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Biomedical subjects

I Jacobs

Publications and source records attributed to I Jacobs.

At least 37 records · Page 2Linked to original sources

Reducing the dose of combined caffeine and ephedrine preserves the ergogenic effect.

BACKGROUND: Ingestion of a combination of 5 mg x kg(-1) caffeine (C), and 1 mg x kg(-1) ephedrine (E) was reported to have an ergogenic effect on high intensity aerobic exercise performance, but 25% of the subjects experienced vomiting and nausea while engaging in hard exercise after the treatment. The present study was undertaken to investigate whether reduced levels of C+E would alleviate the problem and maintain the ergogenic effect. METHODS: Twelve healthy untrained male subjects completed four randomized and double-blind, cycle ergometer trials to exhaustion at a power output equivalent to approximately 85% Vo2peak 1.5-2 hours after ingesting a placebo (P) or a mixture of C+E in the following doses: 5 mg x kg(-1) of C plus 0.8 mg x kg(-1) of E (CLE); 4 mg x kg(-1) of C plus 1 mg x kg(-1) of E (LCE); or 4 mg x kg of C plus 0.8 mg x kg(-1) of E (LCLE). Trials were separated by 1 wk. Venous blood samples were obtained and analyzed for caffeine and ephedrine levels 1.5 h post-drug ingestion. Vo2, Vco2, VE, and RQ were measured every minute throughout the exhaustion ride. Heart rate and perceived exertion (RPE) were also recorded every 5 min and at the end of the exercise session. RESULTS: Plasma levels of C and E immediately before the exhaustion ride were (mean +/- SD): 38.7+/-5.2 micromol x L(-1) C, 1.285+/-0.275 micromol x L(-1) E in the CLE trial; 33.2+/-5.8 micromol x L(-1) C, 1.462+/-0.283 micromol x L(-1) E in the LCE trial; 33.0+/-2.9 micromol x L(-1) C, 1.229+/-0.202 micromol x L(-1) E in the LCLE trial. The times to exhaustion for the treatment trials (CLE = 27.5+/-12.4 min, LCE = 27.6+/-10.9 min, LCLE = 28.2+/-9.3 min) were similar and were significantly greater than placebo (p = 17.0+/-3.0 min). The drugs did not affect Vo2, Vco2, or VE. Heart rates were significantly higher for the drug trials while RPE was lower compared with P. No incidents of nausea or vomiting occurred with the lowest dose of the C+E, LCLE. CONCLUSIONS: A lower dose of C+E resulted in an ergogenic effect similar in magnitude to that reported previously with a higher dose, and with a reduced incidence of negative side effects.

Adult↗

Combination of multiple serum markers using an artificial neural network to improve specificity in discriminating malignant from benign pelvic masses.

A panel of four selected tumor markers, CA 125 II, CA 72-4, CA 15-3, and lipid-associated sialic acid, was analyzed collectively using an artificial neural network (ANN) approach to differentiate malignant from benign pelvic masses. A dataset of 429 patients, 192 of whom had malignant histology, was retrospectively used in the study. A prototype ANN classifier was developed using a subset of the data which included 73 patients with malignant conditions and 101 patients with benign conditions. The ANN classifier demonstrated a much improved specificity over that of the assay CA 125 II alone (87.5% vs 68.4%) while maintaining a statistically comparable sensitivity (79.0% vs 82.4%) in discriminating malignant from benign pelvic masses in an independent validation test using data from the remaining 255 patients which had been set aside and kept blind to the developers of the ANN system. A similar improvement in specificity was observed among patients under 50 years of age (82.3% vs 62.0%). The ANN system was further tested using additional serum specimens collected from 196 apparently healthy women. The ANN system had a specificity of 100.0% compared to that of 94.8% with the assay CA 125 II alone.

Antigens, Tumor-Associated, Carbohydrate↗

A comparison of national cancer registry and direct follow-up in the ascertainment of ovarian cancer.

The National Health Service Central Register (NHSCR) and direct follow-up were used to document ovarian and fallopian tube cancers in 22000 women from 1986 to 1993. Direct follow-up identified 47/49 cases (96%) and the NHSCR 38/49 (78%). NHSCR ascertainment was incomplete and direct follow-up provided additional information. These findings have implications for interpretation of national cancer statistics and for use of the NHSCR in research trials.

Cohort Studies↗

Using clinical indicators in emergency medicine: documenting performance improvements to justify increased resource allocation.

