[Systematic Readability Analysis of Medical Texts on Websites of German University Clinics for General and Abdominal Surgery]. / Systematische Analyse der Lesbarkeit von Patienteninformationstexten auf Internetseiten von Kliniken für Allgemein- und Viszeralchirurgie deutscher Universitätskliniken.

Background: Besides the function as one of the main contact points, websites of hospitals serve as medical information portals. As medical information texts should be understood by any patients independent of the literacy skills and educational level, online texts should have an appropriate structure to ease understandability. Materials and Methods: Patient information texts on websites of clinics for general surgery at German university hospitals (n = 36) were systematically analysed. For 9 different surgical topics representative medical information texts were extracted from each website. Using common readability tools and 5 different readability indices the texts were analysed concerning their readability and structure. The analysis was furthermore stratified in relation to geographical regions in Germany. Results: For the definite analysis the texts of 196 internet websites could be used. On average the texts consisted of 25 sentences and 368 words. The reading analysis tools congruously showed that all texts showed a rather low readability demanding a high literacy level from the readers. Conclusion: Patient information texts on German university hospital websites are difficult to understand for most patients. To fulfill the ambition of informing the general population in an adequate way about medical issues, a revision of most medical texts on websites of German surgical hospitals is recommended.

[Systematic analysis of the readability of patient information on websites of German nonuniversity ENT hospitals]. / Systematische Analyse der Lesbarkeit von Patienteninformationstexten auf Internetseiten deutscher nichtuniversitärer HNO-Kliniken.

BACKGROUND: Besides their function as one of the main contact points, websites of hospitals serve as medical information portals. All patients should be able to understand medical information texts; regardless of their literacy skills and educational level. Online texts should thus have an appropriate structure to ease their comprehension. MATERIALS AND METHODS: Patient information texts on every German nonuniversity ENT hospital website (n = 125) were systematically analysed. For ten different ENT topics a representative medical information text was extracted from each website. Using objective text parameters and five established readability indices, the texts were analysed in terms of their readability and structure. Furthermore, we stratified the analysis in relation to the hospital organisation system and geographical region in Germany. RESULTS: Texts from 142 internet sites could be used for the definite analysis. On average, texts consisted of 15 sentences and 237 words. Readability indices congruously showed that the analysed texts could generally only be understood by a well-educated or even academic reader. CONCLUSION: The majority of patient information texts on German hospital websites are difficult to understand for most patients. In order to fulfil their goal of adequately informing the general population about disease, therapeutic options and the particular focal points of the clinic, a revision of most medical texts on the websites of German ENT hospitals is recommended.

[Readability of medical texts on websites of German ENT university hospitals]. / Lesbarkeit von medizinischen Texten im Internetangebot deutscher HNO-Universitätskliniken.

BACKGROUND: A certain proportion of the population has limited literacy skills; therefore, it is important that any patient information published on the internet is readable to the majority of patients for whom the information is intended. MATERIALS AND METHODS: Texts for 10 representative ear nose and throat (ENT) topics were extracted from each website of the 36 German ENT university hospitals. The texts were systematically analyzed by use of the German version of the Flesch ease of reading index. The texts of two topics were additionally analyzed with four more readability tools for the German language. Texts were analyzed in relation to the topic and to the geographical region. RESULTS: On average the texts of 185 websites consisted of 34 sentences and 401 words. Comparably, texts on cochlear implants showed the best readability scores and texts on middle ear pathology the worst. The results of the reading ease index and of the other reading analysis tools showed that all texts require a relatively high literacy level. CONCLUSIONS: To fulfil the ambition of informing the general population about medical issues in an adequate way, a revision of most medical texts on websites of German ENT departments at university hospitals is recommended.

Effect of maleic acid on the kinetics of alpha-methyl-D-glucoside uptake by isolated rat renal tubules.

ALPHA-Methyl-D-glucoside has been used to study the invitro mechanism of the effect of maleic acid on sugar transport, using isolated rat renal tubule fragments. 6 mM maleate maximally inhibits the ability of the tubule to establish a concentration gradient for this model sugar with no evidence of ultrastructural changes. This inhibition is due to a 100% increase in efflux, as well as to a 50% decrease in influx with more prolonged incubation. The data presented here are consistent with those of other workers, but their work does not explain our results, which therefore deserve further investigation by other techniques.

Tissue distribution of succinylacetone in the rat in vivo: a possible basis for neurotoxicity in hereditary infantile tyrosinemia.

