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PubMed1998

Is there a future for spermatid injections?

Microinjection of spermatids into oocytes has proven to be a successful assisted reproduction procedure in the animal model. In the human, low fertilization and cleavage to the 4-cell stage were reported after intracytoplasmic sperm injection (ICSI) with round spermatids. In comparison with a conventional ICSI-testicular sperm extraction (TESE) programme, the implantation rate after round spermatid injection is dramatically low. Different problems have been encountered during the development of the spermatid injection technique and they could be partially responsible for the lower outcome when using round spermatids. Compared with the round spermatid cells, spermatids in the elongation phase are easy to isolate and identify from other round cells present in a wet preparation. The morphological identification does not reveal anything about the viability or the genetic normality of the round spermatids. Severe testicular dysfunction may have consequences on the quality of the few spermatogenic cells present. Others factors, such as the pathology of the patient, play an important role in the successful treatment. Even if the results are extremely low, spermatid injection seems more favourable for men who have already proven their capacity to produce some spermatozoa. A spermatogenic block at the round spermatid level has led to early abortions, increasing the suspicion of the role of a genetic factor. In order for this technique to be safe for use in clinics, more intensive work is needed to improve the selection and handling of cells and to ascertain the genomic imprinting and gene expression necessary for embryonic development. Hence, when using immature cells for conception, the screening of the patient and the follow-up of the pregnancies and babies should be mandatory.

Animals↗
PubMed2005

Promoting fundamental clinical skills: a competency-based college approach at the University of Washington.

The focus on fundamental clinical skills in undergraduate medical education has declined over the last several decades. Dramatic growth in the number of faculty involved in teaching and increasing clinical and research commitments have contributed to depersonalization and declining individual attention to students. In contrast to the close teaching and mentoring relationship between faculty and students 50 years ago, today's medical students may interact with hundreds of faculty members without the benefit of a focused program of teaching and evaluating clinical skills to form the core of their four-year curriculum. Bedside teaching has also declined, which may negatively affect clinical skills development. In response to these and other concerns, the University of Washington School of Medicine has created an integrated developmental curriculum that emphasizes bedside teaching and role modeling, focuses on enhancing fundamental clinical skills and professionalism, and implements these goals via a new administrative structure, the College system, which consists of a core of clinical teachers who spend substantial time teaching and mentoring medical students. Each medical student is assigned a faculty mentor within a College for the duration of his or her medical school career. Mentors continuously teach and reflect with students on clinical skills development and professionalism and, during the second year, work intensively with them at the bedside. They also provide an ongoing personal faculty contact. Competency domains and benchmarks define skill areas in which deepening, progressive attention is focused throughout medical school. This educational model places primary focus on the student.

Clinical Competence↗
PubMed2000

Cardiac responses to exercise in competitive child cyclists.

PURPOSE: Cardiovascular responses to exercise in highly trained child endurance athletes have not been well-defined. This study compared hemodynamic responses with progressive cycle exercise in seven competitive child cyclists (mean age 11.9 yr) compared with 39 age-matched untrained boys. METHODS: Doppler echocardiography and gas exchange variables were utilized to assess cardiovascular changes during submaximal and maximal exercise. RESULTS: Mean VO2max was 60.0 (+/-6.0) and 47.0 (+/-5.8) mL x kg(-1) x min(-1) in the cyclists and nonathletes, respectively. At rest and maximal exercise, the cyclists demonstrated greater stroke index than the untrained subjects (resting mean 59 (+/-6) vs 44 (+/-9) mL x m(-2); maximal mean 76 (+/-6) vs 60 (+/-11) mL x m(-2)), but the ratio of maximal:rest stroke index was similar in both groups (1.31 for cyclists, 1.41 for nonathletes). Both groups showed a plateau in stroke volume beyond low-intensity work levels. No significant difference was observed in maximal arteriovenous oxygen difference. CONCLUSIONS: These findings indicate that 1) maximal stroke volume is the critical determinant of the high VO2max in child cyclists and 2) factors that influence resting stroke volume are important in defining VO2max differences between child endurance athletes and untrained boys.

