Endocrine responses and acute mTOR pathway phosphorylation to resistance exercise with leucine and whey.

Leucine ingestion reportedly activates the mTOR pathway in skeletal muscle, contributing to a hypertrophy response. The purpose of the study was to compare the post-resistance exercise effects of leucine and whey protein supplementation on endocrine responses and muscle mTOR pathway phosphorylation. On visit 1, subjects (X±SD; n=20; age=27.8±2.8yrs) provided baseline blood samples for analysis of cortisol, glucose and insulin; a muscle biopsy of the vastus lateralis muscle to assess mTOR signaling pathway phosphorylation; and were tested for maximum strength on the leg press and leg extension exercises. For visits 2 and 3, subjects were randomized in a double-blind crossover design to ingest either leucine and whey protein (10g+10g; supplement) or a non-caloric placebo. During these visits, 5 sets of 10 repetitions were performed on both exercises, immediately followed by ingestion of the supplement or placebo. Blood was sampled 30 min post-, and a muscle biopsy 45 min post-exercise. Western blots quantified total and phosphorylated proteins. Insulin increased (α<.05) with supplementation with no change in glucose compared to placebo. Relative phosphorylation of AKT and rpS6 were greater with leucine and whey supplementation compared to placebo. Supplementation of leucine and whey protein immediately after heavy resistance exercise increases anabolic signaling in human skeletal muscle.

Focal adhesion kinase signaling is decreased 56 days following spinal cord injury in rat gastrocnemius.

STUDY DESIGN: Descriptive study. OBJECTIVES: The goal of this study was to determine the effects of spinal cord injury (SCI) on aspects of the focal adhesion kinase (FAK) signaling pathway 56 days post injury in rat gastrocnemius. SETTING: This study was conducted in Bronx, NY, USA. METHODS: Three-month-old male Wistar rats were exposed to either a sham surgery (n=10) or complete T4 spinal cord transection (n=10). Rats were killed 56 days following surgery and the muscle was collected. Following homogenization, proteins of the FAK pathway were analyzed by western immunoblotting or reverse transcription-qPCR. In addition, cellular markers for proteins that target the degradation of FAK were investigated. RESULTS: SCI resulted in significantly lower levels of total and phosphorylated FAK, cSrc and p70S6k, and a trend for increased FRNK protein expression. SCI did not change levels of the α7 or ß1 integrin subunits, total or phosphorylated ERK1/2, phosphorylated Akt and TSC2 or total p70S6k. SCI resulted in a greater expression of total Akt. mRNA expression of FAK and the α7 or ß1 integrins remained unchanged between sham and SCI groups. Caspase-3/7 activity and Trim72 mRNA and protein expression remained unchanged following SCI. CONCLUSION: SCI results in diminished FAK signaling and is independent of ERK1/2 and Akt. SCI has no effect on mRNA levels for genes encoding components of the focal adhesion 56 days after injury.

Prolonged space flight-induced alterations in the structure and function of human skeletal muscle fibres.

The primary goal of this study was to determine the effects of prolonged space flight (180 days) on the structure and function of slow and fast fibres in human skeletal muscle. Biopsies were obtained from the gastrocnemius and soleus muscles of nine International Space Station crew members 45 days pre- and on landing day (R+0) post-flight. The main findings were that prolonged weightlessness produced substantial loss of fibre mass, force and power with the hierarchy of the effects being soleus type I > soleus type II > gastrocnemius type I > gastrocnemius type II. Structurally, the quantitatively most important adaptation was fibre atrophy, which averaged 20% in the soleus type I fibres (98 to 79 µm diameter). Atrophy was the main contributor to the loss of peak force (P(0)), which for the soleus type I fibre declined 35% from 0.86 to 0.56 mN. The percentage decrease in fibre diameter was correlated with the initial pre-flight fibre size (r = 0.87), inversely with the amount of treadmill running (r = 0.68), and was associated with an increase in thin filament density (r = 0.92). The latter correlated with reduced maximal velocity (V(0)) (r = 0.51), and is likely to have contributed to the 21 and 18% decline in V(0) in the soleus and gastrocnemius type I fibres. Peak power was depressed in all fibre types with the greatest loss (55%) in the soleus. An obvious conclusion is that the exercise countermeasures employed were incapable of providing the high intensity needed to adequately protect fibre and muscle mass, and that the crew's ability to perform strenuous exercise might be seriously compromised. Our results highlight the need to study new exercise programmes on the ISS that employ high resistance and contractions over a wide range of motion to mimic the range occurring in Earth's 1 g environment.

