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At least 685 records · Page 38Linked to original sources
PubMed2003

Retinoic acids exert direct effects on T cells to suppress Th1 development and enhance Th2 development via retinoic acid receptors.

The vitamin A metabolite, retinoic acid (RA), affects Th1 and Th2 development. The effect is partly exerted through the modulation of antigen-presenting cell functions, but it remains unclear whether RA directly exerts its effect on T cells to influence Th1/Th2 development. To clarify this problem, we used two experimental systems with isolated T cells in vitro. In one system, isolated CD4+CD8+ thymocytes differentiated into Th1 and Th2 by two transient stimulations with defined combinations of ionomycin and phorbol myristate acetate followed by treatment with IL-2 and IL-4 and/or IL-12. In the second system, functional differentiation was induced in purified naive CD4 T cells from DO-11.10 TCR-transgenic and RAG-2-deficient mice with cytokines and antibodies to CD3 and CD28. In both systems, all-trans-RA at > or = 1 nM concentrations suppressed Th1 development, but enhanced Th2 development. 9-cis-RA elicited similar effects. The optimal enhancement of Th2 development in the second system, however, was achieved with a delayed addition of RA. The presence of RA during the initial stimulation period often suppressed Th2 development. The RA receptor (RAR) antagonists, LE540 and LE135, but not the retinoic X receptor (RXR) antagonist, PA452, inhibited the effect of RA on Th1/Th2 development. Accordingly, the RAR agonists, Am80 and Tp80, but not the RXR agonists, HX600 and TZ335, mimicked the effect of RA. The RXR agonists enhanced the effect of the RAR agonists only slightly, if at all. These results indicate that, via RAR, RA directly suppresses Th1 development and directly enhances Th2 development with its timely addition.

Alitretinoin↗
PubMed2005

CD25(+)CD4(+) regulatory T cells exert in vitro suppressive activity independent of CTLA-4.

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is constitutively expressed on CD25(+)CD4(+) regulatory T cells (Treg) and is suggested to play a role in Treg-mediated suppression. However, the results of analysis with anti-CTLA-4 have been controversial. We addressed this issue by analyzing mice over-expressing or deficient in CTLA-4. For over-expression, CTLA-4 transgenic mice expressing a full-length (FL) or a truncated (TL) mutant of CTLA-4 were analyzed. FL T cells expressed similar levels of CTLA-4 to Treg, whereas TL T cells expressed much higher levels on the cell surface. The number of Treg in both mice was decreased, although Foxp3 expression was not altered. Treg from both mice exerted suppressive activity, whereas CD25(-) T cells from FL mice showed no suppression. Furthermore, CD25(+)CD4 thymocytes from young CTLA-4-deficient mice were analyzed and found to exhibit suppressive activity. These results indicate that Treg exert in vitro suppressive activity independent of CTLA-4 expression.

Animals↗
PubMed1976

Susceptibility of normal and transformed cell lines to cytostatic and cytocidal effects exerted by macrophages.

Activated, nonimmune macrophages exerted profound effects on the proliferation and viability of eukaryotic target cells in vitro. Pronounced macrophage-mediated cytostasis was exerted on every rapidly proliferating cell line examined, irrespective of transformation, species derivation, cell type, or growth characteristics. However, the magnitude of cytostasis effected differed markedly among the 40 cell lines tested. There was no evident correlation between susceptibility to cytostasis and degree of transformation. Transformed cell lines with high and with low malignant attributes were affected equally. A comparable pattern was discerned for cytocidal effects of macrophages, in which the susceptibility of transformed targets was independent of the degree of malignancy.

Cell Line↗
PubMed2004

FTY720 exerts differential effects on CD4+ and CD8+ T-lymphocyte subpopulations expressing chemokine and adhesion receptors.

