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[Difficulties and reproducibility of radiological measurement of the proximal tibial axis according to Lévigne].

PURPOSE OF THE STUDY: The angle between the anatomic axis of the tibia and the tangent to the superior borders of the tibial plateaus is, on average, tilted 3 degrees in the varus position. If there is no bone wear, this angle measures the constitutional epiphyseal axis of the proximal tibia. When degenerative joint disease modifies the aspect of the tibial plateaus, this angle measures the sum of the constitutional varus and the bone wear, without distinguishing between the two. It is known however that the respective contribution of these two deformations can have therapeutic implications, particularly when tibial osteotomy for valgus correction or implantation of a unicompartmental prosthesis is proposed. Lévigne proposed a radiographic measurement of the proximal tibial axis to distinguish between these two sources of tibial deformation. We studied the intra- and interobserver reproducibility of these measurements. MATERIAL AND METHODS: Fifty volunteers free of knee disease were chosen at random among a population of patients undergoing upper limb surgery. All patients provided their informed consent for participation in the study. Full-limb radiographs of one lower limb (chosen at random) were obtained using a standardized technique. The proximal tibial axis was measured according to the Lévigne technique using a manual goniometer graduated in degrees. One operator performed two series of measures independently on the same films. Two other operators performed a series of measurements on each film. The intra- and inter-observer reproducibility was determined with the interclass coefficient of correlation (rho). RESULTS: The proximal epiphyseal axis of the tibia could not be determined on 7 to 18 films, depending on the operator. All three operators were able to make the all measurements (four per film) for only 25 patients. The mean epiphyseal axis varied from 2.5 degrees to 4.7 degrees for the four series of measurements. Intra-observer reproducibility was considered good (rho=0.62). Inter-observer reproducibility was considered moderate (rho=0.41). DISCUSSION: The Lévigne technique is to our knowledge the only method described in the literature distinguishing the relative contribution of constitutional varus and bone wear of the proximal tibia. According to the advocates of this method, the angle between the epiphyseal axis linking the center of the tibial plateaus and the center of the proximal growth cartilage scare, and the anatomic axis of the tibia is a measurement of constitutional varus. The average is 3 degrees . The angle between a line perpendicular to the epiphyseal axis and the tangent of the superior borders of the tibial plateaus measures the deformation related to bone wear. In the present work, we found that this technique enables acceptable intra-observer reproducibility but that inter-observer reproducibility is low. The differences observed are certainly related to uncertain identification of the growth cartilage scar. This illustrates the difficulty in generalizing this technique for measuring healthy knees. Such difficulties would be even greater for degenerative knees. CONCLUSION: The Lévigne technique does not appear to be a reliable method for defining indications for different surgical procedures according to the morphology of the proximal tibia.

Anthropometry↗

Dosimetric analysis of intact breast irradiation in off-axis planes.