Sex-related differences in muscle size explained by amplitudes of higher-threshold motor unit action potentials and muscle fibre typing.

AIM: To investigate the relationships between motor unit action potential amplitudes (MUAPAMP ), muscle cross-sectional area (mCSA) and composition (mEI), per cent myosin heavy chain (%MHC) areas and sex in the vastus lateralis (VL). METHODS: Ten males and 10 females performed a submaximal isometric trapezoid muscle action that included a linearly increasing, steady torque at 40% maximal voluntary contraction, and linearly decreasing segments. Surface electromyographic decomposition techniques were utilized to determine MUAPAMPS in relation to recruitment thresholds (RT). Ultrasound images were taken to quantify muscle mCSA and mEI. Muscle biopsies were collected to calculate %MHC areas. Y-intercepts and slopes were calculated for the MUAPAMP vs RT relationships for each subject. Independent-samples t tests and ANOVA models examined sex-related differences in mCSA, mEI, slopes and y-intercepts for the MUAPAMP vs RT relationships and %MHC areas. Correlations were performed among type IIA and total type II %MHC area, mCSA and the slopes and y-intercepts for the MUAPAMP vs RT relationships. RESULTS: Males exhibited greater slopes for the MUAPAMP vs RT relationships (P = .003), mCSA (P < .001) and type IIA %MHC (P = .011), whereas females had greater type I %MHC area (P = .010) and mEI (P = .024). The mCSA, type IIA and total II %MHC area variables were correlated (P < .001-.015, r = .596-.836) with the slopes from the MUAPAMP vs RT relationships. CONCLUSION: Sex-related differences in mCSA and MUAPAMPS of the higher-threshold MUs were likely the result of larger muscle fibres expressing type II characteristics for males.

Androgen responsiveness of the murine beta-glucuronidase gene is associated with nuclease hypersensitivity, protein binding, and haplotype-specific sequence diversity within intron 9.

The tissue specificity and genetic variability of the murine beta-glucuronidase (GUS) response to androgen provide useful markers for identifying elements which underlie this responsiveness. While GUS is expressed constitutively in all examined cell types, kidney epithelial cells uniquely exhibit a manyfold yet slow rise in GUS mRNA and enzyme levels when stimulated by androgens. Three major phenotypes of this androgen response have been described among inbred strains of mice: (i) a strong response in strains of the Gusa haplotype, (ii) a reduced response in strains of the Gusb and Gush haplotypes, and (iii) no response, as observed in Gusor mice. These response variants define a cis-active element(s) which is tightly linked to the GUS structural gene. Nuclease hypersensitivity scans of kidney chromatin within and surrounding the structural gene revealed an androgen-inducible hypersensitive site in intron 9 of the gene in Gusa but not in Gusor mice. When a radiolabeled fragment of Gusa DNA containing this hypersensitive site was incubated with kidney nuclear extracts and then subjected to gel electrophoresis, two shifted bands were observed whose levels were dramatically higher in extracts of androgen-treated than in those of untreated Gusa mice. The shifted bands reflect binding of a kidney-specific factor(s) to a 57-bp region of complex dyad symmetry in Gusa and Gusor mice which is partially deleted in Gusb and Gush mice. This binding site is located approximately 130 bp downstream of a glucocorticoid response element sequence motif which is totally deleted in [Gus]or mice. Taken together, our results suggest that the androgen responsiveness of GUS in murine kidney epithelial cells is controlled by elements within the proximal end of intron 9 of the GUS structural gene.

DNA determinants of structural and regulatory variation within the murine beta-glucuronidase gene complex.

The murine beta-glucuronidase (GUS) gene complex, [Gus], encompasses the GUS structural element, Gus-s, and a set of regulatory elements which serve to modulate Gus-s expression. Three common GUS haplotypes representing virtually all inbred strains of laboratory mice have been compared with respect to GUS mRNA sequence. Results of such comparisons revealed sequence variations which target the location of one of the GUS regulatory elements to sequences within Gus-s and which account for known electrophoretic and heat stability differences among GUS allozymes of the three common GUS haplotypes.

Squamous cell hyperplastic foci: precursors of cutaneous papillomas induced in SENCAR mice by a two-stage carcinogenesis regimen.

