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Memory assessment during the intracarotid amobarbital procedure: influence of injection order.

OBJECTIVE: To analyze, in patients with unilateral regional epilepsy, the influence of intracarotid amobarbital injection order on the level of recognition memory, with both injections performed within approximately half an hour, when the order was varied by a first injection into either the epileptogenic or the nonepileptogenic hemisphere. METHODS: Of a series of 74 consecutive intracarotid amobarbital procedures (IAP), 61 valid bilateral tests were extracted for analysis. The protocol was changed from a congruent sequence (epileptogenic hemisphere injected first; n = 32) to an incongruent sequence (nonepileptogenic hemisphere injected first; n = 29). Memory was quantified by the percentage of presented items recognized before the recovery of full motor power (corrected for guessing). RESULTS: The congruent group showed a poorer recognition percentage after injection into the nonepileptogenic hemisphere than after injection into the epileptogenic hemisphere. The incongruent group had a similar recognition percentage after both injections. This was especially apparent in patients with a right epileptogenic hemisphere. CONCLUSIONS: The commonly used congruent injection order leads to a poorer recognition by the epileptogenic hemisphere than the nonepileptogenic hemisphere. This relation cannot be found with an incongruent sequence. The results raise doubts about the internal validity of the IAP in describing isolated hemispheric memory functions.

Adult↗

Prevalence of asthma, rhinitis and eczema in children from the Bangkok area using the ISAAC (International Study for Asthma and Allergy in Children) questionnaires.

Within the past three decades, there has been a rising trend for prevalences of asthma and allergic diseases worldwide, particularly from developed and industrializing countries. In Thailand, limited studies on epidemiology of atopic diseases have indicated relatively low prevalences of these conditions among the Thais. Recently, a standardized phase I questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC) has been developed to study and to compare geographical and temporal trend for prevalences of asthma, allergic rhinitis and eczema in children. The objectives of phase I ISAAC study in Thailand are to study prevalence of the three most common allergic diseases i.e. asthma, allergic rhinitis and eczema among Thai children of the two age groups (i.e., 6-7 and 13-14 years) living in the Bangkok metropolitan area and to collect basic epidemiologic data of these diseases among these children. The Thai translated version of phase I ISAAC questionnaires was administered to Thai children of the two age groups as above. Questionnaires were answered by parents of younger children, whereas, they were self-administered by 13-14 years old children. In addition, the validated international video questionnaires were used with older children. Fourteen primary schools and 13 secondary schools were randomly selected to cover the entire Bangkok metropolitan area. A total of 7341 questionnaires were eligible for the analysis (3628 from the younger age group and 3713 from the older age group). Data were entered and analysed by the Epi-Info program. The cumulative and 12 month period prevalences of the three conditions for all children were as follows; wheezing, 18.3 per cent, 12.7 per cent; rhinitis, 44.2 per cent, 38.7 per cent; and eczema, 15.4 per cent, 14.0 per cent, respectively. The period prevalence of wheezing for older children (13.6%) was higher than for younger children (11.7%). Prevalences of severe wheeze and exercise wheeze were more common among older children (4.0% and 15.7%). Both age groups reported high percentages for night cough (23.6% and 28.6%). A significantly large number of children from both groups reported symptoms of rhinitis with the majority indicating that symptoms were severe enough to limit their daily activities. Nevertheless, when confined only to those with eye symptoms, the prevalence decreased to 13.1 per cent. Eczema, in contrast to the other two conditions, occurred more frequently among younger children than among older children (period prevalence of 16% vs 9.1%). The rash was of a relatively mild nature since 77 per cent of children reporting symptoms indicated that the rash had cleared within the past 12 months. Allergic conditions are very common among children residing in Bangkok. Compared to the last survey in 1990, the period prevalence of wheezing has increased 4 fold, allergic rhinitis has increased nearly 3 fold whereas, eczema has remained stable. A large number of children in Bangkok are suffering from rhinitis symptoms. Results of this phase I ISAAC study indicate that allergic diseases are perhaps the most common childhood diseases in Thailand and could lead to a substantial economical loss for the country. There is an urgent need for an in-depth study to define epidemiological factors responsible for this increase.