Neurologic dysfunction is a significant component of hereditary infantile tyrosinemia, an autosomal recessive disorder of man. The specific enzyme defect leads to endogenous production of the biochemical marker compound, succinylacetone (SA). Earlier study of the role which SA plays in generation of the renal Fanconi syndrome, also associated with this disorder, led to speculation that SA might also have neurotoxic effects. Thus, we have studied the distribution and impact on heme metabolism of SA in brain, liver and kidney from rats treated in vivo. Our results show far greater retention of SA in brain and kidney than in liver, by a ratio of approx. 3:1. Delta-aminolevulinate dehydratase (ALAD) was reduced to less than 10% of control activity in all three tissues after three daily injections; after a 7-day recovery, activity was regained at different rates in the three tissues. Total heme content of each tissue showed a steady decline beyond the treatment period, the most marked reduction being found in kidney. Porphyrin intermediates, heme oxygenase activity and cytochrome P-450 content evidenced varying responses to SA exposure which differed from tissue to tissue. Our results show that brain tissue sequesters SA and that heme biosynthesis in brain, as distinct from liver and kidney, is adversely affected. Such effects could result in impaired oxidative metabolism in brain, producing the CNS manifestations of tyrosinemia.

Effects of succinylacetone on methyl alpha-D-glucoside uptake by the rat renal tubule.

Succinylacetone, a catabolic end-product of tyrosine, is excreted in large quantities in urine from individuals with hereditary tyrosinemia and the Fanconi syndrome. Succinylacetone inhibits rat renal tubular concentrative uptake of the glucose transport analogue, methyl alpha-D-glucoside, in a noncompetitive and reversible fashion. This compound also depresses oxygen consumption by the rat renal tubule without fine structural damage to mitochondria. It is concluded that succinylacetone may be a useful probe in elucidation of the biochemical mechanism underlying the human Fanconi syndrome.

On the development of glycine transport systems by rat renal cortex.

The initial uptake of glycine by renal cortical slices from newborn Sprague-Dawley and Long-Evans rats is the same as that observed in adult tissues. Both newborn and adult tissue possess similar high and low affinity glycine transport systems which require an examination of velocity measurements over a wide range of concentration (0.02--50.0 mM) for their discernment. Initial rates of glycine uptake by isolated renal tubule fragments from newborn and adults are similar at a physiological substrate concentration but at high glycine levels there appears to be a decrease in velocity of uptake (V) associated with the high Km system in the young. Whatever preparation of renal cortex is studied, there is a consistent finding that immature tissue is able to accumulate much higher intracellular levels of glycine than the adult, a finding consistent with slower efflux from the cell. An interpretation of the etiology of physiologic aminoaciduria in young animals should take this into account.

Renal heme metabolism in hereditary tyrosinemia: use of succinylacetone in rat renal tubules.

Succinylacetone (SA), a metabolic end-product found in urine from individuals with hereditary tyrosinemia and associated renal Fanconi syndrome and a known inhibitor of hepatic 5-aminolevulinic acid dehydratase (ALAD), has been used to study heme metabolism in isolated rat renal tubules. Heme biosynthetic porphyrin precursors are increased selectively in the presence of 4 mmol/1 SA. Total porphyrin content of the tubules are increased approximately 2-fold, while both ferrochelatase and heme oxygenase activities remain unaffected by SA. Nonetheless, total heme content is reduced, as was incorporation of radioactive label from amino[14C]levulinic acid. Cytochrome P-450 content remained unaffected. Impairment of iron uptake and/or transport within the cell or enhancement of heme catabolism via a non-heme oxygenase-dependent pathway could explain the observations.

Renal Fanconi syndrome: developmental basis for a new animal model with relevance to human disease.

Using succinylacetone (SA), a metabolite of tyrosine excreted in excess by infants and children with hereditary tyrosinemia and the renal Fanconi syndrome (FS), we have investigated developmentally-related membrane transport events leading to emergence of the generalized renal tubular dysfunction seen in human FS. SA was found to impair sugar and amino acid uptake by both newborn renal tubules and 7-day renal brush-border membrane vesicles (BBMV). This impairment by SA was due in part to a slowing of substrate cotransport rate of 22Na+-entry into BBMV. Concentration-dependent uptake studies indicated SA inhibited the newborn high-affinity transport systems for sugars and amino acids. SA also caused an increase in membrane fluidity and a shift in the thermotropic transition temperature. The demonstrated dual nature of SA's effect on membrane fluidity and O2 consumption, together with the relative contribution of each component to SA-induced transport impairment helps to provide a basis for an understanding of the age-related increases in glucosuria, aminoaciduria and natriuria seen in infants with FS.

Biotin in clinical medicine--a review.