BACKGROUND: FTY720 (FTY), a novel immunomodulator with the potential to improve immunosuppressive therapy after organ transplantation, is currently under clinical investigation. Previous experimental animal studies have shown that FTY has a unique mechanism of action associated with altered lymphocyte recirculation. METHODS: Participating in a phase I clinical trial, we studied the pharmacodynamic effects of FTY in stable renal allograft recipients. We analysed the effect of FTY on surface marker expression on T-cell subpopulations by flow cytometry. RESULTS: A single oral dose of FTY (0.25-3.5 mg) significantly reduced peripheral lymphocyte counts by 30-70%. FTY reduced all T-lymphocyte subsets, CD4(+) cells more than CD8(+) cells. However, we observed that lower doses of FTY (0.25-2 mg, n = 11) did not affect peripheral CD4(+)CCR5(+) T-lymphocyte counts, while the highest FTY dose of 3.5 mg (n = 2) exerted a rapid reduction of CD4(+)CCR5(+) cells. Peripheral CD8(+)CCR5(+) T-lymphocyte counts were reduced by either low (0.25-2 mg) or high (3.5 mg) doses of FTY. In contrast to CCR5(+) cells, cells expressing CD62L were preferentially reduced after administration of FTY. In particular, CD4(+)CD62L(+) T cells declined after treatment. CD4(+) and CD8(+) T-lymphocyte subpopulations expressing the other chemokine and adhesion receptors (CXCR4, CD11a and CD49d) were reduced to a similar extent as compared with overall CD4(+) or CD8(+) T-lymphocyte counts. CONCLUSIONS: Despite the limited number of patients, especially in the placebo (n = 3) and the high-dose groups (n = 2), our observations suggest that FTY exerts differential effects on T-cell subpopulations. FTY predominantly reduces CD4(+)CD62L(+) cells in the peripheral blood suggesting increased migration into lymph nodes. It seems that only FTY doses above 2 mg are able to reduce peripheral CD4(+)CCR5(+) T lymphocytes, which are potentially capable of infiltrating into the allograft during rejection.

Cell Culture Techniques↗
PubMed1988

Labetalol in the treatment of stable exertional angina pectoris: a comparison with nifedipine.

Labetalol, a combined alpha- and beta-receptor antagonist, was compared with nifedipine in a placebo-controlled, randomized double-blind cross over study (four week treatment periods) of 11 normotensive patients with stable exertional angina pectoris. Standard recommended doses of both drugs (labetalol 200-400 mg twice daily, nifedipine 10-20 mg three times daily) were used. Angina frequency was similar during the placebo washout period and treatment with the two drugs. The duration of treadmill exercise to angina, ischaemia (greater than 1 mm ST segment depression), and end of exercise was increased by both labetalol and nifedipine when compared with placebo, but there was no difference between the two drugs. Ambulatory ST segment monitoring demonstrated that the frequency, duration and magnitude of ST segment depression, whether painful or silent, were unaffected by either drug. Labetalol is an effective agent in improving exercise tolerance in normotensive patients with stable exertional angina pectoris, with an efficacy similar to that of nifedipine.

Adult↗
PubMed2004

Correlation of neutrophil phagocytosis and lymphocyte adhesion molecules in exertional heat stroke.

BACKGROUND: Increased susceptibility to infections has been shown in patients with classic heat stroke. Although immunologic and inflammatory responses may be important factors, the direct role of circulating neutrophil phagocytosis and lymphocyte adhesion molecule expression has yet to be investigated in exertional heat stroke (ExHS). DESIGN: Circulating neutrophil phagocytosis and lymphocyte adhesion molecule CD11a and CD11b expression were examined in 17 patients with ExHS and 17 exertional control subjects (ExC). RESULTS: Patients with ExHS showed significantly increased total leukocyte, neutrophil, and lymphocyte counts, attenuated neutrophil phagocytosis ability, and higher expression of CD11a and CD11b in the acute phase of ExHS, compared with the recovery phase of ExHS and ExC. Although there were no correlations between body temperature and phagocyte function or adhesion molecules, a negative correlation between phagocytosis and CD11a/CD11b was present. CONCLUSION: Increased leukocyte count with decreased circulating neutrophil phagocytic capacity and increased expression of lymphocyte adhesion molecules may in part explain the susceptibility to infections in ExHS.

Adult↗
PubMed1995

Desflurane and isoflurane exert modest beneficial actions on left ventricular diastolic function during myocardial ischemia in dogs.