Adolescent↗

New aspects in the staging of lung cancer. Prospective validation of the International Union Against Cancer TNM classification.

BACKGROUND AND METHODS: To validate the new TNM definitions for lung cancer (International Union Against Cancer [UICC] TNM classification, 4th edition, 1987), the data of 3823 patients were analyzed prospectively in terms of concordance between clinical (TNM) and pathologically confirmed classification (pTNM), the value of the various diagnostic techniques in estimating the pathologically confirmed classification, and the prognostic relevance of the new TNM definitions. RESULTS: With regard to the primary tumor (T), clinical and pathologic classifications were identical in 63%; with regard to lymph node involvement (N), the agreement was 47%; for distant metastasis agreement occurred in 91% of cases and for the stages it occurred in 56%. As to the primary tumor (T), the accuracy of radiography (59%) was nearly identical to that of computed tomography (CT) (58%). Both techniques were less precise in determining the extent of lymph node involvement (CT, correct assessments in 50%; radiography, correct assessments in 43%). The statistically significant differences in the prognosis for the T, N, and M categories and for the stages and the categories of the new R classification could be confirmed. Allowance should be made for the different prognosis between T1N0M0 and T2N0M0 by the new Substages IA and Ib of Stage I. CONCLUSIONS: By the new TNM definitions for bronchus carcinoma, international conformity became feasible and practical, and the improvement of its prognostic relevance provided a more reliable basis for establishing guidelines for individual oncologic concepts.

Bronchial Neoplasms↗

Increasing response rates in telephone surveys: a randomized trial.

BACKGROUND: Sampling frames and mode of contact and administration of questionnaires are important factors contributing to response rates and selection bias in population-based research. The purpose of this paper is to evaluate whether contact by mail before contact by telephone increases response rate, and to assess the concurrent validity of telephone surveys for collecting health research and service data. METHODS: Two thousand households were randomly selected from electronic white pages. Half were randomly allocated to receive or not to receive an explanatory letter before telephone contact. Interviewers were blinded to whether a household received a letter. Respondents aged 18 years or over were randomly selected from within each household using a Kish grid and interviewed by telephone. RESULTS: The overall response rate was 68 per cent [confidence interval (CI) 66-70]. The response rate of those who received the letter was 76 per cent (CI 73-79), and of those who did not receive the letter was 60 per cent (CI 56-63). Use of the Kish grid to select randomly a respondent decreased the response rate by less than 10 per cent. The internal validity of the data was as follows: in a 10 per cent sub-sample, the Kish grid had been correctly applied in 93 per cent of households, and in 99 per cent of households the exclusion criteria had been correctly adhered to. The external validity was as follows: comparisons with data obtained from the same reference population using similar instruments administered face-to-face revealed no meaningful or significant differences in population estimates. CONCLUSIONS: Mail-out before telephone contact greatly increases response rates at low cost. Telephone surveys can yield valid, useful data for health research and service evaluation.

Adult↗

The addition of interleukin-6 soluble receptor and transforming growth factor beta1 improves a preoperative nomogram for predicting biochemical progression in patients with clinically localized prostate cancer.

