The maneuver to release an incarcerated obturator hernia.

An obturator hernia occurs through the pelvic obturator canal, a rigid ring made up of the underside of the superior pubic ramus and the obturator fascia. Obturator hernias have been associated with a high mortality due to the difficulty in diagnosis and the population in which it occurs. We examined four patients diagnosed with incarcerated obturator hernia, and showed that the strangulated intestine was not necrotic. We flexed the diseased leg calmly and repeatedly with slight rotation toward the outside and slight adduction toward the inside at supine position. The pain vanished suddenly during this maneuver. After this maneuver, the patients were able to undergo elective surgery after a certain interval. We discuss the possible use of this maneuver to release an incarcerated obturator hernia.

Diffuse bilateral thalamic astrocytomas as examined serially by MRI.

We report the case of a 13-year-old girl with diffuse bilateral thalamic astrocytomas. Incoordination was observed at the onset. Cranial computed tomography (CT) showed enlarged thalami, and magnetic resonance imaging (MRI) revealed these lesions to be symmetrically enlarged with high intensity on the T2-weighted image. Owing to these atypical findings in the neuroimaging studies, we had difficulty in making the correct diagnosis of a brain tumor. After the diagnosis of diffuse bilateral thalamic astrocytomas was obtained, we performed hyperfractionated radiotherapy followed by chemotherapy. Radiation therapy was effective for a while, but the girl's condition deteriorated again and she died 8 months after admission. Although diffuse bilateral thalamic astrocytomas are difficult to diagnose because they do not resemble most other neoplasms on neuroimaging studies, pediatricians should keep this entity in mind in order to arrive at a precise and prompt diagnosis.

Effects of electrical stimulation or local anesthesia of the rabbit's hypothalamus on the acute phase response.

The effects of electrical stimulation of the rostral hypothalamic region on the acute phase response (APR) were examined in rabbits. As indicators of APR, we measured changes in the plasma concentrations of iron, zinc, copper, and fibrinogen and changes in the red and white blood cell counts. Electrical stimulation of the rostral hypothalamic region near the preoptic and anterior hypothalamic region did not induce any aspect of the APR. However, stimulation near the anteroventral portion of the third ventricle (AV3V) induced responses that were, in part, opposite to those observed in the APR: an increase in the plasma concentration of zinc and a decrease in the circulating leukocyte count. Microinjections of procaine into the brain regions near the AV3V did not induce any changes in the plasma levels of trace metals and fibrinogen but increased the circulating leukocyte count. These results suggest that nonspecific stimulation or inhibition of the rostral hypothalamic region does not induce APR.

ACTH response induced by interleukin-1 is mediated by CRF secretion stimulated by hypothalamic PGE.

We investigated whether hypothalamic prostaglandin E2 (PGE2) and corticotropin releasing factor (CRF) are responsible for the development of the adrenocorticotropic hormone (ACTH) response induced by interleukin-1 alpha (IL-1 alpha). The present results show that ACTH responses induced by intravenous injection of IL-1 alpha were suppressed by systemic pretreatment with indomethacin and that intrahypothalamic injection of PGE2 stimulates the secretion of ACTH. Furthermore, systemic pretreatment with anti-CRF antibody significantly suppressed the ACTH response induced by intrahypothalamic injection of PGE2. These data suggest that the ACTH response induced by IL-1 is mediated by CRF secretion stimulated by hypothalamic PGE2.

Maternal thermal stimulation changes metabolic activity in fetal hypothalamus.

To study whether the central nervous system in the perinatal fetal rat can operate during maternal cooling and warming, we examined the 2-deoxy-D-[14C]glucose ([14C]DG) uptake in the fetal brain. Full-term pregnant rats were placed at three different ambient temperatures of 35-37 degrees C, 24-25 degrees C and 0-10 degrees C. Saline containing 20 microCi/100 g of [14C]DG was injected into the superior caval vein in the pregnant rats. Forty-five min after the injection, the mother rats were decapitated and the fetal brains were taken out for autoradiography. The [14C]DG uptake was significantly influenced by maternal thermal stimulation in the hypothalamus and not in other brain regions examined such as the cerebral cortex, the basal ganglia and the limbic nuclei. Glucose utilization in the fetal anterior hypothalamus, paraventricular hypothalamus and dorsomedial hypothalamus significantly increased when the mother rat was exposed to heat compared to when the mother rat was in the thermoneutral condition. During maternal cooling, glucose utilization in the ventromedial hypothalamus and dorsomedial hypothalamus significantly decreased. There was no area activated by cooling and/or inhibited by warming. Compared to a similar study in adult rats (Am. J. Physiol., 248 (1985) R84-92), the present results suggest that although the perinatal fetal brain does not respond to thermal stimulation in terms of glucose utilization as fully as the adults, a few hypothalamic nuclei have already acquired thermal responses, which might be a possible neuronal basis for the thermoregulatory responses just after birth in rats.

