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PubMed2005

Post-operative obesity and cachexia are risk factors for morbidity and mortality after heart transplant: multi-institutional study of post-operative weight change.

BACKGROUND: The relationship between post-heart transplant cachexia and obesity with subsequent morbidity and mortality has not yet been reported. Therefore, the purposes of this study were to: (1) describe change in body mass index (BMI) from before transplant through 5 years after transplant; (2) identify risk factors for increased BMI at 1 year post-transplant; and (3) determine whether post-transplant BMI is associated with post-transplant morbidity and mortality. METHODS: Patients (n = 3,540) were from a non-random sample having received a heart transplant between January 1, 1996 and December 31, 2001 at 33 institutions of the Cardiac Transplant Research Database (CTRD). Patients were divided into groups using cut-offs for categories of BMI. Data were assessed according to frequencies, measures of central tendency, Pearson correlations, chi-square tests, multiple regression and stratified actuarial analyses with log-rank tests for comparisons. The level of statistical significance was set at p = 0.05. RESULTS: The number of obese patients increased significantly from immediately before heart transplant to 5 years later (17% vs 38%) (p < 0.0001). Risk factors for increased BMI at 1 year after heart transplant (explaining 56% of variance) included increased BMI at transplant, younger age, black race, non-ischemic etiology of heart disease, Status I at time of transplant and non-use of mycophenolate mofetil. Patients who were underweight or obese at 1 year post-transplant were at greater risk for rejection over time than patients who were of normal weight or overweight (p = 0.009). CONCLUSIONS: Both demographic and clinical factors are related to increased BMI at 1 year after heart transplantation. Post-transplant cachexia and obesity are risk factors for poor clinical outcomes after heart transplantation.

Adolescent↗

PubMed1990

Evaluation of modified methods for determining skin irritation.

The premarket testing of household cleaning products for dermal irritancy is best achieved via human testing. Animal dermal irritation testing is generally limited to screening for possible dermal hazard of totally new or unique products or ingredients prior to human testing or to meeting regulatory requirements of government bodies. Alternatives to animal tests are being sought; however, until such time that these alternatives are identified, validated, and accepted by government bodies, the judicious use of animal testing remains a necessity. Modifications to standard animal skin irritation test procedures have been evaluated against human skin irritation results with the objective of defining one method that could be used in place of current standard procedures that differ slightly from one another, and thereby avoid excessive and redundant use of animals. Hill Top Chambers (19 mm) and standard gauze patches (U.S. Department of Transportation procedure) were used to obtain comparative irritation responses for 24 cleaning products, common caustics, and acids in rabbits and humans. Exposure times were 1 or 4 hr, and responses were graded over a 72-hr period. Results indicate that use of the Chamber offers the potential to (1) reduce the number of animals used for skin irritation screening (smaller group size and up to eight test substances/concentrations per animal); (2) eliminate the need for conducting multiple tests to satisfy different governmental requirements; and (3) reduce animal stress by reducing exposure times without compromising the value of the irritancy patch test as a screening tool. When animal data are required, it is suggested that the use of a Chamber and other modifications of traditional test procedures offers advantages that could result in using fewer animals and/or have less potential for producing unnecessarily severe responses in animals.

Animals↗

PubMed2003

Differences among forced-air warming systems with upper body blankets are small. A randomized trial for heat transfer in volunteers.

BACKGROUND: Forced-air warming is known as an effective procedure in prevention and treatment of perioperative hypothermia. Significant differences have been described between forced-air warming systems in combination with full body blankets. We investigated four forced-air warming systems in combination with upper body blankets for existing differences in heat transfer. METHODS: After approval of the local Ethics Committee and written informed consent, four forced-air warming systems combined with upper body blankets were investigated in a randomized cross-over trial on six healthy volunteers: (1) BairHugger trade mark 505 and Upper Body Blanket 520, Augustine Medical; (2) ThermaCare trade mark TC 3003, Gaymar trade mark and Optisan trade mark Upper Body Blanket, Brinkhaus; (3) WarmAir trade mark 134 and FilteredFlow trade mark Upper Body Blanket, CSZ; and (4) WarmTouch trade mark 5800 and CareDrape trade mark Upper Body Blanket, Mallinckrodt. Heat transfer from the blanket to the body surface was measured with 11 calibrated heat flux transducers (HFTs) with integrated thermistors on the upper body. Additionally, the blanket temperature was measured 1 cm above the HFT. After a preparation time of 60 min measurements were started for 20 min. Mean values were calculated over 20 min. The t-test for matched pairs with Bonferroni-Holm-correcture for multiple testing was used for statistical evaluation at a P-level of 0.05. The values are presented as mean+/-SD. RESULTS: The WarmTouch trade mark blower with the CareDrape trade mark blanket obtained the best heat flux (17.0+/-3.5 W). The BairHugger trade mark system gave the lowest heat transfer (8.1+/-1.1 W). The heat transfer of the ThermaCare trade mark system and WarmAir trade mark systems were intermediate with 14.3+/-2.1 W and 11.3+/-1.0 W. CONCLUSIONS: Based on an estimated heat loss from the covered area of 38 W the heat balance is changed by 46.1 W to 55 W by forced-air warming systems with upper body blankets. Although the differences in heat transfer are significant, the clinical relevance of this difference is small.