Bicycling↗
PubMed2006

Regular physical activity increases glutathione peroxidase activity in adolescents with Down syndrome.

OBJECTIVE: The present study was designed to determine the influence of a 12-week exercise program on the activity of erythrocyte glutathione peroxidase (GPX) in adolescents with Down syndrome. DESIGN: An interventional study with before-after comparison. SETTING: Sport Medicine School, University of Cadiz (Andalusia, Spain). PATIENTS: Thirty-one male adolescents (16.3+/-1.1) with Down syndrome. None of them suffered acute medical problems at that moment and had not taken part in any physical activity program in the last 6 months. INTERVENTION: A 12-week training program with 3 days per week, consisting of warm up (15 min) followed by a main part (20 to 35 min) at a work intensity of 60% to 75% of peak heart rate (HRmax=194.5-[0.56xage]) and by a cool-down period (10 min). MAIN OUTCOME MEASUREMENT: Erythrocyte activity of GPX. RESULTS: Preexercise and postexercise GPX activity in adolescents with Down syndrome were 24.8+/-3.1 [23.1 to 26.5] U/g hemoglobin and 29.3+/-2.9 [28.1 to 30.5] U/g hemoglobin, respectively. When compared with baseline values it was increased significantly (24.8+/-3.1 vs. 29.3+/-2.9; P=0.011). CONCLUSION: Regular exercise increased significantly GPX activity. Further studies are required to assess the behavior of other antioxidant enzymes to highlight potential benefits of regular exercise in redox metabolism.

Adolescent↗
PubMed2006

High-energy phosphate metabolism during calf ergometry in patients with isolated aorto-iliac artery stenoses.

OBJECTIVES: Patients with peripheral arterial disease (PAD) and aorto-iliac atherosclerotic lesions suffer from a broad range of complaints, such as pain at the hip, the thigh, and calf claudication. The purpose of this study was to investigate the high-energy metabolism in the calf muscle of patients with PAD with isolated aorto-iliac stenoses during incremental plantar flexion exercise. MATERIALS AND METHODS: Using a 1.5 T whole-body magnetic resonance (MR) scanner, 12 patients with PAD with uni- or bilateral aorto-iliac atherosclerotic lesions and 10 healthy male controls underwent serial phosphor-31 MR spectroscopy during incremental exercise at 2, 3, 4, and 5 W. The phosphocreatine (PCr) time constants were calculated for each increment and recovery using a monoexponential model. In the patient group, the run-off resistance was determined on MR angiograms. In both the patients and the controls, the ankle brachial pressure index was measured. RESULTS: The diseased legs exhibited significantly increased PCr time constants during the second and the third workload increment at 3 and 4 W, but not during the first increment at 2 W and recovery compared with normal controls. Only 3 diseased legs succeeded the last increment at 5 W. We detected significant correlations between the ankle brachial pressure index scores and the PCr time constants when including both the diseased and the control legs. The diseased legs showed a significant correlation with the run-off resistance only during the first increment. CONCLUSIONS: Our study shows that the impairment of muscle metabolism, expressed by prolonged PCr time constants, occurs with greater work intensities in patients with aorto-iliac disease compared with patients with multisegmental PAD, as recently published, whereas our patients collective exhibited normal PCr recovery time constants. Our findings may help to understand variability of clinical symptoms in aorto-iliac PAD.

Aged↗
PubMed1991

Locked-in syndrome: a team approach.

A person who suffers brainstem infarction resulting in quadriplegia, lower cranial nerve paralysis and mutism with intact cortical function may survive in a condition aptly termed "locked-in syndrome" (LIS). Literally a mind locked inside the body, the person remains fully aware without the ability to move or communicate. Because of the awesome nature of the condition and its likely permanent basis, family and staff may feel hopeless and incapacitated when planning care. Anatomical findings, etiologies, manifestations and outcomes are discussed in the literature but offer few suggestions for case management. Our clinical team has worked intensively with several LIS patients and has found that an interdisciplinary team approach is essential for providing creative patient care.

