Effects of hypoxia and ambient temperature on gaseous metabolism of newborn rats.

Whole body metabolic rate was measured by open-flow respirometry in 2-day-old rats at ambient temperatures (Ta) between 40 and 15 degrees C, changed at a rate of 0.5 degrees C/min, during normoxia or hypoxia (10% inspired O2). In normoxia, the thermoneutral range was found to be very narrow, at around 33 degrees C, suggesting a limited effectiveness in the mechanisms controlling heat dissipation. At lower or higher Ta, metabolism was at first increased; this increase could be maintained for at least 30 min at 30 and 35 degrees C, i.e., slightly below or above thermoneutrality, but it was not maintained at lower Ta. The metabolic response to Ta was not sufficient to maintain body temperature (Tb). In hypoxia, at all Ta, oxygen consumption (VO2) was consistently less than in normoxia and was linearly related to Ta (Q10 approximately 1.4). The rat's specific heat was 4 J.g-1.degrees C-1, and the time constant of passive heat exchange was 2.2 +/- 0.5 min; from these values it was calculated that the normoxic VO2 of the 2-day-old rat could be per se sufficient to maintain Tb of 35-36 degrees C at Ta of 33 degrees C, while at lower Ta the metabolic response could not be adequate to maintain Tb. In hypoxia, Tb was directly dependent on Ta.(ABSTRACT TRUNCATED AT 250 WORDS)


Entrainment of respiratory rhythm by periodic lung inflation: effect of airflow rate and duration.

In anesthesized, paralyzed, and mechanically ventilated rabbits, the rate and duration of airflow were varied to investigate the effect on the central respiratory rhythm during 1:1 entrainment (1 phrenic nerve burst for 1 pump inflation). Our results showed that 1) the largest range of 1:1 entrainment was obtained with the longest inflation durations associated with the lowest flow rates and 2) both inspiratory (TI) and expiratory (TE) durations (as estimated by the period of phrenic nerve activity and phrenic nerve silence, respectively) increased when total respiratory duration (TT = TI+TE) increased. The phase relationships we studied were DI (the time elapsing between the onset of phrenic activity and the beginning of pump inflation) and DE (the time between the end of phrenic activity and the end of pump inflation). Both DI and DE increased when the total ventilatory period increased. However, for constant ventilatory period, DI changed with the rate and duration of airflow, whereas DE remained constant. In addition, under these conditions, TI, TE, and the integrated phrenic nerve activity remained constant independently of airflow rate and duration. The present results are discussed with regard to the pulmonary receptors (slowly and rapidly adapting receptors and C fibers) that are stimulated during mechanical ventilation, and hypotheses are drawn regarding their possible contribution to rhythm generation and the mechanism through which they may act.


Carotid baroreflexes and plasma vasopressin in humans during head-up tilt.

To investigate the influence of carotid baroreflexes on plasma arginine vasopressin (AVP) in humans, eight healthy males underwent two sessions of passive head-up tilt to 60 degrees for 15 min each. During one of the sessions (sequence randomized), carotid baroreflexes were simultaneously stimulated by static neck suction of 23 +/- 1 mmHg during the whole period of head-up tilt. Only subjects who did not develop presyncopal symptoms during head-up tilt were included. Head-up tilt increased AVP significantly from 1.0 +/- 0.3 to 4.2 +/- 1.3 pg/ml (P less than 0.05). In contrast to this, AVP did not at any point in time increase significantly during head-up tilt when neck suction was applied. Plasma renin activity and heart rate were unaffected by neck suction, whereas mean arterial pressure and central venous pressure decreased. We conclude that the moderate but significant increase in plasma AVP during nonhypotensive head-up tilt is in part mediated by deloading of carotid baroreceptors induced by the acute fall in hydrostatic pressure at the level of the carotid sinus.


Neural regulation of the vas deferens in the rat: an electrophysiological analysis.