Adult↗

PubMed2002

Extracorporeal photochemotherapy--the Columbia Presbyterian experience.

BACKGROUND: Cutaneous T Cell Lymphoma (CTCL) is a lymphoma of skin homing usually CD4 + lymphocytes. There are numerous treatments available both for the early as well as the more advanced stages of the disease. Extracorporeal photochemotherapy is a well-accepted form of treating CTCL. The purpose of our study was to review the experience of treating 20 CTCL patients with extracorporeal photochemotherapy (ECP) at Columbia Presbyterian Medical Center over a seven-year period. METHODS: The study was conducted as a retrospective chart review of these 20 patients. Summarized demographic characteristics included age at diagnosis, gender, and race. We analyzed the overall response by categorizing patients as having complete response, partial response, stable disease, and progressive disease. We also analysed the predictive value for three factors: peripheral blood CD4 : CD8 (< 10, > 10), LDH level (normal, elevated), and erythrodermic status (erythrodermic or nonerythrodermic). The potential prognostic variables were evaluated for linear association with response using Mantel-Haenszel chi-square tests. All statistical tests were two-sided with alpha = 0.05. The tests were considered to be exploratory and no adjustments for multiple testing were made. RESULTS: There was a significant linear association between response and CD4 : CD8. Patients with a ratio < 10 were more likely to respond than patients with a ratio > 10. There was a marginally significant linear association between response and LDH level. Patients whose LDH was not elevated at the start of treatment, tended to have a better response to ECP compared to patients with an elevated LDH. There was a suggestion of an association between erythroderma and response although this was not statistically significant. The majority of patients with erythroderma were responders compared to the majority of non-erythrodermic patients who were non-responders. The treatment was well tolerated with minimal side-effects. CONCLUSION: Apparent predictors of good response to ECP include erythroderma, a relatively low (closer to normal) peripheral CD4 : CD8, and a normal LDH. This report confirms reports from other institutions indicating that CTCL patients who are erythrodermic with a relatively intact immune system are optimal candidates for ECP.

Adult↗

PubMed2003

Data storage and DNA banking for biomedical research: informed consent, confidentiality, quality issues, ownership, return of benefits. A professional perspective.

The purpose of this paper is to formulate a professional and scientific view on the social, ethical, and legal issues that impact on data storage and DNA banking practices for biomedical research in Europe. Many aspects have been considered, such as the requirements for data storage and DNA banking in the public and private sectors in Europe and the issues relating to DNA banking, that is to say the consent requirements for the banking and further uses of DNA samples, their control and ownership, and the return of benefit derived from DNA exploitation to the community. The methods comprise primarily the review of the existing professional guidelines, legal frameworks and other documents related to the data storage and DNA banking practices in public and private sectors in Europe. Then, the issues related to DNA banking were examined during an international workshop organized by the European Society of Human Genetics Public and Professional Policy Committee in Paris, France, 07-08, April, 2000. A total of 50 experts from 12 European countries attended this workshop. It came out that DNA banking for medical and research purposes is indispensable. It facilitates the constitution of large collections, sharing of samples, multiple testing on the same samples, and repeating testing over the years. However, banking organization is complex, requires multiple actors, and concerns are expressed in various countries. International standardization of ethical requirements and policies with regard to DNA banking has been recommended. Such standardization would facilitate a greater protection of individuals as well as future international cooperation in biomedical research.