Adult↗
PubMed2005

novoSNP, a novel computational tool for sequence variation discovery.

Technological improvements shifted sequencing from low-throughput, work-intensive, gel-based systems to high-throughput capillary systems. This resulted in a broad use of genomic resequencing to identify sequence variations in genes and regulatory, as well as extended genomic regions. We describe a software package, novoSNP, that conscientiously discovers single nucleotide polymorphisms (SNPs) and insertion-deletion polymorphisms (INDELs) in sequence trace files in a fast, reliable, and user-friendly way. We compared the performance of novoSNP with that of PolyPhred and PolyBayes on two data sets. The first data set comprised 1028 sequence trace files obtained from diagnostic mutation analyses of SCN1A (neuronal voltage-gated sodium channel alpha-subunit type I gene). The second data set comprised 9062 sequence trace files from a genomic resequencing project aiming at the construction of a high-density SNP map of MAPT (microtubule-associated protein tau gene). Visual inspection of these data sets had identified 38 sequence variations for SCN1A and 488 for MAPT. novoSNP automatically identified all 38 SCN1A variations including five INDELs, while for MAPT only 15 of the 488 variations were not correctly marked. PolyPhred detected far fewer SNPs as compared to novoSNP and missed nearly all INDELs. PolyBayes, designed for the sequence analysis of cloned templates, detected only a limited number of the variations present in the data set. Besides the significant improvement in the automated detection of sequence variations both in diagnostic mutation analyses and in SNP discovery projects, novoSNP also offers a user-friendly interface for inspecting possible genetic variations.

Animals↗
PubMed2004

Arterial blood pressure and carotid baroreflex function during arm and combined arm and leg exercise in humans.

AIM: During arm cranking (A) blood pressure is higher than during combined arm and leg exercise (A + L), while the carotid baroreflex (CBR) is suggested to reset to control a higher blood pressure in direct relation to work intensity and the engaged muscle mass. METHOD: This study evaluated the function of the CBR by using neck pressure and neck suction during upright A, L and A + L in 12 subjects and, in order to evaluate a potential influence of the central blood volume on the CBR, also during supine A in five subjects. Exercise intensities for A and L were planned to elicit a heart rate response of c. 100 and 120 beats min(-1), respectively, in the upright position and both workloads were maintained during A + L and supine A. RESULTS: The CBR operating point, corresponding to the pre-stimulus blood pressure, was 88 +/- 6 mmHg (mean +/- SE) at rest. During upright A, L and A + L and supine A it increased to 109 +/- 9, 95 +/- 7, 103 +/- 7 and 104 +/- 4 mmHg, respectively, and it was thus higher during upright A than during A + L and supine A (P < 0.05). In addition, the CBR threshold and saturation pressures, corresponding to the minimum and maximum carotid sinus pressure, respectively, were higher during upright A than during supine A, A + L, L and at rest (P < 0.05) with no significant change in the maximal reflex gain. CONCLUSION: These findings demonstrate that during combined arm and leg and exercise in the upright position the CBR resets to a lower blood pressure than during arm cranking likely because the central blood volume is enhanced by the muscle pump of the legs.

Adult↗
PubMed1996

Cardio-respiratory and plasma lactate responses to exercise with low draught resistances in standardbred trotters.