Electrophysiological analysis of the neural control of the vas deferens was performed in urethan-anesthetized rats. Intraluminal distension (0.2 ml/min) or electrical stimulation of hypogastric (threshold 1-5 V, 20 Hz) and pelvic nerves (2-5 V, 20 Hz) produced contractions of the vas deferens. Distension-evoked contractile activity was not abolished by nicotinic ganglionic blockade or ipsilateral hypogastric and pelvic nerve transection. Contractions following hypogastric nerve stimulation were abolished by prazosin, while pelvic nerve-evoked responses were partially blocked by atropine. Hypogastric nerve, pelvic nerve, and sympathetic chain stimulation evoked volleys with latencies of 10-30 ms in vasal nerves. Crude estimates for conduction velocities for these responses (less than 0.5 m/s) corresponded to activation of unmyelinated C-fibers. Stimulation of the dorsal nerve of the penis (DNP) (10-16 V, 10-40 Hz) or administration of 5-methoxy-N,N-dimethyltryptamine, both of which produce seminal emission, elicited reflex discharges in nerves to the vas deferens. Hypogastric nerve but not pelvic nerve transection abolished both spontaneous and evoked (105- to 380-ms latency) reflex activity. These experiments provide insight into the organization of afferents in the DNP and efferents conveyed by autonomic pathways that regulate male reproduction.


Weakness of short-term synchronization among respiratory nerve activities during fictive vomiting.

In decerebrate, paralyzed cats, phrenic (PHR) and lumbar abdominal (ABD) nerve discharges during both neural respiration and fictive vomiting (FV) were subjected to spectral and coherence analyses. During respiration, PHR discharge exhibited high-frequency oscillation (HFO), manifested as a narrow spectral peak (range 57-90 Hz) in autospectra and left-right coherence spectra. During FV, the following occurred: 1) the HFO peak disappeared and was replaced by a broad peak with higher modal frequency (range 84-120 Hz), indicating elimination of inputs from the medullary inspiratory pattern generator. 2) Left-right PHR coherence spectra had no distinct peaks, indicating that correlations between opposite PHR discharges were now not frequency specific. 3) Although ABD and PHR autospectra were similar, PHR-ABD coherences were near zero, indicating lack of common inputs on a short time scale. 4) Nonzero coherences between ABD nerves were confined to ipsilateral pairs. Thus coherence analysis indicates that the outputs of the vomiting pattern generator are temporally dispersed on a short time scale and are not necessarily common to different motoneuron populations.


Divergent effects of intravenous GSH and cysteine on renal and hepatic GSH.

There is a growing interest in the therapeutic use of sulfhydryls. To assess the effect of glutathione (GSH) and cysteine on the cellular thiol status, thiols were administered intravenously to rats in doses ranging from 1.67 to 8.35 mmol/kg with and without pretreatment with 4 mmol/kg buthionine-[S,R]-sulfoximine (BSO), an inhibitor of GSH synthesis. One hour after administration of 1.67 mmol/kg GSH, the concentration of GSH rose from 5.2 +/- 1.0 to 8.4 +/- 0.9 mumol/g and from 2.5 +/- 0.5 to 3.7 +/- 0.7 mumol/g in liver and kidneys, respectively. After 8.35 mmol/kg, hepatic GSH did not increase further, but renal GSH rose to 6.7 +/- 1.8 mumol/g. Infusion of cysteine increased hepatic GSH to the same extent as intravenous GSH, but renal GSH did not increase after 1.67 mmol/kg and even significantly decreased to 0.6 +/- 0.2 mumol/g after 8.35 mmol/kg. In the presence of BSO, GSH resulted in a significant increase in renal but not hepatic GSH, suggesting that the kidneys take up intact GSH and indicating that the increment in hepatic GSH was due to de novo synthesis. The present data show that hepatic GSH can be markedly increased in vivo by increasing the supply of cysteine. Measurements of hepatic cysteine indicate that up to a concentration of approximately 0.5 mumol/g cysteine is a key determinant of hepatic GSH, such that the physiological steady-state concentration of GSH in the liver appears to be mainly determined by the availability of cysteine. At higher concentrations GSH does not increase further, possibly due to feedback inhibition of GSH synthesis or increased efflux.(ABSTRACT TRUNCATED AT 250 WORDS)


Daily torpor in the absence of the suprachiasmatic nucleus in Siberian hamsters.