The recent developments in cofactor therapy of inherited biochemical disease has awakened interest in biotin as a therapeutic agent. This review briefly details the physiological and biochemical aspects of human biotin metabolism. The role of biotin in therapy of human disease is critically examined and the relevant literature extensively reviewed. It is our hope that this review will stimulate further clinical interest in the treatment of biotin-responsive human disorders.

A comparison of the uptake of 3-hydroxy-3-methyl-glutaric acid in newborn and adult rat kidney.

The developmental aspects of the renal uptake of 3-OH-3-CH3-glutaric acid (HMG) was examined using isolated renal tubules prepared from both newborn and adult rats and isolated renal brush border membranes vesicles from adult rats. The accumulation of 70 microM HMG by both newborn and adult tubules reached a steady state and achieved a distribution ratio (DR) of 4.9 and 6.5, respectively; decreased DR's at higher substrate concentrations suggest concentration-dependent uptake. Lineweaver-Burk analysis of the 5 min calculated velocities of HMG uptake by newborn and adult tubules indicate a single transport system with the same apparent Km of 0.2 mM in both age groups. The Vmax in adult rats was twofold greater than in newborn (0.95 versus 0.44 mM/1/5 min). The carrier system for HMG is assumed to be distinct from those of amino acids and sugars because tubule uptake of HMG is not affected by the presence of alpha-NH2-isobutyric acid and alpha-methyl-D-glucoside. Sodium maleate and acetoacetate significantly decreased HMG uptake in tubules of both age groups. HMG uptake by isolated renal brush border membrane vesicles from adult rats suggests that uptake is both carrier-mediated and Na+-dependent. These observations are consistent with renal tubular HMG uptake by an energy-dependent, carrier-mediated system.

Uptake of glycine by human kidney cortex.

The transport of glycine was investigated in histologically normal adult human kidney cortical slices. Uptake occurs against a gradient and shows concentration dependence. Kinetic analysis reveals two systems for transport of glycine with apparent transport Km values of 0.511 and 34.2 mM. Glycine transport on the high-Km system is competitively inhibited by 50 mML-proline. Transport inhibition on the low-Km system could not be directly evaluated, but on theoretic grounds appears not to be inhibited by L-proline or hydroxyproline. Alpha-aminoisobutyric acid, valine, and thioproline are also shown to inhibit glycine uptake. Low medium sodium or anaerobic incubation depress the uptake of glycine. These observations are consistent with previous reports of glycine transport in rat kidney and support the proposals for the mechanism of familial iminoglycinuria based on in vivo investigations.

On 'being led by the nose'. Rapid detection of inborn errors of metabolism.

We reviewed and emphasized the importance of olfaction for the diagnosis of inborn errors of metabolism. The "trained" nose has a remarkable sensitivity and specificity for discriminating odors that are associated with certain inborn errors of metabolism. These odors are often the first abnormality noticed on physical examination and should prompt the pediatrician to seek confirmatory laboratory studies.

Rapid and accurate random urinary porphyrin quantitation.

Urinary metabolite profiling, using randomly voided samples, has become accepted practice for such compounds as organic acids. To date, however, published methods for examining urinary porphyrin excretion have been based upon examination of 24-h urine collections. The inherent difficulties of obtaining an accurate collection, coupled with the intrinsic liabilities of porphyrins suggest that a method based upon random void analysis would be of great use. Thus, we have examined the porphyrin pattern of randomly excreted urine samples from normal adults of both genders, comparing our results with those obtained from analysis of 24-h collections. We have also evaluated the use of different alkalinizing agents. Finally, we have investigated the possibility that an underlying diurnal pattern of porphyrin excretion might influence the results obtained from random urine voids. The results indicate that NaOH retards spontaneous conversion of porphyrins within the first 24 h, thus optimizing recovery of uroporphyrin. Data from random voids mirror those obtained from 24-h collections and diurnal variations were not found to influence these results. Normal values are provided for random samples obtained from males and females. Thus, we conclude that random urine profiling is a rapid and accurate means of initial evaluation.

Defect in alpha-ketobutyrate metabolism: a new inborn error.

A pair of siblings with clinical symptoms of cyclic vomiting and ketoacidosis were found to have a biochemical triad of normoglycemia, ketoacidosis and elevated levels of alpha-hydroxy- and alpha-aminobutyrate in plasma and urine. Methionine loading studies in both sibs produced prompt rises in plasma methionine and alpha-aminobutyrate levels, with a subsequent increase in urinary alpha-hydroxybutyrate, as well. Leukocytes from both siblings showed normal oxidation of [3-14C]propionate. Increased inorganic sulfate excretion after methionine loading implied an intact transsulfuration pathway in both siblings. On the basis of the studies detailed in this report, we conclude that these siblings suffer from a defect in alpha-ketobutyrate oxidation, a newly described defect of organic acid metabolism.