PURPOSE/OBJECTIVE: The purpose of this investigation is to quantify dose inhomogeneity of intact breast irradiation in off-axis planes, and determine how dose inhomogeneity varies according to patient breast size and anatomical region of the breast. METHODS AND MATERIALS: Eleven patients treated with intact breast radiation underwent a treatment-planning computer tomography (CT) scan with 1-cm slices through the entire breast. The area of breast tissue was defined on each CT slice. Treatment planning with lung correction factors was performed using a two-dimensional treatment-planning system that calculates off-axis dose distributions on a slice-by-slice basis. Each plan utilized tangential beams with matched nondivergent posterior borders and with collimator rotation to match the chest wall slope. Dose inhomogeneity within the central plane was minimized during treatment planning by the use of a wedge on the lateral tangent field and by the differential weighting of fields. Dose was normalized at the breast and pectoralis major interface at midseparation in the central plane. Off-axis dose inhomogeneity was not considered in the optimization of the treatment plan. Dose distributions were plotted for each 1-cm slice, and the area of each isodose curve within the breast on each CT slice was calculated. The results of each slice were summed to give an approximation of dose-volume relationships. RESULTS: For the entire population, an average of 10% of the breast volume (range 1-40%) received 110% or greater of the prescribed dose. Increasing dose inhomogeneity was positively correlated with increasing breast sizes (r = 0.72, p = 0.01--Spearmen rank test). Analysis of dose as a function of location within the breast, revealed that the greatest dose inhomogeneity occurred in the lower anatomical quadrants of the breast (p = 0.003-Kruskal-Wallis test). For the group, the mean breast volume that received a 110% or greater dose was: 30% at 6 cm below central axis, 14% at 4 cm below central axis, 6% at central axis, 5% at 4 cm above central axis, and 7% at 6 cm above central axis. CONCLUSION: Our study demonstrates that a significant volume of breast tissue receives 110% or greater of the prescribed dose. This inhomogeneity is greatest in women with larger breast sizes, providing a possible explanation for the poorer cosmetic result seen in this subset of patients compared to women with small breast sizes. In addition, our results show the greatest dose inhomogeneity in the lower quadrants of the breast. Off-axis dose inhomogeneity should be considered in the planning of tumor bed boosts in women with lower quadrant tumors.

Adult↗

Subendocardial motion in hypertrophic cardiomyopathy: assessment from long- and short-axis views by pulsed tissue Doppler imaging.

BACKGROUND: Tissue Doppler imaging (TDI) is a recently developed technique that allows the instantaneous measurement of intrinsic regional myocardial motion velocity. Pulsed TDI is capable of separately assessing left ventricular (LV) regional motion velocity caused by circumferential and longitudinal fiber contraction. This particular feature of function is still controversial in patients with hypertrophic cardiomyopathy (HC). METHODS: To better characterize intrinsic circumferential and longitudinal LV systolic myocardial function in HC, we used pulsed TDI to measure short- and long-axis LV motion velocities, respectively. The subendocardial motion velocity patterns at the middle of the LV posterior wall (PW) and ventricular septum (IVS) in LV parasternal and apical long-axis views were recorded by pulsed TDI in 19 patients with nonobstructive HC and in 21 normal controls (NC). RESULTS: Peak short- and long-axis systolic subendocardial velocities in both the LV PW and IVS were significantly smaller in the HC group than in the NC group, and the time to peak velocity was significantly delayed. Furthermore, peak PW systolic velocity was significantly greater along the long axis than along the short axis in the NC group (8.8 +/- 1.5 cm/s vs 8.2 +/- 1.4 cm/s, P <.05), whereas the opposite was observed in the HC group (6.1 +/- 1.2 cm/s vs 7.5 +/- 1.0 cm/s, P <.0001). No significant differences were found in either group between the long- and short-axis IVS velocities (HC: 5.9 +/- 1.4 cm/s vs 5.5 +/- 1.3 cm/s; NC: 7.8 +/- 1.3 cm/s vs 7.9 +/- 1.6 cm/s). CONCLUSIONS: By using the capability of pulsed TDI for the evaluation of intrinsic myocardial velocity instantaneously in a specific region and direction, we found impairment of LV myocardial systolic function in patients with HC not only in the hypertrophied IVS but also in the nonhypertrophied LV PW. We also found a greater decrease in LV PW velocities along the long axis than the short axis, suggesting greater impairment of long-axis contraction in patients with HC. Because our HC patients did not appear to have excessive intracavitary pressure, these results suggest that the relatively normal-appearing PW is directly affected by the HC pathologic process.

Adult↗

Transcatheter arterial chemoembolization for hepatocellular carcinomas in patients with celiac axis occlusion.