We have conducted a series of experiments to characterize the lesions that are precursors of cutaneous papillomas in SENCAR mice initiated with 7,12-dimethylbenz(a)anthracene (DMBA) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA). The first grossly detectable lesions at sites where papillomas subsequently developed were papules, slightly raised areas of skin ranging in diameter from 0.25 to approximately 1.5 mm. Papules were first detected in DMBA-initiated mice 21 days after the start of dosing with TPA. Of 78 DMBA/TPA-induced papules tracked during 15 weeks of TPA treatments, 68% progressed to papillomas, 9% persisted as papules, and 22% completely regressed. Histological evaluation of serial sections of 69 DMBA/TPA-induced papules revealed that they were focal hyperplastic lesions that we refer to as squamous cell hyperplastic foci (SCHF). These hyperproliferative lesions appeared to progress through two distinct stages. Stage I SCHF were characterized as regular hyperplastic foci involving the interfollicular epidermis and the outer root sheaths of 1 or more hair follicles down to the level of the sebaceous glands. Stage II SCHF were foci of irregular epithelial hyperplasia with increased fibrovascular stroma and involved from 3 to >10 hair follicles. Prominent dilated capillaries and inflammatory cell infiltrates were frequently associated with both stage I and II SCHF. Ha-ras gene codon 61 mutations were detected in 7 of 10 stage I SCHF and 13 of 14 stage II SCHF microdissected from histological sections and 7 of 7 of whole papules by mutation-specific PCR analysis. These data provide molecular evidence that SCHF are foci of initiated cells. Further study of these lesions may contribute to more fully defining the sequence of molecular and cellular changes necessary for tumorigenesis in mouse skin. SCHF may also have utility as early indicators of potential skin tumorigenicity in cancer bioassays.

The change in motor unit firing rates at de-recruitment relative to recruitment is correlated with type I myosin heavy chain isoform content of the vastus lateralis in vivo.

AIM: To investigate the change in motor unit (MU) firing rates (FR) at de-recruitment relative to recruitment and the relation to % type I myosin heavy chain isoform content (type I %MHC) of the vastus lateralis (VL) in vivo. METHODS: Ten subjects performed a 22-s submaximal isometric trapezoid muscle action that included a linearly increasing, steady force at 50% maximal voluntary contraction, and linearly decreasing segments. Surface electromyographic signals were collected from the VL and were decomposed into constituent MU action potentials trains. A tissue sample from the VL was taken to calculate type I %MHC. The y-intercepts and slopes were calculated for the changes (Δ) in FR at de-recruitment (FRDEREC ) relative to FR at recruitment (FRREC ) vs. FRREC relationship for each subject. Correlations were performed between the y-intercepts and slopes with type I %MHC. RESULTS: The majority of MUs had greater FRDEREC than FRREC . The y-intercepts (r = -0.600, P = 0.067) were not significantly correlated, but the slopes (r = -0.793, P = 0.006) were significantly correlated with type I %MHC. CONCLUSION: The majority of the motoneuron pool had greater FRDEREC than FRREC , however, individuals with higher type I %MHC had a greater propensity to have MUs with FRREC > FRDEREC as indicated by the slope values. Overall, the contractile properties of the muscle (MHC) could partially explain the differences in MU firing rates at de-recruitment relative to recruitment. Thus, suggesting the fatigability of the muscle influences the alterations in MU firing rates from recruitment to de-recruitment.

The role of hereditary hemochromatosis in aseptic loosening following primary total hip arthroplasty.

Hereditary hemochromatosis (HH) results in increased iron absorption and subsequent deposition in tissue. This condition occurs predominantly in individuals of Northern European and Celtic origin with Ireland having one of the highest allele frequencies in the world. This study examines the hypothesis that homozygosity for either the C282Y or H63D mutations in the HFE gene may be associated with aseptic loosening following total hip arthroplasty (THA). Two groups of individuals were screened for the C282Y and H63D mutations associated with HH. Group 1 were individuals who had undergone primary hip arthroplasty and group 2 were individuals who had undergone revision hip arthroplasty for aseptic loosening. Exclusion criteria included rheumatoid or other inflammatory arthropathies and revision due to causes other than aseptic loosening. Significantly more patients in the revision THA group were homozygous for the C282Y genotype (P = 0.014). Aseptic loosening occurred earlier in these patients (P = 0.009), in particular in the patients who had clinical signs of hemochromatosis. No association was seen with the H63D mutation and revision THA. The incidence of HH in the group of primary THA patients was no higher than the background incidence. Patients who require primary THA and who are homozygous for the C282Y mutation have an increased risk of developing aseptic loosening, leading to revision THA. Moreover C282Y homozygosity appears to be associated with earlier aseptic loosening than in individuals without the C282Y mutation.

