Stress Response Pattern of Heart Rate Variability in Patients with Functional Somatic Syndromes.

Functional somatic syndromes (FSSs) represent a clinically important group of disorders that are often stress-related. Their autonomic pathophysiology, including reduced heart rate variability (HRV), has been reported. However, the response pattern to mental stress and recovery in FSSs remains unclear. Thus, we aimed to clarify the pattern of autonomic stress response and recovery to mental arithmetic stress in patients with FSS compared to that in healthy controls. This cross-sectional study included 79 patients with FSS who visited the Department of Psychosomatic Medicine at a university hospital in Japan and 39 healthy controls. Following a mood questionnaire and obtaining epidemiologic information, HRV was measured during three periods (5 min each): relaxation baseline resting, stress (mental arithmetic task), and post-stress recovery period. The HRV analysis included inter-beat interval, low frequency power, and high frequency power. Compared to healthy controls, patients with FSS exhibited significantly higher scores on the mood questionnaire, prolonged duration of illness, and decreased functionality in daily activities. While the healthy control group showed a pronounced stress response pattern with a significant decrease in vagal HRV and recovery, the FSS group showed a "flat" vagal stress response pattern, and the HRV in the FSS group was lower at relaxation baseline, remained low during the stress, and did not change post stress. Patients with severe FSS exhibit an altered stress response pattern. Our results could provide significant clues for the diagnosis and treatment of such patients, as well as useful insights into the relationship between stress and illness.

Persistent Idiopathic Facial Pain Associated with Somatoform Disorder in an 11-Year-Old Boy.

Persistent idiopathic facial pain (PIFP) is a poorly understood chronic disorder that rarely occurs in children. An 11-year-old boy initially presented with right cheek pain and a streptococcal infection 6 weeks previously. Facial cellulitis was suspected, which was resolved by antibiotic treatment. The right cheek pain recurred within 4 weeks of this initial visit. Because the antibiotic treatment did not relieve the pain, the patient visited our outpatient clinic. Physical examination revealed facial tenderness in an area that corresponded with the region supplied by the second branch of the trigeminal nerve (maxillary nerve), suggesting trigeminal neuralgia (TN). However, brain magnetic resonance imaging revealed no vascular compression. Furthermore, the continuous nagging and dull nature of the pain experienced by the patient differed from the sudden and severe nature of pain associated with TN. Subsequently, PIFP was diagnosed. The patient was unable to attend school because of prolonged lassitude, nausea, headache, and anorexia. Psychological counseling revealed psychological stress related to his out-of-school life. Upon learning stress management through psychotherapy, his general malaise gradually improved, and he was able to attend school with more facial expressions. This case indicates the psychogenic aspect of PIFP as well as the value of psychological counseling.

The relationship between salivary amylase and the physical and psychological changes elicited by continuation of autogenic training in patients with functional somatic syndrome.

BACKGROUND: The aim of this study was to clarify the changes in biological measures during autogenic training (AT) sessions and the relationship between these biological measures and the changes in physical and psychological measures induced by continuation of AT in patients with functional somatic syndrome (FSS). We used the salivary amylase (SAMY) level, skin temperature of the finger (TEMP), subjective symptom scores, and psychological characteristics to assess these changes. METHODS: We assessed 24 patients with FSS and 23 healthy controls before and after AT. We then conducted the same tests after the participants had practiced AT at home 1 and 2 months later. RESULTS: The baseline SAMY levels in the first session were significantly higher in the FSS group than in the control group. However, this difference was not significant in the second and third sessions. The pattern of changes in TEMP induced by AT was not different between the FSS and control groups. Tension-anxiety and somatic symptoms in patients with FSS were improved by AT. In the FSS group, the baseline SAMY levels in the first session showed a significant negative correlation with the changes in the subjective symptom score and tension-anxiety score at baseline. CONCLUSIONS: The practice of AT, both during the first session and after 1 month of continuation, eased the dysregulation of the autonomic nervous system that is reflected in SAMY in patients with FSS. AT also contributed to decreases in the tension-anxiety and somatic symptoms in patients with FSS. We suggest that SAMY is related to both physical and psychological effects of AT in patients with FSS.

Pain threshold reflects psychological traits in patients with chronic pain: a cross-sectional study.