PURPOSE: To verify the hypothesis that most instances of celiac axis occlusion in patients with hepatocellular carcinoma (HCC) are caused by diaphragmatic compression and, therefore, transcatheter arterial chemoembolization (TACE) can be performed through the compressed lumen of the celiac axis. MATERIALS AND METHODS: The authors attempted to perform TACE in 36 consecutive patients with HCC and celiac axis occlusion. Spiral computed tomographic (CT) images were available in 26 patients. Initially, catheterization of the hepatic arteries was attempted through the occluded celiac axis. If it failed, catheterization was performed through the pancreaticoduodenal arcades. The causes of celiac axis occlusion were evaluated based on spiral CT and angiographic findings, access routes, technical success rates, and related complications in superselective catheterization of hepatic arteries. RESULTS: Among the 26 patients who underwent spiral CT, diaphragmatic compression of the celiac axis was demonstrated in 23. Selective catheterization of hepatic arteries was possible through the occluded celiac axis in 23 patients (64%). In nine (25%) of the remaining 13 patients, TACE was performed through the dilated pancreaticoduodenal arcades from the superior mesenteric artery. As a procedure-related complication, celiac axis dissection occurred in one patient (3%). CONCLUSION: Most patients with celiac axis occlusion had arcuate ligament compression. In TACE, the celiac artery occlusion could be traversed directly and this should be the initial approach.

Adult↗

Perceived orientation of axis of rotation in structure-from-motion.

Perceived orientation of axis of rotation and accuracy in discriminating fixed-axis from nonfixed-axis rotations were investigated for orthographic projections of three-dimensional rotating objects. The principal findings were (a) the slant of the axis of rotation was systematically misperceived; (b) in both two-view and multiview displays, the perceived slant of the axis of rotation was well-predicted by the ratio between the deformation (a property of the first-order optic flow) and the component parallel to the image plane of the global velocity vector; (c) if this ratio was kept constant in each frame transition of the stimulus sequence (or it was varied), then the stimuli tended to be judged as fixed-axis rotations (or as nonfixed-axis rotations), regardless of whether they simulated a fixed-axis rotation or not; and (d) the tilt of the axis of rotation was perceived in two-view displays with a very small error.

Adult↗

The axis of orientation of the synlophe in the Heligmosomoidea (Nematoda, Trichostrongylina): a new approach.

The definition of the axis of orientation of the synlophe is modified for the Heligmosomoidea so that one or two axes may be recognized. When two axes are present, their inclinations to the sagittal axis are different on the right and left sides, and we propose to name them right axis and left axis, respectively. During the course of evolution, starting from a single oblique axis (plesiomorphic state), an independent rotation of this axis on the right and left sides may bring about a double-axis state with a different inclination on both sides (derived state). When the rotation reaches 90 degrees for both sides, the axis becomes simple once again and is superimposed to the frontal axis (most derived state).

Animals↗

Attainment and maintenance of reliability of axis I and II disorders over the course of a longitudinal study.

The baseline interrater reliability, test-retest reliability, follow-up interrater reliability, and follow-up longitudinal reliability of axis I and axis II diagnoses were assessed using the Structured Clinical Interview for DSM-III-R Axis I Disorders (SCID-I) and the Diagnostic Interview for DSM-III-R Personality Disorders (DIPD-R). Excellent kappas (>.75) were found in each of these reliability substudies for the majority of axis II disorders diagnosed five times or more. Dimensional reliability figures for axis II diagnoses were generally somewhat higher than those for their categorical counterparts; most intraclass correlation coefficients (ICCs) were in the excellent range. Excellent kappas were also found in each of these four reliability substudies for over half of the axis I disorders diagnosed five times or more. Taken together, the results of this study suggest that the reliability of axis II disorders is both good to excellent and practically equivalent to that found for most axis I disorders. The results of this study also suggest that high levels of reliability, once achieved, can be maintained over time for both axis I and II disorders.

Adult↗

Rapid quantification of left ventricular function and mass using transoesophageal three-dimensional echocardiography: validation of a method that uses long-axis cutplanes.