Siberian hamsters express torpor spontaneously after several weeks of exposure to short days. In long days, torpor is expressed only when food intake is restricted. Hamsters maintained in a long photoperiod (16 h light/day) at 15 degrees C expressed daily torpor during food restriction both before and after bilateral ablation of the suprachiasmatic nucleus (SCN). Hamsters housed in short days (8 h light/day, ambient temperature 15 degrees C) and fed ad libitum displayed torpor before, but not after, ablation of the SCN (SCNX). Torpor was reinstated in all short-day SCNX hamsters during postoperative food restriction and persisted in several animals even after ad libitum feeding was reinstated. Torpor was entrained to the light-dark cycle in both long- and short-day hamsters preoperatively but appeared to occur in a temporally random fashion in SCNX animals. SCNX hamsters, unlike control animals, displayed multiple torpor bouts per 24 h. The SCN is not essential for the expression of torpor but plays a crucial role in its temporal organization.


Catecholamine depletion of the diagonal band reduces baroreflex inhibition of supraoptic neurons.

In the rat, neurons in the diagonal band of Broca (DBB) participate in baroreceptor-induced depression of spontaneous activity of vasopressin neurons in the supraoptic nucleus (SON). The present study examined the role of the catecholaminergic innervation of the DBB in this response. Male rats were anesthetized with pentobarbital (50 mg/kg ip) and stereotaxically injected in the DBB with either vehicle (2 microliters), 6-hydroxydopamine (6-OHDA; 4 micrograms/2 microliters), or 6-OHDA preceded 20 min earlier by desimipramine (25 mg/kg ip), a norepinephrine uptake inhibitor. Two weeks later, the rats were reanesthetized and a transpharyngeal approach was used for extracellular recording from SON neurons. In vehicle-injected controls, baroreceptor stimulation produced by brief increases in blood pressure from metaraminol injections (10 micrograms/10 microliters iv) transiently arrested the spontaneous activity of 24 of 24 phasically active neurons tested. Sixty-three percent of the vasopressin neurons were not affected by comparable increases in blood pressure in 6-OHDA-treated rats, and the norepinephrine content of the DBB was significantly reduced. In experiments with desimipramine-pretreated rats, 92% of the vasopressin neurons were silenced by increases in blood pressure while the norepinephrine content of the DBB was not affected. Thus the noradrenergic innervation of DBB appears to participate in the baroreceptor sensitivity of SON vasopressinergic neurons.


Arterial chemoreceptor input to nucleus tractus solitarius.

The arterial chemoreceptors play an important role in the reflex regulation of blood pressure and respiration. To investigate the initial integration of chemoreceptor inputs within the central nervous system, intracellular recordings were obtained in pentobarbital-anesthetized, paralyzed, and mechanically ventilated cats, from 58 cells within the nucleus of the tractus solitarius (NTS) that were depolarized by activation of the ipsilateral carotid body chemoreceptors. Close arterial injection of less than 100 microliters CO2-saturated bicarbonate evoked depolarizations of membrane potential with amplitudes of 2.2-4.6 mV and durations of 1.8-6.7 s in 46 cells. In 12 cells, activation of the carotid body chemoreceptors evoked a depolarization-hyperpolarization sequence. Electrical stimulation of the carotid sinus nerve (500 microA, 0.2 ms) evoked EPSPs [mean latency 6.4 +/- 0.5 (SE) ms; range 2.1-18.4 ms] in 46 cells and EPSP-IPSPs (7.3 +/- 0.8 ms; range 4.2-12.4 ms) in 12 cells. The distribution of EPSP latencies exhibited two peaks, one in the 2- to 4-ms range and another in the 7- to 8-ms range. Twenty-nine chemoreceptive cells were tested for the presence of convergent inputs from the ipsilateral carotid sinus baroreceptors. No evidence was found of a convergent postsynaptic inhibitory input from the baroreceptors within the NTS; however, seven cells were found that received an excitatory input from the baroreceptors. The observation that NTS neurons do not integrate chemoreceptor afferent inputs in a homogeneous manner suggests that the multiplicity of NTS unit responses might be related to the specific reflex function of an individual cell (e.g., vagal or sympathetic outflow, respiration).(ABSTRACT TRUNCATED AT 250 WORDS)


Vasopressin and fetal cerebrovascular regulation.

