Effects of fruit and vegetable, consumed in solid vs beverage forms, on acute and chronic appetitive responses in lean and obese adults.

BACKGROUND: The effects of fruits and vegetables in solid vs beverage forms on human appetite and food intake, acutely and chronically, are unclear. METHODS: This 21-week, randomized, crossover study assessed appetitive ratings following the inclusion of fruits and vegetables, in solid and beverage form, into the habitual diet of healthy lean (n=15) and overweight/obese (n=19) adults with low customary consumption. The primary acute outcomes were satiation (amount of challenge meal consumed), satiety (latency of subsequent eating event) and dietary compensation after a 400 kcal fruit preload. Ratings of appetite were also obtained before and after 8 weeks of required increased fruit and vegetable consumption (20% estimated energy requirement). RESULTS: Acutely, overweight/obese participants reported smaller reductions of hunger after consuming the fruit preload in beverage compared with solid form (preload × form × body mass index effects, P=0.03). Participants also consumed significantly less of a challenge meal (in both gram and energy) after the ingestion of the solid fruit preload (P<0.005). However, the subsequent meal latency was not significantly different between the solid and the beverage fruit preloads. Total daily energy intake was significantly higher when the obese participants consumed the beverage fruit preload compared with the solid (P<0.001). Daily energy intake was markedly, but not significantly, higher among the lean with the beverage vs solid food form. Hunger and fullness ratings remained stable when participants consumed fruits and vegetables in solid or beverage form for 8 weeks each. CONCLUSION: Acute post-ingestive appetitive responses were weaker following consumption of fruits in beverage vs solid food forms. Consumption of beverage or solid fruit and vegetable food loads for 8 weeks did not chronically alter appetitive responses.

Age attenuates leucine oxidation after eccentric exercise.

Aging may alter protein metabolism during periods of metabolic and physiologic challenge. The purpose of this study was to assess the effects of age on whole-body amino acid turnover in response to eccentric exercise and hyperglycemia-induced hyperinsulinemia. 16 healthy men were divided into young (N=8) and older (N=8) groups. Protein metabolism was assessed using a [1-13C]-leucine isotopic tracer approach. Measures were obtained under fasted basal conditions and during 3-h hyperglycemic clamps that were performed without (control) and 48 h after eccentric exercise. Exercise reduced leucine oxidation in the younger men (P<0.05), but not in older men. Insulin sensitivity was inversely correlated with leucine oxidation (P<0.05), and was lower in older men (P<0.05). Healthy aging is associated with an impaired capacity to adjust protein oxidation in response to eccentric exercise. The decreased efficiency of protein utilization in older men may contribute to impaired maintenance, growth, and repair of body tissues with advancing age.

Effects of acute pinitol supplementation on plasma pinitol concentration, whole body glucose tolerance, and activation of the skeletal muscle insulin receptor in older humans.

Limited research with rodents and humans suggests that oral ingestion of pinitol (3- O-methyl- D- CHIRO-inositol) might positively influence glucose tolerance. This double-blinded, placebo-controlled, and cross-over study assessed the effects of acute pinitol supplementation on plasma pinitol concentration, glucose tolerance, insulin sensitivity, and activation of the skeletal muscle insulin receptor. Fifteen older, nondiabetic subjects (62+/-1 years, mean+/-SEM) completed four, 1-day trials. Subjects consumed a non-nutritive beverage with nothing (placebo) or 1,000 mg pinitol. Sixty minutes later, the subjects consumed beverages that were either energy- and carbohydrate-free (Sham) or contained 75 g glucose (OGTT). Blood samples were collected frequently over the 240-min testing period. For the OGTT trials only, vastus lateralis samples were obtained before the placebo and pinitol supplementation and 60 min after consuming the 75 g glucose beverage. Plasma pinitol concentration increased and was maintained for 240 min. Pinitol did not influence the fasting state and 180-min area under the curves for plasma glucose and insulin during the Sham and OGTT trials or hepatic (placebo 0.83+/-0.08; pinitol 0.80+/-0.08) and whole-body (placebo 6.10+/-0.54; pinitol 6.22+/-0.52) insulin sensitivities. Activation of the muscle insulin receptor was increased by 140% with glucose ingestion (Pre 0.62+/-0.12; Post 1.49+/-0.35), but pinitol did not influence this response. These results show that the pinitol supplement was quickly absorbed, but did not acutely influence indices of whole-body glucose tolerance and insulin sensitivity, or the activation of the skeletal muscle insulin receptor in older, nondiabetic humans.