Serum and urinary biotin levels during treatment of holocarboxylase synthetase deficiency.

Measurements of blood and urine biotin levels have been performed during treatment of a patient with holocarboxylase synthetase deficiency. During the first 24 hours of therapy, the infant progressed from a moribund, shock-like state to a clinically normal baby. Urinary biotin concentration increased more that 100-fold after 12 hours of treatment. Within 48 hours of treatment, blood biotin levels were greater than 10 times control levels. On the basis of the data presented, it is suggested that therapeutic blood levels of biotin can be achieved by enteral administration of 10 mg of biotin per day.

Prediction of students' USMLE step 2 performances based on premedical credentials related to verbal skills.

PURPOSE: To examine the relationship between the objective premedical credentials and performances on Step 2 on the United States Medical Licensing Examination (USMLE) of 480 students in three classes at the Virginia Commonwealth University Medical College of Virginia School of Medicine. The purpose of the study was to seek those selection criteria that might best predict performance on an examination designed to assess problem-solving skills, the essence of clinical medicine. METHOD: Premedical data from two classes (1193, 1994) were analyzed, and a regression equation was used to calculate theoretical USMLE Step 2 scores for the students in the class of 1995, who had not yet taken this examination. The premedical variables were scores on the verbal and math section on the Scholastic Aptitude Test (SAT), scores on the six sections of the pre-1991 Medical College Admission Test (MCAT), grade-point average (GPA) in science courses required of premedical students, and undergraduate major. Once the class of 1995 had taken the USMLE Step 2, the equation was cross validated, and the theoretical and actual scores of the class of 1995 were correlated. RESULTS: The correlation between theoretical and actual scores was r = .443. In the analysis for the classes of 1993 and 1994, the single variables most highly predictive of USMLE Step 2 performance were scores on the verbal section of the SAT (r = .317) and the Skills Analysis: Reading section of the MCAT (r = .331). However, the MCAT scores were excluded from the final regression analysis because of the pre-1991 MCAT cannot be useful in predicting the performances of present medical school applicants. The resulting regression equation (using the SAT verbal section and premedical GPA) was able to account for 21.2% of the variance for the class of 1995. CONCLUSION: The use of the verbal section of the SAT as a predictive factor is unique. It is significant that this variable was strongly related to premedical GPA, suggesting that high verbal aptitude serves one well, even when coping with complex scientific concepts.

Renal tubular acidosis: a new look at an old problem.

Although the definition of renal tubular acidosis (RTA) is simple, understanding the physiologic basis underlying the various types of this clinical entity is much more difficult. The pathophysiology of this disorder is reviewed using the normal acid-base functions of the involved segments of the nephron as a guide to understanding. Clinical and laboratory features of the subtypes of RTA are addressed, and diagnosis and treatment discussed. New developments in the knowledge and understanding of the associated growth disturbances, mineral metabolism, and molecular biology of RTA are also reviewed to provide the most current view of this relatively common pediatric entity.

Pediatric hematuria and thin basement membrane nephropathy: what is it and what does it mean?

Hematuria is seen frequently in the pediatric population and may signal either benign or serious renal patholosis. A significant proportion of children with asymptomatic hematuria will have thin basement membrane nephropathy (TBMN), a benign disorder, yet there is little information about this entity outside the nephrology literature. This article is designed to provide an information base for pediatric practitioners to assist them in making appropriate decisions regarding diagnosis and care. A review of experience over a decade with 9 children with biopsy-proven TBMN, including follow-up to the present; is presented. In addition, review of literature regarding TBMN, Alport's and Berger's syndromes, which comprise the major clinical entities associated with asymptomatic pediatric hematuria, is presented. Each patient was evaluated for asymptomatic, documented and persistent hematuria. Renal biopsy was performed after clinical evaluation and follow-up. TBMN and Berger's disease (IgA nephropathy) are separable only by renal biopsy results; TBMN is benign and IgA nephropathy may be progressive, mandating referral to a nephrologist. The prognosis of TBMN is excellent.

Asymptomatic gross hematuria followed by persistent microhematuria.

A case of a previously healthy, 13-year-old male with IgA nephropathy is presented in order to illustrate clinical onset and differential diagnosis of this rather common clinical entity. The laboratory and histopathological diagnosis is illustrated and discussed, as well, together with a brief discussion of possible pathogenesis. In this disorder, in which approximately 11% of affected patients experience spontaneous remission, future development of molecular probes to determine prognosis is of great importance.