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Biomedical subjects

I Jacobs

Publications and source records attributed to I Jacobs.

At least 73 records · Page 4Linked to original sources

Is there central fatigue during simulated air combat maneuvering?

This study tested the hypothesis that repeated exposure to high levels of +Gz acceleration, in conjunction with repeated execution of an Anti-G Straining Maneuver (AGSM), causes central fatigue, presumably by impairing central nervous system (CNS) function. We speculated that central fatigue would impair the ability to recruit sufficient musculature at the intensity required to perform an adequate anti-G straining maneuver. Central fatigue was evaluated by measuring maximal force generation and surface electromyographic activity of leg extensor muscles before, during, and immediately upon termination of an SACM, and comparing these values to those obtained when the muscles were electrically stimulated during maximal voluntary contractions (MVCs). We assumed that any observed increase in force generation during the MVCs, caused by the stimulation, would indicate central fatigue. G-tolerance time was 230 +/- 172 s. Hypoxia was induced by the SACM as the arterial oxygen saturation decreased significantly from 97% to 90%. In spite of this hypoxia, there was no significant change in MVC force when the pre- and post-SACM values were compared. Electrical stimulation during the MVC's did not cause an increase in force generation. The average forces generated during the +7 Gz phase of the SACM were only about 35% of MVC force. This force value did not change significantly during the SACM. The results indicate that the inability to continue to perform the AGSM during an SACM is not likely due to central fatigue or to fatigue of the large skeletal muscle groups we have examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerospace Medicine↗

Effect of modafinil on heat production and regulation of body temperatures in cold-exposed humans.

Military personnel often undergo sustained operations that affect vigilance and alertness. Pharmacological agents may be used to enhance vigilance. Most such agents also have thermogenic properties. Whether a new promising stimulant, modafinil (Lyons and French, Aviat. Space Environ. Med. 1991; 62:432-435), has a beneficial effect on cold tolerance in the military context, is not known. The goal of this study was, therefore, to evaluate the effect of this new drug on thermal balance and the regulation of body temperatures in neutral conditions and when challenged by a cold exposure. Nine subjects underwent three trials each: two in the cold (3 h at rest, 10 degrees C) 0.5 h after the ingestion of either placebo or modafinil (200 mg), and one in thermal neutrality with modafinil (same conditions except Tdb = 29.3 degrees C). As expected, cold produced a drop in Tre and Tsk and an increase in Vo2. Although non-significant, there was a tendency for a slightly greater drop in Tre with modafinil (0.65 degrees C vs. 0.57 degrees C with placebo). A similar tendency was found for the heat debt (S) which was greater with modafinil than with placebo (16.1 +/- 0.7 vs. 14.7 +/- 0.6 kJ.kg-1, respectively, +9.5%, p = 0.11). This tendency appears to be the combined result of a slightly lower mean heat production during the test and a slightly greater mean dry heat loss. When tested at thermal neutrality, the drug had no effect on any thermal or metabolic parameters. The results demonstrate that the ingestion of a single dose of modafinil has no significant acute effect on thermal balance in neutral conditions and on thermoregulation in normal subjects exposed to cold. However, a tendency for slightly greater cooling was noted with modafinil. It is not known whether the use of modafinil in conjunction with sleep deprivation (a likely scenario) could magnify this effect.

Adult↗

Electromyographic indices of muscle fatigue during simulated air combat maneuvering.

Pilots exposed to high levels of headward (+Gz) acceleration must perform voluntary muscle contractions in order to maintain head-level arterial pressure. To study the possibility that muscular fatigue can limit human +Gz duration tolerance, electromyographic (EMG) activity and EMG indices of muscular fatigue were measured during a simulated air combat maneuvering (SACM) centrifuge profile. Eight experienced male volunteers were exposed to a +4-7 Gz centrifuge profile until volitional fatigue. Electrical activity (EMG) was recorded from 7 muscles: biceps brachii (BB), latissimus dorsi (LD), pectoralis major (PM), rectus abdominis (RA), vastus lateralis (VL), biceps femoris (BF) and gastrocnemius (GN). EMG and force during isometric contractions of the same muscles were also recorded at 1 G. Root mean square (RMS) and mean power frequency (MPF) were calculated for each second of EMG data. G-tolerance time averaged 256 +/- 33 s (mean +/- SD). RMS activity was expressed relative to activity during a maximal muscle contraction. The mean values (%) for each muscle during the 7 Gz plateaux were: RA, 30.8; BB, 26.4; LD, 44.0; PM, 48.5; VL, 43.4; BF, 31.4; GN, 39.3. The estimated level of contraction relative to a MVC (%) was: RA, 36.6; BB, 30.5; LD, 43.9 and PM, 61.4. There was no significant difference between contraction levels for any of the muscles studied. RMS activity did not increase over time and MPF decreased significantly only in BF and LD, however, these decreases were small. EMG activity and estimated contraction intensities were considered to be low to moderate. These results suggest that it is unlikely that fatigue in the muscles studied would limit G-tolerance time.

