatedby subtracting the hydrogen concentration during fasting fromsubsequent test values.18
Reporting of Symptoms
Subjects rated the occurrence and severity of gastrointestinalsymptoms experienced during the 24-hour period after each testmeal. Bloating, abdominal pain or cramps, and the subjectiveimpression of rectal gas excretion were ranked as follows: 0indicated no symptoms; 1, trivial symptoms; 2, mild symptoms;3, moderate symptoms; 4, strong symptoms; and 5, severe symptoms.19Diarrhea or loose stool was defined as ``an urgent, watery defecation.''20In addition, subjects recorded each passage of flatus.
Statistical Analysis
Data were analyzed by repeated-measures analysis of variance.21,22In addition, because the distribution of the data was skewed,a nonparametric test (McNemar's test) was used to analyze theresults. A binomial distribution was used to calculate the two-tailedP value. Individual symptom scores were analyzed separatelyfor each regimen on each day of the study to evaluate the influenceof time. Since no differences over time were observed for eitherregimen, the mean symptom scores for each one-week period werecompared.
Results
The breath hydrogen concentrations of the 30 subjects afterthey consumed 15 g of lactose are shown in Figure 1. The 21subjects whose breath hydrogen concentrations increased by morethan 10 ppm were classified as having lactose malabsorption.The nine subjects with an increase of less than 10 ppm wereclassified as being able to absorb lactose. Seven of these ninesubjects were retested after consuming 10 g of lactulose in300 ml of water. All seven subjects produced hydrogen in responseto lactulose (Figure 1), confirming the ability of their colonicflora to produce hydrogen.
Figure 1. Breath Hydrogen Concentrations of 30 Subjects after the Ingestion of 15 g of Lactose. Data are expressed as the changes in concentration (means ±SEM) above the base-line (fasting) values. Twenty-one subjects had lactose malabsorption, as evidenced by sizable increases in breath hydrogen concentration ((solid circle)), whereas nine subjects had no increase in hydrogen concentration and were considered able to absorb lactose (solid square). Retesting with 10 g of lactulose of seven of the nine subjects who were able to absorb lactose demonstrated that each responded with a brisk increase in breath hydrogen concentration ((open square)). 1 ppm = 0.045 micromol per liter.
The 21 subjects with lactose malabsorption included 8 men and13 women, 18 to 50 years of age, with a mean age of 29.4 years.One was black, seven were Asian, eight were white, and fivewere Hispanic. The nine who were able to absorb lactose includedfive women and four men, 18 to 45 years of age, with a meanage of 25.1 years. Eight were white and one was East Indian.
During the two study periods, gastrointestinal symptoms reportedby subjects were minimal (mean symptom-severity scores werebetween 0.1 and 1.2, with 0 indicating no symptoms; 1, trivialsymptoms; and 2, mild symptoms). These data are shown in Table 1.The 95 percent confidence intervals for the differences inmean scores for the symptoms of bloating, abdominal pain, diarrhea,and perceived flatus intensity after the subjects drank ordinarymilk and after they drank lactose-hydrolyzed milk include zero.This indicates that the severity of gastrointestinal symptomswas not significantly different in subjects during the two studyregimens. In the lactose-malabsorption group, the mean (±SEM)difference between regimens in episodes of flatus per day was2.5 ±1.1 (95 percent confidence interval, 0.2 to 4.8).A nonparametric statistical test (McNemar's test) showed thatregimen was not associated with significant differences in anyof these symptoms or in the frequency of flatus (data not shown).Daily dietary records indicated a high degree of compliance,with no additional sources of lactose reported.
Table 1. Gastrointestinal Symptoms and Frequency of Flatus in 30 People with Self-Reported Severe Lactose Intolerance Who Drank 240 ml of Ordinary Milk or Lactose-Hydrolyzed Milk Daily for One Week.
Discussion
If the hydrolysis of lactose in the small bowel is incomplete,lactose is transported to the colon. Colonic bacteria fermentthis sugar and produce short-chain fatty acids and gas (hydrogen,carbon dioxide, and methane). The development of diarrhea orgaseous symptoms depends partly on the balance between the productionand the removal of these fermentation products. Short-chainfatty acids are rapidly absorbed by the colonic mucosa; diarrheaoccurs only when the rate of delivery of lactose to the colonexceeds the rate at which the bacteria ferment lactose.23 Thegases produced during fermentation are consumed by bacteriaor are quickly absorbed into the bloodstream.24 Excessive rectalgas or abdominal distention occurs when these disposal mechanismsare overwhelmed. Thus, although even small amounts of lactoseare poorly absorbed by people with lactase deficiency, the malabsorptiondoes not necessarily cause appreciable symptoms.