Brain regions involved in the development of acute phase responses accompanying fever in rabbits.

1. The effects of microinjection of rabbit endogenous pyrogen and human recombinant interleukin-1 alpha on rectal temperature and acute phase responses were extensively examined in forty different brain regions of rabbits. The acute phase responses that were investigated were the changes in plasma levels of iron, zinc and copper concentration and the changes in circulating leucocyte count. 2. The rostral hypothalamic regions, such as nucleus broca ventralis, preoptic area and anterior hypothalamic region, responded to the microinjection of endogenous pyrogen or interleukin-1 by producing both fever and acute phase responses. 3. The microinjection of endogenous pyrogen or interleukin-1 into the rostral hypothalamic regions significantly decreased the plasma levels of iron and zinc concentration 8 and 24 h after injection. The circulating leucocyte count increased 8 h after injection. However, neither the injections of endogenous pyrogen nor interleukin-1 affected the number of red blood cells. 4. The present results show that the rostral hypothalamic regions respond directly to endogenous pyrogen or interleukin-1 with the consequent development of fever and acute phase responses.

Responses of thalamic neurons in rats to skin cooling and hypothalamic temperature.

The responses of rat thalamic neurons to skin cooling were electrophysiologically examined. The responses of cold-excited neurons were classified into two types. One is a steplike response in which the activity abruptly increases with skin cooling, and the other is a graded response in which the activity gradually increases with skin cooling. The sites of these neurons were histologically identified in the ventrobasal complex of the thalamus, ventrolateral thalamus, and posterior thalamus. Two-thirds of them were found in a marginal region of the ventrobasal complex. There is no specific localization between the sites of thalamic neurons showing the steplike response and those showing the graded response. Furthermore, the effects of hypothalamic temperature on the thalamic neurons responding to skin cooling were observed. The response of thalamic neurons to cold stimulation of the skin was markedly suppressed during the hypothalamic warming. These results show that the steplike response is related to converting thermal analog signals to digital signals and that the graded response is related to relaying analog patterns of cold signals. Thermal afferent signals are modulated by hypothalamic temperature and subsequently cold sensation is modulated.

Changes in hypothalamic temperature modulate the neuronal response of the ventral thalamus to skin warming in rats.

1. The influence of hypothalamic temperature on the activity of warm-excited neurones, which responded to skin warming with an increased firing rate, in the ventro-basal (VB) complex of the thalamus of rats was examined electrophysiologically. 2. The warm-excited neurones were classified into three types: hypothalamus-cold neurones in which the firing rate increased with hypothalamic cooling, hypothalamus-warm neurones in which the firing rate increased with hypothalamic warming and hypothalamus-insensitive neurones in which the firing rate was not affected by hypothalamic temperature. The majority of hypothalamus-cold and hypothalamus-warm neurones increased their firing rate at hypothalamic temperature below and above 38 degrees C, respectively. 3. The threshold temperature at which hypothalamus-warm neurones responded to skin warming was lowered by hypothalamic warming. However, hypothalamus-cold neurones responded to lower skin temperatures during hypothalamic cooling. 4. These results show that the neuronal activity of the VB complex in the thalamus, responding to skin warming, is affected by hypothalamic temperature. Thus thermal information from the peripheral thermoreceptors is modulated by hypothalamic temperature at the level of the relay nuclei of the thalamus.

Separate mechanisms inside and outside the blood-brain barrier inducing metabolic changes in febrile rabbits.