BACKGROUND: Volatile anesthetics exert cardioprotective effects during myocardial ischemia. This investigation examined the regional systolic and diastolic mechanical responses to brief left anterior descending coronary artery (LAD) occlusion in the central ischemic zone and in remote normal myocardium in the conscious state and during desflurane and isoflurane anesthesia. METHODS: Eighteen experiments were performed in nine dogs chronically instrumented for measurement of aortic and left ventricular pressure, cardiac output, LAD coronary blood flow velocity, and LAD and left circumflex coronary artery subendocardial segment length. Regional myocardial contractility was evaluated with the slope of the preload recruitable stroke work relationship determined from a series of left ventricular pressure-segment length diagrams in the LAD and left circumflex coronary artery zones. Diastolic function was assessed with a time constant of isovolumic relaxation (tau), maximum segment lengthening velocity in LAD and left circumflex coronary artery regions, and regional chamber stiffness constants derived using monoexponential and three-element exponential curve fitting in each zone. On separate experimental days, hemodynamics and indices of regional functional were obtained in the conscious state and during 1.1 and 1.6 minimum alveolar concentration end-tidal desflurane or isoflurane before and during LAD occlusion. RESULTS: In conscious dogs, LAD occlusion abolished regional stroke work, increased chamber stiffness (monoexponential: 0.39 +/- 0.04 during control to 1.34 +/- 0.39 mm-1 during LAD occlusion), and decreased the rate of early ventricular filling in the ischemic zone. These changes were accompanied by increased contractility (slope: 103 +/- 8 during control to 112 +/- 7 mmHg during LAD occlusion), rapid filling rate (maximum segment lengthening velocity: 46 +/- 5 during control to 55 +/- 7 mm.s-1 during LAD occlusion), and chamber stiffness (monoexponential: 0.43 +/- 0.05 during control to 1.14 +/- 0.25 mm-1 during LAD occlusion) in the normal region. Increases in tau were also observed in the conscious state during the period of myocardial ischemia. Desflurane and isoflurane increased tau and decreased the slope and maximum segment lengthening velocity in a dose-related manner. Monoexponential and three-element element exponential curve fitting were unchanged by the volatile anesthetics in the absence of ischemia. Myocardial contractility and rapid filling rate were enhanced in the nonischemic region during LAD occlusion in the presence of desflurane and isoflurane. In contrast to the findings in the conscious state, ischemia-induced increases in tau and chamber stiffness in the ischemic and normal zones were attenuated during anesthesia induced by desflurane and isoflurane. CONCLUSIONS: The results indicate that increases in contractility of remote myocardium during brief regional ischemia were preserved in the presence of desflurane and isoflurane anesthesia. In addition, desflurane and isoflurane blunted ischemia-induced increases in tau and regional chamber stiffness in both the ischemic and nonischemic zones. These results demonstrate that the volatile anesthetics may exert important beneficial actions on left ventricular mechanics in the presence of severe abnormalities in systolic and diastolic function during ischemia.

Anesthesia, Inhalation↗
PubMed2000

Risk indicators for reported over-exertion back injuries among female nursing personnel.

We conducted a case-referent study to identify and quantify work-related and non-work-related risk indicators for reported over-exertion back injuries among nursing personnel. The source population was all nursing personnel employed in the Stockholm County hospitals during a 32-month period. The 240 cases and 614 referents completed questionnaires about occupation, type of clinic, working hours, shift work, patient transfers, perceived exertion, back pain, prior back injury, job strain, body mass index (BMI), smoking, immigrant status, physical training, and self-rated fitness. The highest relative risks (RR) were observed for work-related factors: working at an orthopedic clinic (RR = 5.2; 95% CI = 2.7-10.2), > or =1 patient transfer/shift (RR = 2.7; 95% CI = 1.6-4.5), and working full-time (RR = 2.4; 95% CI = 1.6-3.6). Training in the use of transfer devices, and regular use of transfer devices, reduced the relative risk from patient transfer. Among the non-work-related factors, only body mass index > or =25 kg/m2 and immigrant status was associated with a slight increase in relative risk.

Accidents, Occupational↗
PubMed1996

1,25 Dihydroxyvitamin D3 exerts regional effects in the central nervous system during experimental allergic encephalomyelitis.