Vasopressin (AVP) may increase cerebral blood flow (CBF) during hypoxemia by selective dilatation of cerebral vessels via endothelium-derived relaxing factor (EDRF) release. To test whether this action is relevant in the fetus, we produced isocapnic hypoxemia in halothane-anesthetized pregnant ewes. Fetal infusion of a V1 AVP antagonist reduced by 55% the increase in CBF during fetal hypoxemia. To test the role of this response during development, we examined the response to AVP in intact and endothelium-denuded femoral and basilar arterial rings in vitro from fetal, newborn, and adult sheep. AVP constricted femoral rings in an endothelium-independent manner, with increased potency in newborn and fetal compared with adult rings. AVP relaxed basilar rings in an endothelium-dependent manner, which was unaffected by indomethacin treatment, with increased potency in newborn and adult compared with fetal rings. We conclude that fetal cerebral vascular endothelium is functional and responsive to AVP and that circulating AVP during fetal hypoxemia contributes to increased CBF via this effect.


Bile is essential for lipid assimilation in Leach's storm petrel, Oceanodroma leucorhoa.

A tritium-labeled glycerol triether was tested as a non-absorbable lipid marker for studies of neutral lipid absorption in normal and cholestryamine-induced steatorrhic chicks of Leach's storm petrel (Oceanodroma leucorhoa). Absorption of triacylglycerol and wax ester (96 +/- 4.2 and 94 +/- 2.1%, respectively) in normal chicks was indistinguishable. Absorption of neutral lipids decreased with increasing quantities of resin, and with the highest dosage (14% wt/wt) less than 30% of dietary lipids were assimilated. The concentration of bile salts (greater than 500 mM) in the gallbladder of Leach's storm petrel is among the highest recorded. The bile salts are predominantly taurine conjugates of chenodeoxycholate and cholate. Biliary cholesterol levels are within the range observed in humans although biliary phospholipid levels are lower and triglyceride levels are higher. Extensive retrograde movement of duodenal contents and biliary secretions to the gizzard and proventriculus were found. Although similarities in fat and bile salt assimilation exist between seabirds and mammals, there do exist differences that make non-polar lipid assimilation (i.e., wax esters) more efficient in seabirds.


Purification and biological activity of alligator bradykinin.

Incubation of plasma form the alligator (Alligator mississipiensis) with glass beads in the presence of a kininase inhibitor resulted in the activation of the kallikrein-kinin system and generation of bradykinin-like immunoreactivity. The kinin peptides were purified to homogeneity and were shown to comprise [Thr6]-bradykinin and des-Arg9[Thr6]bradykinin in the molar ratio of approximately 10:1. Bolus injections of synthetic [Thr6]bradykinin into the jugular vein of the anesthetized alligator resulted in a dose-dependent decrease in mean arterial blood pressure. The minimum dose of kinin producing a significant fall in pressure was 0.07 micrograms/kg body wt and the maximum response (25 +/- 6% fall; mean +/- SD, n = 8) was produced by a dose of 0.56 micrograms/kg body wt. The dose producing a half-maximum response was 0.19 +/- 0.08 micrograms/kg. The data indicate that alligator plasma contains all the components of the kallikrein-kinin system found in mammals and suggest that the system may be of physiological importance in the regulation of cardiovascular function in these reptiles.


Renal afferent input to the ventrolateral medulla of the cat.

Experiments were performed to determine if information from the kidneys projects to the rostral ventrolateral medulla. Extracellular action potentials were recorded from 148 cells within the rostral ventrolateral medulla of alpha-chloralose-anesthetized cats. Cells within the rostral ventrolateral medulla were tested for responses to electrical stimulation of both left and right renal nerves. Electrical stimulation of renal nerves excited 144 cells (97.3%) and inhibited 4. The majority of cells received either bilateral or contralateral renal nerve input. Cells with bilateral renal nerve input responded to contralateral renal nerve stimulation with a significantly greater number of impulses compared with ipsilateral renal nerve stimulation (P less than 0.05). All cells but one responding to renal nerve stimulation had convergent somatic input. Comparisons between thresholds for cell responses and activation thresholds for the A and C volleys of the compound action potential recorded in the least splanchnic nerve revealed that 44 cells required activation of A delta-fibers, and 12 cells required activation of both A delta- and C-fibers. A conditioning stimulus applied to renal nerves on one side significantly decreased the response elicited by a test stimulus applied to the renal nerves on the opposite side for at least 300 ms (P less than 0.05). The demonstration that an afferent connection exists between the kidneys and the ventrolateral medulla suggests that the rostral ventrolateral medulla may play a role in mediating supraspinal reflexes of renal origin.