Adult↗

Prevalence screening for ovarian cancer in postmenopausal women by CA 125 measurement and ultrasonography.

OBJECTIVE: To assess the performance of the sequential combination of serum CA 125 measurement and ultrasonography in screening for ovarian cancer. DESIGN: The serum CA 125 concentration of each subject was determined and those with a concentration > or = 30 U/ml were recalled for abdominal ultrasonography. If ultrasonography gave abnormal results surgical investigation was arranged. Volunteers were followed up by annual postal questionnaire. SETTING: General practice, occupational health departments, ovarian cancer screening clinic. SUBJECTS: 22,000 women volunteers who were postmenopausal and aged over 45 years. MAIN OUTCOME MEASURES: Apparent sensitivity, specificity, positive predictive value, years of cancer detected. RESULTS: 41 women had a positive screening result and were investigated surgically. 11 had ovarian cancer (true positive result) and 30 had other disorders or no abnormality (false positive result). Of the 21,959 volunteers with a negative screening result, eight subsequently presented clinically with ovarian cancer (false negative result) and 21,951 had not developed ovarian cancer during follow up (apparent true negative result). The screening protocol achieved a specificity of 99.9%, a positive predictive value of 26.8%, and an apparent sensitivity of 78.6% and 57.9% at one year and two year follow up respectively. The estimated number of years of cancer detected by the prevalence screen was 1.4 years. CONCLUSIONS: This screening protocol is highly specific for ovarian cancer and can detect a substantial proportion of cases at a preclinical stage. Further investigation is required to determine the effect of the screening protocol on the ratio of early to late stage disease detected and on mortality from ovarian cancer.

Aged↗

Cell growth regulation in epithelial ovarian cancer.

BACKGROUND: As in the case of other epithelial neoplasms, most ovarian cancers arise from single clones of cells that have undergone multiple genetic alterations. A comparison of normal and malignant ovarian epithelium has identified several differences in growth regulation by peptide growth factors, protooncogenes, and tumor suppressor genes. METHODS: Recent articles and abstracts have been reviewed. RESULTS: The malignant ovarian epithelial phenotype has been associated with (1) autocrine growth stimulation by transforming growth factor-alpha, (2) loss of autocrine growth inhibition by transforming growth factor-beta, (3) mutation or amplification of ras in 2-12% of cases, (4) amplification of myc in 23% of specimens, (5) expression of fms in 56% of cases with potential autocrine stimulation by macrophage colony stimulating factor, (6) paracrine stimulation by macrophage products including interleukin-1, interleukin-6 and tumor necrosis factor, (7) overexpression of c-erbB-2 (HER-2/neu) in 30% of cases, and (8) mutation with consequent overexpression of p53 in 50% of advanced ovarian cancers. A poor clinical prognosis is associated with expression or overexpression of the epidermal growth factor receptor, fms, and HER-2/neu. Antibodies against the extracellular domain of the HER-2/neu gene product p185 inhibit the growth of tumor cells that overexpress HER-2/neu and are associated with marked decreases in diacylglycerol levels. The intracellular kinase domain is required for growth inhibition. Antibodies that inhibit growth stimulate phosphorylation of intracellular substrates. Ricin A chain monoclonal antibody conjugates that react with p185 also inhibit the growth of tumor cells that overexpress p185. The intracellular kinase region is not required for immunotoxin-mediated killing. Coexpression of HER-2/neu and the epidermal growth factor receptor has been observed in 65% of epithelial ovarian cancers and in a limited number of normal tissue from a fraction of donors. CONCLUSIONS: Multiple alterations in growth factors, protooncogenes and growth factors have been detected in different epithelial ovarian cancers. Inappropriate signalling from receptor tyrosine kinases may be particularly important for ovarian oncogenesis. Drugs that affect tyrosine kinase and phosphatase activity deserve attention as potential therapeutic agents for ovarian cancer. The extracellular domains of the HER-2/neu gene product p185 and the epidermal growth factor receptor may provide useful targets for serotherapy.