1,25-dihydroxyvitamin D3 (1,25-D3) is already known to prevent clinical signs of experimental allergic encephalomyelitis when animals are treated during the immunization phase. In the present work we have evaluated the ability of 1,25-D3 to inhibit chronic relapsing experimental allergic encephalomylitis (EAE) of the Lewis rat, when administered after the beginning of clinical signs. We observed a significant clinical improvement in 1,25-D3-treated rats. This effect was accompanied by a profound inhibition of CD4 antigen expression by central nervous system (CNS) infiltrating monocytes/macrophages and parenchymal microglia. In addition, immunohistochemical analysis performed at the time of the second attack evidenced a region-specific distribution of inflammatory cells. In the same way, some aspects of the effects exerted by 1,25-D3 appeared to vary depending on the region considered, namely spinal cord, brainstem, cerebellum, midbrain or anterior brain. Thus, in 1,25-D3-treated rats, we observed an almost complete inhibition of CD4 antigen expression in the granule cell layer and the adjacent white matter of the cerebellum as well as a marked decrease in the number of OX42-positive cells (macrophages and activated microglia) in anterior brain sections. We conclude that 1,25-D3 can exert immunomodulatory effects inside the CNS during an ongoing immune process and may thus represent a promising therapy for multiple sclerosis.

Animals↗
PubMed1991

The combination of chlorthalidone with nifedipine does not exert an additive antihypertensive effect in essential hypertensives: a crossover multicenter study.

To evaluate whether the combination of nifedipine with chlorthalidone exerts an additive antihypertensive effect when compared to single-drug treatment, 66 uncomplicated essential hypertensives, whose diastolic blood pressure was greater than 100 and less than 115 mm Hg at the end of a 1-month washout placebo period, received, according to a randomized, double-blind, crossover design, nifedipine (20 mg b.i.d.), chlorthalidone (25 mg o.d.), the two drugs combined at the same doses, and the corresponding placebo. When compared to the randomized placebo the three active treatments significantly (p less than 0.001) reduced blood pressure without changing heart rate and body weight. However, blood pressure values were similarly reduced under nifedipine and the combination and were significantly lower (p less than 0.05) than those under chlorthalidone. Moreover, the percentage of responders and normalized patients under nifedipine and the two drugs combined were similar and significantly (normalized, p less than 0.0001; responders, p less than 0.02) greater than those under chlorthalidone. Under chlorthalidone and its combination with nifedipine, plasma potassium tended to decrease and blood glucose and serum uric acid were significantly (p less than 0.05) increased. These data show that the combination of nifedipine with chlorthalidone does not exert any additive antihypertensive effect when compared to nifedipine alone and that this combination increases both blood glucose and serum uric acid. Taken together these findings indicate that the combination of a dihydropyridine calcium antagonist with a thiazide diuretic is devoid of any clinical significance in the treatment of uncomplicated essential hypertensives.

Adult↗
PubMed1992

Aortic baroreceptors exert a tonically active restraining influence on centrally mediated depressor responses.

This study tested the hypothesis that aortic baroreceptors exert a central restraining influence on centrally mediated depressor responses and that this mechanism is tonically active and is independent of their modulation of basal arterial pressure. The effects of short-term (48-72 h) aortic baroreceptor deafferentation (ABD) on the acute hemodynamic (peripherally mediated pressor and centrally mediated depressor) effects of clonidine were investigated in conscious and anesthetized normotensive rats. ABD caused an immediate increase in basal arterial pressure and heart rate and a significant attenuation of the baroreceptor reflex control of heart rate. Since only arterial pressure subsided to control levels by 48-72 h, the data suggest that central reorganizational changes were potent enough to overcome the tonically active restraining influence of aortic baroreceptors on basal arterial pressure but not heart rate. Clonidine produced a similar pressor effect in conscious ABD and sham rats but its depressor effect was significantly greater in ABD rats whose baroreceptor reflex control of heart rate was significantly attenuated. Intracisternal (i.c.) administration of 0.1 microgram of clonidine, a dose that had no effect when administered i.v., produced a near-maximal depressor effect in conscious ABD rats vs. no effect in sham rats (-16.7 +/- 4.1 vs. -0.3 +/- 2 mm Hg; p less than 0.001). The depressor effect of clonidine was also enhanced in chloralose-anesthetized rats and coincided with an anesthesia-induced attenuation of the baroreceptor reflex control of heart rate. It is concluded that aortic baroreceptors exert a potent restraining influence on the centrally mediated depressor effect of clonidine. Since ABD had no significant effect on the depressor response to nitroprusside, but enhanced the depressor response to ganglion blockade by hexamethonium, the data suggest that a higher peripheral sympathetic neural activity existed in ABD rats. The reorganizational changes that occurred within 48-72 h after ABD were potent enough to overcome the tonically active restraining influence of aortic baroreceptors on basal arterial pressure but not on the centrally mediated depressor responses. Thus, the buffering influence of aortic baroreceptors and their central projections on centrally mediated depressor responses seems to be tonically involved in blood pressure control.

