Influence of hypoxia on the power-duration relationship during high-intensity exercise.

We investigated the influence of hypoxia on the asymptote (critical power, CP) and the curvature constant (W') of the hyperbolic power-duration relationship, as measured by both conventional and all-out testing procedures. 13 females completed 5 constant-power prediction trials and a 3-min all-out test to estimate CP and W', in both normoxia (N) and moderate hypoxia (H; FiO2=0.13). CP was significantly reduced in hypoxia compared to normoxia when estimated by conventional (H:132±17 vs. N:175±25 W; P<0.001) and all-out methods (H:134±23 vs. N:172±30 W; P<0.01). The W' was not significantly different in hypoxia compared to normoxia when established by conventional (H:12.3±2.7 vs. N:13.2±2.2 kJ) and all-out methods (H:12.0±2.6 vs. N:12.5±1.4 kJ). Estimates of CP and W' obtained with conventional and all-out methods were not significantly different either in normoxia or hypoxia. There was a significant relationship between the % change in CP relative to V̇(O2peak) and the % change in W' in normoxia compared to hypoxia (r=0.83, P<0.001; conventional test). Changes in the W' in hypoxia are related to changes in the CP relative to V̇(O2peak), suggesting that the W' may not be defined simply as an 'anaerobic' energy store.

Older type 2 diabetic males do not exhibit abnormal pulmonary oxygen uptake and muscle oxygen utilization dynamics during submaximal cycling exercise.

There are reports of abnormal pulmonary oxygen uptake (Vo(2)) and deoxygenated hemoglobin ([HHb]) kinetics in individuals with Type 2 diabetes (T2D) below 50 yr of age with disease durations of <5 yr. We examined the Vo(2) and muscle [HHb] kinetics in 12 older T2D patients with extended disease durations (age: 65 ± 5 years; disease duration 9.3 ± 3.8 years) and 12 healthy age-matched control participants (CON; age: 62 ± 6 years). Maximal oxygen uptake (Vo(2max)) was determined via a ramp incremental cycle test and Vo(2) and [HHb] kinetics were determined during subsequent submaximal step exercise. The Vo(2max) was significantly reduced (P < 0.05) in individuals with T2D compared with CON (1.98 ± 0.43 vs. 2.72 ± 0.40 l/min, respectively) but, surprisingly, Vo(2) kinetics was not different in T2D compared with CON (phase II time constant: 43 ± 17 vs. 41 ± 12 s, respectively). The Δ[HHb]/ΔVo(2) was significantly higher in T2D compared with CON (235 ± 99 vs. 135 ± 33 AU·l(-1)·min(-1); P < 0.05). Despite a lower Vo(2max), Vo(2) kinetics is not different in older T2D compared with healthy age-matched control participants. The elevated Δ[HHb]/ΔVo(2) in T2D individuals possibly indicates a compromised muscle blood flow that mandates a greater O(2) extraction during exercise. Longer disease duration may result in adaptations in the O(2) extraction capabilities of individuals with T2D, thereby mitigating the expected age-related slowing of Vo(2) kinetics.

von Willebrand disease, pregnancy and neuraxial anesthesia: a multi-disciplinary approach for successful regional anesthesia.

Fearing the devastating neurological complications in a parturient with the von Willebrand disease secondary to paucity of studies defining the guidelines to assess the risk of bleeding complications, anesthesiologists are often reluctant to administer neuroaxial anesthesia. We present a case report of a parturient with type I von Willebrand disease who presented for induction of labor at 39 weeks of gestation. After consultation with the hematologist well ahead of the conception, appropriate laboratory workup including clotting factor levels including FVIII, vWF:RcoF, vWF:Ag on different occasions peripartum, and provision of adequate prophylactic medical treatment, she underwent Cesarean section under epidural anesthesia without neurological or bleeding complications. von Willebrand disease is the most common inherited bleeding disorder that may result in various bleeding complications in a parturient as a result of hemostatic challenges during pregnancy. Yet the recommendations are based on anecdotal observations of the authors of small case series and surveys. Our case report emphasizes the importance of advanced planning, careful patient assessment, and multi-disciplinary team approach for the successful regional anesthesia as suggested by the guidelines based on clinical experiences.

Muscular and pulmonary O2 uptake kinetics during moderate- and high-intensity sub-maximal knee-extensor exercise in humans.