Although many patients are certain that they can link the ingestionof various foods to subsequent abdominal symptoms, it is extremelydifficult to pinpoint accurately which, if any, constituentsof the diet cause abdominal distress. There is a tendency toattribute symptoms to a food that others have declared to bea problem -- for example, lactose or fat. This conclusion isthen reinforced by an apparent improvement in symptoms whenthe food is avoided. Given the enormous placebo effect of dietarymanipulations, to document a food intolerance reliably it mustbe demonstrated that ingestion of the putative offender resultsin symptoms that do not occur when a ``placebo'' that appearsand tastes identical is ingested. Double-blind evaluation isvirtually impossible with most foods but is possible with lactose.
An uncontrolled study found that 59 percent of 44 lactose-intolerantmen experienced symptoms after drinking 240 ml of milk.10 Incontrast, in a series of double-blind studies, Scrimshaw's groupfound that most people with lactose malabsorption (not selectedfor the self-reported severity of their intolerance) tolerated240 ml of a chocolate drink containing 12 g of lactose.12,13,14Our study extends these observations to people who believedthemselves to be extremely intolerant to very small doses oflactose, such as the amounts contained in milk used with coffeeor cereal. In addition, we attempted to evaluate the usual patternof milk ingestion by assessing the severity of a variety ofsymptoms over a one-week period during which 240 ml of milkwas ingested daily. In previous studies that evaluated the responsesto single doses of lactose in a chocolate drink,12,13,14 thechocolate may have had an independent effect on symptoms.25We analyzed each symptom independently, unlike investigatorswho only reported symptoms as present or absent26 or as thesum of symptom intensity.27
Our finding that 240 ml of milk was not associated with a significantincrease in the severity of bloating, abdominal pain, or flatussuggests that people frequently misattribute a variety of abdominalsymptoms to lactose intolerance. A larger study might have uncoveredsome differences. Nevertheless, the symptoms that might be causedby lactose are unlikely to be substantial, particularly in viewof the expectation of many subjects before the study that thedistress caused by ordinary milk would preclude their completingthe study. In most people with lactose malabsorption, the ingestionof 50 g of lactose in a single dose produces symptoms, but thatis equivalent to drinking a liter of milk. Future studies shouldaddress tolerance of 240 ml of milk consumed throughout theday with meals.
A variety of lactose-digestive aids are available over the counter.Overnight incubation of milk with 5 or 15 drops of a liquidlactase preparation per 240 ml of milk is recommended to produce70 percent or 100 percent hydrolysis of lactose, respectively.The cost of this treatment, based on the $7 price of a bottleof the preparation in Minnesota, is about 6 cents per 240 mlof milk (70 percent hydrolysis) or 18 cents per 240 ml (100percent hydrolysis). Lactase is also available as a tablet thatcan be taken with a lactose-containing food. The cost of therecommended dose (two tablets) ranges from 30 cents to 60 centsin Minnesota, depending on whether a carton of 100 or 12 tabletsis purchased. In many areas, commercially prehydrolyzed milkis available at a cost of about 36 cents per 240-ml serving.
The price of milk in Minnesota is about 19 cents per 240 ml.In our area, the use of lactose-digestive aids increases thecost of milk by a minimum of about 6 cents per 240-ml serving(70 percent hydrolysis of lactose by lactase drops) to a maximumof about 41 cents per 240-ml serving (lactase tablets purchasedin small quantities). Although the price of lactose-digestiveaids may vary widely, in our area the minimal additional costfor 100 percent lactose-hydrolyzed milk is about 18 cents per240 ml (lactase drops). The daily ingestion of 240 ml of suchmilk entails an annual expenditure of about $66.
In summary, in a study of 30 people who identified themselvesas severely lactose-intolerant, 9 were found to be able to absorblactose and the other 21, who had lactose malabsorption, tolerated240 ml of milk a day over a one-week period with minimal, ifany, symptoms. We conclude that lactose-digestive aids are notnecessary when lactose intake is limited to the equivalent of240 ml of milk or less a day.