BACKGROUND: Chronic pain enhances sensory sensitivity and induces the biased development of psychological traits such as depression and pain catastrophizing, leading to the formation of heterogeneous conditions. Fluctuations in the sensory-related thresholds of non-injured sites (with normal peripheral tissue) in patients with chronic pain are thought to be related to central sensitization. The objectives of this study were to analyze the association between pain tolerance thresholds (PTTs) in non-injured sites and the psychological traits of patients with chronic pain and to evaluate the usefulness of PTT measures in assessments of pathological conditions related to chronic pain. METHODS: This study included 57 patients with chronic pain. The PTTs were measured in non-injured sites with quantitative sensory testing (QST) with electrical stimulation and then classified with cluster analysis. The Short-Form McGill Pain Questionnaire was used to subjectively assess pain in the injured sites. The Minnesota Multiphasic Personality Inventory (MMPI) was used to assess the patients' psychological traits. RESULTS: Based on the cluster analysis of PTTs, the patients were classified into a High-Sensitivity group and an Others group consisting of the remaining patients. The results of the MMPI profiles showed that the High-Sensitivity group included significantly more patients with the Neurotic Triad pattern and no patients with the Conversion V pattern. The scores of the hypochondriasis and hysteria scales were significantly lower in the High-Sensitivity group than in the Others group. CONCLUSIONS: This study indicated that patients with chronic pain can be classified according to PTTs in non-injured sites and suggests that patients with High-Sensitivity have characteristic psychological traits. Assessment of PTTs in non-injured sites would be useful for evaluating the psychological condition of patients with chronic pain.

Saliva amylase as a measure of sympathetic change elicited by autogenic training in patients with functional somatic syndromes.

The aim of this study was to discuss the effect of autogenic training (AT) on patients with functional somatic syndrome (FSS) using salivary amylase, the skin temperature of the finger, subjective severity of symptoms, and psychological characteristics as measures. We assessed 20 patients with FSS and 23 healthy controls before and after AT. Baseline levels of salivary amylase prior to an AT session were significantly higher in the FSS group than in the control group. However, this difference was not significant after AT. The skin temperature of the finger increased after AT in both the FSS and control groups. AT contributed to the improvement of somatic symptoms in patients with FSS. Our results regarding psychological characteristics suggest that mood disturbances are deeply involved in the pathology of FSS. Individuals with FSS exhibited elevated levels of sympathetic activity compared with healthy controls. Our data indicates that AT eased dysregulation of the autonomic nervous system in patients with FSS. Thus, salivary amylase may be a useful index of change induced by AT in patients with FSS.

Factors responsible for deep-sowing tolerance in wheat seedlings: varietal differences in cell proliferation and the co-ordinated synchronization of epidermal cell expansion and cortical cell division for the gibberellin-mediated elongation of first internodes.

BACKGROUND AND AIMS: A wheat cultivar, Triticum aestivum 'Hong Mang Mai', shows tolerance to deep-sowing conditions by extreme elongation of the first internode, likely mediated by the gibberellin (GA) response. To understand factors involved in the response of this deep-sowing-tolerant cultivar, cell expansion and division that confer elongation on the first internodes of wheat seedlings were investigated. METHODS: The lengths and numbers of epidermal and cortical cells of the first internodes in three wheat cultivars were measured. These parameters were compared in wheat seedlings treated with gibberellin A(3) (GA(3)) or an inhibitor of GA biosynthesis, uniconazole. KEY RESULTS: The varietal differences in the elongation of the first internodes were due to differences in cell numbers resulting from the different abilities of cell division, but not cell expansion. In seedlings treated with GA(3), the first internode of 'Hong Mang Mai' was 2-fold longer than the control. The GA-stimulated elongation of the first internodes was attributed to 2-fold increases in the number of cortical cells and length of epidermal cells. The different GA-responses observed in these two tissues were also detected in other cultivars, although the response was much lower than that noted in 'Hong Mang Mai'. The seedlings treated with uniconazole exhibited reduced numbers of cortical cells and reduced lengths of epidermal cells, with both of these effects being more pronounced in 'Hong Mang Mai'. CONCLUSIONS: The deep-sowing-tolerant cultivar 'Hong Mang Mai' is able to elongate the first internode to a greater degree due to enhanced cell division and a heightened response to GA. In addition, cell expansion in the epidermis and cell division in the cortex are synchronized for the elongation of the first internodes. In response to GA, this well-co-ordinated synchronization yields the rapid elongation of the first internodes in wheat seedlings.

Physicochemical characterization of tamoxifen citrate pseudopolymorphs, methanolate and ethanolate.

Two novel pseudopolymorphs, methanolate and ethanolate of tamoxifen [(Z)-2-[4-(1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylethylamine]citrate, were prepared in addition to forms A and B reported previously. Their crystalline forms were identified and characterized by powder and single crystal X-ray diffractometry, differential scanning calorimetry, thermogravimetric analysis, hot-stage microscopy, scanning electron microscopy and diffuse reflectance infrared Fourier-transform spectroscopy, and their physicochemical stability was also evaluated. The results of single crystal X-ray analysis and thermogravimetric analysis of methanolate and ethanolate suggested that the stoichiometry of tamoxifen citrate : methanol and tamoxifen citrate : ethanol could be composed of a 1 : 1 molecular ratio for both solvates. The results of physicochemical stability evaluations at 75 and 97% RH at 40 and 60 degrees C indicated that the metastable form A was quite stable for at least 2 months even under severe storage conditions, whereas methanolate immediately transformed to a crystalline mixture of forms A and B, and subsequently changed to the stable form B.

