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Junctophilins (JP1 and JP2) are expressed in skeletal muscle and are the primary proteins involved in transverse (T)-tubule and sarcoplasmic reticulum (SR) membrane apposition. During the performance of eccentric contractions, the apposition of T-tubule and SR membranes may be disrupted, resulting in excitation-contraction (EC) coupling failure and thus reduced force-producing capacity. In this study, we made three primary observations: 1) through the first 3 days after the performance of 50 eccentric contractions in vivo by the left hindlimb anterior crural muscles of female mice, both JP1 and JP2 were significantly reduced by approximately 50% and 35%, respectively, while no reductions were observed after the performance of nonfatiguing concentric contractions; 2) following the performance of a repeated bout of 50 eccentric contractions in vivo, only JP1 was immediately reduced ( approximately 30%) but recovered by 3-day postinjury in tandem with the recovery of strength and EC coupling; and 3) following the performance of 10 eccentric contractions at either 15 degrees or 35 degrees C by isolated mouse extensor digitorum longus (EDL) muscle, isometric force, EC coupling, and JP1 and JP2 were only reduced after the eccentric contractions performed at 35 degrees C. Regression analysis of JP1 and JP2 content in tibialis anterior and EDL muscles from each set of experiments indicated that JP damage is significantly associated with early (0-3 days) strength deficits after performance of eccentric contractions (R = 0.49; P < 0.001). As a whole, the results of this study indicate that JP damage plays a role in early force deficits due to EC coupling failure following the performance of eccentric contractions.

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Molecular estimates of the age of angiosperms have varied widely, and many greatly predate the Early Cretaceous appearance of angiosperms in the fossil record, but there have been few attempts to assess confidence limits on ages. Experiments with rbcL and 18S data using maximum likelihood suggest that previous angiosperm age estimates were too old because they assumed equal rates across sites-use of a gamma distribution of rates to correct for site-to-site variation gives 10-30 my (million years) younger ages-and relied on herbaceous angiosperm taxa with high rates of molecular evolution. Ages based on first and second codon positions of rbcL are markedly older than those based on third positions, which conflict with the fossil record in being too young, but all examined data partitions of rbcL and 18S depart substantially from a molecular clock. Age estimates are surprisingly insensitive to different views on seed-plant relationships. Randomization schemes were used to quantify confidence intervals due to phylogenetic uncertainty, substitutional noise, and lineage effects (deviations from a molecular clock). Estimates of the age of crown-group angiosperms range from 68 to 281 mya (million years ago), depending on data, tree, and assumptions, with most ∼140-190 mya (Early Jurassic-earliest Cretaceous). Approximate 95% confidence intervals on ages are wider for rbcL than 18S, ranging up to 160 my for phylogenetic uncertainty, 90 my for substitutional noise, and 70 my for lineage effects. These intervals overlap the oldest occurrences of angiosperms in the fossil record, as well as some estimates from previous molecular studies.

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Recent molecular phylogenetic studies indicate, surprisingly, that Gnetales are related to conifers, or even derived from them, and that no other extant seed plants are closely related to angiosperms. Are these results believable? Is this a clash between molecules and morphology?

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Morphological analyses of seed plant phylogeny agree that Gnetales are the closest living relatives of angiosperms, but some studies indicate that both groups are monophyletic, while others indicate that angiosperms are nested within Gnetales. Molecular analyses of several genes agree that both groups are monophyletic, but differ on whether they are related. Conflicts among morphological trees depend on the interpretation of certain characters; when these are analyzed critically, both groups are found to be monophyletic. Conflicts among molecular trees may reflect the rapid Paleozoic radiation of seed plant lines, aggravated by the long branches leading to extant taxa. Trees in which angiosperms are not related to Gnetales conflict more with the stratigraphic record. Even if molecular data resolve the relationships among living seed plant groups, understanding of the origin of angiosperm organs will require integration of fossil taxa, necessarily using morphology.