Moderately increased protein intake predominately from egg sources does not influence whole body, regional, or muscle composition responses to resistance training in older people.

UNLABELLED: The effects of increased dietary protein on resistance training (RT)-induced changes in body composition and skeletal muscle fiber size are uncertain in older people. OBJECTIVES: We hypothesized that the ingestion of more animal-based foods, especially eggs, to achieve a higher protein intake would enhance RT-induced changes in body composition. SETTING: West Lafayette, IN. PARTICIPANTS: 36 older people (age 61 +/- 1 y; mean +/- SEM). INTERVENTION: Subjects completed RT three d/wk for 12 weeks, and consumed omnivorous diets that contained either 0.9 +/- 0.1 (lower protein) or 1.2 +/- 0.0 (higher protein) g protein x kg(-1) x d(-1) (12 +/- 3 and 17 +/- 5% of energy intakes, respectively), with the higher protein intake achieved by consuming more eggs, meats, and dairy foods. The lower and higher protein diets contained 213 +/- 21 and 610 +/- 105 mg cholesterol/d, respectively. MEASUREMENTS: Strength, body composition, serum lipid-lipoprotein profile, urinary creatinine, skeletal muscle fiber type and size. RESULTS: Among all subjects, over time (i.e. with RT) body weight was unchanged, lean mass (1.1 +/- 0.2 kg) increased, and fat mass (-1.4 +/- 0.2 kg) decreased (all changes P < 0.05). Regional (i.e. trunk, legs, arms) lean mass increased and fat mass decreased. Whole body muscle mass (24-h urinary creatinine excretion) increased, but skeletal muscle (vastus lateralis) type 1, type 2a, and type 2x fiber cross-sectional areas did not change from baseline. Serum total and LDL cholesterol decreased (P < 0.05) and HDL cholesterol and triacylglycerol were unchanged. Dietary protein and cholesterol intakes did not influence these responses to RT. CONCLUSION: Consumption of diets that contained moderately higher protein and variable amounts of cholesterol did not differentially affect body composition, skeletal muscle fiber size, or serum lipid-lipoprotein profile responses to resistance training in older people.

Measurement of body composition changes with weight loss in postmenopausal women: comparison of methods.

BACKGROUND: The accurate measurement of body composition changes is important when evaluating the efficacy of medical nutrition therapy and weight management programs, yet is not well documented in older women. OBJECTIVE: We compared methods of estimating energy-restriction-induced body composition changes in postmenopausal women. DESIGN: 27 women (59 +/- 8 y; BMI 29.0 +/- 2.9 kg/m2; mean +/- SD) completed a 9-wk energy restriction period (5233 kJ/d, (1250 kcal/d)). Changes in % body fat (delta%BF), fat mass (deltaFM), and fatfree mass (deltaFFM) were measured by hydrostatic weighing (HW), air-displacement plethysmography (ADP), dual-energy x-ray absorptiometry (DXA), and deuterium oxide dilution (D2O). The Baumgartner et al. (Am J Clin Nutr 53:1345-1353, 1991) four-compartment (4C) model with body volume from HW was the criterion method. The 4C model with body volume from ADP was also compared. Regression equations were developed based on 4CHW (dependent variable) utilizing results of change (POST-PRE) for each method. RESULTS: The women lost 6.8 +/- 3.2 kg; 9% of baseline weight. Based on 4CHW, the body composition changes were -2.4 +/- 4.5 delta%BF, -4.7 +/- 3.3 kg deltaFM, and -2.6 +/- 4.4 kg deltaFFM. No differences were detected by ANOVA for delta%BF, deltaFM, and deltaFFM among 4CHW, HW, ADP, DXA, D2O, and 4CADP. Bland-Altman limits of agreement showed differences between methods that ranged from 14.5 to -14.1 delta%BF, 7.8 to -8.1 kg deltaFM, and 7.5 to -8.4 kg deltaFFM for individuals. A bias was shown with 4CADP overestimating delta%BF (1.4 %) and FM (0.6 kg) and underestimating deltaFFM (-1.2 kg) compared to 4CHW. The regression model was acceptable for %BF (4CADP, 2CHW, and 2CD2O); FM and FFM (4CADP, 3CDXA, 2CHW, and 2CD2O), but not for other estimates of %BF, FM, FFM. CONCLUSIONS: These body composition assessment methods may be used interchangeably to quantify changes in % body fat, fat mass, and fat-free mass with weight loss in groups of postmenopausal women. 4CADP overestimates delta%BF and underestimates deltaFFM. When utilizing one of these comparison methods (4CADP, 3CDXA, 2CHW, 2CD2O) to quantify changes in fat mass and fat-free mass for an individual postmenopausal woman, regression equations may be used to relate the data to 4CHW.

