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Pharmacological characterization of the new stable antiarrhythmic peptide analog Ac-D-Tyr-D-Pro-D-Hyp-Gly-D-Ala-Gly-NH2 (ZP123): in vivo and in vitro studies.

Antiarrhythmic peptides (AAPs) are a group of compounds with antiarrhythmic properties; however, their use has been hampered by very low plasma stability. The aim of this study was to compare the in vitro and in vivo stability of our new stable AAP analog Ac-d-Tyr-d-Pro-d-Hyp-Gly-d-Ala-Gly-NH2 (ZP123) with the previously described AAP analog AAP10. Moreover, the effect of the two compounds was examined in a murine in vivo model of ouabain-induced second degree AV-block, and the effect on dispersion of action potential duration (APD dispersion) was studied during hypokalemic-ischemia in isolated perfused rabbit hearts. The in vitro t1/2 of ZP123 in rat and human plasma was about 1,700 times longer than t1/2 of AAP10. Due to rapid elimination, it was not possible to obtain an in vivo pharmacokinetic characterization of AAP10; however, calculations suggested that the clearance of ZP123 was at least 140 times slower than for AAP10. AAP10 and ZP123 produced a dose-dependent delay in onset of ouabain-induced AV-block in mice at doses of 10-11 to 10-7 mol/kg i.v. ZP123 and 10-11 to 10-6 mol/kg i.v. AAP10. Maximal efficacy of ZP123 was reached at a 10-fold lower dose (10-8 mol/kg i.v.) than with AAP10. In the isolated rabbit hearts, ZP123 and AAP10 had no effect on dispersion during control conditions. The increased APD dispersion during hypokalemic ischemia is considered a major arrhythmic substrate and only ZP123 prevented the increase in APD dispersion. In conclusion, ZP123 is a new potent AAP analog with improved stability.

Action Potentials↗

Adeno-associated Virus (AAV) Capsid Chimeras with Enhanced Infectivity Reveal a Core Element in the AAV Genome Critical for both Cell Transduction and Capsid Assembly.

Adeno-associated viruses (AAV) have attracted significant attention in the field of gene and cell therapy due to highly effective delivery of therapeutic genes into human cells. The ability to generate recombinant AAV vectors compromised of unique or substituted protein sequences has led to the development of capsid variants with improved therapeutic properties. Seeking novel AAV vectors capable of enhanced transduction for therapeutic applications, we have developed a series of unique capsid variants termed AAV X-Vivo (AAV-XV) derived from chimeras of AAV12 VP1/2 sequences and the VP3 sequence of AAV6. These AAV variants showed enhanced infection of human primary T cells, hematopoietic stem cells, and neuronal cell lines over wildtype parental viruses, and superiority over AAV6 for genomic integration of DNA sequences by AAV alone or in combination with CRISPR gene editing. AAV-XV variants demonstrate transduction efficiency equivalent to AAV6 at multiplicities of infection 2 logs lower, enabling T cell engineering at low AAV doses. The protein coding sequence of these novel AAV chimeras revealed disruptions within the assembly-activating protein (AAP) which likely accounted for observed lower virus yield. A series of genome alterations, reverting the AAP sequence back to wildtype AAV6, had a negative impact on the enhanced transduction seen with AAV-VX, indicating overlapping functions within this sequence for both viral assembly and effective T cell transduction. Our findings show these AAV-XV variants are highly efficient at cell transduction at low dose and demonstrates the importance of the AAP coding region in both viral particle assembly and cell infection.IMPORTANCE A major hurdle to the therapeutic potential of AAV in gene therapy lies in achieving clinically meaningful AAV doses, and secondarily, ability to manufacture commercially viable titers of AAV to support this. By virtue of neutralizing antibodies against AAV that impede patient repeat-dosing, the dose of AAV for in vivo gene delivery has been high, which has resulted in unfortunate recent safety concerns and deaths in patients given higher-dose AAV gene therapy. We have generated new AAV variants possessing unique combinations of capsid proteins for gene and cell therapy applications termed AAV-XV, which have high levels of cell transduction and gene delivery at lower MOI. Furthermore, we demonstrate a novel finding, and an important consideration for recombinant AAV design, that a region of the AAV genome encoding the capsid viral protein and AAP is critical for both virus yield and the enhancement of infection/transduction.