Biomedical Research↗

PubMed2001

Associated positive patch test reactions to standard contact allergens.

BACKGROUND: Patch testing with a standard allergen series often yields positive reactions to more than 1 allergen in a patient. OBJECTIVE: To identify all significantly associated pairs of positive reactions and to assess their relation to the strength of the reactions and to the irritative potential of the allergens. METHODS: Based on the filed data of 57,822 patients, associations between positive reactions to 2 different allergens were quantified with odds ratios. Statistical methods included Fisher's exact test, the Bonferroni adjustment to account for the effect of multiple testing, and the Spearman rank correlation. RESULTS: Out of the 32,779 patients with complete readings of 24 standard allergens, 7,501 had shown more than 1 positive reaction. Statistically significant associations were detected for 166 out of the 276 possible different combinations of 2 distinct positive reactions, including combinations that had not been identified before. Patients with a strong reaction or a positive reaction to an allergen with a high irritative potential tended to have additional positive reactions to further allergens more often than others, but the number of significant associations was not dependent on these parameters. CONCLUSION: There are more significant associations that have to be taken into account for patch testing than has been known so far. Although irritation can favor a higher number of positive reactions, significant associations of positive reactions to distinct allergens are probably caused by other mechanisms that require further analyses.

Adult↗

PubMed1996

The range of normal.

One of the primary aspects of any test is its capacity to distinguish "normal" from "abnormal." However, the issue of what normal truly is remains complex. There are two categories: correlated normality and isolated normality. Each has numerous advantages and disadvantages, but the latter is much more common for defining normal. The method of establishing limits of normal varies depending on whether correlated or isolated normality is utilized. With correlated normality, the limits are dependent on whether the purpose of the test is discovery, exclusion, or confirmation. Isolated normality limits are frequently based on the consequences of being termed abnormal. It is imperative that normal limits be based on values of an appropriate reference group: the normal group should be healthy equivalents of the individual being tested. Finally, both intrapersonal and menstruational variations that result when multiple tests are performed on the same individual should be accounted for.

Diagnostic Tests, Routine↗

PubMed1999

Unusual haplotype structure at the proximal breakpoint of In(2L)t in a natural population of Drosophila melanogaster.

The existence of temporally stable frequency clines for In(2L)t in natural populations of Drosophila melanogaster suggests a role for selection in the maintenance of this polymorphism. We have collected nucleotide polymorphism data from the proximal breakpoint junction regions of In(2L)t to infer its evolutionary history. The finding of a novel LINE-like element near the In(2L)t breakpoint junction in sampled inverted chromosomes supports a transposable element-mediated origin for this inversion. An analysis of nucleotide variation in a Costa Rican population sample of standard and inverted chromosomes indicates a unique and relatively recent origin for In(2L)t. Additional In(2L)t alleles from three geographically diverse populations reveal no detectable geographic differentiation. Low levels of In(2L)t nucleotide polymorphism suggest a recent increase in the inversion's frequency in tropical populations. An unusual feature of our sample of standard alleles is a marked heterogeneity in levels of linkage disequilibrium among polymorphic sites across the breakpoint region. We introduce a test of neutral equilibrium haplotype structure that corrects both for multiple tests and for an arbitrarily chosen window size. It reveals that an approximately 1.4-kb region immediately spanning the breakpoint has fewer haplotypes than expected under the neutral model, given the expected level of recombination in this genomic region. Certain features of our data suggest that the unusual pattern in standard chromosomes is the product of selection rather than demography.

Animals↗

PubMed2005

Age- and gender-related test performance in community-dwelling adults.

OBJECTIVE: Interpretation of patient scores on functional tests is enhanced by an understanding of test performance in reference groups. The purpose of this study was to expand performance values, by age and gender, on balance tests [the Multi-Directional Reach (MDRT); Berg Balance (BBS); Sharpened Romberg, eyes open (SREO), eyes closed (SREC); Activities-Specific Balance Confidence (ABC)], and a general mobility test [Physical Performance Test, (PPT-7, PPT-9)]. The study also examined relationships between test performance and subject characteristics. DESIGN AND SUBJECTS: Eighty-three community-dwelling adults over 50 participated in the study and completed the 5 functional tests during one test session. Means, standard deviations, and confidence intervals were calculated for each of the tests. Multiple linear regression analysis was used to examine relationships between test scores and age, gender, height, and weight. RESULTS: Test performance is reported by gender,within 10-year age cohorts. Regression analysis showed that age contributed significantly to prediction of performance on all of the tests and gender contributed significantly to prediction of scores on the Berg, SREO, and SREC. CONCLUSIONS: Test performance values, in a sample of community-dwelling adults, is provided by age and gender cohorts to provide additional reference data that can be used by clinicians for comparison with client data. The small sample size for subjects over 80 years limits the reference value of data for this age group. In regression analyses, age and gender help predict outcomes on the dependent variables used in the study.