Development of a Novel Six-Month Nutrition Intervention for a Randomized Trial in Older Men with Mobility Limitations.

OBJECTIVES: Nutrition impacts the development of sarcopenia and protein intake is an important modulator of skeletal muscle mass loss in older people. The Optimizing Protein Intake in Older Men with Mobility Limitation (OPTIMEN) Trial was designed to assess the independent and combined effects of higher protein intake and a promyogenic agent, testosterone, on lean body mass, muscle strength and physical function in older men with mobility disability. The purpose of this paper is to describe the experimental design and nutrition intervention, including techniques used by research dietitians to develop and deliver energy and protein-specific meals to the homes of community-dwelling participants. Strategies to enhance long-term dietary compliance are detailed. DESIGN: Randomized, double-blind, placebo-controlled six-month intervention trial. SETTING: Participants were recruited from Boston MA USA and surrounding communities. PARTICIPANTS: Older men who were mobility-limited (Short Physical Performance Battery (SPPB) 3-10) and consuming less protein (<0.83 g/kg/day) were recruited for this study. INTERVENTION: Here we report the successful implementation of a double-blind, placebo-controlled, parallel group, randomized controlled trial with a 6-month intervention period among community-living men, age 65 years and older with a mobility limitation. A controlled feeding plan was used to deliver required energy intakes and prescribed protein quantities of 0.8 or 1.3 grams/kilogram/day (g/kg/d) in three meals plus snacks and supplements. A 2x2 factorial design was used to assess the effects of protein level alone and in combination with testosterone (vs. placebo) on changes in lean body mass (primary outcome), muscle strength, and physical function. RESULTS: A total of 154 men met the eligibility criteria; 112 completed a 2-week run-in period designed to evaluate compliance with the nutrition intervention. Of these, 92 subjects met compliance eligibility criteria and agreed to be randomized; 85% completed the full trial. The study successfully delivered three meals per day to subjects, with a high degree of compliance and subject satisfaction. Overall self-reported compliance rates were 80% and 93% for the meals and supplements, respectively. Details of compliance strategies are discussed. CONCLUSION: This community-based study design may serve as a model for longer-term nutritional interventions requiring monitoring of dietary compliance in a home-based feeding and supplementation trial.

Short-term moderate weight loss and resistance training do not affect insulin-stimulated glucose disposal in postmenopausal women.