Androgen responsiveness of mouse kidney beta-glucuronidase requires 5'-flanking and intragenic Gus-s sequences.

Genetics studies of natural variants of the androgen response of mouse beta-glucuronidase (GUS) reveal a cis-active element closely linked to the GUS structural gene (Gus-s) that is necessary for this kidney-specific response. Results of our previous studies suggested sequences within or near an androgen-inducible deoxyribonuclease I-hypersensitive site (DH site) located in the ninth intron of Gus-s are associated with the androgen response of GUS. Using transgenic mice, we now demonstrate that at least two regions of sequence within Gus-s are involved in regulating the androgen response of GUS. The first, located within 3.8 kb of Gus-s 5'-flanking sequence, directs the response and its tissue specificity, while the second, located within a 6.4-kb fragment of Gus-s extending from the third through the ninth intron of Gus-s, protects the androgen responsiveness of the transgene from repressive influences of the insertion site.

Reduction in hybrid single muscle fiber proportions with resistance training in humans.

The purpose of this investigation was to examine the effects of 12 wk of progressive resistance training (PRT) on single muscle fiber myosin heavy chain (MHC; I, I/IIa, I/IIa/IIx, IIa, IIa/IIx, IIx) isoform proportions in young individuals. Young, untrained men (YM; n = 6) and women (YW; n = 6) (age = 22 +/- 1 and 25 +/- 2 yr for YW and YM, respectively) received pre- and post-PRT muscle biopsies from the right vastus lateralis for single muscle fiber MHC distribution by electrophoretic analysis (192 +/- 5 pre- and 183 +/- 6 post-fibers/subject analyzed; 4,495 fibers total). Data are presented as percentages of the total fibers analyzed per subject. The PRT protocol elicited an increase in the pure MHC IIa (Delta = + 24 and + 27; YW and YM, respectively; P < 0.05) with no change in the pure MHC I distribution. The hybrid MHC distributions decreased I/IIa/IIx (Delta = -2; YM and YW; P < 0.05), IIa/IIx (Delta = -13 and -19 for YM and YW, respectively; P < 0.05), and total hybrid fiber proportion (I/IIa + I/IIa/IIx + IIa/IIx) decreased (Delta = -19 and -30 for YM and YW, respectively; P < 0.05) with the training, as did the MHC IIx distribution (Delta = -2; YW only; P < 0.05). Alterations in the predominance of MHC isoforms within hybrid fibers (decrease in MHC I-dominant I/IIa and nondominant MHC IIa/IIx, increase in MHC IIa-dominant IIa/IIx; P < 0.05) appeared to contribute to the increase in the MHC IIa proportion. Electrophoresis of muscle cross sections revealed an approximately 7% increase (P < 0.05) in MHC IIa proportion in both groups, whereas the MHC IIx decrease by 7.5 and 11.6% post-PRT in YW and YM, respectively. MHC I proportions increase in YM by 4.8% (P < 0.05) post-PRT. These findings further support previous resistance training data in young adults with respect to the increase in the MHC IIa proportions but demonstrate that a majority of the change can be attributed to the decrease in single-fiber hybrid proportions.

Effects of postexercise carbohydrate-protein feedings on muscle glycogen restoration.

The purpose of this investigation was to determine the effects of postexercise eucaloric carbohydrate-protein feedings on muscle glycogen restoration after an exhaustive cycle ergometer exercise bout. Seven male collegiate cyclists [age = 25.6 +/- 1.3 yr, height = 180.9 +/- 3.2 cm, wt = 75.4 +/- 4.0 kg, peak oxygen uptake (VO(2 peak)) = 4.20 +/- 0.2 l/min] performed three trials, each separated by 1 wk: 1) 100% alpha-D-glucose [carbohydrate (CHO)], 2) 70% carbohydrate-20% protein (PRO)-10% fat, and 3) 86% carbohydrate-14% amino acid (AA). All feedings were eucaloric, based on 1.0 g. kg body wt(-1). h(-1) of CHO, and administered every 30 min during a 4-h muscle glycogen restoration period in an 18% wt/vol solution. Muscle biopsies were obtained immediately and 4 h after exercise. Blood samples were drawn immediately after the exercise bout and every 0.5 h for 4 h during the restoration period. Increases in muscle glycogen concentrations for the three feedings (CHO, CHO-PRO, CHO-AA) were 118 mmol/kg dry wt; however, no differences among the feedings were apparent. The serum glucose and insulin responses did not differ throughout the restoration period among the three feedings. These results suggest that muscle glycogen restoration does not appear to be enhanced with the addition of proteins or amino acids to an eucaloric CHO feeding after exhaustive cycle exercise.

