[Psychosomatic treatment].
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Behavior Therapy↗
Biomedical subjects
M Munakata
Publications and source records attributed to M Munakata.
[A patient with hemorrhage originating from an unknown coagulation pathway inhibitor].
The hemorrhagic disorders associated with circulating anticoagulant are rare but well known as the disease derived from inhibitors(alloantibody or autoantibody), which arise against specific coagulation factors. We encountered a patient with hemorrhage at the lower limbs originating from an unknown coagulation pathway inhibitor. Activated partial thromboplastin time(APTT) prolonged and cross mixing test indicated a coagulation pathway inhibitor. Levels of coagulation factors VIII, IX, XI, and XII were extremely low. Predonine therapy was effective to stop the hemorrhage. To clarify the inhibitor, we treated the patient's plasma with protein A Sepharose, and the factor VIII activity was recovered to a normal level after passing through the column. Gel filtration of the patient's plasma and protein A Sepharose adsorbed fraction of the patient's plasma with Superdex 200 revealed that the inhibitor activity against blood coagulation eluted at the position of IgG, which was detected by the prolongation of APTT of normal pooled plasma. These data indicated that the inhibitor was IgG and its inhibitory spectrum was non-specific and broad. The results of laboratory tests and the clinical features in our patient were similar to those in a previous study by Dahlback(Blood 62, 218-225, 1983). The hemorrhagic abnormality of that patient was derived from the autoantibody to phospholipid, which inhibits the activation of prothrombin. An investigation into the effect of anti-phospholipid antibody in our patient is currently being performed in our laboratory.
Adult↗
Investigation of the time delay between variations in heart rate and blood pressure.
Relationships between fast variations in heart rate and blood pressure are known mainly to reflect parasympathetic activity. To assess parasympathetic function, relationships are investigated using a mutual information analysis, by assuming an information channel between blood pressure (BP) and inter-R-wave interval (RR) derived from the electrocardiogram. The differential sequences of BP and RR are coded into 'alphabets' for analysing fast variations. The averaged mutual information (AMI) is obtained as a function of delay d (beats) of the differential sequence of RR with reference to BP. The AMIs for supine and standing positions are compared. For 23 patients with renal failure, the AMI against d shows posture-independent and delayed-transfer characteristics from fast variations in BP to those in RR. The closest relationship is found with a 2-beat delay with an out of phase relationship. The 28 control subjects exhibit the 2-beat delayed transfer characteristics in the standing position, but are almost synchronous in the supine position. The mutual information analysis of the delay between fast variations in BP and RR explicitly shows a deficit in the parasympathetic regulation in the patients with renal failure.
Adult↗
The origin of hypsarrhythmia and tonic spasms in West syndrome: evidence from a case of porencephaly and hydrocephalus with focal hypsarrhythmia.
We report on a 3-year-old girl with West syndrome and with focal hypsarrhythmia. The left hemisphere of the patient was virtually completely defective and continuous hypsarrhythmia was only seen in the residual right frontal cortex, where an interictal single photon emission computed tomography (SPECT) showed hyperperfusion. Despite a focal epileptic pattern, the tonic spasms were quite symmetrical. In our patient, spasms might not require the sensorimotor cortex, but the brainstem containing the descending pathways that control spinal reflexes and other infratentorial structures seem to be essential for the occurrence of spasms. This is in accordance with the result of an ictal SPECT that showed hyperperfusion of the brainstem and cerebellum. These findings suggest that hypsarrhythmia originates from cortical lesions, while subcortical structures may be primarily responsible for the tonic spasms in this patient.
Brain↗
Altered sympathetic and vagal modulations of the cardiovascular system in patients with pheochromocytoma: their relations to orthostatic hypotension.