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PURPOSE: The preadmission assessment of patients one to two weeks preoperatively has become the standard across North America. We have devised a new approach that utilises a preoperative screening questionnaire, and this study attempted to determine the effectiveness of this technique. METHODS: Over six weeks, the attending anaesthetist for each patient undergoing non-cardiac surgery processed through the preadmission clinic (PAC) completed a study survey. This survey questioned if the assessment was appropriate with reasons, the consequences of no assessment, and if time was saved/lost on the day of surgery. RESULTS: Three hundred and seventy patients were processed (243 same-day (SD), 111 outpatient (O/P), and 16 inpatients (I/P)). Of these, 224 were assessed in the PAC (101 by medicine, 84 by anaesthesia and 39 by both): 42% (94) based on the questionnaire, 12% (26) due to consultation, and 46% (104) due to positive questionnaires and consultation. The physician assessments were appropriate 184/219 (84%) times, inappropriate in 35 (16%), while there was no answer for five. Assessments were inappropriate because 25/35 (71%) were unnecessary, while in nine (26%) the patient was not optimised. Of the patients not assessed in the PAC only 9/145 (6%) should have been assessed. CONCLUSION: The use of our screening tool in combination with direct referrals appropriately determines assessment needs of patients and allows for more efficient use of medical personnel in the PAC.

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BACKGROUND AND OBJECTIVES: In an effort to further decrease postoperative opioid requirements and improve analgesia in patients undergoing elective knee joint replacement, a study was made of the effectiveness of adding morphine to an intra-articular bupivacaine injection given immediately following surgery. METHODS: In random, double-blind fashion, 75 patients received a 31-mL intra-articular injection consisting of either 30 mL 0.5% bupivacaine with 1:200,000 epinephrine and 1 mL normal saline (group BUP), 30 mL 0.5% bupivacaine with 1:200,000 epinephrine and 1 mg (1 mL) preservative-free morphine (group BUP-MORPH), or 30 mL normal saline with 1:200,000 epinephrine and 1 mg preservative-free morphine (group MORPH). Postoperative analgesia was supplied by patient controlled analgesia (PCA) with morphine. Patients were assessed at 1, 2, 4, and 24 hours for pain (visual analog and verbal rating scales), morphine utilization, and side effects. Knee range of motion was measured before operation and at hospital discharge. RESULTS: There was no difference among the three groups in PCA morphine requirements, pain scores by either scale, range of motion, or incidence of side effects, including somnolence, urinary retention, nausea and vomiting, and pruritus. CONCLUSION: The addition of 1 mg morphine to an intra-articular injection of 30 mL 0.5% bupivacaine with 1:200,000 epinephrine given at wound closure does not improve analgesia in patients undergoing elective knee joint replacement.

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OBJECTIVE: To investigate whether the type of perfusion, pulsatile (PP) or nonpulsatile (NP), has any effect on the pressure gradient that exists between the aortic root and the radial artery after cardiopulmonary bypass (CPB). DESIGN: Prospective, randomized study. SETTING: Tertiary care, university hospital. PARTICIPANTS: Eighty patients undergoing elective, hypothermic coronary artery bypass graft (CABG) surgery. INTERVENTIONS: Pulsatile perfusion with a pulse pressure of 10 to 20 mmHg and a frequency of 60 to 80 beats/min was created during the hypothermic phase of CPB. Both the radial artery and aorta were cannulated and attached to separate transducers but displayed and analyzed on the same monitor. MEASUREMENTS AND MAIN RESULTS: Simultaneous recordings of radial artery and aortic root blood pressure were made prebypass, during CPB, and after discontinuation of CPB at 2, 5, and 10 minutes. During CPB, the PP group had a significantly higher mean pulse pressure measured at the aortic root than the NP group (15.5 +/- 8.1 v 1.7 +/- 2.7, p < 0.0001). The aortic-to-radial-artery gradient within both groups was significantly different after CPB for systolic (SBP), diastolic (DBP), and mean pressure (MAP) (p < 0.0001). There were, however, no statistically significant differences between the PP and NP groups in the aortic-to-radial-artery gradient after CPB for either SBP, DBP, or MAP. CONCLUSIONS: Pulsatile perfusion had no effect on the aortic root radial artery blood pressure gradient after CPB in elective CABG surgery patients.