OBJECTIVES: To demonstrate how emergency department triage scale and thrombolysis indicator data can be used to document the impact of a substantial increase in resource allocation. METHODS: Descriptive study in an emergency department of an adult tertiary hospital in Perth, Australia during similar periods of the year both before and after a substantial increase in emergency department staff, equipment, and system resources. The study group comprised a total of 11,048 emergency department attendances and all cases of emergency department initiated thrombolysis or acute angioplasty. Outcome was measured using numbers seen and percentage seen within indicator threshold time together with admission rates in each of the five triage categories as well as by using time from presentation to initiation of reperfusion treatment in acute myocardial infarction. RESULTS: The proportion of patients seen within the prescribed indicator time increased by 16.4% (95% confidence interval 14.4% to 18.2%). The increase was most pronounced in triage category 2 (32.7%). Median time to thrombolysis fell by 30 minutes to 37 minutes (p = 0.0002). CONCLUSIONS: Use of the Australasian national triage scale and time to thrombolysis clinical indicator data allows a quantitative assessment of the impact of increased emergency department resource allocation.

Adult↗

Physiological responses of exercised-fatigued individuals exposed to wet-cold conditions.

Thirteen healthy and fit men [age = 27 +/- 8 (SD) yr, height = 177 +/- 5 cm, mass = 75 +/- 7 kg, body fat = 14 +/- 5%, maximal O2 consumption = 51 +/- 4 ml. kg-1. min-1] participated in an experiment designed to test their thermoregulatory response to a challenging cold exposure after 5 h of demanding mixed exercise during which only water was consumed. Subjects expended 7,314 +/- 741 kJ on cycling, rowing, and treadmill-walking machines, performed 8,403 +/- 1,401 kg. m of mechanical work during resistance exercises, and completed 120 inclined sit-ups. Subjects then assumed a seated position in a 10 degrees C air environment while wearing shorts, T-shirt, rain hat, and neoprene gloves and boots. After 30 min the subjects were showered continuously with cold water ( approximately 920 ml/min at 10 degrees C) on their backs accompanied by a 6 km/h wind for up to 4 h. Blood samples were taken from the nondominant arm every 30 min during the exposure and assayed for energy metabolites, hormones, indexes of hydration, and neurotransmitters. Counterbalanced control trials without prior exercise were also conducted. Blood insulin was higher during the control trial, whereas values of glycerol, nonesterified fatty acids, beta-hydroxybutyrate, lactate, cortisol, free triiodothyronine, and thyroxine were lower. Three subjects lasted the maximum duration of 4.5 h for control and fatigue trials, with final rectal temperatures of 36.43 +/- 0.21 and 36.08 +/- 0.49 degrees C, respectively. Overall, the duration of 172 +/- 68 (SD) min for the fatigue trial was not significantly different from that of the control trial (197 +/- 72 min) and, therefore, was not affected by the preexposure exercise. Although duration was positively correlated to body fatness and shivering intensity, the latter was not correlated to any physical characteristic or the fitness level of the individual.

Adult↗

The Philadelphia story: the 22q11.2 deletion: report on 250 patients.

A submicroscopic deletion of chromosome 22q11.2 has been identified in the majority of patients with the DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes, and in some patients with the Opitz G/BBB and Cayler cardiofacial syndromes. We have been involved in the analysis of DiGeorge syndrome and related diagnoses since 1982 and have evaluated a large number of patients with the deletion. We describe our cohort of 250 patients whose clinical findings help to define the extremely variable phenotype associated with the 22q11.2 deletion and may assist clinicians in providing genetic counseling and guidelines for clinical management based on these findings.

Abnormalities, Multiple↗

Combined caffeine and ephedrine ingestion improves run times of Canadian Forces Warrior Test.

The ingestion of a combination of caffeine (C) and ephedrine (E) has been reported to prolong exercise time to exhaustion during cycle ergometry at 85% VO2max. The present study was undertaken to investigate whether this enhancement would occur in a field setting and if drug ingestion on 1 d would affect performance 1 d later. Two hours after ingesting either a combination of 375 mg of C and 75 mg E (C+E), or a placebo (P), 9 healthy male recreational runners completed six balanced and double-blind trials of the Canadian Forces Warrior Test (WT), a 3.2 km run wearing "fighting order" which weighed about 11 kg. The trials were performed in sets of two runs, i.e., two runs were done 24 h apart, and these sets were separated by a minimum of 7 d. The sets were: C+E trial on day 1 (D1), placebo on day 2 (P2); placebo first (P1), C+E second (D2); and placebo first (P3), placebo second (P4). In addition, 1 wk before the treatment trials the subjects performed a control trial WT. During the WT, heart rates (HR) were recorded every minute. Plasma C and E levels immediately before the WT were similar for both C+E trials, but were undetectable for all P trials. Run times (mean+/-SD) were 15.3+/-0.6, 15.4+/-0.9, 15.5+/-1.2, 15.4+/-0.9, 15.4+/-0.9, 14.8+/-0.7, and 14.6+/-0.8 min for control, P1, P2, P3, P4, D1, D2 trials, respectively. The two C+E trial run times were similar and both were significantly faster (p < 0.05) than control and all placebo trials. HR during the WT was significantly higher (p < 0.05) for the C+E trials compared with the other trials. WT performance was not impaired by C+E ingestion 24 h earlier. In conclusion, performance of the WT was improved by ingestion of C+E.