Five Standardbred trotters performed treadmill exercise with incrementally increasing trotting velocities for 2 min intervals in three different tests until fatigue. Each test was performed with draught loads of either 10, 20 or 30 kilopond (kp). Each trotting interval was followed by 2 min periods at a walk without draught load. Recordings were made of heart rate (HR), respiratory rate (RR), plasma lactate (PLA) and stride frequency (SF) at the end of each trotting interval. The HR increased to average values of 191 +/- 10,203 +/- 10 and 214 +/- 7 bpm and PLA increased to 3.8 +/- 0.7, 7.3 +/- 3.8 and 10.8 +/- 6.4 mmol/l at 9 m/s in the three tests, respectively. The HR response to exercise was significantly higher with increasing draught loads, and PLA was significantly higher with 30 kp compared to 10 kp draught resistance. The lowest respiratory rate was seen in the test with 30 kp loading. Peak oxygen uptake (VO2peak) was measured in a separate test on a sloped treadmill with increasing velocities without draught load and averaged 70.4 +/- 9.11/min. Muscle biopsies were taken from the gluteus muscle. Individual variations were seen in VO2peak, muscle fibre composition and HR and PLA responses to exercise. In conclusion, at a certain velocity a small increase in draught resistance from 10 to 30 kp significantly increases both the HR and PLA responses. At comparable work intensities the horses differed in circulatory and metabolic responses to exercise.

Animals↗
PubMed2006

The Fountain House movement, an alternative rehabilitation model for people with mental health problems, members' descriptions of what works.

The clubhouse model is a method of rehabilitation where people suffering from mental health problems organise themselves in order to create change in their lives. Work is considered the main tool of rehabilitation within the clubhouse. The aim of the study was to explore the members' perception of the rehabilitation process. The study was participant oriented, which means that a group of members conducted the study in co-operation with the researcher. The study was explorative and research data were collected in a variety of ways including detailed notes, flipcharts, taped interviews and cognitive maps. As for ethical considerations, the members were guaranteed anonymity, voluntary participation and confidentiality in various ways. As a model of rehabilitation Göteborgsfontänen demonstrates a particular thematic subculture that has the goal of creating links between people that are characterised by mutual trust, habits of co-operation, solidarity and responsibilities undertaken voluntarily. Three keystones on which the thematic subculture rests were identified: meaningful relationships, meaningful work tasks and a supportive environment. The member must, in the first place, internalise the ideology as well as view differences between people as a resource rather than an obstacle. This was experienced as a turning point. The work-ordered day functioned as a framework and a resource for members and staff to work intensively with relationships. Some members experienced their membership as too intense at times which could result in a temporary withdrawal. A limitation of the study is that only members who experienced a turning point were involved in the study. This means that the data may lack some critical views of the ideology of the clubhouse.

Attitude to Health↗
PubMed1985

Ammonia metabolism during exercise in man.

Physical exercise is accompanied by increased plasma levels of ammonia but it is not known whether this rise primarily reflects accelerated formation in muscle or decreased removal by the liver. Consequently, leg and splanchnic exchange of ammonia was examined, using the catheter technique, in 11 healthy subjects at rest, during three consecutive 15 min periods of bicycle exercise at gradually increasing work loads (35%, 55% and 80% of maximum oxygen uptake) and for 60 min during post-exercise recovery. The basal arterial ammonia level was 22 +/- 2 mumol/l, the concentration rose curvilinearly in response to increasing work loads (peak value 84 +/- 12 mumol/l), and fell rapidly after exercise, reaching basal levels after 30-60 min. A linear regression was found for ammonia levels in relation to lactate concentrations at rest and during exercise (r = 0.85, P less than 0.001). A significant relationship was also observed between arterial ammonia and alanine levels (r = 0.75, P less than 0.001). Leg tissues showed a net uptake of ammonia in the basal state (2.4 +/- 0.5 mumol/min). During exercise this changed to a net production, which increased curvilinearly with rising work intensity (peak value 46 +/- 15 mumol/min) but reverted to a net ammonia uptake at 30-60 min after exercise. Splanchnic ammonia uptake (basal 12 +/- 2 mumol/min) did not change in response to exercise but increased transiently during the early post-exercise period. From the above observations we conclude that the hyperammonaemia of exercise comes primarily from muscle release, while the splanchnic removal of ammonia is essentially unaltered. Part of the ammonia formed in contracting muscle is most likely used in the synthesis of amino acids, mainly glutamine and probably alanine.

Adult↗
PubMed1990

Discrepancy between estimated energy intake and requirement in female dancers.