Beta-hydroxy-beta-methylbutyrate ingestion, Part I: effects on strength and fat free mass.

PURPOSE: The purpose of this investigation was 1) to determine whether HMB supplementation results in an increase in strength and FFM during 8 wk of resistance training and 2) determine whether a higher dose of HMB provides additional benefits. METHODS: Thirty-seven, untrained, college-aged men were assigned to one of three groups: 0, 38, or 76 mg x kg(-1) x d(-1) of HMB (approximately equal to 3 and 6 g x d(-1), respectively). Resistance training consisted of 10 different exercises performed 3 d x wk(-1) for 8 wk at 80% of 1-repetition maximum (1RM). The 1RM was reevaluated every 2 wk with workloads adjusted accordingly. RESULTS: No differences were observed in 1RM strength among the groups at any time. However, the 38 mg x kg (-1) x d(-1) group showed a greater increase in peak isometric torque than the 0 or 76 mg.kg(-1) x d(-1) groups (P < 0.05). The 76 mg x kg(-1) x d(-1) group had a greater increase in peak isokinetic torque than the 0 or 38 mg x kg(-1) x d(-1) groups at 2.1, -3.15, and -4.2 rad x s(-1) (P < 0.05). Plasma creatine phosphokinase (CPK) activity was greater for the 0 mg x kg(-1) x d(-1) versus the 38 or 76 mg x kg(-1) x d(-1) groups at 48 h after the initial training bout (P < 0.05). In addition, no differences were observed in body fat between the three groups. However, the 38 mg x kg(-1) x d(-1) group exhibited a greater increase in FFM (P < 0.05). CONCLUSIONS: Although the IRM strength gains were not significantly different, HMB supplementation appears to increase peak isometric and various isokinetic torque values, and increase FFM and decrease plasma CPK activity. Lastly, it appears that higher doses of HMB (i.e., > 38 mg x kg(-1) x d(-1)) do not promote strength or FFM gains.

Beta-hydroxy-beta-methylbutyrate ingestion, part II: effects on hematology, hepatic and renal function.

PURPOSE: The purpose of this investigation was to examine the effects of differing amounts of beta-hydroxy-beta-methylbutyrate (HMB), 0, 36, and 76 mg x kg(-1) x d(-1), on hematology, hepatic and renal function during 8 wk of resistance training. METHODS: Thirty-seven, untrained collegiate males and were randomly assigned to one of the three groups, 0, 38, or 76 mg x kg(-1) x d(-1). Resistance training consisted of 10 exercises, performed 3 d x wk(-1) for 8 wk at 80% of their 1-repetition maximum. Blood and urine was obtained before training, 48 h after the initial session, 1 wk, 2 wk, 4 wk, and at 8 wk of resistance training. Blood was analyzed for glucose, blood urea nitrogen, hemoglobin, hepatic enzymes, lipid profile, total leukocytes, and individual leukocytes. Urine was analyzed for pH, glucose, and protein excretion. RESULTS: The 38 mg x kg(-1) x d(-1) group had a greater increase in basophils compared with 0 or 76 mg x kg(-1) x d(-1) groups (P < 0.05). No difference occurred in any other blood and urine measurements. CONCLUSION: These data indicate that 8 wk of HMB supplementation (< or = 76 mg x kg(-1) x d(-1)) during resistance training had no adverse affects on hepatic enzyme function, lipid profile, renal function, or the immune system.

Outcome of patients admitted to an acute geriatric medical unit.