OBJECTIVES: Moderate weight loss and exercise have been proposed as important tools in the treatment and prevention of type 2 diabetes. Therefore, we tested the hypothesis that short-term (4 weeks) moderate energy restriction (-750 kcal/day) would result in a significant increase in insulin-stimulated glucose disposal (40 mU x m(-2) x min(-1) hyperinsulinemic-euglycemic clamp) in moderately overweight postmenopausal women and that when combined with resistance training (RT) an even greater effect would be seen. RESEARCH DESIGN AND METHODS: Older women were randomly assigned to energy restriction (WLoss group; n = 9) or energy restriction plus RT (RT + WLoss group; n = 10). RESULTS: For the WLoss versus the RT + WLoss groups, changes in body weight (-3.0 +/- 0.2 kg vs. -3.2 +/- 0.3 kg), fat mass (FM) (-3.0 +/- 0.3 kg vs. -3.2 +/- 0.3 kg), and percent body fat (BF) (-2.1 +/- 0.4 vs. -2.4 +/- 0.3%) were not different between groups. Muscle mass (group-by-time interaction, P = 0.04) was preserved in RT + WLoss (0.40 +/- 0.40 kg) and reduced in WLoss (-0.64 +/- 0.18 kg). There were no changes in fat-free mass (FFM) and waist-to-hip ratio in either group. Whole body glucose disposal (WLoss 6.14 +/- 0.57 vs. 6.03 +/- 0.53, RT + WLoss 5.85 +/- 0.60 vs. 6.09 +/- 0.56 mg/kg of FFM/min) did not change in either group. CONCLUSIONS: The results of this study demonstrate that short-term energy restriction resulting in moderate decreases in body weight (4.0 +/- 0.3%) and FM (8.2 +/- 0.7%) did not improve insulin-stimulated glucose disposal. The addition of RT to the hypoenergetic diet preserved muscle mass but provided no synergistic effect on insulin action. These results suggest that a greater change in body weight or FM may be necessary to observe a significant improvement in insulin action.

In vivo effects of dietary quercetin and quercetin-rich red onion extract on skeletal muscle mitochondria, metabolism, and insulin sensitivity.

Red onions and low doses of the flavonoid, quercetin, increase insulin sensitivity and improve glucose tolerance. We hypothesized that dietary supplementation with red onion extract (RO) would attenuate high fat diet (HFD)-induced obesity and insulin resistance similar to quercetin supplementation by increasing energy expenditure through a mechanism involving skeletal muscle mitochondrial adaptations. To test this hypothesis, C57BL/6J mice were randomized into four groups and fed either a low fat diet (LF), HFD (HF), HFD + quercetin (HF + Q), or HFD + RO (HF + RO) for 9 weeks. Food consumption and body weight and composition were measured weekly. Insulin sensitivity was assessed by insulin and glucose tolerance tests. Energy expenditure and physical activity were measured by indirect calorimetry. Skeletal muscle incomplete beta oxidation, mitochondrial number, and mtDNA-encoded gene expression were measured. Quercetin and RO supplementation decreased HFD-induced fat mass accumulation and insulin resistance (measured by insulin tolerance test) and increased energy expenditure; however, only HF + Q showed an increase in physical activity levels. Although quercetin and RO similarly increased skeletal muscle mitochondrial number and decreased incomplete beta oxidation, establishing mitochondrial function similar to that seen in LF, only HF + Q exhibited consistently lower mRNA levels of mtDNA-encoded genes necessary for complexes IV and V compared to LF. Quercetin- and RO-induced improvements in adiposity, insulin resistance, and energy expenditure occur through differential mechanisms, with quercetin-but not RO-induced energy expenditure being related to increases in physical activity. While both treatments improved skeletal muscle mitochondrial number and function, mtDNA-encoded transcript levels suggest that the antiobesogenic, insulin-sensitizing effects of purified quercetin aglycone, and RO may occur through differential mechanisms.

Anterior horn changes of motor neuron disease associated with demyelinating radiculopathy.

Morphologic study of the spinal cord of a patient with generalized motor deficits revealed changes in the anterior horns characterized by the selective loss of large motor neurons, gliosis and the abnormal accumulation of 10 nm filaments which appeared as argyrophilic spheroids in the perikarya and axons of motor neurons. The ventral roots were predominantly affected and showed a variable loss of axons. The remaining axons displayed prominent onion-bulb formations, frequent axonal sprouting and occasionally evidence of active demyelination. The coexistence of a demyelinating motor radiculopathy and anterior horn changes simulating those of amyotrophic lateral sclerosis (ALS) may contribute to our understanding of the unresolved question of whether the neuronal perikaryon or its axon is the primary target in the pathogenesis of ALS. These observations also indicate that a rigid separation of pathogenetic mechanisms into neuronopathy, axonopathy and myelinopathy may not be always possible.