The purpose of this investigation was to determine the contribution of muscle O(2) consumption (mVO2) to pulmonary O(2) uptake (pVO2) during both low-intensity (LI) and high-intensity (HI) knee-extension exercise, and during subsequent recovery, in humans. Seven healthy male subjects (age 20-25 years) completed a series of LI and HI square-wave exercise tests in which mVO2 (direct Fick technique) and pVO2 (indirect calorimetry) were measured simultaneously. The mean blood transit time from the muscle capillaries to the lung (MTTc-l) was also estimated (based on measured blood transit times from femoral artery to vein and vein to artery). The kinetics of mVO2 and pVO2 were modelled using non-linear regression. The time constant (tau) describing the phase II pVO2 kinetics following the onset of exercise was not significantly different from the mean response time (initial time delay + tau) for mVO2 kinetics for LI (30 +/- 3 vs 30 +/- 3 s) but was slightly higher (P < 0.05) for HI (32 +/- 3 vs 29 +/- 4 s); the responses were closely correlated (r = 0.95 and r = 0.95; P < 0.01) for both intensities. In recovery, agreement between the responses was more limited both for LI (36 +/- 4 vs 18 +/- 4 s, P < 0.05; r = -0.01) and HI (33 +/- 3 vs 27 +/- 3 s, P > 0.05; r = -0.40). MTTc-l was approximately 17 s just before exercise and decreased to 12 and 10 s after 5 s of exercise for LI and HI, respectively. These data indicate that the phase II pVO2 kinetics reflect mVO2 kinetics during exercise but not during recovery where caution in data interpretation is advised. Increased mVO2 probably makes a small contribution to during the first 15-20 s of exercise.

Influence of pacing strategy on O2 uptake and exercise tolerance.

Seven male subjects completed cycle exercise bouts to the limit of tolerance on three occasions: (1) at a constant work rate (340+/-57 W; even-pace strategy; ES); (2) at a work rate that was initially 10% lower than that in the ES trial but which then increased with time such that it was 10% above that in the ES trial after 120 s of exercise (slow-start strategy; SS); and, (3) at a work rate that was initially 10% higher than that in the ES trial but which then decreased with time such that it was 10% below that in the ES trial after 120 s of exercise (fast-start strategy; FS). The expected time to exhaustion predicted from the pre-established power-time relationship was 120 s in all three conditions. However, the time to exhaustion was significantly greater (P<0.05) for the FS (174+/-56 s) compared with the ES (128+/-21 s) and SS (128+/-30 s) conditions. In the FS condition, (.)VO2 increased more rapidly toward its peak such that the total O2 consumed in the first 120 s of exercise was greater (ES: 5.15+/-0.78; SS: 5.07+/-0.83; FS: 5.36+/-0.84 L; P<0.05 for FS vs ES and SS). These results suggest that a fast-start pacing strategy might enhance exercise tolerance by increasing the oxidative contribution to energy turnover and hence "sparing" some of the finite anaerobic capacity across the transition to high-intensity exercise.

The benefits and risks of over-the-counter availability of levonorgestrel emergency contraception.

Removing the prescription requirement for Plan B will help ensure that the product plays a larger role nationally in the reduction of unintended pregnancy and abortion-important public health goals. Over-the-counter (OTC) sale of Plan B should present no serious safety issues. OTC consumers are able to understand and follow the instructions for proper use of Plan B. Efficacy of the OTC product is likely to be the same as, or better than, the prescription product, given more timely access to treatment. Based on the results of a growing body of literature and foreign marketing experience, the risk of unintended health consequences also appears to be minimal. There is no evidence to suggest that American women will abuse Plan B as an OTC product.

Transcriptional control of the testis-specific histone H1t gene.

The mammalian testis-specific linker histone H1t is synthesized only in pachytene primary spermatocytes during spermatogenesis. In this review we summarize some of the progress made in our laboratory and in other laboratories in understanding transcriptional regulation of this gene. The gene is transcriptionally active in pachytene primary spermatocytes and is repressed in all other germinal and non-germinal cell types. To place the transcriptional control of the testis-specific histone H1t gene in the proper context, we briefly review recent literature concerning mammalian linker histone genes in general and we compare and contrast these with the testis-specific histone H1t gene.

Transcutaneous oxygen measurements predict a beneficial response to hyperbaric oxygen therapy in patients with nonhealing wounds and critical limb ischemia.