Dietary intake of energy, protein, fat and carbohydrates in female dance students compared to female music students was estimated by a dietary history method. Energy requirement was estimated from body weight and physical activity both by a standard formula and from the measured work intensity during dance training. Meal patterns showed significant differences in four types of meals on week-days and in one type on weekends. The intake of protein, fat and carbohydrates in absolute amounts and the percentage of energy derived from protein were not significantly different between the two groups. The fraction of energy derived from carbohydrates was higher and that from fat was lower in the dancers than in the musicians. Energy intake was of similar magnitude for the dancers and the musicians (8.3 +/- 1.9 MJ vs. 8.3 +/- 1.7 MJ), while the estimated energy requirement was greater for the dancers (10.3 +/- 0.7 MJ vs. 8.9 +/- 0.4 MJ). The reason for the apparent discrepancy between energy intake and energy requirement of approximately 2 MJ in the dancers is not obvious. The energy intake may have been underestimated. Alternatively, the energy requirement may have been overestimated. The resting metabolic rate may have been depressed by years of low energy intake. In addition, as suggested by some authors, training as such may lower the resting metabolic rate as well as the diet-induced thermogenesis.

Adult↗
PubMed2006

Forearm blood flow and oxygen consumption in patients with bilateral repetitive strain injury measured by near-infrared spectroscopy.

Despite the social impact of repetitive strain injury (RSI), little is known about its pathophysiological mechanism. The main objective of this study was to assess the local muscle oxygenation (mVO2) and blood flow (mBF) of the forearm in individuals with RSI during isometric contractions of the forearm. We employed the non-invasive optical technique near-infrared spectroscopy to assess forearm VO2 and BF. These variables were assessed at 10%, 20%, and 40% of their individual maximal voluntary strength. Twenty-two patients with RSI symptoms in both arms (bilateral RSI) and 30 healthy age-matched subjects participated in this cross-sectional study. The results showed lower mVO2 during exercise and a reduced mBF after exercise. The results suggest that mVO2 and mVO2 are lower in the forearms of individuals with RSI compared with their controls at similar working intensities. This finding indicates that the underlying vasculature may be impaired. Although these findings contribute to the understanding of RSI, future research is necessary to further unravel the mechanisms of this area.

Adult↗
PubMed1981

Skin and mucous membrane problems from "no carbon required" paper.

The Copenhagen Telephone Company uses 800,000-900,000 sets of no carbon required paper per year. Since 1977 the employees have related itching, dermatitis and symptoms from the mucous membranes to contact with the paper. In 35 employees a total of 4000 epicutaneous tests were performed with negative results. A questionnaire study of 2400 in the company revealed a close relationship between the symptoms and the work intensity with the NCR paper.

Adolescent↗
PubMed1998

Reproducibility and validity of physiological parameters measured in cyclists riding on racing bikes placed on a stationary magnetic brake.

UNLABELLED: The purpose of this study was: 1) To evaluate the reproducibility of physiological parameters measured during cycle exercise, and 2) To validate the predictive capacity of physiological parameters related to endurance performance. Therefore, physiological variables were measured twice during cycling exercise in a group of seven cyclists. Each cycle exercise session was separated by one week and included progressive submaximal cycling followed by a 5-km time trial. Two and three weeks later, endurance performance was evaluated by calculating average work output during a 50-km time trial (W50km). To simulate cycle performance, the cyclists' private racing bikes were placed on a stationary magnetic brake. No differences were observed between paired physiological observations in the test-retest (P>0.05). The coefficient of variation (CV) was calculated from the differences between test-retest parameters. CV for the maximal oxygen uptake (VO2max), average work output during the 5-km trial (W5km), the calculated work intensity which increased the blood lactate concentration to 2 and 4 mmol/l (W2mM and W4mM) and W50km were 1.9, 2.7, 6.1, 5.9 and 6.3%, respectively, while the 95% confidence interval (CI) showing the expected range for variation in a retest was calculated to be 80 ml.min(-1), 9, 16, 18 and 18 W, respectively. Simple linear regression showed significant correlations between VO2max, W5km, W2mM, W4mM and W50km (r-values: range 0.83-0.98, P<0.01). IN CONCLUSION: 1) Physiological parameters can be reproduced during an exercise test procedure in cyclists riding on racing bikes placed on a stationary magnetic brake, and 2) The validity of VO2max, W5km, W2mM, and W4mM as predictive parameters of endurance was demonstrated.