Increased protein requirements in elderly people: new data and retrospective reassessments.

Dietary protein requirements of elderly people were determined by short-term nitrogen-balance techniques and using calculations recommended by the 1985 Joint FAO/WHO/UNU Expert Consultation. Twelve men and women aged 56-80 y were randomly assigned to groups that consumed either 0.80 +/- 0.01 or 1.62 +/- 0.02 g protein.kg-1.d-1 (mean +/- SEM). Net nitrogen balance was negative for the lower-protein group (-4.6 +/- 3.4 mg N.kg-1.d-1) and positive for the higher-protein group (13.6 +/- 1.0 mg N.kg-1.d-1); the intake required for nitrogen equilibrium was estimated to be 1.00 g.kg-1.d-1. Nitrogen-balance data from three previous protein requirement studies in elderly people were recalculated by using the same balance formula and combined with the current study data to provide an overall weighted mean protein requirement estimate of 0.91 +/- 0.043 g.kg-1.d-1. Together, the current and retrospective nitrogen-balance data suggest that the mean protein requirement in elderly adults is considerably greater than the 0.60 g.kg-1.d-1 established by the 1985 Joint FAO/WHO/UNU Expert Consultation. A safe protein intake for elderly adults would be 1.0-1.25 g.kg-1.d-1 of high-quality protein.

Increased energy requirements and changes in body composition with resistance training in older adults.

Body composition and the components of energy metabolism were examined in 12 men and women, aged 56-80 y, before and after 12 wk of resistance training. Subjects were randomly assigned to groups that consumed diets that providing either 0.8 or 1.6 g protein.kg-1.d-1 and adequate total energy to maintain baseline body weight. Fat mass decreased 1.8 +/- 0.4 kg (P < 0.001) and fat-free mass (FFM) increased 1.4 +/- 0.4 kg (P < 0.01) in these weight-stable subjects. The increase in FFM was associated with a 1.6 +/- 0.4 kg increase in total body water (P < 0.01) but no significant change in either protein plus mineral mass or body cell mass. With resistance training, the mean energy intake required for body weight maintenance increased by approximately 15%. Increased energy expenditure included increased resting metabolic rate (P < 0.02) and the energy cost of resistance exercise. Dietary protein intake did not influence these results. Resistance training is an effective way to increase energy requirements, decrease body-fat mass, and maintain metabolically active tissue mass in healthy older people and may be useful as an adjunct to weight-control programs for older adults.

Chromium picolinate supplementation and resistive training by older men: effects on iron-status and hematologic indexes.

Chromium competes with iron for binding to transferrin, and high-dose chromium supplementation has been hypothesized to adversely affect iron status. This study examined the effects of chromium picolinate supplementation on hematologic indexes and selected indexes of iron status in 18 men aged 56-69 y who participated in an introductory resistive training program. The men were randomly assigned (double-blind design) to groups (n = 9) that consumed either 17.8 mumol Cr/d (924 micrograms Cr/d) as chromium picolinate or a low-chromium placebo for 12 wk while engaging in resistive training twice weekly (3 sets of 8-12 repetitions at 80% of one repetition maximum for 5 exercises). Hematocrit, hemoglobin, red blood cell (erythrocyte) count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cell distribution width, platelet count, and mean platelet volume were within normal clinical ranges and were unchanged by either chromium picolinate supplementation or resistive training. Resistive training decreased total-iron-binding capacity from 38.4 +/- 9.3 to 27.3 +/- 5.6 mumol/L (P < 0.0001) and increased transferrin saturation from 35.7 +/- 16.3% to 45.4 +/- 16.9% (P = 0.050). Chromium picolinate supplementation did not influence these responses. Serum iron concentrations and serum ferritin concentrations were unchanged by either resistive training or chromium picolinate supplementation. These data suggest that high-dose chromium picolinate supplementation for 12 wk did not influence hematologic indexes or indexes of iron metabolism or status in older men. The decrease in total-iron-binding capacity and increase in transferrin saturation (%) with resistive training are largely opposite to changes associated with iron depletion and suggest a novel effect of resistive training on iron transport.