Journal Article↗

(Alkylamino) piperidine bis(heteroaryl)piperizine analogs are potent, broad-spectrum nonnucleoside reverse transcriptase inhibitors of drug-resistant isolates of human immunodeficiency virus type 1 (HIV-1) and select for drug-resistant variants of HIV-1IIIB with reduced replication phenotypes.

The (alkylamino)piperidine bis(heteroaryl)piperizines (AAP-BHAPs) are a new class of human immunodeficiency virus type 1 (HIV-1)-specific inhibitors which were identified by targeted screening of recombinant reverse transcriptase (RT) enzymes carrying key nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance-conferring mutations and NNRTI-resistant variants of HIV-1. Phenotypic profiling of the two most potent AAP-BHAPs, U-95133 and U-104489, against in vitro-selected drug-resistant HIV-1 variants carrying the NNRTI resistance-conferring mutation (Tyr->Cys) at position 181 of the HIV-1 RT revealed submicromolar 90% inhibitory concentration estimates for these compounds. Moreover, U-104489 demonstrated potent activity against BHA-P-resistant HIV-1MF harboring the Pro-236->Leu RT substitution and significantly suppressed the replication of clinical isolates of HIV-1 resistant to both delavirdine (BHAP U-90152T) and zidovudine. Biochemical and phenotypic characterization of AAP-BHAPresistant HIV-1IIIB variants revealed that high-level resistance to the AAP-BHAPs was mediated by a Gly-190->Glu substitution in RT, which had a deleterious effect on the integrity and enzymatic activity of virion-associated RT heterodimers, as well as the replication capacity of these resistant viruses.

Antiviral Agents↗

The effectiveness of auriculoacupoint treatment for artificially induced acute hepatic injury in dogs.

This study was to investigate effects of auriculoacupoint (AAP) treatment on carbon tetrachloride (CCl4)-induced acute hepatic injury in ten dogs (four females and six males). Dogs have been divided into two groups: the control group (four dogs), not stimulated after induction of hepatic injury and the experimental group (six dogs), stimulated with AAP and massaged at the affected liver region of internal ear after induction of hepatic injury. Serum enzyme activities and histopathological findings were examined after the application of AAP. Compared to the control group, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in the experimental group were significantly decreased at the 4th day (p < 0.05) and at the 5th day (p < 0.05), respectively. Histopathological findings of the experimental group showed decrease of necrotic region and size of lipid droplets compared to the control group. In conclusion, AAP treatment had a therapeutic effect on the recovery of liver injury induced by CCl4 in dogs.

Acupuncture Points↗

Quantitative enzymatic histophotometry of morphologic alterations caused by urologically relevant tubular kidney damages using computed image analysis device technique.

The tissue concentration of tubular marker enzymes were evaluated in sections of kidneys from 86 patients with various underlying diseases such as hydronephrosis, interstitial nephropathies, ischemia due to renal arterial stenosis and chronic allograft rejection. In addition, as an experimental model, kidney tissue sections of 166 Wistar rats were analyzed due to hydronephrosis caused by ureteral obstruction, ischemia and obstruction of the renal vein. The tissue concentration of indicator enzymes, such as alkaline phosphatase (AP) and alanine-aminopeptidase (AAP), was considered as a parameter describing the extent of kidney tubule damage. Quantitative evaluation of enzymatic activity was performed by histophotometry using a computed image analysis device technique. As compared to normal human kidney (enzyme activity 100%), the concentrations of brush border enzymes were significantly (p less than 0.001) lower under pathological conditions (AP less than 15%, AAP less than 55%). In similar manner investigations of kidneys in animal experiments with rats exhibited lower enzyme concentrations following kidney injury caused by ureteral obstruction for 10 and 21 days (AP less than 12%, AAP less than 65%; 2p less than 0.01). Kidneys after an ischemic period of 2 h and a subsequent 14-day recirculation period displayed a significant (2p less than 0.01) decrease of normally present indicator enzyme concentrations (AP less than 22%, AAP less than 77%) as compared to normal renal organs (100%). Computed image analysis of kidney tissue sections might be a useful aid in evaluating morphologic and enzymatic patterns of human and animal kidney alterations.