Activities of Daily Living↗

PubMed2003

The anticonvulsant effects of progesterone and 5alpha-dihydroprogesterone on amygdala-kindled seizures in rats.

PURPOSE: Progesterone has been shown to be anticonvulsant in several animal seizure models. The purpose of the present study was to investigate the anticonvulsant actions of progesterone and its primary metabolite 5alpha-dihydroprogesterone in the amygdala kindling model. METHODS: Female Wistar rats were implanted in the right basolateral amygdala with a long-term, bipolar electrode. The subjects were kindled to 30 stage 5 seizures and stability tested. Multiple doses of progesterone and 5alpha-dihydroprogesterone were then tested for anticonvulsant activity against focal electrographic and generalized convulsive kindled seizures. The time course of progesterone's anticonvulsant action also was examined. RESULTS: Progesterone had a median effective dose (ED50) of 103 mg/kg against generalized convulsions at 15 min after injection. Subjects were not sedated at the time of seizure testing, although sedation developed later (40-60 min after injection). In time-course experiments, it was found that 120 mg/kg of progesterone caused complete suppression of the generalized convulsion from 20 to 160 min after injection. Suppression of the focal discharge also was seen in some animals between 20 and 160 min. 5alpha-dihydroprogesterone had an ED50 of 2.9 mg/kg against generalized kindled convulsions and an ED50 of 4.3 mg/kg against focal afterdischarge 15 min after injection. 5alpha-dihydroprogesterone did not produce sedation 15 min after injection, or at any later time interval. CONCLUSIONS: Progesterone is anticonvulsant only at high doses when tested against amygdala kindled seizures. 5alpha-dihydroprogesterone is considerably more potent than progesterone. At low, nonsedative doses, it was effective against both the kindled amygdala focal afterdischarge and the generalized convulsion.

5-alpha-Dihydroprogesterone↗

PubMed2003

MR imaging features of primary sclerosing cholangitis: patterns of cirrhosis in relationship to clinical severity of disease.

PURPOSE: To evaluate the spectrum of magnetic resonance (MR) imaging appearances of the liver in primary sclerosing cholangitis (PSC) and to examine their correlation with clinical stage of disease. MATERIALS AND METHODS: Fifty-two patients (25 female, 27 male; mean age, 43 years; age range, 11-87 years) with PSC underwent nonenhanced and gadolinium-enhanced MR imaging. Two abdominal radiologists retrospectively reviewed all images (independently and then in consensus) for the imaging pattern of the liver parenchyma, presence and grade of intrahepatic biliary ductal dilatation, and presence of areas of parenchymal atrophy or abnormal signal intensity and/or gadolinium enhancement. Imaging findings were correlated with Child class, Child-Turcotte-Pugh score, and Mayo end-stage liver disease (MELD) score. Statistical analyses (kappa scoring for interobserver agreement, McNemar test, Mann-Whitney U test, multiple regression analysis, Spearman correlation) were performed. RESULTS: Of 52 patients, seven (13%) had no imaging findings of cirrhosis, 17 (33%) had a diffuse pattern of cirrhosis, and 28 (54%) had a large macronodular pattern (with nodules >or=3 cm) (kappa = 0.84). Intrahepatic biliary ductal dilatation was observed in 44 (85%) patients and was general in 18 (35%) and segmental in 26 (50%). Peripheral wedge-shaped areas of parenchyma were observed with atrophy in 23 (44%) and 25 (48%) patients by the two readers (kappa = 0.76) and without atrophy in 18 (35%) patients by both readers (kappa = 1.00). No correlation was found between imaging findings and clinical scores (P >.05, multiple regression analysis; P =.25-.75, Mann-Whitney U test; Spearman correlation coefficients between -0.33 and 0.33). CONCLUSION: The spectrum of MR imaging appearances of PSC is diverse and comprises distinct patterns that do not appear to correlate with severity of disease. Large regenerative nodules are a frequent finding and may help to establish the diagnosis.