Supported in part by the Department of Veteran Affairs, theNational Institute of Diabetes and Digestive and Kidney Diseases(RO1-DK-13093-25), and the University of Minnesota AgriculturalExperiment Station.
Source Information
From the Department of Food Science and Nutrition, University of Minnesota, St. Paul (F.L.S., D.A.S.), and the Minneapolis Veterans Affairs Medical Center, Minneapolis (M.D.L.).
Address reprint requests to Dr. Levitt at the Minneapolis Veterans Affairs Medical Center, 1 Veterans Dr., Minneapolis, MN 55417.
References
Gilat T, Russo S, Gelman-Malachi E, Aldor TAM. Lactase in man: a nonadaptable enzyme in man. Gastroenterology 1972;62:1125-1127. [Medline]
Simoons FJ. The geographic hypothesis and lactose malabsorption: a weighing of the evidence. Am J Dig Dis 1978;23:963-980. [CrossRef][Medline]
Friedl J. Lactase deficiency: distribution, associated problems, and implications for nutritional policy. Ecol Food Nutr 1981;11:37-48.
Sahi T. The inheritance of selective adult-type lactose malabsorption. Scand J Gastroenterol Suppl 1974;30:1-73.
Lisker R, Gonzalez B, Daltabuit M. Recessive inheritance of the adult type of intestinal lactase deficiency. Am J Hum Genet 1975;27:662-664. [Medline]
Kruse TA, Bolund L, Grzeschik KH, et al. The human lactase-phlorizin hydrolase gene is located on chromosome 2. FEBS Lett 1988;240:123-126. [CrossRef][Medline]
Bourlioux P, Pochart P. Nutritional and health properties of yogurt. World Rev Nutr Diet 1988;56:217-258. [Medline]
Scrimshaw NS, Murray EB. The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance. Am J Clin Nutr 1988;48:Suppl:1079-1159.
Cook GC, Dahlqvist A. Jejunal hetero--galactosidase activities in Ugandans with lactase deficiency. Gastroenterology 1968;55:328-332. [Medline]
Bayless TM, Rothfeld B, Massa C, Wise L, Paige D, Bedine MS. Lactose and milk intolerance: clinical implications. N Engl J Med 1975;292:1156-1159. [Abstract]
Paige DM, Bayless TM, Huang S, Wexler R. Lactose hydrolyzed milk. Am J Clin Nutr 1975;28:818-822. [Free Full Text]
Rorick MH, Scrimshaw NS. Comparative tolerance of elderly from differing ethnic backgrounds to lactose-containing and lactose-free dairy drinks: a double-blind study. J Gerontol 1979;34:191-196. [Free Full Text]
Haverberg L, Kwon PH, Scrimshaw NS. Comparative tolerance of adolescents of differing ethnic backgrounds to lactose-containing and lactose-free dairy drinks. I. Initial experience with a double-blind procedure. Am J Clin Nutr 1980;33:17-21. [Free Full Text]
Unger M, Scrimshaw NS. Comparative tolerance of adults of differing ethnic backgrounds to a lactose-free and lactose-containing dairy drink. Nutr Res 1981;1:1227-33.
Solomons NW, Garcia-Ibanez R, Viteri FE. Hydrogen breath test of lactose absorption in adults: the application of physiological doses and whole cow's milk source. Am J Clin Nutr 1980;33:545-554. [Free Full Text]
Jellinek G. Sensory evaluation of food: theory and practice. Deerfield Beach, Fla.: Weinheim, 1985.
Levitt MD, Donaldson RM. Use of respiratory hydrogen (H2) excretion to detect carbohydrate malabsorption. J Lab Clin Med 1970;75:937-945. [Medline]
Martini MC, Kukielka D, Savaiano DA. Lactose digestion from yogurt: influence of a meal and additional lactose. Am J Clin Nutr 1991;53:1253-1258. [Free Full Text]
Suarez FL, Savaiano DA. Lactose digestion and tolerance in adult and elderly Asian-Americans. Am J Clin Nutr 1994;59:1021-1024. [Free Full Text]
Vasquez-Velasquez L, Torun B, Ogden E, Solomons NW. How much malabsorbed sugar causes ``diarrhea''? Gastroenterology 1985;88:856-857. [Medline]
Sachs L. Applied statistics: a handbook of techniques. 5th ed. New York: Springer-Verlag, 1982.