Alkaline Phosphatase↗

Quantitative histophotometry analysing significant inductive and alterative effects of aminoglycoside application (gentamicin, tobramycin, amikacin) upon tubular kidney proteins.

In order to evaluate quantitative changes in kidney proteins, computer-assisted histophotometry of tissues was performed. Kidney marker enzyme concentrations were considered to be involved in inductive and alterative developments in the proximal tubule. These effects were caused by the administration of aminoglycosides. Indicator enzymes of the proximal tubule such as membrane-bound alkaline phosphatase (AP) and alanine-aminopeptidase (AAP) as well as lysosomal beta-glucuronidase (beta-Gl) were stained in kidney tissues. Graphic monitoring and digital display of kidney cortex sections were registered by electronic image analysis using the 'Micro-Videomat' 2 system. As an experimental design, 160 kidneys of Wistar rats were studied. Their kidneys were analyzed after one, two and three intravenous applications of gentamicin, 25 mg/kg/day, or tobramycin, 25 mg/kg/day, or amikacin, 50 mg/kg/day, on consecutive days. In a fourth test group, the kidneys were examined after the third application and a 5-day recovery period. Concentrations of tubular marker enzymes were significantly increased (2p less than 0.01, Wilcoxon test) after two applications of gentamicin: AP 37.6%, AAP 6.3% and beta-Gl 11.8%. Contrary to these findings, after two injections of tobramycin or amikacin only slight alterations were documented: tobramycin, AP 14.5%, AAP -0.1% and beta-Gl 0.4%; amikacin, AP 6.0% and AAP 4.2%. The studies indicate that tobramycin induces less severe nephrotoxic and inductive reaction than gentamicin and partly than amikacin in doses administered during our experiments. In all cases, enzyme activities studied were nearly normalized after three applications of aminoglycosides and a recovery period of 5 days. Quantitative computer-assisted evaluation of the proteins located in the tubule appears to be a tool for monitoring the degree of alterations caused by enzyme induction, enzyme release and excretion of kidney proteins.

Alkaline Phosphatase↗

Effect of chronic hyperinflation on diaphragm length and surface area.

We have used three-dimensional reconstructions obtained with spiral computed tomography to measure total diaphragm length (Ldl) and surface area (Adl), the length (Ldo) and surface area (Ado) of the dome, and the length (Lap) and surface area (Aap) of the zone of apposition in 10 hyperinflated patients with severe chronic obstructive pulmonary disease, or COPD (FEV1 = 27% predicted: FRC = 225% predicted) and 10 normal subjects matched for age, sex, and height. Measures of Ldl, Adl, Lap, and Aap decreased linearly between FRC and TLC in the two groups, but Ldo and Ado did not change. On average, patients' Adl and Aap at FRC were reduced to 73% and 54% of normal values, whereas Ado was unaffected. When compared at similar absolute lung volumes, mean diaphragm dimensions were similar in patients with COPD and normal subjects, but individual values were very variable in both groups. This variability was partly accounted for by differences in body weight: i.e., the greater the weight, the longer the diaphragm. We conclude that (1) patients with COPD have marked reductions in Adl and Aap at FRC but have diaphragm dimensions similar to those of normal subjects when compared at similar absolute lung volumes, and (2) normal subjects and patients with COPD show substantial intersubject variability in diaphragm dimensions that is partly explained by differences in body weight.

Aged↗

A lipid-immune network signature defines susceptibility to asparaginase-associated pancreatitis.