AIMS: Despite its proven superiority compared to conventional echocardiographic techniques, three-dimensional (3D) echocardiography has not gained widespread acceptance in clinical medicine for the quantification of left ventricular volumes, function and mass. This is mainly due to the large, time-consuming process of data analysis. We sought to validate a new method that enables the accurate quantification of the left ventricle in a clinically acceptable short period of time. METHODS AND RESULTS: Left ventricular volumes, ejection fraction and mass were determined in 44 patients using 3D echocardiography. The 3D echocardiographic data sets were analysed: (i) using the conventional 'summation of slices' algorithm (slice thickness 5 and 10mm), which is based on the analysis of the 3D reconstructed left ventricle in short-axis cross-sections; and (ii) using the new method which is based on the analysis of the 3D reconstructed left ventricle in long-axis images. In each patient measurements were repeated using 3, 6, 7, 8, 9, 12 and 15 long-axis images. For all volumetric measurements there was a continuous reduction of measurement variability using increasing numbers of long-axis images. The use of more than nine long-axis images for volumes, and eight long-axis images for ejection fraction and mass, did not result in a further reduction of variability. The analysis time for volumes and masses averaged less than 5 min for the long-axis method using nine component images, compared to 20-43 min for the short-axis method. CONCLUSION: 3D echocardiography combined with a novel method based on the analysis of long-axis cross-section allows accurate quantification of left ventricular volumes, function and mass in a clinically acceptable short period of time. In the future, the combination of a real-time 3D echocardiographic acquisition technique with this analysis method should have important implications for the introduction of 3D echocardiography in clinical practice.

Echocardiography, Three-Dimensional↗

The role of short- and long-axis function in determining late diastolic left ventricular filling in patients with hypertension: assessment by pulsed Doppler tissue imaging.

Left ventricular (LV) wall motion velocity during atrial systole is mediated by both transmitral flow and LV myocardial compliance at end-diastole. LV wall distensibility along the long- and short-axis during atrial systole and late diastolic LV filling may vary according to the remodeling of LV morphology. We measured LV wall motion velocities along the long and short axes using pulsed Doppler tissue imaging in 127 patients with hypertension to evaluate the relationship between the hemodynamic changes and LV morphology and to determine the role of both long- and short-axis function in late diastolic LV filling. Participants were classified into 3 groups according to LV dimension and end-diastolic wall thickness determined by M-mode echocardiography: group A (n = 62) without LV dilation or hypertrophy, group B (n = 55) with LV hypertrophy, and group C (n = 10) with LV dilation and systolic dysfunction. The time constant of the LV pressure decay during isovolumic diastole and the LV end-diastolic pressure were longest and greatest, respectively, in group C, compared with groups B and A. There were no significant differences in active left atrial emptying volume during atrial contraction determined by computerized echocardiographic 3-dimensional reconstruction among patient and control groups. The peak atrial systolic motion velocity of the LV posterior wall along the long axis was significantly lower in groups B and C, particularly in the latter group, than in group A. The peak atrial systolic motion velocity of the LV posterior wall along the short axis was greatest in group B and was lowest in group C compared with the other groups, respectively. The peak atrial systolic motion velocity of the LV posterior wall was greater along the long axis than the short axis in group A, but was less than the short axis in group B. In conclusion, the long- and short-axis function of the LV wall during atrial systole varies in patients with hypertension according to the severity of hemodynamic and morphologic abnormalities. The degree of LV wall expansion along the short axis is an important factor resulting from the atrial kick, and a determinant of its effectiveness.

Aged↗

Automated determination of the left ventricular long axis in cardiac positron tomography.