Adolescent↗

PubMedDate not supplied

What white blood cell count should prompt antibiotic treatment in a febrile child? Tutorial on the importance of disease likelihood to the interpretation of diagnostic tests.

Most diagnostic tests are not dichotomous (negative or positive) but, rather, have a range of possible results (very negative to very positive). If the pretest probability of disease is high, the test result that prompts treatment should be any value that is even mildly positive. If the pretest probability of disease is low, the test result needed to justify treatment should be very positive. Simple decision rules that fix the cutpoint separating positive from negative test results do not take into account the individual patient's pretest probability of disease. Allowing the cutpoint to change with the pretest probability of disease increases the value of the test. This is primarily an issue when the pretest probability of disease varies widely between patients and depends on characteristics that are not measured by the test. It remains an issue for decision rules based on multiple test results if these rules fail to account for important determinants of patient-specific risk. This tutorial demonstrates how the value of a diagnostic test depends on the ability to vary the cutpoint, using as an example the white blood cell count in febrile children at risk for bacteremia.

Anti-Bacterial Agents↗

PubMed2003

Sex genes for genomic analysis in human brain: internal controls for comparison of probe level data extraction.

BACKGROUND: Genomic studies of complex tissues pose unique analytical challenges for assessment of data quality, performance of statistical methods used for data extraction, and detection of differentially expressed genes. Ideally, to assess the accuracy of gene expression analysis methods, one needs a set of genes which are known to be differentially expressed in the samples and which can be used as a "gold standard". We introduce the idea of using sex-chromosome genes as an alternative to spiked-in control genes or simulations for assessment of microarray data and analysis methods. RESULTS: Expression of sex-chromosome genes were used as true internal biological controls to compare alternate probe-level data extraction algorithms (Microarray Suite 5.0 [MAS5.0], Model Based Expression Index [MBEI] and Robust Multi-array Average [RMA]), to assess microarray data quality and to establish some statistical guidelines for analyzing large-scale gene expression. These approaches were implemented on a large new dataset of human brain samples. RMA-generated gene expression values were markedly less variable and more reliable than MAS5.0 and MBEI-derived values. A statistical technique controlling the false discovery rate was applied to adjust for multiple testing, as an alternative to the Bonferroni method, and showed no evidence of false negative results. Fourteen probesets, representing nine Y- and two X-chromosome linked genes, displayed significant sex differences in brain prefrontal cortex gene expression. CONCLUSION: In this study, we have demonstrated the use of sex genes as true biological internal controls for genomic analysis of complex tissues, and suggested analytical guidelines for testing alternate oligonucleotide microarray data extraction protocols and for adjusting multiple statistical analysis of differentially expressed genes. Our results also provided evidence for sex differences in gene expression in the brain prefrontal cortex, supporting the notion of a putative direct role of sex-chromosome genes in differentiation and maintenance of sexual dimorphism of the central nervous system. Importantly, these analytical approaches are applicable to all microarray studies that include male and female human or animal subjects.

Algorithms↗

PubMed1999

Effects of anomalous language representation on neuropsychological performance in temporal lobe epilepsy.

OBJECTIVE: To examine the effects of anomalous language representation (i.e., mixed- and right-cerebral dominant) on neuropsychological performance. BACKGROUND: Right cerebral language dominance resulting from early cerebral injury is associated with relatively preserved language function with decreased visuospatial ability. However, previous reports of this phenomenon have examined patients with relatively large cerebral injuries (e.g., infantile hemiplegia) or limited sample sizes. METHODS: A total of 561 patients with complex partial seizures of left temporal lobe origin were studied. Patients were classified into left (n = 455), bilateral (n = 58), and right (n = 48) language dominant groups based on Wada testing. RESULTS: Right language dominant patients performed more poorly on multiple tests of visuospatial function, including Performance IQ (PIQ), than did left language patients. No significant group differences were detected for measures of language or general verbal function. The effects of bilateral language on PIQ differed according to handedness. Lowered PIQ was present in the bilateral nondextral group but not for bilateral dextral patients, and this pattern was observed with other visuospatial measures. CONCLUSIONS: In patients with relatively small lesions restricted to the left mesial temporal lobe, a shift in language dominance to the right hemisphere is associated with decreased visuospatial functions but preserved verbal abilities. Nondextral patients with bilateral language representation also displayed decreased visuospatial performance, although dextral patients with bilateral language did not.