Adult↗

Thermal regulation in the heat during exercise after caffeine and ephedrine ingestion.

BACKGROUND: Ingesting a combination of caffeine and ephedrine (C+E) has been shown to raise metabolic heat production and body temperature. This side effect of C+E ingestion may be positive during a cold stress scenario, however, during heat stress it could prove to be detrimental. Thus, the purpose of this study was to clarify the effect of C+E ingestion on body temperature regulation during moderate exercise in a hot dry environment. METHODS: Ten, healthy, non heat acclimated, males exercised at 50% VO2peak in a 40 degrees C and 30% RH environment until rectal temperature reached 39.3 degrees C; heart rate (HR) remained at 95% of peak value or greater for 3 min, dizziness or nausea precluded further exercise, or 3 h had elapsed. They did this four times at weekly intervals: familiarization (Fam), control (Cont), placebo, and C+E (5 mg . kg(-1) caffeine + 1 mg . kg(-1) ephedrine) trials. The Fam and Cont treatments were done first and sequentially while the placebo and C+E treatments were balanced and double-blind. Tolerance times, mean skin temperature (Tsk), rectal temperature (Tre), Vo2, Vco2, VE, sweat rate (SR), HR, and sensation of thermal comfort were measured. RESULTS: Tolerance times (mean+/-SD in minutes) were similar for the placebo (120.0+/-28.4) and C+E (121.3+/-33.9) trials and both times were significantly longer than Cont (106.6+/-24.0) trial. C+E did not affect Tsk, initial TrC, delta Tre, SR or the sensation of thermal comfort. VO2 and VF, were significantly increased by C+E. HR was elevated by C+E compared with the other trials, but only during the initial 20 min of exercise. CONCLUSION: Although the metabolic rate was slightly increased with C+E treatment, it was sufficiently offset by increased heat loss mechanisms so that internal body temperature was not increased during moderate exercise in a hot, dry environment.

Adult↗

Dietary creatine monohydrate supplementation.

This paper summarizes and interprets the research published about physiological aspects of dietary supplementation with creatine monohydrate and the effects on physical performance. A nitrogenous molecule that occurs naturally in the flesh consumed by meat-eaters, creatine is also synthesized endogenously and is stored primarily in skeletal muscle. The research literature in which direct measurements of muscle creatine content have been reported indicates that most, but not all, subjects respond to "creatine loading" by increasing the total intramuscular concentration of creatine, including the concentration of phosphocreatine. The factors that affect muscle creatine stores are reviewed, as are the widely ranging results on physical performance. The mechanism of action by which increased intramuscular creatine could enhance performance is not yet clear. Original speculation was that increased phosphocreatine levels prior to commencing exercise, in conjunction with higher free creatine concentration, would prolong the time required until performance-limiting levels of phosphocreatine were reached during intense exercise. It was also speculated that restoration of phosphocreatine levels between bouts of such exercise would be more rapid. More recent studies question such speculation. This review includes a discussion of what is known about the health risks and side-effects associated with creatine loading. The paper concludes with speculation about the unprecedented attention given to creatine supplementation by recreational and competitive athletes and the media.

Creatine↗

Cold stress increases lipolysis, FFA Ra and TG/FFA cycling in humans.