SYSTAT for the Macintosh, version 5.2. Evanston, Ill.: SYSTAT, 1992.
Saunders DR, Wiggins HS. Conservation of mannitol, lactulose, and raffinose by the human colon. Am J Physiol 1981;241:G397-G402. [Free Full Text]
Gibson GR, Cummings JH, Macfarlane GT, et al. Alternative pathways for hydrogen disposal during fermentation in the human colon. Gut 1990;31:679-683. [Free Full Text]
Lee CM, Hardy CM. Cocoa feeding and human lactose intolerance. Am J Clin Nutr 1989;49:840-844. [Free Full Text]
Johnson AO, Semenya JG, Buchowski MS, Enwonwu CO, Scrimshaw NS. Correlation of lactose maldigestion, lactose intolerance, and milk intolerance. Am J Clin Nutr 1993;57:399-401. [Free Full Text]
Lisker R, Aguilar L. Double blind study of milk lactose intolerance. Gastroenterology 1978;74:1283-1285. [Medline]
Lactose Intolerance
Medow M. S., Sloan H. R., Bayless T. M., Paige D. M., Bedine M. S., Roberts H.J., Morris D. L., Fenster D. L., Suarez F. L., Savaiano D. A., Levitt M. D.
Extract |
Full Text
N Engl J Med 1995;
333:1358-1359, Nov 16, 1995.
Correspondence
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51: 340-342
[Full Text]
Sheikh, K. A., Nachamkin, I., Ho, T. W., Willison, H. J., Veitch, J., Ung, H., Nicholson, M., Li, C. Y., Wu, H. S., Shen, B. Q., Cornblath, D. R., Asbury, A. K., McKhann, G. M., Griffin, J. W.
(1998). Campylobacter jejuni lipopolysaccharides in Guillain-Barre syndrome: Molecular mimicry and host susceptibility. Neurology
51: 371-378
[Abstract][Full Text]
Ma, J. J., Nishimura, M., Mines, H., Kuroki, S., Nukina, M., Ohta, M., Saji, H., Obayashi, H., Saida, T., Kawakami, H., Uchiyama, T.
(1998). HLA and T-cell receptor gene polymorphisms in Guillain-Barre syndrome. Neurology
51: 379-384
[Abstract][Full Text]
Barber, P. A., Darby, D. G., Desmond, P. M., Yang, Q., Gerraty, R. P., Jolley, D., Donnan, G. A., Tress, B. M., Davis, S. M.
(1998). Prediction of stroke outcome with echoplanar perfusion- and diffusion-weighted MRI. Neurology
51: 418-426
[Abstract][Full Text]
Leker, R. R., Abramsky, O.
(1998). Early anticoagulation in patients with prosthetic heart valves and intracerebral hematoma. Neurology
50: 1489-1491
[Abstract][Full Text]
Villar-Cordova, C., Morgenstern, L. B., Barnholtz, J. S., Frankowski, R. F., Grotta, J. C.
(1998). Neurologists' attitudes regarding rt-PA for acute ischemic stroke. Neurology
50: 1491-1494
[Full Text]
Takano, K., Carano, R.A.D., Tatlisumak, T., Meiler, M., Sotak, C. H., Kleinert, H. D., Fisher, M.
(1998). Efficacy of intra-arterial and intravenous prourokinase in an embolic stroke model evaluated by diffusion-perfusion magnetic resonance imaging. Neurology
50: 870-875
[Abstract][Full Text]
Fagan, S. C., Morgenstern, L. B., Petitta, A., Ward, R. E., Tilley, B. C., Marler, J. R., Levine, S. R., Broderick, J. P., Kwiatkowski, T. G., Frankel, M., Brott, T. G., Walker, M. D., The NINDS rt-PA Stroke Study Group*,
(1998). Cost-effectiveness of tissue plasminogen activator for acute ischemic stroke. Neurology
50: 883-890
[Abstract][Full Text]
Greenberg, S. M., Vonsattel, J.-P. G., Segal, A. Z., Chiu, R. I., Clatworthy, A. E., Liao, A., Hyman, B. T., Rebeck, G. W.
(1998). Association of apolipoprotein E {epsilon}2 and vasculopathy in cerebral amyloid angiopathy. Neurology
50: 961-965
[Abstract][Full Text]
Zivin, J. A.