Animals↗
PubMed2000

Children's OMNI scale of perceived exertion: mixed gender and race validation.

PURPOSE: The newly developed Children's OMNI Scale of Perceived Exertion (category range: 0 to 10) was validated using separate cohorts of female and male, African American and white subjects. Each of the four cohorts contained 20 clinically normal, nonobese children, 8-12 yr of age. METHODS: A cross-sectional, perceptual estimation paradigm using a single multi-stage cycle ergometer test protocol was used. Oxygen uptake (VO2; mL x min(-1)), heart rate (HR; beats x min(-1)) and ratings of perceived exertion for the overall body (RPE-Overall), legs (RPE-Legs), and chest (RPE-Chest) were determined at the end of each continuously administered 3-min power output (PO) (i.e., 25, 50, 75, and 100 W) test stage. RESULTS: The range of responses over the four POs for all cohorts was VO2: 290.8 to 1204.0 mL x min(-1); HR: 89.2 to 164.4 beats x min(-1); and RPE-Overall, RPE-Legs, and RPE-Chest: 0.85 to 9.1. First-order correlation and linear regression analyses were performed for each cohort separately and the total sample using a repeated measures paradigm over the four POs. For all correlation/regression paradigms RPE-Overall, RPE-Legs, and RPE-Chest distributed as a positive linear function of both VO2 and HR; r = 0.85 to 0.94; P < 0.01. Differences between RPE-Overall, RPE-Legs, and RPE-Chest were examined with ANOVA for the repeated measures paradigm. RPE-Legs was higher (P < 0.01) than RPE-Chest and RPE-Overall at 25, 50, 75, and 100 W. RPE-Chest did not differ from RPE-Overall at 25 and 50 W but was lower (P < 0.01) than RPE-Overall at 75 and 100 W. CONCLUSION: The psycho-physiological responses provide validity evidence for use of the Children's OMNI Scale over a wide range of dynamic exercise intensities.

Black People↗
PubMed2001

Long-term follow-up after exertional heat illness during recruit training.

PURPOSE: To evaluate long-term susceptibility to subsequent serious exertional heat illness (EHI) in military recruits who suffered exertional heat illness during basic training. METHODS: We identified Marine Corps members who completed at least 6 months of military service and suffered EHI treated as outpatients (N = 872) or inpatients (N = 50) during basic training in 1979-1991 at the Parris Island Marine Corps Recruit Depot, SC (EHI cases). We compared them to 1391 similar members (noncases) who did not experience EHI during basic training. These subjects were followed from 6 months after accession into the military through the subsequent 4 yr. Follow-up was through military personnel records to determine retention and military hospital databases to determine subsequent hospitalizations during military service. RESULTS: Military retention rates were slightly lower for those who suffered EHI during basic training, compared with those who did not (24% vs 30% at 4 yr, respectively). Outpatient EHI cases also had about 40% higher subsequent hospitalization rates in military hospitals than noncases during their continued military service, although these differences declined over time and diagnoses showed little relationship to EHI. EHI cases had higher rates of subsequent hospitalization for EHI, but the number was too small (five hospitalizations) to provide stable comparisons. CONCLUSION: Hospitalization for EHI is uncommon during subsequent military service after an initial episode during basic training, and occurrence of EHI during basic training has only a small impact on subsequent military retention and hospitalization.

Adult↗
PubMed1992

The force exerted by the halo pin. A study comparing different halo systems.

Seven different halo systems were evaluated biomechanically to compare the force exerted by the halo pin in each system. In three different experiments torque values of 2, 4, 6, 7, and 8 in lb were applied to the halo pin, and the force at the skull end of the halo pin was measured using a load cell. In the first experiment, the threads on the halo pin were dry, in the second experiment saline was applied to the threads on the pin, and in the third experiment cadaveric bone from the skull was interposed between the pin and the load cell. The results showed that for a given value of applied torque to the pin, the force exerted by the pin end varied widely according to the halo system and whether or not the pin was "lubricated."