Endotoxin-induced fever is modulated by endogenous glucocorticoids in rats.

This study was designed to determine if the febrile response, similar to the inflammatory response, can be modulated by endogenous glucocorticoids. A single intraperitoneal injection of lipopolysaccharide (LPS, 200 micrograms/kg) induced a significant increase in rectal temperature of unrestrained rats maintained within the thermoneutral zone. The febrile response was fully abolished following treatment with a glucocorticoid, dexamethasone (DEX), but was not affected by a mineralocorticoid, deoxycorticosterone acetate (DOCA). Adrenalectomized (ADX) rats were markedly more sensitive to the lethal effects of LPS (200 micrograms/kg), such that all the animals died during the course of the experiment. In addition, ADX rats showed an enhanced febrile response to LPS (10 micrograms/kg ip) in comparison with sham-operated or adrenal-demedullated rats. This enhanced response was reduced by chronic or acute treatment with DEX, but not DOCA. LPS (10 micrograms/kg) also induced a marked rise in plasma corticosterone levels in control rats. In contrast, ADX rats displayed very low plasma corticosterone levels, which were not changed by LPS. In conclusion, the present results reveal that endogenous glucocorticoids are important modulators of LPS-induced fever.


High-intensity light for circadian adaptation to a 12-h shift of the sleep schedule.

Male subjects had their sleep schedules shifted 12 h to accommodate eight or more consecutive simulated night shifts. They were exposed to artificial light (approximately 5,000 lux, 3- to 6-h durations) each night, slept at home in very dark bedrooms during the day, and wore dark welders goggles whenever they went outside during daylight. Body temperature was continuously measured, and daily questionnaires provided estimates of sleep time and mood. The circadian temperature rhythm phase shifted, usually approximately 2 h/day, in 21 of 24 subjects. The temperature rhythms of the other three subjects appeared to remain entrained to the 24-h zeitgebers. In the subjects whose temperature rhythms shifted, the direction of shift (advance or delay) depended on the timing of light exposure relative to the baseline temperature phase, consistent with a phase-response curve. Sleep was disturbed, and fatigue was increased during the first few days after the shift of the sleep-wake schedule.


Splanchnic nerve response to A5 area stimulation in rats.

Microinjection of the excitatory amino acid N-methyl-D-aspartate (NMDA, 0.5 nmol) into ventrolateral pons (the A5 area) of halothane-anesthetized, paralyzed rats increased splanchnic (sSND) and renal sympathetic nerve discharges (approximately 45%) and usually decreased lumbar SND. These effects were accompanied by 1) regionally specific changes in vascular resistances, 2) an increase in the gain of the sympathetic baroreflex, and 3) modest reductions in blood pressure and heart rate. sSND activation was greatest when NMDA injections were made in the vicinity of A5 noradrenergic (NE) cells. Injection of 6-hydroxydopamine (6-OH-DA) into A5 area (after 15 days) destroyed 83% of NE neurons and reduced NMDA activation of sSND by 76%. Stimulation of sSND by NMDA in A5 area was reduced 1) 1-2 h after bilateral intraspinal injection of 6-OHDA, but not vehicle or 5,7-dihydroxytryptamine, and 2) by administration of prazosin [alpha 1-NE receptor antagonist, 1 mg/kg iv or 10-20 micrograms intrathecal (it)], but not by idazoxan (alpha 2-NE receptor antagonist, 10-20 micrograms it) or propranolol (0.2 mg/kg iv). We conclude that A5 NE cells have a visceral vasomotor sympathoexcitatory function mediated in large part by their spinal projection.


Cholecystokinin (CCK-8) affects gastric pressure and ratings of hunger and fullness in women.