Adult↗
PubMed1980

The effects of pharmacological treatment on pulmonary function in children with exercise-induced asthma.

The effects of two therapeutic regimens were investigated in eleven boys and eight girls (8--13 years) with a history of exercise-induced asthma (EIA), who reacted with subjective signs of EIA and a decrease in FEV1.0 exceeding 10% after an exercise test. A test program (TP) including complete spirometry, bicycle ergometer and treadmill exercise tests preceded and followed by dynamic spirometry at one and five min after exercise, was performed before and after each treatment period. In 12 patients with sporadic medication before the trials, continuous peroral treatment with a combination of a beta 2-stimulating drug and a xanthine derivative for three weeks did not significantly improve TP data. In 13 children (six from the above group) who were already on continuous treatment as above, addition of disodium cromoglycate (DSCG) inhalations for 3--4 weeks improved the response to acute administration of a beta-receptor stimulatory aerosol but did not influence EIA. Seven of the children continued their DSCG treatment for one year. Minor improvement of EIA provoked by cycling but not by treadmill was seen after this. The ventilatory effort in relation to working intensity was lowered. No significant differences were found between treadmill running and cycling in provoking asthma.

Adolescent↗
PubMed1996

Fingerprinting of HLA class I genes for improved selection of unrelated bone marrow donors.

The degree of matching of HLA genes between the selected donor and recipient is an important aspect of the selection of unrelated donors for allogeneic bone marrow transplantation (UBMT). The most sensitive methods currently used are serological typing of HLA class I genes, mixed lymphocyte culture (MLC), IEF and molecular genotyping of HLA class II genes by direct sequencing of PCR products. Serological typing of class I antigenes (A, B and C) fails to detect minor differences demonstrated by direct sequencing of DNA polymorphic regions. Molecular genotyping of HLA class I genes by DNA analysis is costly and work-intensive. To improve compatibility between donor and recipient, we have set up a new rapid and non-radioisotopic application of the 'fingerprinting PCR' technique for the analysis of the polymorphic second exon of the HLA class I A, B and C genes. This technique is based on the formation of specific patterns (PCR fingerprints) of homoduplexes and heteroduplexes between heterologous amplified DNA sequences. After an electrophoretic run on non-denaturing polyacrylamide gel, different HLA class I types give allele-specific banding patterns. HLA class I matching is performed, after the gel has been soaked in ethidium bromide or silver-stained, by visual comparison of patients' fingerprints with those of donors. Identity can be confirmed by mixing donor and recipient DNAs in an amplification cross-match. To assess the technique, 10 normal samples, 22 related allogeneic bone marrow transplanted pairs and 10 unrelated HLA-A and HLA-B serologically matched patient-donor pairs were analysed for HLA class I polymorphic regions. In all the related pairs and in 1/10 unrelated pairs, matched donor-recipient patterns were identified. This new application of PCR fingerprinting may confirm the HLA class I serological selection of unrelated marrow donors.

Base Sequence↗
PubMed1977

Intramuscular substrate utilization during prolonged exercise.

Large stores of intramuscular substrates are found in the different fiber types of human skeletal muscle, and with prolonged exercise both glycogen and triglyceride stores are utilized. The contribution from intramuscular glycogen stores is greatest at higher work intensities while triglyceride stores are utilized at moderate intensities. In man all fiber types have a similar glycogen content whereas the highest lipid content is found in the more oxidative fibers. The muscle metabolism is well adapted to the supply of substrate as well as to the demand for energy. Among several regulatory mechanisms, changes in citrate concentration seems to be an important factor in the interplay between carbohydrate and lipid metabolism.

Diet↗