Interpretation of emission tomographic images of the heart is typically performed using short-axis sections which are oriented perpendicular to the long axis of the left ventricle. A completely automated method is presented to find the orientation and length of the long axis in positron emission tomographic studies of the heart. The correlation coefficient is maximized between the measured transaxial images and an ellipsoid model of the left ventricular myocardium. The major axis of this fitted ellipsoid corresponds to the long axis of the left ventricle. The orientation and position of the long axis (with respect to the measured transaxial images) define two rotation angles and a 3D coordinate origin which are used to re-orient the transaxial images into a series of standard short-axis sections. The accuracy and precision of this technique are validated on phantom data as well as on patients with documented myocardial infarction. The transaxial and vertical long-axis rotation angles are determined with standard deviations of 3.3 degrees and 1.5 degrees, respectively. The 3D coordinate origin (centre) of the ellipsoid is accurate to within 1.5 mm on average. The estimated length of the left ventricle is accurate to within 3 mm. All parameters are insensitive to statistical noise found in typical 18F-fluorodeoxyglucose (FDG) patient studies. The technique produces accurate estimates even in the presence of moderate uptake defects in the lateral wall and septum. Apical defects in the uptake of FDG do not increase the variance of the length estimate. These results demonstrate that an ellipsoid model can be fitted accurately to the myocardium of the left ventricle. Standard short-axis sections are produced with no inter-operator or intra-operator variability because the technique is fully automatic.

Deoxyglucose↗

Polyamine Anabolism in Germinating Glycine max (L.) Seeds : Dynamics of Cadaverine and Putrescine Formation in the Embryonic Axis.

Active polyamine biosynthesis occurs in the embryonic axis, but not in the cotyledons, during germination of Glycine max (L.) cv Williams seeds and subsequent growth of the young seedlings. The hypocotyl and radicle synthesize and accumulate considerable amounts of cadaverine (Cad) and putrescine (Put) during the early stages of growth. Most of the amino acid precursors for the diamines are supplied from breakdown of the cotyledonary protein.In the axis, Cad synthesis which is catalyzed by l-lysine decarboxylase precedes the onset of growth (dry weight accumulation) of the axis and its accumulation continues as the growth progresses. After 2 days of imbibition, Cad is synthesized and accumulated at 37.4 nanomoles per axis per hour for at least 6 days. The rate then gradually decreases as the supply of free l-lysine from the cotyledons diminishes. Approximately 40 to 50% of the lysine resulting from breakdown of the cotyledonary protein ends up in Cad in the hypocotyl and radicle. Cad represents about 3.5% of the axis nitrogen derived from the cotyledons, which is equivalent to about 50% of the lysine content ( approximately 7%) of the seed protein.The synthesis and accumulation of Put in the axis also precedes the onset of growth of the axis. Both l-arginine decarboxylase and l-ornithine decarboxylase are involved in catalyzing the Put formation. The increased content of spermidine (Spd), but not spermine (Spm), parallels growth of the axis. Spm is maintained at a nearly undetectable level. After 2-day imbibition, Put and Spd are synthesized and accumulated at 0.94 and 0.17 nanomoles per axis per hour, respectively. The rate of Put accumulation, like that of Cad, decreases about 8 days after imbibition. The hypocotyl and radicle contain millimolar concentrations of Cad and Put which are primarily associated with the elongated zones. In contrast, Spd level or the molar ratio of Spd:Put appears to decrease as cell differentiation or elongation progresses.

Journal Article↗

Determination of left ventricular long-axis orientation using MRI: changes during the respiratory and cardiac cycles in normal and diseased subjects.