Effects of an omnivorous diet compared with a lactoovovegetarian diet on resistance-training-induced changes in body composition and skeletal muscle in older men.

BACKGROUND: Very limited data suggest that meat consumption by older people may promote skeletal muscle hypertrophy in response to resistance training (RT). OBJECTIVE: The objective of this study was to assess whether the consumption of an omnivorous (meat-containing) diet would influence RT-induced changes in whole-body composition and skeletal muscle size in older men compared with a lactoovovegetarian (LOV) (meat-free) diet. DESIGN: Nineteen men aged 51-69 y participated in the study. During a 12-wk period of RT, 9 men consumed their habitual omnivorous diets, which provided approximately 50% of total dietary protein from meat sources (beef, poultry, pork, and fish) (mixed-diet group). Another 10 men were counseled to self-select an LOV diet (LOV-diet group). RESULTS: Maximal strength of the upper- and lower-body muscle groups that were exercised during RT increased by 10-38% (P < 0.001), independent of diet. The RT-induced changes in whole-body composition and skeletal muscle size differed significantly between the mixed- and LOV-diet groups (time-by-group interactions, P < 0. 05). With RT, whole-body density, fat-free mass, and whole-body muscle mass increased in the mixed diet group but decreased in the LOV- diet group. Type II muscle fiber area of the vastus lateralis muscle increased with RT for all men combined (P < 0.01), and the increase tended to be greater in the mixed-diet group (16.2 +/- 4.4 %) than in the LOV diet group (7.3 +/- 5.1%). Type I fiber area was unchanged with RT in both diet groups. CONCLUSION: Consumption of a meat-containing diet contributed to greater gains in fat-free mass and skeletal muscle mass with RT in older men than did an LOV diet.

Periodic alternating nystagmus in phenytoin intoxication.

A patient with alcoholic cerebellar degeneration had periodic alternating nystagmus during a period of phenytoin intoxication. The nystagmus resolved as the serum phenytoin level fell, as demonstrated by electronystagmography. Periodic alternating nystagmus generally implies structural brainstem disease, especially at the craniocervical junction. To our knowledge, its drug-related occurrence has not been previously reported.

Malignant thymoma with dysautonomia and disordered neuromuscular transmission.

A 42-year-old man had prominent dysautonomia accompanied by clinical and electrophysiological features of both myasthenia gravis and the Lambert-Eaton myasthenic syndrome. Antiacetylcholine receptor antibodies were present in high titer. Invasive thymoma was found at thymectomy; later, a solitary metastasis to the spleen required a splenectomy. Complete remission followed surgery. There was evidence of antibody activity directed against postsynaptic acetylcholine receptors, presynaptic somatic motor terminals, and autonomic effector junctions. To our knowledge, the association of thymoma with a myasthenia gravis-Lambert-Eaton overlap syndrome has not been reported previously.

Hypertrophia musculorum vera in familial ataxia.

A kindred with dominantly inherited ataxia demonstrated hypertrophia musculorum vera as a phenotypic feature of the disease. The proband had fasciculations, cramps, absent sensory nerve action potentials, an increased creatine kinase level, dramatic enlargement of calf muscles, and a muscle biopsy specimen showing denervation accompanied by true muscle fiber hypertrophy; ataxia and other clinical signs of spinocerebellar degeneration were also present. Other family members displayed progressive ataxia and calf muscle enlargement to varying degrees. Though peroneal atrophy is a more common feature of the familial ataxias, some kindreds may have muscle enlargement simulating the pseudohypertrophy of muscular dystrophy that is due instead to denervation-induced compensatory individual fiber hypertrophy.

Facial myokymia in syringobulbia.

A patient with a 2-year history of progressive ataxia and tingling in the right hand had prominent facial myokymia. Magnetic resonance imaging revealed syringomyelia and syringobulbia. After successful syringosubarachnoid shunting, the patient died of massive pulmonary embolism. Postmortem examination revealed a syrinx involving the spinal cord and lower half of the medulla; neither the facial nucleus nor facial nerve fibers were directly involved. We hypothesize that interruption of aberrant corticobulbar fibers in the medulla produced disinhibition of a rhythmic neural generator in the facial nucleus.