To examine sympathetic and vagal cardiovascular regulatory mechanisms in the pathogenesis of orthostatic hypotension in pheochromocytoma, we continuously monitored blood pressure (Finapres) and RR interval (electrocardiogram) in supine and standing positions in 12 patients with pheochromocytoma, 43 patients with essential hypertension, and 30 normotensive subjects. Mayer wave power spectrum of systolic blood pressure variability (approximately 0.1 Hz) and respiratory power spectrum of the RR interval variability (approximately 0.25 Hz) were taken as measures of sympathetic vascular and cardiac vagal modulations, respectively. Systolic blood pressure decreased more upon standing in pheochromocytoma patients (-21 +/- 7 mm Hg) than in normotensive subjects (-5 +/- 2 mm Hg) or essential hypertensive patients (-3 +/- 2 mm Hg) (P < .005 for both), whereas heart rate tended to increase most in the pheochromocytoma group. Postural reduction in systolic blood pressure was highly correlated with postural increase in heart rate (reciprocal change in RR interval) in the pheochromocytoma group (r = 0.716, P < .01) suggesting that baroreflex is well functioning in those patients. The Mayer wave power spectrum in recumbency was extremely depressed in pheochromocytoma patients (1.1 +/- 0.2 mm Hg2) compared with normotensives (4.5 +/- 0.8 mm Hg2) or essential hypertensives (5.6 +/- 0.6 mm Hg2) (P < .001 for both). This parameter increased significantly with standing in all groups but remained lower in patients with pheochromocytoma (5.1 +/- 1.0 mm Hg2) than in normotensives (7.1 +/- 0.9 mm Hg2, P = NS), whereas essential hypertensive patients demonstrated far greater value (19.2 +/- 3.8, P < .01 for both). The respiratory power spectrum of the RR interval in recumbency of pheochromocytoma patients (189 +/- 54 msec2) was less than in normotensive subjects (714 +/- 100 msec2, P < .001) but did not differ from that in patients with essential hypertension (214 +/- 41 msec2). The respiratory power spectrum of the RR interval upon standing was markedly suppressed in pheochromocytoma patients (36.9 +/- 16.7 msec2) compared with normotensive subjects (129.5 +/- 23.6 msec2) or essential hypertensive patients (126.6 +/- 28.6 msec2) (P < .001 for both). Postural decrement in the respiratory power spectrum of the RR interval correlated positively with postural increase in heart rate (r = 0.577, P < .05) in patients with pheochromocytoma. After successful surgery (n = 9), the Mayer wave power spectrum of the systolic blood pressure and the blood pressure response to orthostasis were normalized. These data suggest that altered sympathetic vascular regulation is central to the pathogenesis of orthostatic hypotension in pheochromocytoma, whereas cardiac vagal regulation acts to compensate.
Adrenal Gland Neoplasms↗
Type A behavior is associated with an increased risk of left ventricular hypertrophy in male patients with essential hypertension.
OBJECTIVE: To determine whether type A behavior, which is associated with a risk of coronary heart disease, affects left ventricular hypertrophy in patients with essential hypertension. DESIGN: Cross-sectional study of 88 untreated patients with mild to moderate essential hypertension (33 men, mean +/- SEM age 54 +/- 1 years). METHODS: We measured the type A behavior score using a standardized questionnaire, left ventricular mass index using M-mode echocardiography and 24 h mean ambulatory blood pressure (recorded every 30 min). Beat-to-beat blood pressure was also measured using a Finapres device in patients at rest and during mental stress (counting backward) to determine the blood pressure response to stress. RESULTS: The left ventricular mass index was correlated with the type A behavior score (r = 0.214, P < 0.05), age (r = 0.266, P < 0.05), 24 h mean systolic and diastolic blood pressures (r = 0.391, P < 0.001, and r = 0.382, P < 0.001, respectively), systolic blood pressure both at rest and during stress (r = 0.255, P < 0.05, and r = 0.215, P < 0.05, respectively), and the variability of both systolic and diastolic blood pressures at rest (r = 0.253, P < 0.05, and r = 0.321, P < 0.01, respectively). Stepwise multiple linear regression analysis demonstrated that age was associated with an increase in the left ventricular mass index for both sexes (P = 0.004 for males, P = 0.003 for females). The type A behavior score predicted a greater increase in left ventricular mass index in men (P = 0.018) but not in women. The 24 h mean systolic blood pressure was associated with a greater increase in left ventricular mass index in women (P < 0.001) but not in men. CONCLUSION: Type A behavior is an independent risk factor for left ventricular hypertrophy in male patients with essential hypertension.