Hyperbaric oxygen (HBO) therapy may be a useful adjunct in the treatment of patients with wounds associated with critical limb ischemia. These patients either cannot undergo a successful bypass or may not heal after vascular reconstruction alone. Identification of patients likely to benefit from HBO is essential before treatment, as this therapy is time-consuming, costly, and not without risk. Transcutaneous oxygen measurements (TCOM) can be used to evaluate the degree of hypoxia in ischemic tissue. In this study we evaluated whether TCOM could be used to identify those patients who would or would not benefit from HBO therapy. Our hypothesis is that a difference in transcutaneous oxygen tension readings measured near the ischemic lesion with the patient breathing room air and while breathing 100 per cent oxygen at ambient pressure may be predictive of wound healing with adjunctive hyperbaric oxygen therapy. Thirty-six patients with critical limb ischemia and nonhealing ulcers were referred for HBO therapy. They were deemed either nonreconstructible from a vascular surgical viewpoint, had failed prior revascularization attempts, or could not achieve complete wound healing even after a successful revascularization. Pretreatment assessment included a room air and post-100 per cent-O2 challenge TCOM reading obtained in the vicinity of the open wound. Hyperbaric oxygen treatments at 2.0 to 2.5 atm were then administered until healing occurred or failure was confirmed. All patients undergoing HBO had a baseline TCOM of <40 torr. Twenty-seven patients had an increase in TCOM of >10 torr with oxygen inhalation at initial evaluation. Of these patients, 19 (70%) healed their wounds with HBO therapy. Conversely the increase in TCOM was <10 torr in nine patients, and only one of these patients (11%) ultimately healed (P < 0.01). Patients with nonhealing ischemic extremity wounds may heal with adjunctive HBO therapy. We can predictably identify patients who are likely to benefit from this modality using TCOM at the time of initial evaluation. An increase of tissue O2 tension of > or =10 torr when breathing pure O2 suggests that the patient may benefit from HBO therapy. Those patients with an increase of <10 torr are unlikely to receive benefit from this treatment modality.

Locating the centric relation prematurity with a computerized occlusal analysis system.

Locating the first tooth contact that interferes with freedom of movement in and out of centric relation has been the diagnostic and treatment objective of most occlusal therapies. The centric relation prematurity can be located by various methods, which involve operator-guided mandibular positioning combined with the patient's subjective assessment of his or her perceived first tooth contact. The method known as bimanual manipulation has been widely recognized and accepted as a predictable method of determining and verifying the centric relation position. The first occlusal contact that results when the mandible is closed on a correct centric relation axis is known as the centric relation prematurity. An alternative procedure combines bimanual manipulation with the simultaneous recording of the sequence of resultant tooth contacts using a computerized occlusal analysis system. This alternative offers a significant improvement in the precision of locating the first tooth contact. This article describes a method of identifying the first tooth contact while not relying on the patient's subjective assessment of his or her perceived occlusal feel.

Testis-specific histone H1t gene is hypermethylated in nongerminal cells in the mouse.

The testis-specific histone H1t gene is expressed only in pachytene primary spermatocytes during spermatogenesis. There is a correlation between the specific binding of testis nuclear proteins to a rat histone H1t promoter sequence, designated the H1t/TE element, and the onset of transcription in primary spermatocytes. Our laboratory has shown that mice bearing the rat gene with a deletion of the TE promoter element and replacement with a heterologous stuffer DNA fragment fail to express the rat H1t transgene in any tissue. In this study we report that five CpGs located within the H1t proximal promoter, including two CpGs located within the essential TE promoter element, contain unmethylated cytosines in vivo in genomic DNA derived from primary spermatocytes where the H1t gene is expressed. All seven CpGs are hypermethylated in vivo in genomic DNA derived from liver cells where gene expression is repressed. Further, in vitro methylation of an H1t promoter-driven reporter plasmid markedly reduced expression in a transient transfection assay system. These results suggest that cytosine methylation may contribute to the transcriptional silencing of the testis-specific histone H1t gene in nonexpressing tissues such as liver.

Impact of HIV-positive speakers in a multicomponent, school-based HIV/STD prevention program for inner-city adolescents.

Qualitative and quantitative data from Safer Choices, a school-based multicomponent HIV prevention program, were examined to determine the impact of HIV-positive speakers on inner-city adolescents' HIV risk perception and empathy for people with HIV or AIDS. Inductive analyses were used to assess student reactions to speakers. Multilevel regression modeling techniques were used to analyze student survey data (n = 1,491) to determine the effect of speakers alone, as well as in combination with the multicomponent intervention, and a knowledge-based curriculum (comparison condition). Results showed that speakers were highly popular with students and teachers, and had a positive short-term impact on students' attitudes. Although not statistically significant, the combination of intervention and speakers had the greatest impact on outcome variables. Integrating HIV-positive speakers into multicomponent programs may have a positive impact on inner-city youth. Utilizing speakers without other educational components may have minimal effects. Strategies for training and utilizing HIV-positive speakers in school settings are included.