To find out what happens to patients admitted to an acute geriatric medical unit, all admissions during 1982 were reviewed. Demographic features were compared with those of the community served, and rehabilitation, inpatient mortality and mortality in the year following discharge were assessed. Inpatients accounted for 4% of the community aged over 65, and most patients were discharged back to the community. Inpatient mortality was 25% and mortality in the year following discharge was 23%, giving a two year mortality of 42%, which was similar in all age groups. The achievement of high rehabilitation rates was tempered by the considerable mortality rates following discharge.

Effects of short-term concentric vs. eccentric resistance training on single muscle fiber MHC distribution in humans.

The purpose of this investigation was to determine the effects of a concentric vs. eccentric resistance training program on single muscle fiber myosin heavy chain (MHC) adaptations in humans. Fifteen sedentary, healthy males were divided into three groups: concentric training (CTG) (n = 6, 24.2 +/- 1.7 y, 181 +/- 2 cm, 82.5 +/- 4.6 kg), eccentric training (ETG) (n = 6, 23.7 +/- 1.6 y, 178 +/- 3 cm, 90.4 +/- 6.1 kg), and control (CTL) (n = 3, 23 +/- 1.5 y, 181 +/- 2 cm, 97 +/- 13.2 kg). The subjects performed 4 sets of 8 unilateral repetitions starting at 80 % of concentric 1-RM, 3 days/week for a total of 4 weeks. Subjects were tested pre- and post-training for concentric 1-RM. Muscle biopsies were obtained from the vastus lateralis pre- and post-training for determination of single fiber MHC isoform distribution using SDS-PAGE/silver staining (100 fibers analyzed/subject pre- and post-training). Fibers expressing more than one MHC isoform (i.e., hybrid fibers) were analyzed for relative MHC isoform proportions via densitometry. The training program resulted in a 19 % 1-RM strength gain for CTG (p < 0.05) with no change in ETG or CTL. MHC-IIx fibers decreased by 7 % in CTG (p < 0.05) and ETG had an 11 % increase in total hybrids (MHC-I/IIa + MHC-IIa/IIx) (p < 0.05). No other differences were noted in MHC distribution among the three groups. Densitometry analysis of hybrid fibers showed no change in relative MHC isoform proportions pre- to post-training for any group. These data suggest that the MHC distribution did not change dramatically as a result of 4 weeks of concentric vs. eccentric resistance training despite the increase in whole muscle strength from concentric muscle actions.

Accident-prone norms: implications for clinical laboratories. A methods for examining groups norms and interaction networks.

Employee accidents are a costly problem for clinical laboratories. Consequently, investigation and prevention of accidents are integral parts of the clinical laboratory manager's job. There are a wide variety of traditional modes of accident research; however, they usually do not include investigations of work group norms and interaction networks. Group norms that contradict formal safety norms can arise in clinical laboratory work groups. These accident-prone norms often result in problematic procedures and activities. Examples of these accident-prone norms include: failure to use safety equipment, failure to follow safety procedures, alcohol or drug use on the job, failure to pass on information about equipment problems, and failure to report job-related accidents. These norms are frequently transmitted through interaction networks. Sociometric techniques can provide insights about the networks and can be used to develop solutions to accident-prone norms.

Comparing telephone and mail responses to the CAHPS survey instrument. Consumer Assessment of Health Plans Study.

OBJECTIVES: The Consumer Assessment of Health Plans (CAHPS) survey is designed to collect member experiences with getting medical care. The objective was to evaluate the comparability of answers to CAHPS questions when data are collected by mail and by telephone interview. METHODS: Two studies comparing phone and mail responses used a pretest instrument with parallel samples drawn from Medicaid beneficiaries in California (n = 217 telephone, 97 mail) and adults with chronic conditions who had health insurance through the State of Washington (n = 98 telephone, 109 mail). A third study used a revised instrument with two parallel cross-section samples of adults covered through the State of Washington (n = 446 telephone, 609 mail). Questions covered respondents' experiences with getting medical care through their health plans. RESULTS: In the first two tests, numerous significant differences were found in the rates at which questions that potentially did not apply to all respondents were answered: some ratings were more positive on the telephone. In the test of a revised instrument, nine of 58 comparisons differed significantly by mode. The systematic differences in response to questions that did not apply to all respondents were greatly reduced. Only one of four ratings and one of seven multi-item composite measures of quality of care were significantly different by mode. CONCLUSION: Although further steps to reduce the remaining mode effects are needed, the data indicate that when the revised CAHPS questions are used, mode of data collection will have little effect on the key results.