Carcinoma↗

The three bellies of the canine posterior cricoarytenoid muscle: implications for understanding laryngeal function.

The posterior cricoarytenoid (PCA) muscle is known to be active during phonation and respiration. The presence of muscle compartments (bellies) that might subserve these functions was investigated in the canine PCA by anatomical dissection and muscle fiber histochemistry. Five PCA muscles were microdissected and the origins and insertions of all muscle bundles were recorded. An additional six PCA muscles were frozen, sectioned, and stained for adenosine triphosphatase (ATPase) activity. The total number of fast- and slow-twitch fibers were counted and their proportion was determined for each region of the muscle. The PCA muscle was found to contain three distinct neuromuscular compartments. The vertical compartment is oriented at 24 degrees from true vertical, inserts on the lateral aspect of the muscular process of the arytenoid, and is composed of 65% type 2 (fast) muscle fibers. The oblique is oriented at 44 degrees from vertical, inserts on the top of the muscular process of the arytenoid, and is composed of 77% type 2 muscle fibers. The horizontal is oriented at 63 degrees from vertical, inserts on the medial aspect of the muscular process of the arytenoid, and is composed of 59% type 2 muscle fibers. The cricoarytenoid joint is capable of three arcs of motion and the physical arrangement of each compartment appears to correspond to each of these motions. Moreover, the histochemical profiles show that the activity of the three bellies is quite different. These results suggest that the different compartments of the PCA perform distinctive motions during phonation and inspiration.

Adenosine Triphosphatases↗

Reliability, reproducibility and validity of the individual anaerobic threshold.

The individual anaerobic threshold (IAT) has been defined as the highest metabolic rate at which blood lactate (La) concentrations are maintained at a steady state during prolonged exercise. The validity of this definition, however, has not been substantiated. Eleven men [maximum oxygen uptake (VO2max), mean (SD), 57.8 (6.9) ml.kg-1 x min-1) did two maximal incremental cycle exercise tests (30 W and 4 min per step). Blood was sampled repeatedly during exercise and for 9 min during the subsequent recovery period with light activity. The subjects then exercised at the power output equivalent of IAT for 45 min, until they could no longer continue or until rectal temperature reached 39 degrees C. Subjects performed two additional exercise tests. The intensity of these tests depended upon the LA and acid-base responses during the last 15 min of at least 30 min of exercise at IAT. If a steady state was achieved (La, pH and PCO2 changed by less than 0.5 mmol.l-1, 0.005 pH units and 0.3 kPa, respectively) or decreasing La and increasing pH values were observed, then the second test was performed at IAT +5% VO2max and the third session at either IAT +2.5% or +7.5% VO2max. Conversely if a steady state was not achieved during exercise at the calculated IAT, the intensity of the second test was set at IAT -5% VO2max. Depending on the La and acid-base responses during this test, the final session was performed at either IAT -2.5% or -7.5% VO2max.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

Is energy substrate mobilization a limiting factor for cold thermogenesis?

Energy substrate mobilization has been suggested as being a limiting factor for the rate of cold-induced thermogenesis (M), and consequently in delaying hypothermia. The evidence supporting this hypothesis in humans, however, is not convincing and the hypothesis has yet to be tested in a rigorous manner using a full heat balance analysis (partitional calorimetry). The goal of this study was therefore to re-investigate whether enhancing energy substrate mobilization by feeding cold-exposed subjects would improve M and affect heat debt (S; the minute-by-minute balance of M and heat losses) as well as rectal (Tre) and mean skin temperatures (Tsk). Nine healthy semi-nude fasted subjects were exposed to 5 degrees C (3 h at rest, 1 m.s-1 wind) on three occasions following the ingestion at min 0 and 90 of either: (1) a placebo, (2) 710 kJ of pure carbohydrates (100%-CHO), or (3) 710 kJ of a high-carbohydrate bar (High-CHO). As expected in the cold, Tre and Tsk decreased whereas M, S and heat losses increased (P < 0.01). However, there were no differences between treatments, including the final Tre [mean (SEM); 36.4 (0.2); 36.5 (0.3) and 36.5 (0.2) degrees C for the placebo, 100%-CHO and High-CHO tests, respectively]. During the 100%-CHO treatment, rates of carbohydrate oxidation were the highest and fat oxidation the lowest (P < 0.05), whereas the High-CHO treatment caused smaller changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A computational method for determination of the individual anaerobic threshold.