BACKGROUND: It has previously been shown that magnetic resonance imaging (MRI) can be used to accurately determine left ventricular (LV) long-axis orientation in healthy individuals. However, the inter- and intra-observer variability in patients with acute coronary syndrome (ACS) and chronic heart failure (CHF) has not been explored. Furthermore, the changes in LV long-axis orientation because of respiration and during the cardiac cycle remain to be determined. METHODS: LV long-axis orientation was determined by MRI in the frontal and transverse planes in 44 subjects with no cardiac disease, 20 ACS patients and 13 CHF patients. Changes in LV long-axis orientation because of respiration were assessed in a subset of 25 subjects. Changes during the cardiac cycle were assessed in six subjects from each subject group. Reproducibility was assessed by a re-examination of 17 subjects after 28 days. RESULTS: The inter- and intra-observer variability for LV long-axis orientation was low for all subject groups. The difference between the baseline and the 28 days examinations was -1.4+/-5.9 degrees and -0.8+/-4.4 degrees in the frontal and transverse planes, respectively. No significant change in LV long-axis orientation was found between end-expiration and end-inspiration (frontal plane, P=0.63 and transverse plane, P=0.42; n=25). No significant difference in change of the LV long-axis orientation during the cardiac cycle was found between the subject groups (frontal plane, chi-square 1.8, P=0.40 and transverse plane, chi-square 5.7, P=0.06). CONCLUSIONS: There is a low inter-and intra-observer variability and a high reproducibility for determining LV long-axis orientation in patients with no cardiac disease as well as in patients with ACS or CHF. There is no significant change in LV long-axis orientation due to respiration, and only small changes during the cardiac cycle in these groups.

Adult↗

Off-axis primary-dose measurements using a mini-phantom.

The characterization of the incident photon beam is usually divided into its dependence on collimator setting (head-scatter factor) and off-axis position (primary off-axis ratio). These parameters are normally measured "in air" with a build-up cap thick enough to generate full dose build-up at the depth of dose maximum. In order to prevent any influence from contaminating electrons, it has been recommended that head-scatter measurements are carried out using a mini-phantom rather than a conventional build-up cap. Due to the volume of the mini-phantom, the effects from attenuation and scatter are not negligible. In relative head-scatter measurements these effects cancel and the head scatter is thus a good representation of the variation of the incident photon beam with collimator setting. However, in off-axis measurements, attenuation and scatter conditions vary due to beam softening and do not cancel in the calculation of the primary off-axis ratio. The purpose of the present work was to estimate the effects from attenuation and phantom scatter in order to determine their influence on primary off-axis ratio measurements. We have characterized the off-axis beam-softening effect by means of narrow-beam transmission measurements to obtain the effective attenuation coefficient as a function of off-axis position. We then used a semi-analytical expression for the phantom-scatter calculation that depends solely on this attenuation coefficient. The derived formalism for relative "in air" measurements using a mini-phantom is clear and consistent, which enables the user to separately calculate the effects from scatter and attenuation. For the investigated beam qualities, 6 and 18 MV, our results indicate that the effects from attenuation and scatter in the mini-phantom nearly cancel (the combined effect is less than 1%) within 12.5 cm from the central beam axis. Thus, no correction is needed when the primary off-axis ratio is measured with a mini-phantom.

Evaluation Studies as Topic↗

Effect of viewing distance and location of the axis of head rotation on the monkey's vestibuloocular reflex. I. Eye movement responses.