Cholecystokinin (CCK) may affect food intake by augmenting neural activity from the distended stomach, thereby amplifying satiety signals. To test the hypothesis that subjects would report more fullness and less hunger with gastric distension when CCK-8 (112 ng/min) was infused than when saline was infused, a gastric balloon was inflated in the stomachs of four women. When the balloon was inflated to 500 ml, there was no difference in gastric pressure between the CCK-8 and saline conditions. Nonetheless, ratings of fullness were higher with CCK-8 administration. When the balloon was inflated to the maximum volume tolerated, the pressure rise was significantly smaller with CCK-8 infusion. In addition, fullness ratings rose and hunger ratings declined more steeply in relation to gastric pressure when CCK-8 was infused. In all conditions, gastric contractions were practically abolished with CCK-8 infusion. CCK-8 relaxed the stomach and concurrently sensitized the subjects to gastric pressure.


Thyroid function during L-asparaginase therapy in children with acute lymphoblastic leukemia: difference between induction and late intensification.

Parameters of thyroid function were measured in nine children during induction therapy for acute lymphoblastic leukemia (ALL). Seven patients were reevaluated during the late intensification phase. Vincristine, anthracycline drugs (daunorubicin and adriamycin), corticosteroids, and L-asparaginase were used in the two phases of therapy. During induction, L-asparaginase (5,000 U/m2) was given daily on days 1-21. During late intensification, the drug was given on days 1, 4, 8, and 11 (10,000 U/m2). During induction, total T4 significantly decreased from 10.1 +/- 2.3 to 4.0 +/- 1.0 micrograms/dl, FT4 decreased from 1.4 +/- 0.3 to 0.7 +/- 0.2 ng/dl, total T3 decreased from 134 +/- 32 to 57 +/- 21 ng/dl, and thyroxine binding globulin (TBG) decreased from 2.1 +/- 0.6 to 0.8 +/- 0.3 mg/dl. During late intensification therapy, significant decreases in T3 (from 180 +/- 26 to 93 +/- 40 ng/dl) and TBG (from 1.9 +/- 0.5 to 1.1 +/- 0.5 mg/dl) were observed, but there were no significant changes in T4 and FT4. We conclude that during induction, the impairment of thyroid function is attributable to L-asparaginase, whereas during late intensification, low T3 and low TBG is due to glucocorticoid administration.


Limb deformity and metaphyseal abnormalities in thalassaemia major.

Regular bone survey radiographs have allowed identification of limb deformity and metaphyseal changes in several patients with thalassaemia major treated at the Adelaide Children's Hospital. Following the progression of limb deformity in five of these patients who were receiving human growth hormone therapy, the records of 25 thalassaemia patients were reviewed. Six patients had evidence of limb deformity, four of whom also had metaphyseal changes. Three additional patients had metaphyseal changes alone. Patients with either type of skeletal change shared similar characteristics, including younger age, earlier commencement of desferrioxamine therapy, better compliance and, in general, lower levels of ferritin. Females predominated in both groups. The frequency of sensorineural hearing loss was similar in affected and nonaffected groups and biochemical parameters, especially plasma calcium, phosphate, alkaline phosphatase, and zinc, which were normal in all patients. The cause of these skeletal changes is not clear; however, several potential factors need to be considered. Among these are focal marrow expansion in the metaphyseal region due to incomplete suppression of erythropoiesis and possible effects of desferrioxamine, including direct interference with bone growth, altered response of bone to inflammation or infection, and altered bone metabolism related to chelation of trace metals. While we can only speculate on aetiological factors, it is clear that human growth hormone therapy has resulted in exaggeration of deformity due to an increased rate of bone growth or decreased rate of mineralization of physeal cartilage. We believe that bone survey radiographs are useful in early identification of skeletal changes.(ABSTRACT TRUNCATED AT 250 WORDS)


Continued remission in children with neuroblastoma despite elevations of urinary catecholamine metabolites.

Our experience at the Children's Hospital of Pittsburgh with a patient with neuroblastoma suggested that renewed elevations of urinary catecholamine metabolites may not necessarily be an indication of progressive disease. To test this possibility, we reviewed the courses of children with neuroblastoma who achieved a clinical status of "no evidence of disease" (NED), and in whom homovanillic acid (HVA) and/or vanillylmandelic acid (VMA) levels were subsequently noted to exceed normal limits initially in the presence of normal restaging studies. Five patients were identified. Of these, one had stage I, one had stage II, two had stage III, and one had stage IV disease at diagnosis. Elevations of their HVA and/or VMA levels following achievement of NED status ranged from 1 1/2 to 4 times maximal normal levels for age, and abnormalities persisted for 17 to 47 months. Only one patient relapsed, while the other four remain disease-free 8-12 years following diagnosis. These results confirm that in patients with neuroblastoma, mild elevations of HVA and/or VMA may be compatible with continuous remission.