1. We investigated the acute phase response induced by either intravenous (I.V.) or intracerebroventricular injections of bacterial endotoxin or endogenous pyrogen. These caused either monophasic or biphasic fever, and the response includes changes in plasma concentration of iron, zinc, copper, fibrinogen and in circulating leucocyte count.2. The I.V. injection of a small dose of endotoxin or endogenous pyrogen produced a monophasic fever, while a large dose produced a biphasic fever. The ventricular injection of endogenous pyrogen produced a fever similar to the second phase of the biphasic fever.3. The I.V. injection of a small dose of endotoxin or endogenous pyrogen produced a low plasma zinc 8 h after injection, while the ventricular injection of endogenous pyrogen produced a low plasma zinc 24 h after injection. The I.V. injection of a large dose of endotoxin or endogenous pyrogen induced a low plasma zinc 8 and 24 h after injection, suggesting that the hypozincaemia induced by the large dose was mediated by both peripheral and central action of endogenous pyrogen with different time courses.4. The I.V. injection of the small dose did not affect the level of the plasma copper concentration but the I.V. injection of the large dose and the ventricular injection increased it 24 h after injection. It is considered that the plasma copper concentration is mainly controlled by the central action of endogenous pyrogen.5. The changes in the plasma iron and fibrinogen concentration and the circulating white blood cell count induced by the different doses and by the different routes showed very similar patterns, indicating that these are simultaneously controlled by both peripheral and central actions of endogenous pyrogen.6. The present results show that there are two separate mechanisms involved in the acute phase response, one inside and one outside the blood-brain barrier. From the consideration that endogenous pyrogen released from the phagocytic leucocytes induces fever and acute phase response by its action on both the peripheral target organs and the central nervous system, it is suggested that endogenous pyrogen acts both centrally and peripherally, in the same manner as other hormonal agents such as corticosteroids.

Fever and acute phase response induced in rabbits by human recombinant interferon-gamma.

1. Intravenous (I.V.) and intracerebroventricular (I.C.V.) injections of human recombinant interferon-gamma (IFN-gamma) produced dose-dependent fevers in rabbits. The fever induced by I.V. injection was monophasic and the maximum elevation occurred 80-110 min after injection. The fever induced by I.C.V. injection was observed from about 20 min after injection and was remarkably prolonged over 4 h. 2. The development of pyrogenic tolerance to IFN-gamma was observed when rabbits were given I.V. injections on 3 successive days. Furthermore, the pyrogenicity of IFN-gamma was significantly attenuated by heating at 60 degrees C for 40 min. The I.V. injection of IFN-gamma enhanced the febrile response induced by endotoxin but had no effect on that induced by endogenous pyrogen. 3. The I.V. injection of a large dose of IFN-gamma (6 x 10(6) units/kg) induced an acute phase response, which included a reduction in plasma concentration of iron and zinc. 4. The present results suggest that IFN-gamma released from lymphocytes is one of the endogenous mediator proteins responsible for producing fever and acute phase response.

Effects of endogenous pyrogen and prostaglandin E2 on hypothalamic neurons in rat brain slices.

We investigated the effects of endogenous pyrogen and prostaglandin E2 (PGE2) on the preoptic and anterior hypothalamic (POAH) neurons using brain slice preparations from the rat. Partially purified endogenous pyrogen did not change the activities of most of the neurons in the POAH region when applied locally through a micropipette attached to the recording electrode in proximity to the neurons. This indicates that partially purified endogenous pyrogen does not act directly on the neuronal activity in the POAH region. The partially purified endogenous pyrogen, applied into a culture chamber containing a brain slice, facilitated the activities in 24% of the total neurons tested, regardless of the thermal specificity of the neurons. Moreover, PGE2 added to the culture chamber facilitated 48% of the warm-responsive, 33% of the cold-responsive, and 29% of the thermally insensitive neurons. The direction of change in neuronal activity induced by partially purified endogenous pyrogen appears to be almost the same as that induced by PGE2 when these substances were applied by perfusion to the same neuron in the culture chamber. These results suggest that partially purified pyrogen applied to the perfusate of the culture chamber stimulates some constituents of brain tissue to synthesize and release prostaglandin, which in turn affects the neuronal activity of the POAH region.

Evidence for separate mechanisms of induction of biphasic fever inside and outside the blood-brain barrier in rabbits.