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A comparative immunohistochemical study was performed on skin biopsies from 10 patients with lichen planus and 10 patients with discoid lupus erythematosus (DLE). A panel of antibodies against T lymphocytes (UCHL-1, OPD-4, CD8, CD43), B lymphocytes (L-26), granulocytes (Leu-M1), activation markers (Ki-1, LN-3), macrophages, fibroblasts and dendritic cells (FXIIIa, S-100, Mac-387, KP-1, vimentin), endothelial cells (CD34), and epithelial cells (epithelial membrane antigen) was employed using a peroxidase-anti-peroxidase technique. The recently released CD8 antiserum required microwave antigen retrieval of formalin-fixed, paraffin-embedded tissue to label lymphocytes. The results showed many similarities in the lymphocyte subsets and macrophages between lichen planus and discoid lupus erythematosus. The most important differences between the two conditions were statistically significant increases in the number of S-100+ cells in the epidermis and dermis, FXIIIa+ cells in the dermis and CD34+ vessels within the inflammatory infiltrate in lichen planus.

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STUDY OBJECTIVE: To investigate the effect on the use of intravenous patient-controlled analgesia (PCA) of varying the dose (D) and lockout interval (LI) while keeping the hourly maximum dose constant. DESIGN: Randomized, prospective study. SETTING: Teaching hospital. PATIENTS: 75 patients scheduled to receive PCA morphine following abdominal surgery. INTERVENTIONS: Postoperatively, patients were randomly assigned to receive PCA morphine with the following parameters: D = 1 mg, LI = 6 min (Group 1-6), D = 1.5 mg, LI = 9 min (Group 1.5-9), or D = 2 mg, LI = 12 min (Group 2-12), so that each group could receive a maximum hourly dose or 10 mg. Inadequate analgesia was managed by increasing the dose and lockout interval, while excessive sedation or respiratory rate less than 10 breaths/min resulted in decreasing the dose and lockout interval. MEASUREMENTS AND MAIN RESULTS: Patients were assessed for pain [visual analog scale (VAS), verbal rating scale (VRS)] and side effects at 1, 2, 4, and 24 hours. The number of doses administered, missed attempts, and morphine used for the first 24 hours was recorded by automatic printout from the PCA machine. There was no difference in the total 24-hour morphine consumption, analgesia, or incidence of side effects among the three groups at any of the measurement times. Two patients, one each in the 1.5-9 and 2-12 groups, required naloxone for respiratory depression. The number of PCA injections, attempts, missed attempts, and the incidence of dosage adjustment were all significantly higher for the 1-6 group (p < 0.05). CONCLUSION: The use of 1.0 mg with a 6-minute lockout may represent appropriate dose titration because this group obtained equivalent analgesia, morphine use, and side effects as the two larger dose and lockout groups. However, the increased number of PCA attempts and missed attempts may reflect lower satisfaction with PCA therapy.

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The effectiveness of an intra-articular injection of bupivacaine, administered before the incision or after closure of the wound, was studied in an effort to decrease the need for postoperative narcotics and to improve analgesia for patients who have elective knee replacement. Eighty-two patients received two intra-articular injections in a random, double blind fashion. Twenty-eight of them received thirty milliliters of 0.5 percent bupivacaine and 1:200,000 epinephrine in saline solution before the incision and an injection of thirty milliliters of plain saline solution after closure of the wound (Group 1). Twenty-seven patients received an injection of thirty milliliters of plain saline solution before the incision and thirty milliliters of 0.5 percent bupivacaine and 1:200,000 epinephrine in saline solution after closure of the wound (Group 2). Twenty-seven patients were given thirty milliliters of plain saline solution (a placebo) for both injections (Group 3). The patients who had received bupivacaine after closure of the wound (Group 2) used less morphine from the patient-controlled analgesia pumps than the patients who had received bupivacaine before the incision (Group 1) and the patients who had received the placebo (Group 3). In the first twenty-four hours after the operation, the administration of morphine (mean and standard deviation) was 59 +/- 27 milligrams for Group 2 compared with 68 +/- 30 milligrams for Group 1 (p = 0.26) and 81 +/- 30 milligrams for Group 3 (p = 0.006). At the time of discharge from the hospital, the patients in Group 2 also had a significantly greater mean range of motion (85.2 +/- 8.0 degrees) compared with that of the patients in Groups 1 (80.6 +/- 6.8 degrees, p = 0.02) and 3 (80.1 +/- 6.2 degrees, p = 0.009). However, there was no difference among the groups with respect to the effectiveness of the analgesia, as measured with use of either the visual-analog or the verbal pain-rating scale, or in the prevalence of side effects, including somnolence, urinary retention, nausea and vomiting, or pruritus. Serum concentrations of bupivacaine were well below toxic levels. It was our conclusion that that and intra-articular injection of thirty milliliters of 0.5 percent bupivacaine and 1:200,000 epinephrine in saline solution after closure of the wound decreases the need for narcotics and increases the range of motion after an elective knee replacement. The clinical importance of the amount of increased motion is questionable and needs long-term monitoring.