Prognostic factors in metastatic neuroblastoma. A multivariate analysis of 182 cases.

The purpose of our study was to investigate the interrelationship of known and possible new risk factors in patients with metastatic neuroblastoma and to define groups at risk. The possible influence of 37 variables on event-free survival (EFS) was analyzed univariately in 308 consecutive patients using the Kaplan-Meier estimate. Fifteen factors were identified (p less than 0.05, logrank greater than 3.84) of whom eight showed a nonrandom correlation to several others (chi 2-test, p less than 0.05). Seven noncorrelated factors [lactate dehydrogenase (LDH) level, resectability of the primary tumor, histologic grade, leukopenia, presence of symptoms, general condition, and age at diagnosis] were included in the multivariate analysis of 182 patients according to the Cox model. The variables LDH (p = 0.0007), resectability (p = 0.0063), histologic grade (p = 0.0055), and leukopenia (p = 0.0470) were identified multivariately as prognostic factors for EFS. These results permitted the classification of patients into three prognostic groups. The 6 year event-free survival for group IV-A (LDH normal) was 0.37 +/- 0.12, for group IV-B (LDH abnormal, additional risk factors favorable) 0.18 +/- 0.10, and for group IV-C (LDH abnormal, 1-3 additional risk factors unfavorable) was 0.08 +/- 0.03. We conclude that the proposed clinicopathological classification may prove to be a reliable and easily applicable tool for estimating the outcome of metastatic neuroblastoma in children.


Continuous epidural anesthesia for postoperative analgesia in the pediatric oncology patient.

When compared with conventional techniques, epidural anesthesia not only provides improved analgesia, but also has several beneficial effects on the postoperative respiratory, cardiovascular, and metabolic status of the patient. Although the efficacy of this technique in children has been demonstrated, extensive experience in the pediatric oncology patient has not been previously reported. We retrospectively reviewed our 2-year experience with epidural analgesia and discuss the techniques involved in implementing this service for the pediatric oncology patient. An epidural catheter was successfully placed in 58 of 60 patients (97%) who ranged in age from 4 months to 19 years and in weight from 4.1 to 68 kg. Postoperative analgesia was provided by a continuous infusion of a bupivacaine/fentanyl mixture, supplemented with intermittent epidural fentanyl by bolus dose as needed. No complications related to epidural catheters were noted. Our review supports the efficacy of this technique for providing postoperative analgesia after various major surgical procedures in the pediatric oncology patient.


Oxygen therapy in sickle cell disease.

The effect of oxygen therapy on the number of irreversibly (ISC) and reversibly (RSC) sickled cells was studied in patients with sickle cell anemia. Inhalation of 50% oxygen in patients who were not in crisis produced a significant fall in RSCs and a lesser fall in ISCs. Twenty-five subjects in sickle cell crisis were chosen at random to receive either oxygen (15 patients) or air (10 patients). Those who received oxygen showed a significant reduction in RSCs, but not in ISCs. No significant change in RSCs or ISCs occurred in the group who received air. Despite the reduction in RSCs in the oxygen-treated group, there was no significant difference between the air and oxygen groups in the duration of severe pain, opioid administration, and hospitalization. It was also observed that crisis was associated with arterial desaturation and a reduction in the number of RSCs. We conclude that, although RSCs may be involved in the pathophysiology of sickle cell crisis, reduction in RSCs by oxygen therapy in these studies did not result in any reduction in the duration of crisis.


Survival of children with chronic myeloid leukemia.

We analyzed survival in 203 children with Philadelphia-chromosome-positive chronic myeloid leukemia (CML). Median survival was 4.1 years; average annual risk of death was 20%. These survival data are similar to those reported in adults. Because there is no possibility of long-term disease-free survival in children with CML with conventional therapies, the findings of this study suggest that bone marrow transplantation should be considered in these patients.


HIV infection of multiply-transfused pediatric oncology patients in a low-prevalence area.