The individual anaerobic threshold (IAT) has received attention recently in the field of exercise physiology. The IAT is defined as the point during progressive exercise when lactate elimination from the blood is both maximal and equal to the diffusion from the working muscles. It has been theorized that an individual can maintain exercise for relatively long periods when working at the IAT. A common method for determination of the IAT is to perform a visual determination from plots of lactate concentration versus power output. This paper briefly describes the theoretical basis for determination of the IAT and presents an algorithm for its accurate calculation.

Algorithms↗

The adnexal mass: benign or malignant? Evaluation of a risk of malignancy index.

OBJECTIVE: To validate a risk of malignancy index incorporating menopausal status, serum CA 125 level and pelvic ultrasound features in the pre-operative diagnosis of ovarian cancer. DESIGN: A retrospective observational study. SETTING: Department of Obstetrics and Gynaecology, The Royal London Hospital. SUBJECTS: One hundred and twenty-four women admitted consecutively to the gynaecology department for surgical exploration of an adnexal mass. MAIN OUTCOME MEASURES: The sensitivities and specificities of menopausal status, serum CA 125 level and ultrasound features, in isolation and combined (the risk of malignancy index (RMI)), for diagnosing ovarian cancer. RESULTS: Tested on a new population of women, the RMI retained the high sensitivity for diagnosing ovarian cancer seen in the original report describing its derivation. The specificity, however, was lower. The study confirmed that the RMI is more accurate than the individual criteria in diagnosing ovarian cancer, and was comparable with other scoring systems. CONCLUSIONS: The risk of malignancy index is a simple scoring system for ovarian cancer. Application of the risk of malignancy index in clinical practice may provide a rational basis for specialist referral of patients with ovarian cancer before diagnostic surgery.

Antigens, Tumor-Associated, Carbohydrate↗

Adequacy of food rations in soldiers during an arctic exercise measured by doubly labeled water.

To investigate the adequacy of food rations to supply energy needs in cold-temperature environments, caloric expenditure and intake and body composition changes were measured in a group of infantrymen during a 10-day field exercise in the Canadian Arctic. Energy expenditure was measured by the doubly labeled water method (n = 10), and caloric intake was measured by complete food intake records (n = 20). Body composition was determined by isotope dilution (n = 10) and bioelectrical impedence analysis (n = 20) on days 0 and 10. Baseline isotopic enrichment shifts due to geographical relocation were also monitored (n = 5). Mean body weight decreased 0.63 +/- 0.83 (SD) kg over the study period (P < 0.005), although fat-free and fat mass compartment changes were not significant. Baseline isotopic changes were -4.65 +/- 2.54 and -0.48 +/- 0.07 /1000/day for deuterium and 18O, respectively. Mean baseline corrected energy expenditure level was 4,317 +/- 927 kcal/day. Self-reported caloric intakes obtained from food records were 2,633 +/- 499 kcal/day (61.0% of expenditure). Rations packs contained 4,350 kcal/day. Results suggest that 1) food intake was significantly underreported and 2) the energy needs of most subjects were being met by rations and available supplements.

Arctic Regions↗

Effects of prior exercise or ammonium chloride ingestion on muscular strength and endurance.

Previous studies linked muscular fatigue with a decrease in blood pH. This study investigated if the means of altering pH affected the extent of muscular fatigue. Drug-induced and exercise-induced acidosis were compared to test the hypothesis that exercise-induced acidosis impairs subsequent muscular performance more than chemically induced acidosis. In eight male subjects acidosis was induced by ingesting 0.3 g.kg-1 ammonium chloride (AC) for one trial, by upper body exercise (UBE) for another trial, and after placebo (PL) treatment. They then completed a performance test (PT) of 50 maximal, bilateral isokinetic knee extensions. Whole blood pH before (pHpre) and after (pHpost) the PT was 7.412, 7.264, and 7.261 for PL, UBE, and AC, respectively; both AC and UBE decreased pH similarly compared with PL. Peak torque and total work during the PT were similar for PL and AC, and were significantly greater than after UBE. Six subjects performed a fourth trial after combined AC and UBE treatments causing a pHpre of 7.081, but there was no greater performance impairment than that caused by UBE alone. The results dissociate the extent of the impairment from the magnitude of the disruption in blood pH.