PURPOSE: Several preoperative prostate cancer nomograms have been developed that predict risk of progression using pretreatment prostate-specific antigen (PSA) level, clinical stage, and biopsy Gleason grade. We describe the development and performance of a new nomogram. The nomogram adds new markers to the standard clinical predictors that reflect the biologic behavior of prostate cancer: pretreatment plasma levels of interleukin-6 soluble receptor (IL6SR) and transforming growth factor beta1 (TGF-beta1). PATIENTS AND METHODS: Between November 7, 1994 and December 22, 1997, 714 patients with stage cT1c to cT3a prostate cancer and no prior therapy were treated with radical prostatectomy at the Methodist Hospital, Houston TX. Plasma levels of IL6SR and TGF-beta1 were measured in banked preoperative plasma. With these data, a nomogram was developed to predict the probability of PSA progression within 5 years of surgery. The nomogram was validated with bootstrapping to assess its discrimination and calibration performance. RESULTS: In the multivariable Cox model, PSA (P =.004), IL6SR (P <.001), TGF-beta1 (P <.001), primary Gleason grade (P <.002), and secondary Gleason grade (P =.029) were associated with PSA progression, whereas clinical stage (P =.696) was not. The nomogram seemed to be well calibrated and had a bootstrap-corrected area under the receiver operating characteristic curve (ie, concordance index) of 0.83. For comparison, a nomogram that omitted IL6SR and TGF-beta1 achieved a concordance index of only 0.75. CONCLUSION: We found that pretreatment plasma levels of IL6SR and TGF-beta1 improved the ability to predict biochemical progression by a prognostically substantial margin. A nomogram including the pretreatment levels of these molecular markers, along with standard clinical markers, has been developed and internally validated.

Adult↗

Validation of an ELISA test kit for the detection of total aflatoxins in grain and grain products by comparison with HPLC.

An ELISA Microtiter Plate, Total Aflatoxin Test called AgraQuant was validated to measure total aflatoxins in a range from 4 to 40 ppb in corn, corn meal, corn gluten feed, corn gluten meal, corn germ meal, corn/soy blend, popcorn, sorghum, wheat, milled rice, soybeans, peanuts and cottonseed. The test is performed as a solid phase direct competitive ELISA using a horseradish peroxidase conjugate as the competing, measurable entity. For the test method, aflatoxins are extracted from ground samples with 70% methanol and sample extracts plus conjugate are mixed and then added to the antibody-coated microwells. After 15 min incubation at room temperature, the plate is washed and enzyme substrate is added and allowed to incubate for an additional 5 min. Stop solution is then added and the intensity of the resulting yellow color is measured optically with a microplate reader at 450 nm. Results obtained from internal validation studies assessing accelerated stability indicate a minimum of 1 year shelf life for the kits; accuracy and precision are comparable to HPLC in the range of 0-320 ppb and limit of detection in corn is 2.5 ppb. Comparison of the method to HPLC, ability to detect individual aflatoxins and ruggedness of the test kits at 18-30 degrees C determined this test to be rugged, sensitive, accurate, precise and effective comparable to HPLC for measuring total aflatoxins ranging from 4 to 40 ppb in the commodities evaluated.

Aflatoxins↗

Remission and active disease in rheumatoid arthritis: defining criteria for disease activity states.

OBJECTIVE: Several composite scores are available to assess the activity of rheumatoid arthritis (RA). Criteria for remission and active RA based on these continuous scores are important for use in clinical practice and clinical trials. We aimed to reevaluate or to define such criteria for the Disease Activity Score in 28 joints (DAS28) and the Simplified Disease Activity Index (SDAI). METHODS: We sampled patient profiles from an observational RA database that included clinical and laboratory variables. Thirty-five rheumatology experts classified these profiles into 1 of 4 categories: remission, low, moderate, or high disease activity. Cutoff values were estimated by mapping scores on the DAS28 and SDAI to these ratings, and analyses of agreement (kappa statistics) and a diagnostic testing approach (receiver operating characteristic curves) were used to validate the estimates. The final criteria were validated using 2 observational cohorts (a routine cohort of 767 patients and an inception cohort of 91 patients). RESULTS: Results from the 3 analyses were very similar and were integrated. The criteria for separating remission, low, moderate, and high disease activity based on the SDAI were scores of 3.3, 11, and 26, respectively; those based on the DAS28 were scores of 2.4, 3.6, 5.5, respectively. In the routine cohort, these cutoff values showed substantial agreement (weighed kappa = 0.70) and discriminated between groups of patients with clearly different functional capacities (P < 0.001). In the inception cohort, these cutoff scores differentiated responders (those with a 20% response on the American College of Rheumatology improvement criteria) from nonresponders (P < 0.01), as well as patients with and without radiologic progression (P < 0.05). CONCLUSION: New criteria for levels of RA disease activity were determined and internally validated. These criteria, which are based on current and explicit expert judgment, are valuable in this era of rapidly advancing therapeutic approaches.