BACKGROUNDAsparaginase is essential for curing acute lymphoblastic leukemia (ALL), but its use is limited by asparaginase-associated pancreatitis (AAP), a severe and unpredictable toxicity lacking validated prospective biomarkers. We sought to define early systemic molecular features of susceptibility to AAP.METHODSWe performed longitudinal lipidomic and proteomic profiling in two independent pediatric ALL cohorts (n = 161; 79 AAP cases, 82 controls) using paired blood samples collected before asparaginase exposure and at the end of induction therapy (including a single dose of asparaginase), thereby capturing pre-injury biology rather than consequences of pancreatitis. We applied differential abundance and network-based analyses and integrated lipid-cytokine associations using proteomics.RESULTSAcross cohorts, we identified a reproducible lysophosphatidylcholine-centered (LPC-centered) signature characterized by attenuated induction therapy-associated LPC responses and disruption of LPC coregulation at the network level. Proteomic profiling revealed enrichment of cytokine signaling pathways, and integrative analyses demonstrated altered lipid-cytokine coupling, including a flip in association direction for LPC species and IL-18 between cases and controls. Although IL-18/LPC ratios did not differ globally, elevated postinduction IL-18/LPC ratios identified AAP risk within a protocol-defined very high-risk ALL subgroup (AUC = 0.81).CONCLUSIONThese findings support a systems-level model in which failure of coordinated lipid-immune responses under therapeutic stress confers vulnerability to AAP, providing a framework for validation and mitigation strategies.TRIAL REGISTRATIONNCT00400946; NCT01574274; NCT03020030 (parent trials).FUNDINGServier Pharmaceuticals (IIT-95014-027-USA); SDRC (P30DK116074); Stanford SPARK; Fonds de Recherche du Qu&#xe9;bec - Sant&#xe9;; Fondation Charles-Bruneau; Leukemia & Lymphoma Society of Canada.

Adolescent↗

Physician beliefs and practices regarding SIDS and SIDS risk reduction.

The AAP has alerted pediatricians to the importance of safe sleep environment for infants. The elements of a safe sleep environment include supine sleep position, safe crib, and avoidance of smoke exposure, soft bedding, and overheating. With the Back to Sleep campaign, prone sleeping among all U.S. infants has decreased to less than 20%, and the incidence of SIDS has decreased 40%. However, the decline in SIDS and prone sleeping has leveled off in recent years. Further declines may be possible with decreasing other modifiable risk factors, such as prenatal and postnatal exposure to cigarette smoking. Prior studies have demonstrated that health care professional advice is influential in determining infant care practices. It is important that physicians caring for infants be aware of the importance of a safe sleep environment and understand other modifiable risk factors for SIDS. We surveyed a random sample of 3,717 physicians in North Carolina and the metropolitan Washington, DC, area to determine knowledge, beliefs, and practices regarding SIDS and SIDS risk reduction among physicians caring for pregnant women and infants. Twenty-three percent (835) responded. Most physicians are aware of prone sleeping and cigarette smoke exposure as risk factors for SIDS. Almost all physicians agree that there are measures that can be taken to reduce the risk of SIDS, and they consider it important to discuss SIDS and SIDS risk reduction strategies with parents of young infants. In spite of this belief, only 56% of family/general practitioners, 18% of obstetrician-gynecologists, and 79% of pediatricians discuss SIDS routinely. Only 35% of pediatricians, 15% of family/general practitioners, and 16% of obstetrician-gynecologists provide written information. In addition, only 38% of physicians recommend supine, while 50% recommend side or back, 6% side, and 7% prone. Only two thirds of pediatricians and one third of family/general practitioners are aware that the AAP recommends supine as the preferred sleep position for infants. Pediatricians are more likely to be aware of the AAP recommendation (p<0.0001) and to discuss SIDS risk reduction strategies with parents (p=0.03). We conclude that many physicians who care for infants are unaware of the AAP's most current recommendation for sleep position and are incorrectly recommending the side position. Physicians may also be unaware of other sleep environment hazards. Further educational efforts must continue for physicians who provide care to pregnant women and children to ensure a continued decline in the incidence of SIDS.

Attitude of Health Personnel↗

Use of cough and cold preparations during breastfeeding.