Current issues in rehabilitation outcome measurement: implications for audiological rehabilitation.

OBJECTIVE: This paper will describe several key issues current in rehabilitation outcome measurement that should be considered in the establishment or choice of any new outcome measurement system or tools. DESIGN: The paper is a concept piece based on a review of literature rather than on experimental design. RESULTS: Social and political forces of the 1990s are affecting the need for outcome measurement and management: consumerism, or empowerment of the end user of services; the global Internet and information age; and the pervasiveness of the concept of quality improvement. In this context, several underlying concepts are important in effective outcome management approaches. Rehabilitation's focus on the person served provides a frame for measurement. Measurement in terms of the domains of the World Health Organization's International Classification of Impairments, Activities and Participation reflects meaningful dimensions of rehabilitation for people with hearing loss. Activities in the arena of rehabilitation performance indicator development are summarized and challenges in developing outcome management systems are discussed. CONCLUSIONS: The paper proposes that choice is a key outcome of interest in rehabilitation. Persons served in audiological rehabilitation and providers alike can benefit from systematic outcome measurement, but more can be learned about outcomes. Attention to consistent and uniform outcome measurement in audiological rehabilitation is consistent with the trends in the rehabilitation community at large.

Optimal outcome measures, research priorities, and international cooperation.

The participants in the Eriksholm Workshop on "Measuring Outcomes in Audiological Rehabilitation Using Hearing Aids" debated three issues that are reported in this article. First, it was agreed that the characteristics of an optimal outcome measure vary as a function of the purpose of the measurement. Potential characteristics of outcome self-report tools for four common goals of outcome measurement are briefly presented to illustrate this point. Second, 10 important research priorities in outcome measurement were identified and ranked. They are presented with brief discussion of the top five. Third, the concept of generating a brief universally applicable outcome measure was endorsed. This brief data set is intended to supplement existing outcome measures and to promote data combination and comparison across different social, cultural, and health-care delivery systems. A set of seven core items is proposed for further study.

Supervised training of general surgery residents in carotid endarterectomy performed on awake patients under regional block is safe and desirable.

Previous studies have documented the safety and efficacy of general surgery residents and vascular fellows performing carotid endarterectomy (CEA) under the supervision of an attending surgeon. With the proper supervision of the attending surgeon, these operations can be performed with an acceptably low perioperative stroke and mortality rate. The question remains, however, whether these desirable results can be obtained by general surgery residents when operating on awake patients under regional block (RB) anesthesia. We set out to determine whether it is prudent to promote this technique in this teaching setting. We analyzed 128 CEAs performed at a community teaching hospital training three chief residents a year. These operations were performed by residents under the direct supervision of a single attending vascular surgeon. RB was preferred and was used in 67 operations. General anesthesia (GA) was used in the remaining 61 procedures. Overall mortality was 0 per cent. Patients in the RB group were converted intraoperatively to GA in 4 of 67 (6%) procedures. There was one perioperative stroke in this series (1/128, 0.78%), occurring in a patient under RB (1/67, 1.5 %) leaving the patient with a minor sensory deficit. No strokes occurred in the GA group. There were five temporary cranial nerve deficits (3.9%). Three were in the RB group (4.5%) and two in the GA group (3.3%). General surgery residents can be trained in the performance of carotid endarterectomy using regional block anesthesia in awake patients without compromising patient safety. Suggestions to the effect that only attending physicians and/or vascular fellows can perform these procedures under regional block are without merit.

Chlorhexidine lavage in the treatment of experimental intra-abdominal infection.