Adult↗

PubMedDate not supplied

Antiplatelet therapy and carotid plaque hemorrhage and its clinical implications.

UNLABELLED: One hundred and fifty-four carotid endarterectomy plaques were studied to determine the correlation of multiple intraplaque hemorrhages to (1) carotid symptoms, (2) the percentage of carotid stenosis, and (3) the preoperative antiplatelet therapy. The plaques were evaluated histopathologically for the presence of multiple hemorrhages. The data were analyzed using the chi 2 test. Multiple hemorrhages were noted in 60.4% and single or not hemorrhage in 39.6% of patients with hemispheric symptoms. In patients with nonhemispheric symptoms, 9.4% had multiple hemorrhages and 90.6% has single or no hemorrhages; 89.4% plaques with multiple hemorrhages had stenosis greater than 75% in contrast to 37.5% in plaques with single or no hemorrhage; and 62.5% with single or no hemorrhage had stenosis of less than 75% (p less than 0.001). In patients receiving antiplatelet therapy, 80.1% of plaques with multiple hemorrhages were removed, in contrast to 19.7% from patients not receiving antiplatelets (p less than 0.001). IN CONCLUSION: Multiple intraplaque hemorrhages were seen more often in patients with hemispheric symptoms and are associated with more critical carotid stenosis. Preoperative antiplatelet therapy increases the incidence of repeated plaque hemorrhages; therefore, we question the validity of this therapy in certain patients with carotid disease.

Arterial Occlusive Diseases↗

PubMed1995

Probability revision.

This article examines the principles of probability revision and four different ways of obtaining post-test probabilities: the hypothetical cohort method, likelihood ratios and odds, the Nomogram, and precalculation. The authors then show where pre-test probabilities can be obtained, and then how to interpret multiple tests.

Coronary Disease↗

PubMed2006

Fine mapping by genetic association implicates the chromosome 1q23.3 gene UHMK1, encoding a serine/threonine protein kinase, as a novel schizophrenia susceptibility gene.

BACKGROUND: Linkage studies by us and others have confirmed that chromosome 1q23.3 is a susceptibility locus for schizophrenia. Based on this information, several research groups have published evidence that markers within both the RGS4 and CAPON genes, which are 700 kb apart, independently showed allelic association with schizophrenia. Tests of allelic association with both of these genes in our case control sample were negative. Therefore, we carried out further fine mapping between the RGS4 and CAPON genes. METHODS: Twenty-nine SNP and microsatellite markers in the 1q23.3 region were genotyped in the United Kingdom based sample of 450 cases and 450 supernormal control subjects. RESULTS: We detected positive allelic association after the eighth marker was genotyped and found that three microsatellite markers (p = .011, p = .014, p = .049) and two SNPs (p = .004, p = .043) localized in the 700 kb region between the RGS4 and CAPON genes, within the UHMK1 gene, were associated with schizophrenia. Tests of significance for marker rs10494370 remained significant following Bonferroni correction (alpha = .006) for multiple tests. Tests of haplotypic association were also significant for UHMK1 (p = .009) using empirical permutation tests, which make it unnecessary to further correct for both multiple alleles and multiple markers. CONCLUSIONS: These results provide preliminary evidence that the UHMK1 gene increases susceptibility to schizophrenia. Further confirmation in adequately powered samples is needed. UHMK1 is a serine threonine kinase nuclear protein and is highly expressed in regions of the brain implicated in schizophrenia.

Adaptor Proteins, Signal Transducing↗

PubMedDate not supplied

Evaluation of multiple-frequency rotatory testing in patients with peripheral labyrinthine weakness.

Multiple-frequency rotatory testing was performed in a series of 12 normal subjects and 27 patients who had significant labyrinthine paralysis. Fourteen of the patients had total loss of labyrinthine function. Phase leads of the responses were much greater in the lower-frequency measurements and measured gains of the responses to ampullopetal stimulation were qualitatively greater than those of the responses to ampullofugal stimulation. However, many patients' responses continued to fall within the normal range because of the large variability of the responses of normal subjects. The value of rotatory testing in clinical diagnosis is discussed.

Caloric Tests↗