Adverse reactions in infants from maternal drug ingestion depend largely on the amount of milk consumed by the infant, timing of breastfeeding in relation to dosing, dose of the medication, dosing interval, and duration of therapy. When taking medications, breastfeeding mothers should be instructed to take their medication after breastfeeding, at the lowest effective dose and for the shortest duration. Overall, there are few data from human studies on the use of antihistamines, decongestants, and cough products during breastfeeding. Studies of pseudoephedrine, triprolidine, and loratadine in humans conclude that low levels of each drug would reach a breastfed infant. Since triprolidine and pseudoephedrine are also considered compatible with breastfeeding by the AAP, these 2 drugs should be the first-line choices. Codeine is considered compatible with breastfeeding by the AAP, and would be an acceptable choice for short-term use as a cough suppressant. It is important to note that many of the liquid cough and cold products contain alcohol. In addition, many of the combination products are a mixture of an antihistamine and a decongestant and may also contain aspirin, acetaminophen, ibuprofen, or caffeine. It is preferable for nursing mothers to only take medications that are necessary and to avoid such combination products. The AAP considers alcohol, acetaminophen, ibuprofen, and caffeine compatible with breastfeeding. Aspirin has been associated with significant negative effects on some nursing infants, and the AAP recommends giving aspirin to nursing mothers with caution. Mothers taking cough and cold products should watch for adverse events in their breastfed infants. Infants may experience paradoxical central nervous stimulation from antihistamines and irritability and insomnia from decongestants.

Antitussive Agents↗

Assessment of the enzymuria resulting from gentamicin alone and combinations of gentamicin with various beta-lactam antibiotics.

OBJECTIVE: To determine the propensity of beta-lactam antimicrobials to ameliorate or potentiate aminoglycoside-induced renal enzymuria. DESIGN: Two open, randomized, double-blind, parallel-group studies were conducted in young, healthy, male volunteer subjects. Using a common protocol, 24-hour urine collections were analyzed for the renal tubular enzymes alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG), as well as for creatinine. Antimicrobial combinations studied included gentamicin plus placebo and gentamicin plus ticarcillin/clavulanate (protocol 1); and gentamicin plus placebo, gentamicin plus piperacillin, and gentamicin plus ceftazidime (protocol 2). The antimicrobial regimens were administered for 7 days. Eight subjects completed each treatment group. RESULTS: There were no significant differences between treatment groups with regard to urine creatinine excretion or serum gentamicin concentrations in either protocol. Enzymuria (AAP [p = 0.039] and NAG [p = 0.337]) was decreased in the gentamicin plus ticarcillin/clavulanate treatment compared with that in the gentamicin plus placebo treatment. Increased enzymuria, as indicated by increased urine concentrations of AAP and NAG, was observed in the gentamicin plus ceftazidime treatment (p < 0.05) compared with the other two treatments. CONCLUSIONS: Based on relative enzymuria, ticarcillin/clavulanate may be renal protective. Piperacillin neither potentiated nor ameliorated aminoglycoside-induced enzymuria. Since acute elevations in AAP and NAG reflect insults to the kidney, these studies suggest that ceftazidime may enhance aminoglycoside-induced renal injury. Piperacillin had no effect on enzymuria and would appear not to enhance or protect against aminoglycoside-induced renal injury.

Acetylglucosaminidase↗

Histochemical labeling of beta-adrenergic receptors in the mouse central nervous system by 9-amino-acridin propranolol.

A new fluorescent beta-adrenergic antagonist, 9-amino-acridin propranolol (9-AAP), was administered intravenously to living mice. In the cerebral cortex, the highest concentration of 9-AAP was noted in the hippocampal formation, where it distinctly labeled the hippocampal pyramidal cell layer and the granule cell layer of the dentate gryus. High uptake occurred in the pyramidal cell layer of the piriform cortex. In the neocortex, fluorescence was less dense and more diffuse but confined to the basal layers. A similar pattern was observed in the basal layers of the cingulate cortex, but an additional high-density dotted fluorescence labeled its layer II. In the cerebellar cortex, 9-AAP was localized within the Purkinje cell layer. In the spinal cord, the highest density of fluorescence was observed in the nuclear collections of alpha-motoneurons. The findings were similar to those observed in the central nervous system of the rat and support the reproducibility of the method. 9-AAP may be used in vivo as a fluorescent probe to map out the central beta-adrenergic receptor system.

Acridines↗

Influence of pH and phospholipid species on release of acetaminophen from tablets containing phospholipids.