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Computer image analysis enables large numbers of hairs to be measured in an automated fashion. In this study, we examined horizontal scalp biopsies from 10 patients with a histological diagnosis of androgenetic alopecia and 10 normal control subjects. The density of hair follicles and the ratio of terminal to vellus hairs were determined. Hair shaft, hair canal and hair follicle diameter, inner root sheath width and outer root sheath area were measured using the Chromatic Colour Image Analysis program. This study showed a statistically significant progressive decrease in size of hair canal diameters from normal terminal hairs (85.93 +/- 10.07 microns) through to androgenetic alopecia terminal (68.83 +/- 13.60 microns) and vellus hairs (28.67 +/- 5.60 microns). This pattern is also seen with hair follicle diameters; normal terminal (268.41 +/- 24.88 microns), androgenetic alopecia terminal (236.34 +/- 17.23 microns), and vellus hairs (130.88 +/- 19.96 microns). Outer root sheath areas, hair shaft diameters and ratio of terminal to vellus hairs were significantly larger in normal (18,500 +/- 4222 microns 2; 82.71 +/- 13.79 microns; 36:1; respectively) compared with androgenetic alopecia scalp biopsies (8403 +/- 3322 microns 2; 61.11 +/- 14.42 microns; 3:1; respectively), whereas inner root sheath width and density did not vary significantly. Computer image analysis can be adapted for use in clinical trials where large numbers and objectivity are critical in determining the efficacy of hair growth promoters.

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Eccentric contractions appear to reduce muscle glycogen replenishment during the 1- to 10-day period after exercise. The main purpose of this study was to determine whether consuming a large amount of carbohydrate (1.6 g.kg-1.h-1) during the 4 h after glycogen-reducing exercise would produce different patterns of glycogen replenishment in human muscle that had undergone either eccentric or concentric contractions approximately 2 or 48 h earlier. Subjects cycled for 75 min and undertook interval exercise to deplete glycogen on days 1 and 3. After cycling exercise on day 1 only, subjects performed 10 sets of 10 repetitions of either concentric or eccentric contractions in opposite legs. During the 4 h after exercise, subjects consumed 0.4 g carbohydrate/kg body wt every 15 min. Biopsies were obtained immediately before the feedings and 4 h later, and blood was sampled every 15 min. For days 1 and 3 combined, total integrated areas for the glucose and insulin response curves averaged 1,683 mumol.ml-1.240 min-1 and 21,450 microU.ml-1.240 min-1, respectively. For days 1 and 3 combined, muscle glycogen replenishment after concentric exercise averaged 10 mmol.kg-1.h-1. On day 1 glycogen replenishment was similar for subjects performing either concentric or eccentric contractions. On day 3, however, glycogen replenishment was 25% lower (P < 0.05) in muscle that had undertaken eccentric contractions 48 h earlier than in concentrically exercised muscle. In conclusion, glycogen replenishment can be stimulated to a high rate when a large amount of carbohydrate is consumed after glycogen-depleting concentric exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

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The effects of moderate- or high-carbohydrate diets on muscle glycogen and performance in runners and cyclists over 7 consecutive days of training were determined. Muscle biopsies were performed on 4 separate days before exercise for 1 h at 75% peak oxygen consumption (VO2) followed by five, 1-min sprints. After the training session on day 7, subjects ran or cycled to exhaustion at 80% peak VO2. Muscle glycogen for cyclists and runners was maintained with the high-carbohydrate diet but was reduced 30-36% (P < 0.05) with the moderate-carbohydrate diet. All subjects completed all training sessions, and there were no differences in times to exhaustion on day 7. For cyclists and runners, consuming a moderate-carbohydrate diet over 7 d of intense training reduces muscle glycogen but has no apparent deleterious effect on training capability or high-intensity exercise performance. A high-carbohydrate diet maintains muscle glycogen, but this has no apparent benefit on training capability or high-intensity exercise performance.