1. The vestibuloocular reflex (VOR) stabilizes images on the retina against movements of the head in space. Viewing distance, target eccentricity, and location of the axis of rotation may influence VOR responses because rotation of the head about most axes in space rotates and translates the eyes relative to visual targets. To study the VOR response to combined rotation and translation, monkeys were placed on a rate table and rotated briefly in the dark about a vertical axis that was located in front of or behind the eyes. The monkeys fixated a near or far visual target that was extinguished before the rotation. Eye movements were recorded from both eyes by the use of the search coil technique. 2. Peak eye velocity evoked by the VOR was linearly related to vergence angle for any axis of rotation. The percent change in the VOR with near target viewing relative to far target viewing at a vergence angle of 20 degrees was linearly related to the location of the axis of rotation. Axes located behind the eyes produced positive changes in VOR amplitude, and axes located in front of the eyes produced negative changes in VOR amplitude. An axis of rotation located in the coronal plane containing the centers of rotation of the eyes produced no modification of VOR amplitude. For any axis, the VOR compensated for approximately 90% of the translation of the eye relative to near targets. 3. The initial VOR response was not correct in magnitude but was refined by a series of three temporally delayed corrections of increasing complexity. The earliest VOR-evoked eye movement (10-20 ms after rotation onset) was independent of viewing distance and rotational axis location. In the next 100 ms, eye speed appeared to be sequentially modified three times: within 20 ms by viewing distance; within 30 ms by otolith translation; and within 100 ms by eye translation relative to the visual target. 4. These data suggest a formal model of the VOR consisting of four channels. Channel 1 conveys an unmodified head rotation signal with a pure delay of 10 ms. Channel 2 conveys an angular head velocity signal, modified by viewing distance with a pure delay of 20 ms, but invariant with respect to the location of the axis of rotation. Channel 3 conveys a linear head velocity signal, dependent on the location of the axis of rotation, that is modified by viewing distance with a pure delay of 30 ms.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Hypothalamic-pituitary-adrenal axis suppression and inhaled corticosteroid therapy. 2. Review of the literature.

In the first part of this two-part review it was noted that inhaled corticosteroids had become the mainstay of treatment for chronic asthma and yet the effects of long-term use of these compounds on the hypothalamic-adrenal-pituitary (HPA) axis were largely being determined by testing methods of limited reliability, especially by morning plasma cortisol measurements. It was established in our examination of the published literature and in our presentation of current knowledge of the structure and function of the HPA axis that safe, accurate and discriminating techniques to assess the functional status of the HPA axis were available. It was concluded that two state-of-the-art tests that have been insufficiently used were the ACTH stimulation test and measurement of the 24-hour integrated serial plasma cortisol concentrations. These two tests can detect adrenal suppression before the appearance of clinical effects. For part 2 of this review we conducted an exhaustive search of the English language clinical and pharmacological literature on the use of inhaled corticosteroids from 1988 until the present time to identify studies in which one or both of these testing methods have been used. We present our analysis of this limited number of studies to determine what accurately can be known of the HPA axis safety profile of three of the most commonly used and investigated inhaled corticosteroids - beclomethasone dipropionate, budesonide and fluticasone propionate. The first finding of significance was that only 50 reports were identified in which information on the HPA axis safety effects of orally inhaled steroids in asthma patients or in clinical pharmacological studies met our inclusion requirements. By analysis of the data presented in these reports we were able to reach the following conclusions: (1) inhaled corticosteroids administered chronically, and prudently, within recommended dose ranges do not endanger the functioning of the HPA axis, (2) the increasing tendency to use higher doses of inhaled corticosteroids on the assumption that there are clear dose-response benefits and no adverse HPA axis effects from long-term high-dose regimens is misguided and not supported by reliable published information, (3) the corollary - that higher corticosteroid potencies (as measured, for example, by skin-blanching activity) can have greater therapeutic effect in lung tissue without greater concomitant systemic activity - is a flawed concept, and (4) the limited clinical and pharmacological data support our part 1 conclusions that discriminating techniques to assess the functional HPA axis status should be an integral part of the drug development process and that further HPA axis function studies are required on existing inhaled corticosteroids - if they lack a rigorous testing history or long-term record of clinical safety.

Adrenal Cortex Hormones↗

Hypothalamic-pituitary-adrenal axis activity in panic disorder: prediction of long-term outcome by pretreatment cortisol levels.