Arthritis, Rheumatoid↗

A methodological basis for improving the reliability of measurements of opiate abstinence responses in the guinea-pig ileum made dependent in vitro.

The purpose of this study was to find a neurogenic response of the isolated guinea-pig ileum that could serve as an internal standard to normalize abstinence responses, which are also neurogenic, during opiate dependence produced in vitro. The internal standard is required because of baseline variability in these responses of the ileum and a time-dependent decay in neuroeffector responsiveness with prolonged incubation. Systematic studies were made of the variability in the responses to neurogenic stimulation by 1) electrical field stimulation, 2) nicotinic stimulation, and 3) precipitation of opiate abstinence with opiate antagonists as well as studies of the time-dependent decay in responsiveness with prolonged incubation. The three neurogenic responses show covariation but the best correlation is found between the nicotinic and the abstinence responses. The nicotinic system presents a pharmacological sensitivity to specific acute opiate action and also shows an improving correlation with abstinence which develops with the progression of dependence. This correlation tends to a direct linear relation with a slope approaching 1.0. The nicotinic response of the ileum seems to be a valid internal control to normalize its abstinence responses after incubation with opiates for different intervals of time.

Animals↗

Validity of the 24-hr. recall. Analysis of data obtained from elderly subjects.

Tests of the validity of the 24-hr. dietary recall were done by comparing actual with recalled intakes for eight nutrients and the MAR (mean adequacy ratio) for a sample of seventy-six subjects age sixty years or older. Validity was tested by using paired-t tests and regression analysis. In the paired-t test, no significant difference was found between the mean recalled and the mean actual intake of nutrients, with the exception of calories. Using regression analysis, results indicated that for three of the eight nutrients considered (calories, protein, and vitamin A), small intakes tend to be over-reported and large intakes under-reported (p less than .05). Thus, for these three nutrients, the recall seems to be statistically conservative for group comparisons; it would seldom, if ever, indicate a difference in intake where no difference exists. But, it could yield a false negative, i.e., an indication of no significant difference, when, in fact, a difference does exist. Clearly, more research is needed, both to replicate this study and to develop techniques with greater internal validity for comparing the dietary intakes of groups.

Aged↗

A measure of critical care nurses' post-code stress.

AIM: The purpose of this research was to develop an instrument to measure critical care nurses' post-code stress and then to examine the psychometric properties. BACKGROUND: Critical care nurses experience stress from multiple sources. One source of stress may arise from participation in resuscitation attempts and this has been labelled post-code stress; however, no means exist for measuring this source of stress. DESIGN/METHOD: In phase 1, 47 items were developed and submitted to a panel of experts for content validity. Based on content experts' ratings, 20 items were retained for phase 2 instrument testing. To test the instrument, a convenience sample of critical care nurses was obtained from four institutions in north-eastern United States. Each nurse received the Post-Code Stress Scale and completed it anonymously. A subsample completed the Post-Code Stress Scale a second time to assess stability reliability. The Nursing Stress Scale was also administered to assess construct validity. RESULTS/FINDINGS: An exploratory principal components factor analysis with varimax rotation suggested five dimensions to post-code stress. These five dimensions accounted for 66% of the variance and indicated that stress arose from feeling discomposed, oppressed, uncertain, burdened and morally conflicted. The Pearson product moment correlation between the Post-Code Stress Scale and the Nursing Stress Scale was 0.46, providing preliminary evidence of construct validity. Internal consistency reliability estimates for the five-factor subscales ranged from 0.57 to 0.77 with only one factor being <0.70. The internal consistency reliability estimate for the final 14 items on the scale was 0.79. CONCLUSIONS: The instrument shows promise as a measure of post-code stress based on the evidence obtained in this study; however, further psychometric testing is warranted.