Acid-Base Equilibrium↗

Influence of temperature and metabolic rate on work performance with Canadian Forces NBC clothing.

This study examined the effects of environmental temperature and metabolic rate on soldiers' work tolerance time (WTT) while wearing various levels of nuclear, biological, and chemical (NBC) defence protective clothing. There were 23 unacclimatized males (23 +/- 3 years, 76 +/- 8 kg, 1.77 +/- 0.08 m) assigned to exercise at either a light (walking 1.11 m.s-1 0% grade, alternating with lifting 10 kg) or heavy metabolic rate (walking 1.33 m.s-1 7.5% grade, alternating with lifting 20 kg) in an environmental chamber at either 18 degrees C, 50% R.H. (cool) or 30 degrees C, 50% R.H. (warm). Subjects were tested wearing three levels of clothing protection: combat clothing (L); combats and a semi-permeable NBC overgarment (M); combats and NBC overgarment, gloves, boots and respiratory (H). WTT was the time until rectal temperature (Tre) reached 39.3 degrees C, heart rate reached 95% maximum, dizziness or nausea precluded further exercise, or 5 h had elapsed. During the light and cool trials (N = 5), wearing M or H did not impair WTT (277 +/- 47 min). For the light and warm experiments (N = 6), WTT was significantly impaired with H (82.7 +/- 10.6 min). With the heavy and cool condition (N = 6), WTT was reduced with M (240.5 +/- 73.8 min) and H (56.7 +/- 17.9 min). Finally, during the heavy and warm trials (N = 6), WTT was progressively impaired for L (172.5 +/- 52.8 min), M (65.8 +/- 18.2 min), and H (34.0 +/- 9.7 min) levels of protection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Continuous vs. intermittent work with Canadian Forces NBC clothing.

This study examined the benefits of work and rest schedules on soldiers' work tolerance (WTT) while wearing various levels of nuclear, biological and chemical (NBC) defence protective clothing in a warm environment (30 degrees C and 50% R.H.). Eight unacclimatized males were assigned to exercise at either a light (walking 1.11 m.s-1 0% grade, alternating with lifting 10 kg) or heavy metabolic rate (walking 1.33 m.s-1 7.5% grade, alternating with lifting 20 kg). Subjects were tested wearing three levels of clothing protection: combat clothing (L); combats and a semi-permeable NBC overgarment with the hood down (M); combats and NBC overgarment, gloves, boots and respirator (H). For each clothing configuration, subjects were evaluated using both a "continuous" exercise protocol and an intermittent work and rest schedule. WTT was defined as the time until rectal temperature (Tre) reached 39.3 degrees C, heart rate reached 95% maximum, dizziness or nausea precluded further exercise, or 5 h had elapsed. Assuming a resting VO2 of 4 ml.kg-1 x min-1 an average metabolic rate was calculated for all trials. A decreasing hyperbolic function described the relationship between WTT and metabolic rate for M and H. These relationships facilitate quantification of appropriate work and rest schedules if the metabolic rate of a task is known.

Adult↗

Adaptations to training at the individual anaerobic threshold.

The individual anaerobic threshold (Th(an)) is the highest metabolic rate at which blood lactate concentrations can be maintained at a steady-state during prolonged exercise. The purpose of this study was to test the hypothesis that training at the Th(an) would cause a greater change in indicators of training adaptation than would training "around" the Th(an). Three groups of subjects were evaluated before, and again after 4 and 8 weeks of training: a control group, a group which trained continuously for 30 min at the Th(an) intensity (SS), and a group (NSS) which divided the 30 min of training into 7.5-min blocks at intensities which alternated between being below the Th(an) [Th(an) -30% of the difference between Th(an) and maximal oxygen consumption (VO2max)] and above the Th(an) (Th(an) +30% of the difference between Th(an) and VO2max). The VO2max increased significantly from 4.06 to 4.27 l.min-1 in SS and from 3.89 to 4.06 l.min-1 in NSS. The power output (W) at Th(an) increased from 70.5 to 79.8% VO2max in SS and from 71.1 to 80.7% VO2max in NSS. The magnitude of change in VO2max, W at Th(an), % VO2max at Th(an) and in exercise time to exhaustion at the pretraining Th(an) was similar in both trained groups. Vastus lateralis citrate synthase and 3-hydroxyacyl-CoA-dehydrogenase activities increased to the same extent in both trained groups. While all of these training-induced adaptations were statistically significant (P < 0.05), there were no significant changes in any of these variables for the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