Blood Pressure↗
Increases in plasma ouabainlike immunoreactivity during surgical extirpation of pheochromocytoma.
The ouabainlike factor (OLF) is thought to be an important modulator of salt and water metabolism. Plasma OLF could be derived from the central nervous system and/or the adrenal gland. Since the adrenal medulla is of neural origin, the cytology of pheochromocytoma of adrenomedullary origin resembles that of neuronal cells. Ouabainlike immunoreactivity (OLI) is, in fact, present in the adrenal medulla as shown by immunohistochemistry. The plasma levels of catecholamines and OLI were significantly elevated during surgical extirpation of pheochromocytoma in this case. To clarify the origin of circulating OLI in a patient with pheochromocytoma, the relationship between plasma OLI and catecholamines during adrenalectomy was investigated. Plasma catecholamine levels exceeded the normal reference interval, and plasma OLI was positively correlated with the patient's plasma level of norepinephrine. The peak level during operation was about 10 times higher than the baseline level. Both levels reached a maximum when the tumor was mechanically pressed, and then gradually decreased thereafter. The level of OLI in the tumor was higher than that of the normal adrenal cortex. When OLI in the tumor was characterized by reversed-phase high-performance liquid chromatography, the retention time of OLI corresponded with that of authentic ouabain. These results suggest that the circulating OLI in this patients was derived mainly from the pheochromocytoma of adrenomedullary origin.
Adrenal Gland Neoplasms↗
[Histidine buffered cardioplegic solution (HBS) provides effective myocardial preservation with wider safety margin in patients with prolonged ischemia].
Increasingly complex techniques of cardiac surgery often require prolonged myocardial ischemia. We previously reported a better myocardial preservation with histidine containing cardioplegia (HBS) in human open heart surgery. To see a safety margin of this cardioplegia for prolonged myocardial preservation, this study was retrospectively done. One hundred twenty-six patients received either intermittent multidose (20-30 minute) cold blood cardioplegia (CBC) plus topical cooling (aotric cross clamp time (ACC) < 120 minutes, n = 63) or HBS (n = 63). HBS group was divided into two groups with either short ACC (< or = 120 minutes, HBS-S, n = 46) or long ACC (> 120 minutes, HBS-L, n = 17). Cardiac index (C.I.) and dopamin/dobutamine requirement were measured 3, 6, and 12 hours post-bypass. Incidence of homologous blood transfusion was also studied. There was two deaths due to LOS in HBS-S group; four patients in HBS group required 5 DC cardioversion, whereas six patients required a total of 12 DC cardioversion in CBC group. Functional recovery were significantly better with significantly lower inotropic requirements in HBS-S group than CBC group and HBS-L group. Although preoperative ejection fraction and C.I. were significantly lower in HBS-L group, post-operative cardiac function and inotropic requirements in HBS-L was comparable to that seen in CBC group. We conclude that the highly buffered histidine crystalloid cardioplegia solution provides effective myocardial preservation with a wider safety margin for prolonged myocardial preservation in open heart surgery.
Adult↗
Temperature-dependent effect of zolpidem on the GABAA receptor-mediated response at recombinant human GABAA receptor subtypes.
The effects of zolpidem on the two forms of recombinant human GABAA receptors (alpha1beta2gamma2s and alpha3beta2gamma2s) at different temperatures were functionally investigated, using the whole-cell patch recording configuration. In both forms, zolpidem potentiated the response to GABA in a concentration-dependent manner. At 16 degrees C, the apparent dissociation constant (KD) values for the alpha1beta2gamma2s and alpha3beta2gamma2s forms were 3.7 x 10(-8) and 5.6 x 10(-7) M, respectively. When the temperature was increased to 36 degrees C, the KD values for the alpha1beta2gamma2s and alpha3beta2gamma2s forms were 2.1 x 10(-7) and 1.5 x 10(-6) M, respectively. Although the affinity ratio was reduced from 15.1 to 7.1-fold the selectivity of zolpidem for the alpha1beta2gamma2s still remained at 36 degrees C.