Kinetic study of the transformation of mefenamic acid polymorphs in various solvents and under high humidity conditions.

The transformation kinetics of mefenamic acid form II to form I in three kinds of solvents and under high humidity conditions were extensively investigated. Form II crystals were suspended in water, 50% ethanol and ethanol at 28, 33 and 37 degrees C, or stored at 50, 60 and 70 degrees C at 97% RH. Form II transformed to form I under all storage conditions and the rate of transformation depended on the kind of solvent. The transformation followed the three-dimensional nuclei growth mechanism, depending on temperature. The nuclei formation and growth processes were significantly accelerated in ethanol compared with water. The addition of seed crystals of the stable form I shortened the both nuclei formation and growth processes and therefore the transformation was accelerated.

Comparative determination of polymorphs of indomethacin in powders and tablets by chemometrical near-infrared spectroscopy and x-ray powder diffractometry.

The purpose of this research was to develop a rapid chemometrical method based on near-infrared (NIR) spectroscopy to determine indomethacin (IMC) polymorphic content in mixed pharmaceutical powder and tablets. Mixed powder samples with known polymorphic contents of forms alpha and gamma were obtained from physical mixing of 50% of IMC standard polymorphic sample and 50% of excipient mixed powder sample consisting of lactose, corn starch, and hydroxypropylcellulose. The tablets were obtained by compressing the mixed powder at 245 MPa. X-ray powder diffraction profiles and NIR spectra were recorded for 6 kinds of standard materials with various polymorphic contents. The principal component regression analysis was performed based on normalized NIR spectra sets of mixed powder standard samples and tablets. The relationships between the actual and predicted polymorphic contents of form g in the mixed powder measured using x-ray powder diffraction and NIR spectroscopy show a straight line with a slope of 0.960 and 0.995, and correlation coefficient constants of 0.970 and 0.993, respectively. The predicted content values of unknown samples by x-ray powder diffraction and NIR spectroscopy were reproducible and in close agreement, but those by NIR spectroscopy had smaller SDs than those by x-ray powder diffraction. The results suggest that NIR spectroscopy provides a more accurate quantitative analysis of polymorphic content in pharmaceutical mixed powder and tablets than does conventional x-ray powder diffractometry.

Physicochemical stability of cimetidine amorphous forms estimated by isothermal microcalorimetry.

The effect of humidity on the physicochemical properties of amorphous forms of cimetidine was investigated using differential scanning calorimetry, isothermal microcalorimetry, and x-ray diffraction analysis. Amorphous forms were obtained by the melting (amorphous form M [AM]) and the cotton candy (amorphous form C [AC]) methods. Thermal behaviors of AM and AC with or without seed crystals were measured using an isothermal microcalorimeter under various conditions of relative humidity (RH) and temperature, respectively. The crystallization kinetics of amorphous solids was analyzed based on 10 kinds of solid-state reaction models. AM transformed into form A at 11% RH, 50 degrees C but transformed into a mixture of form A and monohydrate at 51% and 75% RH at 25 degrees C. The mean crystallization times (MCTs) of the heat flow curve of AM and AC at 11% RH, 50 degrees C were 47.82 and 32.00 hours, respectively, but at 11% RH, 25 degrees C both were more than 4320 hours. In contrast, AC transformed into form A under all storage conditions. The MCTs of AC at 51% and 75% RH were 29.61 and 11.81 hours, respectively; whereas the MCTs of AM were 46.79 and 15.52 hours, respectively. The crystallization of amorphous solids followed the three-dimensional growth of nuclei (Avrami equation) with an induction period (IP). The IP for AM at 11% RH, 50 degrees C was more than 2 times that for AC, but the difference in the crystal growth rate constant (CR) between AC and AM was within 10%. The IP for AM at 75% RH, 25 degrees C was reduced to only 10% of the IP at 51% RH with increasing humidity, but the CR did not change significantly. In contrast, the IP for AC was slightly reduced at 75% RH compared with 51% RH, but the CR was about 5 times greater. At 75% RH, 25 degrees C, the IP and CR of AM were about one-fourth the values of AC. This result suggests that the crystallization process consists of an initial stage during which the nuclei are formed and a final stage of growth.