Adult↗
PubMed2002

Death of an adolescent athlete with sickle cell trait caused by exertional heat stroke.

OBJECTIVE: To report a case of fatal rhabdomyolysis secondary to exertional heat stroke and the potential influence of sickle cell trait on the outcome of this case. DESIGN: Descriptive case report. SETTING: Pediatric intensive care unit in an academic children's hospital. MAIN RESULTS: A description of the presentation and clinical course of exertional heatstroke with rhabdomyolysis in an adolescent athlete. The implications of the patient's clinical course and a possible connection to sickle cell trait are also discussed. CONCLUSION: Young athletes with sickle cell trait may be at an increased risk of heat-related illnesses and their complications. Epidemiologic studies are warranted to address this possibility.

Journal Article↗
PubMed1998

A static dynamometer measuring simultaneous torques exerted at the upper limb.

The majority of available dynamometers are designed to measure force or torque in one specific direction, one joint at a time. For the quantification of motor incoordination in neurological patient populations, these dynamometers provide limited information about the global behavior of the limb under investigation. This report describes the potential use and function of a static dynamometer measuring torques exerted simultaneously at the shoulder (flexion-extension, abduction-adduction, internal-external rotation), elbow (flexion-extension), and forearm (pronation-supination). Orthogonal forces were measured at the arm and wrist using strain gauge transducers interfaced with a laboratory computer. The lever arms were specified to a software program and the joint torques were calculated in real time according to static equilibrium equations. The use of the dynamometer is illustrated by characterizing for one hemiparetic subject, the joints torques recorded at the shoulder, elbow, and forearm during isolated submaximal grip exertions at different force levels on both sides. The torques generated at the shoulder, elbow and forearm during the hand grip tasks on the affected side were significantly higher than those obtained on the nonaffected side and increased with the grip force level. These differences probably reflect the loss of movement selectivity observed following a lesion in the central nervous system. Further studies are currently being undertaken in neurological patient populations to characterize and quantify motor deficits using this dynamometer. As a long term goal, we hope that the method and technologies described here will contribute to the evaluation and rehabilitation of these populations.

Biofeedback, Psychology↗
PubMed2004

Bougie-assisted difficult airway management in a manikin - the effect of position held on placement and force exerted by the tip.

In a randomised cross-over study, 50 anaesthetists attempted to place a multiple-use bougie in the trachea of a manikin, when holding it at either 20 cm or 30 cm from the tip. A grade 3 laryngoscopic view was simulated. The anaesthetists were blinded to success (tracheal placement) or failure (oesophageal placement). The success rates when held at 20 and 30 cm distance from the tip were 68 and 62%, respectively (p = 0.55). In a separate experiment, multiple and single-use bougies were held at four different positions and pressed onto a disc attached to a force transducer. The peak force exerted by the single-use bougies was two to three times greater than that which could be exerted by the multiple-use bougies (p < 0.0001). Holding the bougie at either 20 or 30 cm distance from the tip is unlikely to influence bougie placement. The single-use bougie is much more likely to cause trauma to tissue during placement, particularly if held close to the tip.

Cross-Over Studies↗
PubMed1988

Lateral forces exerted on the abutment tooth of complete mandibular overdentures.

The purpose of this study was to analyse the magnitude and direction of lateral forces exerted on the abutment tooth of a complete mandibular overdenture. A newly developed transducer was used for measuring forces. It was small enough to be embedded in the lower denture base, and could detect the magnitude and direction of forces. Five subjects, 38 to 77 years of age, with an edentulous maxilla and one or two canines remaining in the mandible were selected for this experiment. An upper complete denture and a lower complete overdenture with only one abutment tooth were fabricated for each subject. Forces exerted on the abutment tooth were measured during tapping and chewing of kamaboko (a Japanese cooked fish paste with soft consistency) and also peanuts, a few days and about 20 days after the denture insertion. The following results were obtained: (i) the average magnitude of lateral forces ranged from 0.5 to 2.0 kgf, and there were significant differences of the mean value between subjects; (ii) lateral forces were mainly observed on an imaginary line drawn through the experimental tooth (lower canine) and the opposite retromolar pad. There were no significant differences between the first and the second measurement.

Adult↗