HYPOTHESIS: Closed postoperative peritoneal lavage (CPPL) with chlorhexidine gluconate reduces the number of intraperitoneal bacteria and improves the outcome of intra-abdominal infection. DESIGN: Laboratory animal trial. INTERVENTIONS: Intra-abdominal infection was produced in mice by the cecal ligation and puncture technique. After 16 to 18 hours, the animals underwent relaparotomy and placement of an intra-abdominal catheter for CPPL. In the first experiment animals were randomly divided into 4 groups: no lavage (served as a control), CPPL with chlorhexidine. CPPL with cefoxitin, and CPPL with lactated Ringer solution (LR). Lavage was continued intermittently every 8 hours for 24 hours. All animals received systemic cefoxitin every 8 hours for 7 days. Mortality was recorded every 8 hours for 10 days. In the second experiment, animals were divided into 3 groups: no lavage (served as a control), CPPL with chlorhexidine, and CPPL with LR. Lavage was continued intermittently every 8 hours for 24 hours. The animals were killed 48 hours after reoperation. Bacterial counts from peritoneal fluid and biopsy specimens, as well as peritoneal white blood cell counts, were measured before and after lavage. RESULTS: Closed postoperative peritoncal lavage with chlorhexidine reduced mortality from 71% in a control group to 37% (P = .003). There was no survival benefit in either the CPPL with cefoxitin (91% mortality) (P = .14) or CPPL with LR groups (90% mortality) (P = .17). The statistically significant findings of analysis of variance evaluation demonstrated a decrease in bacterial counts after cecal excision in all 3 groups. There was a greater reduction in bacterial counts in the chlorhexidine group compared with the control group (P<.05). Bacterial counts decreased in peritoneal fluid, as well as in tissue biopsy specimens, after cecal excision. White blood cell counts significantly decreased after cecal excision in all 3 groups. There was no difference in white blood cell counts between the groups. Correlation analyses demonstrated weak interaction between bacterial and white blood cell counts before or after treatment in all the groups. Pearson r ranged from -0.37 to +0.35, none of which were statistically significant. CONCLUSIONS: In our experiments chlorhexidine lavage resulted in a 50% reduction in mortality and a significant reduction in bacterial counts compared with the control group. There was no survival benefit from lavage with either cefoxitin or LR. There was no reduction in bacterial counts in the LR group relative to the control group. Thus, the survival benefit and the reduction in bacterial numbers are attributed to the antibacterial properties of chlorhexidine rather than to the mechanical washing of the abdominal cavity. Closed postoperative peritoneal lavage with 0.05% chlorhexidine gluconate might be useful in the multimodal treatment of intra-abdominal infection.

Outcome-oriented standards and performance indicators for substance dependency rehabilitation programs.

This paper discusses the differences between accreditation standards and performance indicators for substance user treatment programs in the context of Commission on Accreditation of Rehabilitation Facilities (CARF's) accreditation system and its performance indicators project. Accreditation standards that require outcomes data collection and analysis are summarized. Standards undergo regular periodic review and revision, and outcome standards are a focus for refinement in 2000. Although draft performance indicators identified by work groups facilitated by CARF are also summarized, the reader is encouraged to seek the latest version of the CARF documents published on this topic. Standards and indicators for programs using methadone treatment are also described. Substantial input from consumers of substance use and other behavioral health rehabilitation programs is being sought through CARF's project and will need be incorporated in the proposed set of indicators.

Needle-localized breast biopsy for mammographic abnormalities: a community hospital experience.

Increased awareness of benefits of early detection of breast cancer has resulted in increased numbers of screening mammographies and breast biopsies for nonpalpable lesions. Tertiary hospital studies have demonstrated positive biopsy rates from abnormal mammographic findings at 18 to 32 per cent. We examined the effectiveness of needle biopsy for nonpalpable radiographic abnormalities in our community hospital. We reviewed 167 records of patients biopsied over a 2-year period. Mammographic assessment, biopsy, and pathological assessment were performed using accepted methods. Malignancy was detected in 34 of 167 biopsies (20%). The biopsy yield rate was highest for mammographic findings of spiculated or stellate masses (75%, P < 0.01). Most biopsies (83%) were performed because of mammographic findings of microcalcifications or circumscribed enlarging masses/nodular developing densities for a positive biopsy yield rate of 16 per cent. Rates were higher in patients with personal (44%) or family history (30%) of breast cancer and in postmenopausal women (30%). These results demonstrate that 1) factors such as age, personal or family history of breast cancer, and certain mammographic features of breast lesions are associated with high biopsy yield rates, and 2) the biopsy yield rate in our community setting is comparable to tertiary hospital experience.

Accreditation and the use of outcomes-oriented information systems.

Rehabilitation programs of all types and sizes must be able to use information technology to respond to both internal and external forces. One can anticipate that consumer-driven care will mean a desire for and access to more public information about health plans, specialty components of health care (eg, rehabilitation), and the quality of plans and providers. Providers need information with which to plan and manage their outcomes and resource allocation, to monitor and improve the quality of services, and to communicate with external stakeholders. The Commission on Accreditation of Rehabilitation Facilities (CARF) has for more than two decades required accredited organizations to have active outcome-oriented program evaluation systems. Yet, accreditation requirements have historically been process-oriented. This process orientation is now evolving toward an outcome orientation, both in the accreditation environment at large, and at CARF. This article describes these outcome-oriented initiatives, including CARF SCoRsSM, a standards conformance rating system under development at CARF, and a project to identify a limited, uniform set of performance indicators for rehabilitation programs. In addition, the article reflects on the significance of a potential National Information System for brain injury to the accreditation and outcomes arena.