Adult↗

Validity of pelvic autonomic nerve stimulation with intraoperative monitoring of bladder function following total mesorectal excision for rectal cancer.

PURPOSE: This prospective study was designed to clarify whether the results of the intraoperative stimulation of parasympathetic pelvic nerves performed in 31 patients after mesorectal excision for rectal carcinoma allowed predictions in terms of the postoperative bladder function of the patients. METHODS: After monopolar stimulation of the splanchnic pelvic nerves using a constant voltage stimulator (Screener 3625), intravesical pressure increase was measured manometrically. The results were related to the postoperative residual urine volume, requirement of recatheterization and long-term catheterization, just as to the results of the validated International Prostatic Symptom Scores and the Quality of Life Index caused by urinary symptoms. The median follow-up period was nine (range, 2-14) months. RESULTS: Parasympathetic nerve stimulation was performed at 61 sites and results in intravesical pressure increase up to 6 cm water column in median. In 11 patients (33.3 percent), a negative test result was achieved: 5 with unilateral and 6 with bilateral pressure increases of < or = 2 cm water column. Recatheterization was necessary in four patients, and all of them showed negative neuromonitoring results. Two of these patients were discharged with an in situ urinary bladder catheter. Postoperative increased residual urine volumes (> or =100 ml) resulted more frequently in the group with negative test results (63.6 vs. 21.1 percent; P = 0.047), and the International Prostatic Symptom Score and Quality of Life Index showed the worst results (9.9 +/- 6.7 vs. 3 +/- 4.9, P = 0.021; 2.4 +/- 1.7 vs. 0.7 +/- 1.3, P = 0.021). CONCLUSIONS: Intraoperative neurostimulation and manometric measurement of bladder pressure may contribute to the identification of parasympathetic pelvic nerves during total mesorectal excision. This method is suitable for intraoperative recording of nerve preservation and therefore associated with postoperative bladder function.

Adult↗

Development and validation of a model to diagnose cirrhosis in patients with hepatitis C.

OBJECTIVE: Although noninvasive markers predictive of cirrhosis in patients with chronic hepatitis C have been examined, none has proved sufficiently accurate for clinical use. The aim of this study was to develop an accurate model that can be easily used by clinicians to predict the probability of cirrhosis in hepatitis C patients from readily available clinical and laboratory information. METHODS: We identified 264 consecutive patients with established chronic hepatitis C infection and extracted multiple physical examination and biochemical variables (recorded before liver biopsy). Similar data were extracted from charts at another hospital. RESULTS: Logistic regression identified the following independent predictors of cirrhosis: platelet count < or = 140,000/ mm3, spider nevi, AST > 40 IU/L, and male gender. Male and female patients with normal values for platelet count and AST and no spider nevi had low probabilities of cirrhosis: 1.8% (95% CI = 0.4-7) and 0.03% (95% CI = 0.003-0.04), respectively. Male patients with abnormal values on all three other predictors had a probability of cirrhosis of 99.8% (95% CI = 98.7-100). Over 48% of study patients had a low (< or = 1.8%) or a very high (> or = 99.8%) predicted probability of cirrhosis. The model had area under the receiver operating characteristic curve of 0.938 (95% CI = 0.91-0.97) and 93.4% in an internal validation. The model accurately distinguished patients with and without cirrhosis (area under the receiver operating characteristic curve = 93.3%) in 102 hepatitis C patients from another hospital. CONCLUSIONS: In patients with hepatitis C, four readily available variables together predict cirrhosis accurately. Successful validation in hepatitis C patients at another hospital with lower prevalence of cirrhosis suggests this model's potential for broad applicability.

Adult↗

Developing a measure of attitudes: the holistic complementary and alternative medicine questionnaire.