The release of acetaminophen (AAP) from tablets containing phospholipids was examined using hydrogenated soybean phospholipid (HSL) and its main components, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI), although the PI was not well purified (PI rich). Tablets compressed with 400 kgf had about 9% porosity and 2-4 kgf hardness. The release patterns of AAP from the tablets were fitted to Higuchi's square root of time law. The release rate was influenced by the pH of the medium, though solubility of AAP did not change with pH. PC tablets showed faster release at pH of less than 3 than that at pH of above 3, whereas PI rich and HSL tablets showed faster release at pH of above 3 than that at pH of less than 3. The release rate from PE tablets was little affected by pH. A linear relationship exists between the release rate of AAP and the rate of water absorption by the tablet. The ionization state of the phospholipids changes with the pH of the medium, and affects the hydration characteristics. The fully ionized state, at pH of less than 3 in the case of PC and above 3 in the case of PI is most effective on hydration. PE does not fully ionize because of intermolecular hydrogen bonding.

Absorption↗

Comparative study of alanine-amino-peptidase and gamma-glutamyl-transferase activity in normal Wistar rat urine.

24 h urinary alanine-amino-peptidase (AAP) and gamma-glutamyl transferase (GGT) activities were studied from the 3rd-7th month of life in male Wistar rats. A close relationship was found between AAP and GGT activity, except at the beginning and at the end of this period. At the end there appear 2 subgroups, the larger (70%) showing a strong correlation between AAP and GGT activity and the other (30%), demonstrating no correlation at all. A good correlation between AAP and GGT activities, creatinine, 24 h urine volume and 24 h creatinine output was found.

Aging↗

Effects of exposure to low levels of environmental cadmium on renal biomarkers.

We conducted a study among residents of a small community contaminated with heavy metals from a defunct zinc smelter and residents from a comparison community to determine whether biologic measures of cadmium exposure were associated with biomarkers of early kidney damage. Creatinine-adjusted urinary cadmium levels did not differ between the smelter and comparison communities; thus we combined individuals from both communities (n = 361) for further analyses. The overall mean urinary cadmium level was low, 0.26 microg/g creatinine, similar to reference values observed in the U.S. general population. For children ages 6-17 years, urinary concentration of N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and albumin were positively associated with urinary cadmium, but these associations did not remain statistically significant after adjusting for urinary creatinine and other potential confounders. For adults ages 18 or older, urinary concentration of NAG, AAP, and albumin were positively associated with urinary cadmium. The associations with NAG and AAP but not with albumin remained statistically significant after adjusting for creatinine and other potential confounders. We found a positive dose-effect relationship between levels of creatinine-adjusted urinary cadmium and NAG and AAP activity, and statistically significant differences in mean activity for these two enzymes between the highest (> or =1.0 microg cadmium/g creatinine) and the lowest (< or =0.25 microg cadmium/g creatinine) exposure groups. The findings of this study indicate that biologic measures of cadmium exposure at levels below 2.0 microg/g creatinine may produce measurable changes in kidney biomarkers.

Acetylglucosaminidase↗

Compliance with vision-screening guidelines among a national sample of pediatricians.

OBJECTIVE: The American Academy of Pediatrics (AAP) recommends vision screening from birth through adolescence, with visual acuity testing and binocular screening to begin at age 3 years. The 1996 AAP guidelines advised referral for visual acuity worse than 20/40 for children aged 3 to 5 years and worse than 20/30 for children aged 6 years and older. Our objective was to describe vision-screening and referral practices in a national sample of primary care pediatricians. METHODS: We mailed a survey to a random sample of US pediatricians. Initial nonresponders were mailed up to 3 additional surveys. All mailings occurred between May and October 1998. Analyses focused on primary care pediatricians and consisted of descriptive statistics and regression analyses. The main outcome measure was compliance with 1996 AAP recommendations for vision screening. RESULTS: Of the 1491 surveys mailed, 888 (60%) were returned, including 576 (65%) from primary care pediatricians. Vision-screening methods included visual acuity testing (92%), cover test (64%), red reflex test (95%), fundoscopic examinations (65%), and stereopsis testing (32%). Respondents routinely performed visual acuity testing at 3 years (37%), 4 years (79%), 5 years (91%), 6 years (80%), 7-12 years (82%), and 13-18 years (80%). Visual acuity thresholds for referring 3- and 4-year-olds were 20/40 (47%, 51%), 20/50 (36%, 32%), or worse than 20/50 (14%, 12%). The majority of pediatricians referred children aged 5 years and older at 20/40, although thresholds worse than 20/40 were reported commonly (18%-33%). Logistic regressions were done to identify factors associated with higher likelihood of performing specific screening tests. Although no factor was consistently associated with use of all screening tests, size of the practice was significant in several regression models. CONCLUSIONS: Many pediatricians do not follow AAP guidelines for vision screening and referral, especially in younger children. Two thirds of pediatricians do not begin visual acuity testing at age 3 years as recommended, and about one fifth do not test until age 5 years. In addition, one fourth do not perform cover tests or stereopsis testing at any age.