GABA Agonists↗
Characterization of electrogenic Na/K pump in rat neostriatal neurons.
The electrogenic Na/K pump current (Ip) was studied in the dissociated neostriatal neurons of the rat by using the nystatin-perforated patch recording mode. The Ip was activated by external K+ in a concentration-dependent manner with an EC50 of 0.7 mM at a holding potential (VH) of -40 mV. Other monovalent cations also caused Ip and the order of potency was Tl+>K+, Rb+>NH4+, Cs+>>>Li+. The Ip decreased with membrane hyperpolarization in an external solution containing 150 mM Na+, while the Ip did not show such voltage dependency without external Na+. Ouabain showed a steady-state inhibition of Ip in a concentration- and temperature-dependent manner at a VH of -40 mV. The IC50 values at 20 and 30 degrees C were 7.1 x 10(-6) and 1.3 x 10(-6) M, respectively. The decay of Ip after adding ouabain well fitted with a single exponential function. At a VH of -40 Mv, the association (k+1) and dissociation (k-1) rate constants estimated from the time constant of the current decay at 20 degrees C were 4.0 x10(2) s-1 M-1 and 6.3 x 10(-3) s-1, respectively. At 30 degrees C, k+1 increased to 2.8 x 10(3) s-1 M-1 while k-1 showed no such change with a value of 1.8 x 10(-3) s-1. A continuous Na+ influx was demonstrated by both the Na+-dependent leakage current and tetrodotoxin-sensitive Na+ current, which resulted in the continuous activation of the Na/K pump. It was thus concluded that the Na/K pump activity was well-maintained in the dissociated rat neostriatal neurons with distinct functional properties and that the activity of the pump was tightly connected with Na+ influxes.
Animals↗
A case of sarcoidosis that developed three years after the onset of hard metal asthma.
A 23-year-old man who worked at a hard metal factory from 1988 had developed bronchial asthma in 1990. He was diagnosed as having bronchial asthma by inhalation challenge with cobalt. He never developed a severe attack after that by avoiding inhalation of cobalt. In 1993, he developed iridocyclitis, and his chest radiograph showed bilateral hilar lymph node swelling. He was diagnosed as having sarcoidosis with pathological certainty and an increased serum angiotensin-converting enzyme (ACE) level. On second admission, an inhalational challenge with cobalt resulted in no significant decrease of FEV1. Cobalt is well known to cause occupational asthma and other interstitial lung diseases. Although we could not get clear evidence suggesting an association between the sarcoidosis and his history of cobalt exposure, there is a possibility that changes in the immune reaction to cobalt might explain the improvement of asthma followed by sarcoidosis in this case.
Adult↗
Histamine modulates high-voltage-activated calcium channels in neurons dissociated from the rat tuberomammillary nucleus.
The effects of histamine on high-voltage-activated Ca2+ channels in the histaminergic neurons acutely dissociated from the rat tuberomammillary nucleus were investigated in the nystatin-perforated patch recording mode under voltage-clamp conditions. Histamine suppressed the high-voltage-activated Ca2+ channel currents in neurons which were positive for histidine decarboxylase with immunocytochemistry. The half-maximum inhibitory concentration and maximum inhibition were 2.6 x 10(-7) M and 16.6+/-1.90%, respectively. An H3 receptor agonist, R(-)-alpha-methylhistamine, mimicked the response to histamine, and thioperamide, an H3 receptor antagonist, inhibited the response to histamine. On the other hand, neither 2-methylhistamine, an H1 receptor agonist, nor dimaprit, an H2 receptor agonist, had a significant effect on the Ca2+ channel currents. Pretreatment with pertussis toxin blocked the inhibitory effect of histamine on Ca2+ channels, suggesting the involvement of Gi/Go proteins in the action of histamine. Omega-conotoxin-GVIA, omega-agatoxin-IVA, nicardipine, and omega-conotoxin-MVIIC blocked the high-voltage-activated Ca2+ channel currents by 15.6, 4.3, 27.1, and 31.2% of the total current, respectively, suggesting the existence of N-, P-, L-, and Q-type Ca2+ channels. A current that was insensitive to these blockers was also found. This residual current, "R-type", was completely suppressed by the addition of 200 microM Cd2+. Histamine significantly inhibited both the N- and P-type current components among these five types of Ca2+ channel currents. We concluded that histamine suppresses the N- and P-type Ca2+ channels in histaminergic neurons through an H3 receptor which is linked to a pertussis toxin-sensitive G-protein.