1. Intravenous bacterial endotoxin, or endogenous pyrogen, in high concentration both caused biphasic fever in rabbits. In low concentration they produced only the first phase of fever. 2. Subcutaneous indomethacin suppressed the first phase of fever produced by high concentration of intravenous endotoxin or endogenous pyrogen, but not the second phase. 3. Intraventricular cerebral injection of indomethacin reduced the second phase of fever produced by high concentration of intravenous endotoxin or endogenous pyrogen, but not the first phase. 4. Intraventricular cerebral injection of endotoxin or of endogenous pyrogen caused slow monophasic fever. This was suppressed by intraventricular, but not by subcutaneous, indomethacin. 5. It is concluded that the first phase of biphasic fever is caused by pyrogen acting via structures outside the blood-brain barrier, presumably peripheral nerves, and the second phase by pyrogen acting via structures within the blood-brain barrier, presumably hypothalamic neurones.

Suppression of non-shivering thermogenesis in the rat by heat-seeking behaviour during cold exposure.

Changes in rectal temperature (Tre) during cold exposure (0 +/- 1 degrees C) were observed in three groups of rats: heat-seeking, no-behaviour and semi-restrained groups. Significant increases in Tre were observed in the no-behaviour and the semi-restrained groups during cold exposure. In the heat-seeking behaviour group Tre remained constant during cold exposure. The increased Tre in the semi-restrained group during cold exposure was markedly attenuated by the systemic injection of beta-blocker (propranolol: 10 mg/kg, I.P.), indicating that this increase of Tre was caused by activation of non-shivering thermogenesis (n.s.t.). Furthermore, the rise in Tre in the semi-restrained group was preceded by a greater increase in the temperature of the interscapular brown adipose tissue. Using the autoradiographic [14C]deoxyglucose technique, it was revealed that the enhanced n.s.t. in the no-behaviour and the semi-restrained groups was accompanied by a significant increase of metabolic activity in the anterior part of the ventromedial hypothalamus. We conclude that during cold exposure motionlessness of slightly restrained animals increase n.s.t. when thermoregulatory behaviour to gain heat is not available. This increased n.s.t. is mediated by activation of hypothalamic function.

Effect of amine on temperature-responsive neuron in slice preparation of rat brain stem.

Using slice preparations we investigated the effect of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) on thermoresponsive neurons in the hypothalamus, midbrain, and the medulla oblongata. NE inhibits the activities of most of the warm-responsive neurons (11 out of 13 neurons) but 5-HT activates the warm-responsive neurons (10 out of 11 neurons) in the hypothalamus. However, the direction of neuronal response of the midbrain was opposite of that in the hypothalamus when 5-HT was applied. In the medulla oblongata, 5-HT facilitates both warm- and cold-responsive neurons and NE facilitates or inhibits these neurons in equal proportions. Furthermore, the dose-response relationships were determined using slice preparations. In the hypothalamus and the midbrain, NE and 5-HT started to effect the warm-responsive neurons at the minimum concentration of 5 X 10(-6) M, whereas the maximum responses were obtained at the concentration of 5 X 10(-5) M. In the medulla oblongata, NE or 5-HT changed the activities of the warm-responsive neurons in the range of 5 X 10(-5) to 10(-3) M or 10(-6) to 10(-5) M, respectively. It is concluded that the thermoresponsive neurons respond to 5-HT and NE in different ways, at both various levels in the central nervous system and the applied concentration of amines.

[14C]deoxyglucose incorporation into rat brain regions during hypothalamic or peripheral thermal stimulation.

The central nervous structures involved in thermoregulatory responses induced by hypothalamic or peripheral thermal stimulation were investigated in conscious rats by means of the 2-deoxy-D-[14C]glucose ([14C]-DG) autoradiographic technique. According to autoradiographs, many brain regions with significant increases or decreases in [14C]-DG incorporation were observed during thermoregulatory responses. Based on the present changes in [14C]-DG incorporation of brain regions obtained from two kinds of thermal stimulation, the following conclusions were drawn. 1) The medial preoptic area and the medial forebrain bundle are common sites for development of thermoregulatory responses being activated during cooling and warming. 2) The anterior hypothalamic area is activated during hypothalamic or peripheral warming and not during cooling. 3) The ventromedial hypothalamus, dorsomedial thalamus, caudate-putamen, globus pallidus, pars compacta of the substantia nigra, red nucleus, and the midbrain reticular formation are activated with hypothalamic or peripheral cooling. 4) The lateral preoptic area, suprachiasmatic nucleus, ventroposteromedial thalamus, pars reticulata of the substantia nigra, and the hippocampus change their activities only during peripheral cooling and warming.