(1998). Factors determining the therapeutic window for stroke. Neurology
50: 599-603
[Abstract][Full Text]
Yasaka, M., O'Keefe, G. J., Chambers, B. R., Davis, S. M., Infeld, B., O'Malley, H., Baird, A. E., Hirano, T., Donnan, G. A., The Australian Streptokinase Trial Study Group,
(1998). Streptokinase in acute stroke: Effect on reperfusion and recanalization. Neurology
50: 626-632
[Abstract][Full Text]
Bandmann, O., Sweeney, M. G., Daniel, S. E., Wenning, G. K., Quinn, N., Marsden, C. D., Wood, N. W.
(1997). Multiple-system atrophy is genetically distinct from identified inherited causes of spinocerebellar degeneration. Neurology
49: 1598-1604
[Abstract][Full Text]
Kay, R., Wong, K. S., Perez, G., Woo, J.
(1997). Dichotomizing stroke outcomes based on self-reported dependency. Neurology
49: 1694-1696
[Abstract][Full Text]
Finelli, P. F., Onyiuke, H. C., Uphoff, D. F.
(1997). Idiopathic granulomatous angiitis of the CNS manifesting as diffuse white matter disease. Neurology
49: 1696-1699
[Abstract][Full Text]
Wu, H.-S., Liu, T. C., Lu, Z. L., Zou, L. P., Zhang, W. C., Zhaori, G., Zhang, J.
(1997). A prospective clinical and electrophysiologic survey of acute flaccid paralysis in Chinese children. Neurology
49: 1723-1725
[Abstract][Full Text]
SUAREZ, F., LEVITT, M.
(1997). Assessing food intolerance: don't lose control. Gut
41: 715-716
[Full Text]
Jorgensen, H. S., Nakayama, H., Raaschou, H. O., Olsen, T. S.
(1997). Acute stroke: Prognosis and a prediction of the effect of medical treatment on outcome and health care utilization: The Copenhagen Stroke Study. Neurology
49: 1335-1342
[Abstract][Full Text]
Clark, W. M.
(1997). Cytokines and reperfusion injury. Neurology
49: S10-S14
[Full Text]
Kummer, R. v., Weber, J.
(1997). Brain and vascular imaging in acute ischemic stroke: The potential of computed tomography. Neurology
49: S52-S55
[Full Text]
Kaste, M.
(1997). Current therapeutic options for brain ischemia. Neurology
49: S56-S59
[Full Text]
Hacke, W.
(1997). rtPA in acute ischemic stroke: European perspective. Neurology
49: S60-S62
[Full Text]
Morgenstern, L. B.
(1997). rtPA in acute ischemic stroke: the North American perspective. Neurology
49: S63-S65
[Full Text]
Sacchetti, M. L., Toni, D., Fiorelli, M., Argentino, C., Fieschi, C.
(1997). The concept of combination therapy in acute ischemic stroke. Neurology
49: S70-S74
[Full Text]
Pujol, J., Kulisevsky, J., Moreno, A.
(1997). Markers of reversible hepatic encephalopathy. Neurology
49: 1188-1188
[Full Text]
Krieger, D., Krieger, S.
(1997). Markers of reversible hepatic encephalopathy. Neurology
49: 1187-1188
[Full Text]
Alter, M., the Quality Standards Subcommittee, AAN,
(1997). Thrombolytic therapy for acute ischemic stroke. Neurology
49: 901-901
[Full Text]
De Keyser, J.
(1997). Thrombolytic therapy for acute ischemic stroke. Neurology
49: 900-901
[Full Text]
Tennis, P., Stern, R. S.
(1997). Risk of serious cutaneous disorders after initiation of use of phenytoin, carbamazepine, or sodium valproate: A record linkage study. Neurology
49: 542-546
[Abstract][Full Text]
Tamaru, Y., Hirano, M., Kusaka, H., Ito, H., Imai, T., Ueno, S.
(1997). {alpha}-Tocopherol transfer protein gene: Exon skipping of all transcripts causes ataxia. Neurology
49: 584-588
[Abstract][Full Text]
Rostand, S. G.
(1997). Ultraviolet Light May Contribute to Geographic and Racial Blood Pressure Differences. Hypertension
30: 150-156
[Abstract][Full Text]
Bernat, J. L., Ringel, S. P., Vickrey, B. G., Keran, C.