We have developed an 11-item scale, the Holistic Complementary and Alternative Medicine Questionnaire (HCAMQ). Six of the HCAMQ items relate to beliefs about the scientific validity of complementary and alternative medicine (CAM), and five to beliefs about holistic health (HH). The HCAMQ was completed by 50 patients attending a CAM clinic and 50 attending rheumatology outpatients; the former completed it twice. Factor analysis (oblique rotation) showed that the CAM and HH items measured distinct but related constructs. The HCAMQ has good test retest reliability (r=0.86, 0.82 and 0.77 for the total, CAM subscale and HH subscale, respectively). The individuals attending CAM clinics were significantly more positive on the CAM but not the HH subscale of the HCAMQ and also used less antibiotics than those attending rheumatology outpatients. Positivity towards CAM on the total HCAMQ and subscales was significantly associated with lower age, increased vitamin use, reduced painkiller use, and, other than on the HH subscale, less antibiotic use. The reason why the HH subscale failed to distinguish between the two patient groups or predict less antibiotic use is unknown. The HCAMQ appears to have good internal validity, but its external validity remains to be established.

Age Factors↗

Quality of dental implants.

BACKGROUND: Clinicians need quality research data to decide which dental implant should be selected for patient treatment. AIM(S)/OBJECTIVE(S): To present the scientific evidence for claims of relationship between characteristics of dental implants and clinical performance. STUDY DESIGN: Systematic search of promotional material and Internet sites to find claims of implant superiority related to specific characteristics of the implant, and of the dental research literature to find scientific support for the claims. MAIN OUTCOME MEASURES: Critical appraisal of the research documentation to establish the scientific external and internal validity as a basis for the likelihood of reported treatment outcomes as a function of implant characteristics. RESULTS: More than 220 implant brands have been identified, produced by about 80 manufacturers. The implants are made from different materials, undergo different surface treatments and come in different shapes, lengths, widths and forms. The dentist can in theory choose among more than 2,000 implants in a given patient treatment situation. Implants made from titanium and titanium alloys appear to perform well clinically in properly surgically prepared bone, regardless of small variations of shapes and forms. Various surface treatments are currently being developed to improve the capacity of a more rapid anchorage of the implant into bone. A substantial number of claims made by different manufacturers on alleged superiority due to design characteristics are not based on sound and long-term clinical scientific research. Implants are, in some parts of the world, manufactured and sold with no demonstration of adherence to any international standards. CONCLUSIONS: The scientific literature does not provide any clear directives to claims of alleged benefits of specific morphological characteristics of dental implants.

Clinical Trials as Topic↗

Assessing the validity of the endoscopic shunt insertion trial: did surgical experience affect the results?

OBJECT: Most surgical procedures are associated with a learning curve in which the success rate is lower early in the experience before mistakes have been identified and modifications made to the procedure. Negative results obtained early in a trial's learning curve may be a matter of timing rather than a reflection of the procedure's effectiveness. The recently published results of the Endoscopic Shunt Insertion Trial (ESIT) represent the notion that endoscopically placed shunts were no more likely to survive than conventionally placed shunts. This negative result may be due to inexperience in performing endoscopic surgeries. METHODS: . Surgical experience was assessed in two ways. Shunt survival rates were compared between cases treated endoscopically in the 1st and last years of the ESIT. The effect of center volume was evaluated using a Cox proportional hazard model in which the following variables were analyzed: age at registration, the diagnosis of myelomeningocele, head size, method of shunt placement (endoscopic compared with conventional), and center volume. There was no difference in survival (endurance) of the shunt between patients enrolled in the 1st and last years (log rank = 0.08, p = 0.77). Likewise, no variable in the Cox multivariate model, including center volume, was a significant factor in predicting shunt survival. CONCLUSIONS: The primary result of the ESIT was found to be internally valid. The fact that endoscopic shunt placement did not benefit patients evaluated in the study was not due to early timing of the trial. Any learning curve among the participating surgeons did not adversely affect the results.

Cerebrospinal Fluid Shunts↗

Transportation, stress, and community psychology.