OBJECTIVE: The authors sought to determine whether hypothalamic-pituitary-adrenal (HPA) axis activity in patients before their treatment for panic disorder can predict follow-up functional status. Although baseline HPA axis disturbances in patients with panic disorder appear to attenuate with treatment, there is evidence that they may be linked to poorer long-term outcomes. METHOD: Follow-up clinical data were obtained for 18 of 20 patients with panic disorder who participated in a detailed study of HPA axis activity in panic, both before and during their treatment with alprazolam. HPA axis assessment included monitoring of adrenocorticotropin and cortisol over a full circadian cycle. The relationships between disability and clinical status at 2-year follow-up and HPA axis overactivity at entry were examined. RESULTS: Mean 24-hour cortisol levels before treatment provided a strong, positive predictor of disability scores at follow-up. Those patients who achieved the treatment goal of medication-free remissions had less evidence of HPA axis overactivity at entry than those who were not in remission. CONCLUSIONS: HPA axis activity before treatment did predict outcome 2 years later. This relationship appears robust and reproducible. Further work is needed to define the neuroendocrine mechanisms underlying the HPA axis markers that are linked to long-term functioning and to determine the biological, psychological, and social processes that link HPA axis disturbance to poorer outcomes.

Adolescent↗

Axis I psychiatric comorbidity and its relationship to historical illness variables in 288 patients with bipolar disorder.

OBJECTIVE: Bipolar disorder often co-occurs with other axis I disorders, but little is known about the relationships between the clinical features of bipolar illness and these comorbid conditions. Therefore, the authors assessed comorbid lifetime and current axis I disorders in 288 patients with bipolar disorder and the relationships of these comorbid disorders to selected demographic and historical illness variables. METHOD: They evaluated 288 outpatients with bipolar I or II disorder, using structured diagnostic interviews and clinician-administered and self-rated questionnaires to determine the diagnosis of bipolar disorder, comorbid axis I disorder diagnoses, and demographic and historical illness characteristics. RESULTS: One hundred eighty-seven (65%) of the patients with bipolar disorder also met DSM-IV criteria for at least one comorbid lifetime axis I disorder. More patients had comorbid anxiety disorders (N=78, 42%) and substance use disorders (N=78, 42%) than had eating disorders (N=9, 5%). There were no differences in comorbidity between patients with bipolar I and bipolar II disorder. Both lifetime axis I comorbidity and current axis I comorbidity were associated with earlier age at onset of affective symptoms and syndromal bipolar disorder. Current axis I comorbidity was associated with a history of development of both cycle acceleration and more severe episodes over time. CONCLUSIONS: Patients with bipolar disorder often have comorbid anxiety, substance use, and, to a lesser extent, eating disorders. Moreover, axis I comorbidity, especially current comorbidity, may be associated with an earlier age at onset and worsening course of bipolar illness. Further research into the prognostic and treatment response implications of axis I comorbidity in bipolar disorder is important and is in progress.

Adult↗

Difficulties in interpersonal relationships associated with personality disorders and axis I disorders: a community-based longitudinal investigation.

A longitudinal study was conducted to investigate the association between Axis I and Axis II psychiatric disorders, interpersonal relationships, and global functioning among men in the community. Structured clinical interviews assessing Axis I and Axis II psychiatric disorders, global assessments of functioning, and questionnaires assessing social support, social conflict, and loneliness were administered to a community sample of 95 HIV+ and 45 HIV- men. The questionnaires were readministered 1 year later. Results indicated that (a) Personality disorders (PDs) and unipolar depressive disorders were associated with loneliness, social conflict, and low levels of social support after HIV status was controlled statistically; (b) PDs were associated with interpersonal and global impairment after HIV status and co-occurring Axis I disorders were controlled statistically; (c) Axis I disorders were associated with global impairment, but were not associated with interpersonal difficulties after HIV status and PDs were controlled statistically; (d) PDs, but not Axis I disorders, predicted increases in social conflict and global impairment after HIV status was controlled statistically; (e) PDs continued to predict increases in global impairment after both Axis I disorders and HIV status were controlled statistically; and (f) HIV+ men reported more loneliness, less social support, and had a higher prevalence of substance use disorders than HIV- men. The present findings are of particular interest because they suggest that PDs are associated with loneliness, social conflict, and a lack of social support among men in the community, whether or not Axis I disorders are present.

Adult↗