Animals↗
Decreased blood pressure variability at rest in patients with primary aldosteronism.
Increased blood pressure (BP) variability in essential hypertension (EH) is attributed in part to a reduction in baroreflex sensitivity. We previously showed that baroreflex sensitivity is not reduced in hypertension associated with primary aldosteronism (PA) compared with normotensive (NT) subjects. This study examined whether the preservation of baroreflex function in patients with PA would prevent an increase in BP variability. The beat-to-beat BP (measured with Finapres) and RR interval (from electrocardiograms) were monitored for 10 min in the supine and standing positions in 34 patients with PA, 60 patients with EH, and 45 NT subjects. Recordings were also performed during mild ergometer exercise in 7 PA patients, 8 EH patients, and 9 NT subjects. Blood pressure variability was assessed by both standard deviation (SD) and coefficient of variation (CV). Baroreflex sensitivity (BRS) was assessed by the closed-loop gain between systolic BP and RR interval variability. The SD and the CV of systolic BP (SBP) and the CV of diastolic (DBP) BP were significantly smaller in patients with PA than in patients with EH in both supine and standing positions. The SD of SBP and DBP were similar in patients with PA and NT subjects, although the CV were significantly smaller in patients with PA. The BRS was inversely correlated with both the SD and CV for SBP in the supine (r = -0.397 and -0.440, P < .05, respectively) and standing (r = -0.457 and -0.412, P < .05, respectively) positions in patients with PA. Exercise reduced the BRS in all groups (70%, 26%, and 64% for PA, EH, and NT, respectively, P < .01). Blood pressure variability did not change significantly during exercise, compared with rest, in the PA and NT groups but was decreased (P < .05) in the patients with EH. In conclusion, primary aldosteronism is characterized by decreased supine and standing BP variability, which is due in part to the preservation of baroreflex function. Our data further showed that BP variability is minimized by nonbaroreflex mechanisms during mild exercise.
Adult↗
Molecular studies of bronchial asthma, sarcoidosis and angiotensin converting enzyme inhibitor-induced cough.
The role of genetic factors was reviewed with respect to the pathophysiology of bronchial asthma, sarcoidosis and cough induced by angiotensin converting enzyme (ACE) inhibitor administration. The so-called 'atopy gene' in 11q13 is not linked to atopy but is associated with serum IgE levels. The beta2-adrenergic receptor gene on 5q32-33 was found to have polymorphism by Ban I and to be related to beta2-receptor function; a defect of a 2.3 kb allele is related to lowered sensitivity to beta2-agonists. This defect is also related to higher prevalence on non-atopic bronchial asthma. The occurrence of amino acid mutation (Arg16 to Gly) of beta2-receptors was lower and Gln27 to Glu mutation is extremely rare in the Japanese population compared with Caucasians. There is polymorphism of ACE genotypes among normal subjects and patients with sarcoidosis, II, ID and DD. The genotype is a significant determinant of serum ACE activity and may determine the prognosis of sarcoid patients. Genotype II has a higher incidence of coughing induced by ACE inhibitors.
Alleles↗
Psychobehavioral factors involved in the isolated office hypertension: comparison with stress-induced hypertension.