(1997). Attitudes of US neurologists concerning the ethical dimensions of managed care. Neurology
49: 4-13
[Abstract][Full Text]
Lyden, P. D., Grotta, J. C., Levine, S. R., Marler, J. R., Frankel, M. R., Brott, T. G.
(1997). Intravenous thrombolysis for acute stroke. Neurology
49: 14-20
[Full Text]
Seino, M., Yeh, E. A.
(1997). Patterns of epilepsy care in Japan. Neurology
48: S8-S15
[Full Text]
Willmore, L. J.
(1997). Care of adults with epilepsy in the United States. Neurology
48: S39-S43
[Full Text]
Henderson, V. W.
(1997). The epidemiology of estrogen replacement therapy and Alzheimer's disease. Neurology
48: 27S-35S
[Abstract][Full Text]
Ho, T. W., Li, C. Y., Cornblath, D. R., Gao, C. Y., Asbury, A. K., Griffin, J. W., McKhann, G. M.
(1997). Patterns of recovery in the Guillain-Barre syndromes. Neurology
48: 695-700
[Abstract][Full Text]
Ho, T. W., Hsieh, S.-T., Nachamkin, I., Willison, H. J., Sheikh, K., Kiehlbauch, J., Flanigan, K., McArthur, J. C., Cornblath, D. R., McKhann, G. M., Griffin, J. W.
(1997). Motor nerve terminal degeneration provides a potential mechanism for rapid recovery in acute motor axonal neuropathy after campylobacter infection. Neurology
48: 717-724
[Abstract][Full Text]
Lippa, C. F., Smith, T. W., Saunders, A. M., Hulette, C., Pulaski-Salo, D., Roses, A. D.
(1997). Apolipoprotein E-epsilon 2 and Alzheimer's disease: Genotype influences pathologic phenotype. Neurology
48: 515-519
[Abstract][Full Text]
Rao, D.R.
(1997). Oral supplements to improve lactose digestion and tolerance / Aportes orales para mejorar la digestion y la tolerancia de la lactosa. Food Science and Technology International
3: 87-92
[Abstract]
Mojon, D. S., Kaufmann, P., Odel, J. G., Lincoff, N. S., Marquez-Fernandez, M., Santiesteban, R., Fuentes-Pelier, D., Hirano, M.
(1997). Clinical Course of a Cohort in the Cuban Epidemic Optic and Peripheral Neuropathy. Neurology
48: 19-22
[Abstract][Full Text]
Lederman, R. J., Wilbourn, A. J.
(1996). Postpartum neuralgic amyotrophy. Neurology
47: 1213-1219
[Abstract][Full Text]
Fisher, M., Garcia, J. H.
(1996). Evolving stroke and the ischemic penumbra. Neurology
47: 884-888
[Full Text]
Tarr, R., Taylor, C. L., Selman, W. R., Lewin, J. S., Landis, D.
(1996). Good clinical outcome in a patient with a large CT scan hypodensity treated with intra-arterial urokinase after an embolic stroke. Neurology
47: 1076-1078
[Abstract][Full Text]
Visser, L. H., van der Meche, F.G.A., Meulstee, J., Rothbarth, P., Jacobs, B. C., Schmitz, P. I.M., van Doorn, P. A.
(1996). Cytomegalovirus infection and Guillain-Barre syndrome: The clinical, electrophysiologic, and prognostic features. Neurology
47: 668-673
[Abstract][Full Text]
(1996). Practice Advisory: Thrombolytic therapy for acute ischemic stroke--Summary Statement. Neurology
47: 835-839
[Full Text]
Newman, N. J.
(1996). Optic neuropathy. Neurology
46: 315-322
[Full Text]
Medow, M. S., Sloan, H. R., Bayless, T. M., Paige, D. M., Bedine, M. S., Roberts, H.J., Morris, D. L., Fenster, D. L., Suarez, F. L., Savaiano, D. A., Levitt, M. D.
(1995). Lactose Intolerance. NEJM
333: 1358-1359
[Full Text]
(1995). Is Intolerance to Small Amounts of Lactose Real?. Journal Watch Dermatology
1995: 14-14
[Full Text]
(1995). IS INTOLERANCE TO SMALL AMOUNTS OF LACTOSE REAL?. JWatch General
1995: 1-1
[Full Text]
-galactosidase activities in Ugandans with lactase deficiency. Gastroenterology 1968;55:328-332. [Medline]