Adolescent↗

TV guides: exposure of hospitalized children to inappropriate programming.

OBJECTIVE: To determine if the policy recommendations of the American Academy of Pediatrics (AAP) regarding television viewing are heeded in an inpatient pediatric setting. SETTING: An inner-city academic medical center. PARTICIPANTS: Consecutive sample of 199 pediatric inpatients. METHODS: An investigator visited all pediatric inpatient rooms. Observations were made when the patient was present in the room, alert, and awake. The main outcome measure was exposure to inappropriate programming. In accordance with AAP guidelines, we used the established television rating system to code programs as appropriate versus inappropriate for children. We classified G- and PG-rated shows that centered on adult themes or that were not informational, educational, and nonviolent as inappropriate. We tested parental demographics, age of child, time of day, and presence of an adult in the room as possible predictors. RESULTS: Ninety-one percent of the patients had the television turned on. Of these, 53% were tuned to inappropriate programming. Exposure to inappropriate programming did not differ by parental ethnicity, language, or education. Exposure was highest for infants and toddlers as compared with children or adolescents (74% vs 40% vs 52%, P =.001); it did not vary by time of day. Exposure was higher when an adult was present in the room (58% vs 42%, P =.05); this effect was most pronounced for adolescents (68% vs 41%, P =.05). CONCLUSIONS: Despite AAP recommendations, hospitalized children are exposed to inappropriate programming, especially when parents are present in the room. Hospital stays may be a unique opportunity to educate parents about the AAP recommendations for television viewing by children.

Academic Medical Centers↗

Trends in practice characteristics: analyses of 19 periodic surveys (1987-1992) of Fellows of the American Academy of Pediatrics.

OBJECTIVE: To examine 6 years of practice characteristics data of Fellows of the American Academy of Pediatrics (AAP), focusing on sex differences for specialty area, primary activity, practice setting, and practice location. METHODS: We analyzed data from 19 Periodic Surveys that were fielded between 1987 and 1992. The Periodic Survey is used to survey AAP members regularly about current issues in pediatric practice. There are no duplicate respondents in these analyses of the first 19 Periodic Surveys. We collapsed the 19 surveys into the years in which they were fielded, and analyzed sex differences for each of the 6 years. In addition, we ran logistic regressions on several questions, including all 16 868 respondents, to examine how the characteristics of the specialty have been affected by the increase in the number of female pediatricians, controlling for survey year, age of respondents, and specialty area practiced. RESULTS: The proportion of nonresident AAP members who are female has grown throughout the 6 years; in 1987, 26.9% were female, and in 1992, 36.4% were female. For 5 of the 6 years there were sex differences in specialty area, usually concerning pediatric subspecialties. Substantial sex differences occurred in primary activity, in which each year women were more likely than men to be salaried. Men were more often in group practices, whereas women were generally more likely to practice in hospitals or clinics. Logistic regression demonstrated that there are sex differences in practice characteristics across time, but there is also a substantial change in practice characteristics accountable to survey year, eg, a pediatrician of either sex was 75% more likely to be salaried in 1992 than in 1987. CONCLUSIONS: Throughout the 6-year period, AAP members became increasingly more likely to practice general pediatrics, to be salaried, and to be younger-all effects independent of sex, all effects stronger for females. Rapid transformations in the health care system will likely reduce current sex differences in practice characteristics of the future.

Adolescent Medicine↗