Aged human muscle demonstrates an altered gene expression profile consistent with an impaired response to exercise.

The gene expression profile of skeletal muscle from healthy older (62-75 years old) compared with younger (20-34 years old) men demonstrated elevated expression of genes typical of a stress or damage response, and decreased expression of a gene encoding a DNA repair/cell cycle checkpoint protein. Although the expression of these genes was relatively unaffected by a single bout of resistance exercise in older men, acute exercise altered gene expression in younger men such that post-exercise gene expression in younger men was similar to baseline gene expression in older men. The lack of response of muscle from older subjects to resistance exercise was also apparent in the expression of the inflammatory response gene IL-1beta, which did not differ between the age groups at baseline, but increased within 24 h of the exercise bout only in younger subjects. Other genes with potentially important roles in the adaptation of muscle to exercise, specifically in the processes of angiogenesis and cell proliferation, showed a similar response to exercise in older compared with younger subjects. Only one gene encoding the multifunctional, early growth response transcription factor EGR-1, showed an opposite pattern of expression in response to exercise, acutely decreasing in younger and increasing in older subjects. These results may provide a molecular basis for the inherent variability in the response of muscle from older as compared with younger individuals to resistance training.

The numb cheek syndrome: a sign of infraorbital neuropathy.

Three patients with skin cancer had numbness isolated to one cheek, in the distribution of the infraorbital nerve. Hypesthesia also involved the medial and lateral upper incisors and canine teeth, and adjacent gingiva, sparing the more posterior teeth and gums. The molar and premolar teeth and gums are innervated by the posterior and middle superior alveolar nerves; because these structures were spared, the pathologic process was localized to the infraorbital foramen, and we could exclude involvement of the maxillary division more proximally. In two patients, cheek numbness heralded recurrent squamous cell carcinoma. Analogous anatomy at the mental foramen should help distinguish intracranial leptomeningeal from local mandibular lesions producing isolated numbness of the chin.

Randomized controlled trial of IVIg in untreated chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVE: To determine the efficacy of IV immunoglobulin (IVIg) given patients with untreated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: A randomized, double-blind, multicenter, investigator-initiated study compared IVIg (Aventis Behring LLC, King of Prussia, PA) with placebo (5% albumin). On days 1, 2, and 21, IVIg (1 g/kg) or placebo was given. The primary outcome measure was the change in muscle strength from baseline to day 42, using the average muscle score (AMS). Secondary outcome measures included change from baseline AMS at days 10 and 21, the Hughes' functional disability scale, forced vital capacity (FVC), and nerve conduction studies (NCS) of four motor nerves (median, ulnar, peroneal, and tibial). RESULTS: The patients (n = 33) were randomized. Of these, 30 (14 women, 16 men, aged 54 +/- 20 years, range 13 to 82) received IVIg and 23 were given placebo (12 women, 11 men, aged 50 +/- 18 years, range 23 to 73). Baseline AMS values of the groups were similar (IVIg 7.06 +/- 1.31 versus placebo 7.28 +/- 1.18, p = 0.53). There were two dropouts in placebo group and one in the IVIg group. Mean AMS improved at day 42 comparing IVIg with placebo (0.63 versus -0.1, p = 0.006). Improved strength was seen by day 10. The placebo group lost strength over this same interval. In the IVIg, 11 subjects improved by the functional disability scale; none worsened. This differed (p = 0.019) from those in the placebo-treated group (two improved, two got worse, remainder unchanged). Forced vital capacity did not improve with IVIg treatment. IVIg improved ulnar motor distal latency (p = 0.005), tibial distal compound muscle amplitude (p = 0.003), and peroneal nerve conduction velocity (p = 0.03). CONCLUSIONS: IVIg improves strength in patients with untreated CIDP by day 10 with continued benefit through day 42; more than one third improve by at least a functional grade on a disability scale. This study provides data supporting IVIg as the initial treatment for CIDP.