OBJECTIVE: To investigate the psychobehavioral factors involved in the isolated clinic blood pressure elevation and hypertension induced by mental stress. DESIGN AND METHODS: We studied 73 untreated patients with essential hypertension defined as World Health Organization stage I or II (28 men and 45 women, mean age 55 +/- 11 years). The amount of isolated clinic blood pressure elevation was examined in terms of the difference between clinic and daytime ambulatory blood pressures. Blood pressure (measured using a Finapres device) and R-R interval (measured electrocardiographically) were continuously monitored with subjects at rest and under mental stress (counting backward) to examine the cardiovascular response to the stress. Psychobehavioral characteristics such as anger, anxiety, tension, type A behavior pattern, and nervousness were evaluated and scored using structured interviews and self-reporting questionnaires. RESULTS: The anger score was inversely correlated to the clinic-ambulatory blood pressure difference for the systolic (r = -0.308, P < 0.01) and diastolic (r = -0.233, P < 0.05) blood pressures. The score for type A behavior pattern tended to be inversely correlated to the clinic-ambulatory blood pressure difference for diastolic blood pressure (r = -0.209, P < 0.1). The nervousness score was positively correlated to stress-induced increase in the systolic (r = 0.249, P < 0.05) and diastolic (r = 0.232, P < 0.05) blood pressures. The clinic-ambulatory blood pressure difference was not related to the blood pressure rise induced by mental stress (r = 0.170 for systolic blood pressure; r = 0.112 for diastolic blood pressure). CONCLUSION: The isolated clinic blood pressure elevation and hypertension due to mental stress were related to different psychobehavioral factors.
Adult↗
Heterogeneity of ictal SPECT findings in nine cases of West syndrome.
We evaluated the ictal and interictal single photon emission computed tomography (SPECT) of 9 patients with West syndrome (WS). In this group, we noted two clear patterns of cortical hyperperfusion and subcortical hyperperfusion in the ictal SPECT. Both patterns were different from the previously documented ictal patterns for complex partial seizures (CPS) or secondarily generalized seizures. Our results suggest that the tonic spasms of WS do not always have a single neurophysiological basis; e.g., patients with hemihypsarrhythmia and focal hypsarrhythmia did not show ictal hyperperfusion of the lesion with hypsarrhythmia. These findings indicate that the origin of hypsarrhythmia as an EEG feature and the origin of tonic spasms may be different in such patients. In particular, hypsarrhythmia appears to originate from cortical lesions, whereas the subcortical structures may be primarily responsible for the tonic spasms. Our report is the first published study of ictal SPECT in patients with WS.
Adolescent↗
Expression of epidermal growth factor and epidermal growth factor receptor immunoreactivity in the asthmatic human airway.
Chronic airway inflammation, one of the pathophysiologic features of bronchial asthma, is suspected to be responsible for irreversible pathological changes of airways, called airway remodeling. To examine the mechanisms of airway remodeling in asthma, we investigated the expression of epidermal growth factor (EGF) and its receptor immunohistochemically in asthmatic human airways. Airway specimens from seven patients with asthma were obtained from autopsied and surgically resected lungs. Control specimens were obtained from lungs of eight subjects without asthma and other pulmonary complications at autopsy. We stained those specimens by the avidin-biotin-peroxidase complex (ABC) method with anti-human polyclonal EGF antibody and monoclonal EGF receptor antibodies. Three different portions of airways-large bronchi (about 1 cm in diameter), small bronchi (about 3 mm in diameter), and peripheral airways (less than 2 mm in diameter)-were examined. The thickness of the bronchial smooth muscle and basement membrane was significantly greater in the asthmatic airways than in controls. Clear immunoreactivities of EGF were widely observed on bronchial epithelium, glands, and smooth muscle in asthmatic airways. In the controls, the bronchial epithelium and the bronchial glands partially expressed faint EGF immunoreactivity. For the EGF receptor, clear immunoreactivities were also observed on bronchial epithelium, glands, smooth muscle, and basement membrane in asthmatic airways. In control airways, only part of the bronchial epithelium and smooth muscle weakly expressed EGF receptor immunoreactivity. These results suggest a possible contribution of EGF to the pathophysiology of bronchial asthma, including airway remodeling.
Adult↗