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The belief that high-carbohydrate diets enhance training capacity (mean power output) has been extrapolated from studies that have varied dietary carbohydrate over a few days and measured muscle glycogen but did not assess power output during training. We hypothesized that a high-carbohydrate (HI) diet (10 g.kg body mass-1.day-1) would promote greater muscle glycogen content and greater mean power output during training than a moderate-carbohydrate (MOD) diet (5 g.kg body mass-1.day-1) over 4 wk of intense twice-daily rowing training. Dietary protein intake was 2 g.kg body mass-1.day-1, and fat intake was adjusted to maintain body mass. Twelve male and 10 female collegiate rowers were randomly assigned to the treatment groups. Training was 40 min at 70% peak O2 consumption (VO2) (A.M.) and either three 2,500-m time trials to assess power output or interval training at 70-90% peak VO2 (P.M.). Mean daily training was 65 min at 70% peak VO2 and 38 min at greater than or equal to 90% peak VO2. Mean muscle glycogen content increased 65% in the HI group (P less than 0.05) but remained constant at 119 mmol/kg in the MOD group over the 4 wk. Mean power output in time trials increased 10.7 and 1.6% after 4 wk in the HI and MOD groups, respectively (P less than 0.05). We conclude that a diet with 10 g carbohydrate.kg body mass-1.day-1 promotes greater muscle glycogen content and greater power output during training than a diet containing 5 g carbohydrate.kg body mass-1.day-1 over 4 wk of intense twice-daily rowing training.(ABSTRACT TRUNCATED AT 250 WORDS)

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The fascia had received little attention until Shulman's delineation of EF. Evidence is now accumulating that in addition to EF and scleroderma, significant fascial inflammation may be seen in polymyositis, dermatomyositis, eosinophilic polymyositis, systemic lupus erythematosus, and mixed connective tissue disease. It is still unclear whether EF represents a variant of scleroderma; however, it is becoming increasingly recognized that scleroderma shares many features in common with EF including eosinophilia, hypergammaglobulinemia, positive ANA and rheumatoid factor, and an association with hematologic disease. The rarity of Raynaud's phenomenon and significant visceral changes help distinguish EF from systemic scleroderma. In this regard, however, EF more closely resembles the localized scleroderma syndromes, especially morphea profunda and pansclerotic morphea. Biopsy in EF, systemic scleroderma, and localized scleroderma will show comparable changes, the essential difference being the levels at which they occur.

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The clinical course of 52 cases with eosinophilic fasciitis observed at the Mayo Clinic has been described. Cutaneous changes included pitting edema, peau d'orange, and induration, and may affect virtually any body surface area. In addition, localized morphea was present in 15 cases. Arthritis was observed in 21 patients; 29 patients had flexion contractures and 12 had carpal tunnel syndrome. Associated hematologic diseases were found in five patients; thrombocytopenia in two, myeloproliferative disorder in one, myelomonocytic leukemia in one, and chronic lymphocytic leukemia in one. Peripheral blood eosinophilia was noted in 33 of 52 patients, hypergammaglobulinemia was noted in 17 of 49, and elevated sedimentation rate was noted in 15 of 52. Nonspecific EMG changes were seen in 11 of 15 patients. None had clinical involvement of the kidneys, lungs, or heart. No significant association between any HLA-A, -B, or -DR and eosinophilic fasciitis was seen. Prednisone and hydroxychloroquine seemed equally beneficial in treatment; however, some cases showed spontaneous recovery, making evaluation of therapeutic efficacy difficult. Relapses occurred in some cases.

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