Conditions of transportation were investigated as sources of psychological stress as they affect the physiology, task performance, and mood of commuters. Participants in the study were 100 employees of industrial firms. Traffic congestion was construed as a behavioral constraint in terms of the concept of impedance which is defined by the parameters of distance and time. It was expected that the effects of impedance would be mediated by personality factors, such as locus of control. Multivariate tests of the internal validity of the impedance factor were significant. However, significant main effects for impedance were obtained only for mood and residential adaptation. The predicted interactions of impedance with locus of control were obtained across task performance indices. In multiple regression analyses, the distance and speed of the commute to work were found to account for significant proportions of variation in blood pressure, while several indices of personal control had significant regression effects on the task measures. The implications of the results for research in community psychology are discussed.

Adult↗

Epidermal nerve fiber density: normative reference range and diagnostic efficiency.

BACKGROUND: The sensitivity of neuron-specific antibodies permit the identification of the small unmyelinated nerve fibers within the skin. OBJECTIVES: To develop a reference range of epidermal nerve fiber density in humans, and to evaluate their diagnostic efficiency for sensory neuropathies. METHODS: Ninety-eight normal controls (age range, 13-82 years) were examined with both directed neurologic examinations and quantitative sensory testing. The diagnostic utility was examined in 20 patients with sensory neuropathies. Each subject had 2 punch biopsies performed at each site in the thigh and distal part of the leg (total of 392 biopsies). After formalin fixation, 50-microm-thick free-floating sections were stained with a polyclonal antibody to neuron-specific ubiquitin hydrolase, anti-protein gene product 9.5. We enumerated intraepidermal nerve fibers per millimeter to derive a "linear density." The linear density technique was validated against a stereological technique that used the fractionator to measure the total length of intraepidermal nerve fibers per 3-mm punch. RESULTS: The biopsy technique was well tolerated, with no notable complications. The linear density quantitation was rapid and had high intraobserver and interobserver reliability. We determined that the density of intraepidermal fibers in normal controls was 21.1+/-10.4 per millimeter (mean +/- SD) in the thigh (fifth percentile, 5.2 per millimeter), and was 13.8+/-6.7 per millimeter at the distal part of the leg (fifth percentile, 3.8 per millimeter). Significantly higher intraepidermal fiber densities were seen in the youngest group (P = .004), and we observed no significant effect of race, sex, height, or weight. The density at the thigh was significantly correlated with that at the distal part of the leg (P = .01) and was consistently higher by about 60%, a reflection of the normal proximal-distal gradient. The results obtained with stereology and the linear density correlated significantly (P=.001), providing internal validation for the technique. Epidermal nerve fiber density was significantly reduced (P = .001) in patients with sensory neuropathies. With a cutoff derived from the fifth percentile of the normative range for the distal part of the leg, the technique had a positive predictive value of 75%, a negative predictive value of 90%, and a diagnostic efficiency of 88%. CONCLUSIONS: We have established a reference range for intraepidermal nerve fiber density in normal humans by means of a simple quantitation method based on enumeration of individual intraepidermal nerve fibers on vertical sections of punch skin biopsy specimens stained with the sensitive panaxonal marker anti-protein gene product 9.5. The utility of the density measurement was confirmed for sensory neuropathy with a diagnostic efficiency of 88%. Skin biopsies may be useful to assess the spatial distribution of involvement in peripheral nerve disease and the response to neurotrophic and other restorative therapies.

Adolescent↗

Treatment outcomes for students with learning disabilities: how important are internal and external validity?

This study analyzed the magnitude of experimental intervention outcomes as a function of violations in internal and external validity for studies that included students with learning disabilities. The results indicated that treatment outcomes were significantly affected by the following violations: teacher effects, establishing criterion levels of instructional performance, reliance on experimental measures, using different measures between pretest and posttest, using a sample heterogenous in age, and using incorrect units of analysis. Furthermore, the underreporting of information related to ethnicity, locale of the study, psychometric data, and teacher applications positively inflated the magnitude of treatment outcomes. A weighted hierarchical regression analysis revealed that composite scores of the aforementioned high-risk variables accounted for 16% of the total variance in effect size. The implications for interpreting intervention research to practice are discussed.

Analysis of Variance↗