BACKGROUND: To characterize the important changes in the selection and mobilization of metabolic fuel during cold stress, six males rested for 3 h at 29 degrees C and at 5 degrees C dressed only in shorts while 2H5 glycerol, 1-13C palmitate and 6,6 2H2 glucose were continuously infused for 3 h in each condition to determine their rate of turnover (Ra). METHODS: Metabolic rate (M) as well as rates of carbohydrate (CHOox) and lipid oxidation (FATox) were assessed by indirect calorimetry whereas all isotopic enrichments were determined by mass spectrometry. RESULTS: Cold exposure decreased rectal and mean skin temperatures and increased M, FATox and CHOox compared with the same test at thermal neutrality (p<0.05). As expected, cold increased plasma glucose Ra and plasma FFA Ra (from 4.58+/-0.19 to 14.69+/-1.07 micromol kg(-1) x min(-1); p < 0.05). However, in absolute terms, plasma FFA Ra in the cold remained more than twice greater than FATox (FATox only increased up to 6.9 +/-0.85 micromol kg(-1) x min(-1)), suggesting an enhanced non-oxidative disposal of fatty acids (i.e., TG/FFA cycling) to account for all FFA Ra. Indeed, cold increased extracellular TG/FFA recycling rate (2.23+/-0.40 vs 7.77+/-1.19 micromol kg(-1) x min(-1); p<0.05) whereas intracellular cycling was unaffected. CONCLUSION: Even though lipolysis and FFA Ra are greatly increased by cold stress in humans, the present results demonstrate that only about half the rate of FFA Ra is ultimately oxidized, suggesting that under the present cold conditions: 1) non-oxidative FFA disposal or TG/FFA cycling is significantly enhanced; 2) white adipose tissue-derived fatty acids could easily account for most of FATox. The results further emphasize the importance of the TG/FFA cycle in amplifying the ability of stored TG to react quickly to major changes in energy expenditure induced by a sustained cold stress.

Adipose Tissue↗

Effects of UV on the migration and function of epidermal antigen presenting cells.

Depletion of epidermal Langerhans cells (LC) and the concomitant depression of the skin immune system after excessive exposure to ultraviolet B light (UVB) has been established in the international literature for some time. Our investigations were intended to determine whether or not these phenomena occurred as a direct result of increased LC migration being triggered by the UVB exposure. To test this hypothesis, a sheep model was established in which the lymphatic vessels draining a defined region of skin were cannulated and the cells migrating towards the regional lymph node continuously collected. Cell populations in these collections were identified and enumerated by indirect immunofluorescence and flow cytometry. These experiments showed there was a significant, dose-dependent increase in the rate of LC migration from sheep skin after exposure to doses of UVB light exceeding 1 minimal erythemal dose (MED). In a series of parallel experiments, the functional characteristics of dendritic cells (DC) migrating from normal or UVB irradiated sheep were studied. To assay them, enriched preparations of DC were collected via cannulated afferent lymphatic vessels and pulsed with antigen prior to incubation with autologous peripheral blood lymphocytes. The relative efficiency of antigen presentation was determined by the ability of DC to induce T cell proliferation. Our data clearly demonstrate that there is a profound loss of normal antigen-presenting cell function after exposure to UVB light. Various experiments were undertaken to determine the mechanism(s) associated with these changes in migration kinetics and cellular function. Electron microscopic examinations of LC migrating from normal or UVB irradiated skin have demonstrated a profound loss of dendritic processes after UVB exposure. This provides a possible explanation for the changes in skin immunity after UVB exposure.

Animals↗

Effects of caffeine, ephedrine and their combination on time to exhaustion during high-intensity exercise.

This study investigated the effects of acute ingestion of caffeine (C), ephedrine (E) and their combination (C+E) on time to exhaustion during high-intensity exercise. Using a repeated-measures, double-blind design, eight male subjects exercised on a cycle ergometer at a power output that led to exhaustion after about 12.6 min during a placebo (P) control trial. They did this 1.5 h after ingesting either C (5 mg x kg[-1]), E (1 mg x kg[-1]), C+E, or P. Trials were separated by 1 week. Venous blood was sampled before and during exercise. The mean (SD) times to exhaustion were 12.6 (3.1) (P), 14.4 (4.1) (C), 15.0 (5.7) (E) and 17.5 (5.8) (C+E) min. Only the C+E treatment significantly increased time to exhaustion compared to P. Oxygen consumption (VO2), carbon dioxide production (VCO2), minute ventilation (VE) and the respiratory exchange ratio (RER) were similar during exercise for all trials. Heart rate during exercise was significantly increased for the C+E and C trials compared to P. Subjective ratings of perceived exertion during exercise were significantly lower after C+E compared to P. All treatments significantly increased lactate levels. Free fatty acid (FFA) levels were significantly increased by C ingestion. Glycerol levels were increased by C+E and C ingestion. Glucose levels were also higher with the drug treatments compared to P. Increased monamine availability after C+E treatment was suggested by measurements of catecholamines and dopamine. In conclusion, the combination of C+E significantly prolonged exercise time to exhaustion compared to P, while neither C nor E treatments alone significantly changed time to exhaustion. The improved performance was attributed to increased central nervous system stimulation.

Adult↗

Ovarian cancer screening.

Despite advances in molecular biology, surgical oncology, and chemotherapy, the prognosis for ovarian cancer remains poor. The excellent survival rates for stage I disease provide the rationale for efforts to screen for early-stage ovarian cancer. However, there are doubts about the feasibility of screening related to the natural history of the disease, the performance of the available tests, and health economic considerations. The investigators use the World Health Organization criteria for a screening program as a framework for discussing current issues in ovarian cancer screening. These include screening modalities and strategies, high- and low-risk populations, and the acceptability, psychological impact, and cost of screening. As a result of developments during the last decade, there are now real prospects for practical and effective ovarian cancer screening programs. Research to date has made important progress, but information about the impact of screening on mortality from ovarian cancer is still awaited. Three large randomized controlled trials of ovarian cancer screening are currently recruiting volunteers and will yield important results in the next few years.

Algorithms↗

Physical damage to rat cortical axons mimics early Alzheimer's neuronal pathology.

We investigated the reactive cytoskeletal changes following physical damage to axons in the rodent neocortex and compared these with the earliest neuronal alterations seen in Alzheimer's disease (AD). Insertion of a 25 gauge needle into the rodent somatosensory cortex resulted in ring- and club-like axonal changes characterized by an accumulation of neurofilaments. Morphologically and neurochemically identical abnormal axons were present within neocortical beta-amyloid deposits of individuals in the early stages of AD. Physically damaged rat cortical axons may therefore serve as a model for the early neuronal pathology of AD. Furthermore, these results suggest that insoluble beta-amyloid deposition may physically damage local axons, with further neurofibrillary changes due to the reactive neuronal response to this type of injury.

Aged↗

Creatine ingestion increases anaerobic capacity and maximum accumulated oxygen deficit.

The purpose of this study was to test the hypothesis that ingestion of creatine monohydrate increases anaerobic exercise capacity, as reflected by the maximal accumulated oxygen deficit (MAOD). Subjects were assigned, double-blind, to placebo (PL, n = 12) or creatine (CR, n = 14) groups and ingested 5-g doses 4 times daily of artificial sweetener or artificially sweetened creatine monohydrate, respectively, for 5 days. On a separate day subjects exercised to exhaustion at 125% VO2max. After two familiarization trials, MAOD was again determined before treatment, after 5 days of PL or CR treatment, and 7 days later. MAOD increased after CR treatment from 4.04 +/- 0.31 to 4.41 +/- 0.34 L (p < .001) and remained elevated for another 7 days (4.31 +/- 0.33, p < .001). Time to exhaustion also increased in CR from 130 +/- 7 to 141 +/- 7 s (p < .01) and remained increased for another 7 days (139 +/- 8 s, p < .01). These data demonstrate that ingesting creatine monohydrate for 5 days increases the MAOD, and is likely to have an ergogenic effect on supramaximal exercise performance that persists for at least a week after treatment.

Administration, Oral↗

Effect of upper respiratory tract infection in patients with neuromuscular disease.

Respiratory muscle strength during acute upper respiratory tract infection (URI) was assessed in patients with various forms of neuromuscular disease. Vital capacity (VC), oxygen saturation, end-tidal PCO2, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) were determined in 25 stable patients with various forms of neuromuscular disease. Thirteen episodes of URI developed in 10 patients. Respiratory parameters were reassessed within 24-36 h following the onset of symptoms in each patient. In patients with URI, mean baseline VC, MIP, and MEP were 1.16 L +/- 0.14, 49.2 cm H2O +/- 6.8, and 35.5 cm H2O +/- 3.8 and fell to 1.01 L +/- 0.15, 37.1 cm H2O +/- 6.2, and 25.5 cm H2O +/- 3.0 during URI (p < 0.05 for each), respectively. Mean baseline PCO2 and oxygen saturation were 39.1 mm Hg +/- 1.1 and 95.1% +/- 1.0, and during URI, 43.9 mm Hg +/- 2.1 (p < 0.05) and 95.0% +/- 1.0 (NS), respectively. Five episodes of significant hypercapnia were observed in 4 patients. All parameters returned to near baseline values following recovery. We conclude that patients with various forms of neuromuscular disease develop reductions in respiratory muscle strength in association with URI. Unlike normal subjects, however, these decrements in respiratory muscle function may result in symptoms of shortness of breath, reductions in vital capacity, and acute hypercapnia in this patient population.

Acute Disease↗