We attempted to determine the occurrence of transfusion-acquired HIV-1 infection in multiply-transfused pediatric oncology patients receiving blood products prior to donor HIV antibody screening in March 1985. We identified 85 multiply-transfused pediatric oncology patients (initially HIV-1 antibody negative) who had received 4,346 transfusions (968 red blood cells, 3,192 platelets, 137 fresh frozen plasma, and 49 leukocytes). Only one (1.2%) of these multiply-transfused pediatric oncology patients seroconverted following transfusion. Transfusion-acquired HIV-1 infection in our multiply-transfused pediatric oncology patients was infrequent despite marked exposure to blood products (average 51.2 donor exposures per multiply transfused pediatric oncology patients) and occurred at a frequency consistent with the prevalence of HIV-1 infection in our donor population (Central Ohio--2 of 10,000 donors were HIV-1 antibody positive). While our findings may not be unexpected, they offer documentation of a lower risk for transfusion-acquired HIV infection in our blood recipients than in some previous studies conducted in areas where donor HIV antibody prevalence is higher. We also document that the efforts associated with performing "Lookback" evaluations (contacting recipients of blood products from donors subsequently identified as HIV antibody positive) are valuable since our only HIV-1-infected, multiply-transfused pediatric oncology patient was identified in this manner.


Growth retardation in childhood leukemia and lymphoma. Special reference to patients with CNS relapse.

We studied the growth of 89 patients who were long-term survivors of childhood leukemia and lymphoma. Eight patients with CNS relapse had a greater decrease in height standard deviation score (SDS) after the relapse than 81 patients without CNS relapse (p less than 0.0001). Two patients who received cranial irradiation when they were younger than 2 years of age demonstrated a marked decrease in height SDS more than 3.0 SD. Five patients appeared to have a decline in height SDS before their CNS relapse. There were no apparent changes in the weight of patients with or without CNS relapse. In endocrine studies, all eight patients with CNS relapse failed to show the normal growth hormone (GH) response to arginine, GH-releasing factor, and glucagon-propranolol tests, while spontaneous GH secretion during sleep was normal. Magnetic resonance imaging (MRI) revealed small pituitary glands in seven patients with CNS relapse. These findings suggest that in leukemia and lymphoma patients with CNS relapse, GH secretion is impaired at the hypothalamic level, resulting in a secondary atrophy of the pituitary gland. The MRI together with selected endocrinologic tests may help to clarify the mechanism of growth impairment in such patients. A decline in height SDS in each patient may be a useful marker for predicting a CNS relapse in a child with leukemia or lymphoma.


Megakaryocytes and megakaryocyte progenitors in human cord blood.

Thrombocytopenia contributes significantly to morbidity in the sick term or preterm infant. However, few data exist on newborn's megakaryocytes and megakaryocyte progenitor cells (CFU-MK). We therefore studied CFU-MK in term and preterm infant cord blood and compared the results with data on CFU-MK from adult bone marrow and adult peripheral blood in a plasma clot culture with postirradiated aplastic canine serum (PIACS) as a source of megakaryocyte colony-stimulating activity. The number of CFU-MK and the number of cells per CFU-MK were counted with an immunofluorescent method at day 12. The effect of T-lymphocyte depletion on cord blood cultures for CFU-MK was studied with PIACS and a partially purified product of PIACS. We also studied individual megakaryocytes from newborns. The number and sizes of circulating megakaryocytes, isolated from adult peripheral blood and term venous cord blood by elutriation, were compared. Term and preterm cord blood contained more CFU-MK than adult peripheral blood. The numbers of CFU-MK in preterm cord blood were comparable to those in adult bone marrow. When the number of cells per colony were compared, cord blood contained significantly more cells than adult marrow CFU-MK. The depletion of T lymphocytes did not significantly change the growth of CFU-MK compared to nondepleted cultures. A substantial number of circulating megakaryocytes were obtained from venous cord blood, though they were significantly smaller than adult peripheral blood megakaryocytes. Since cord blood is easily obtained and contains large numbers of megakaryocytes and CFU-MK, it may provide a convenient model for studying the regulation of fetal megakaryocytopoiesis.


New observations in a child with angiofollicular lymph node hyperplasia (Castleman's disease) originated from the mesenteric root.

Localized plasma cell type Castleman's disease (CD) is an unusual pathologic entity. It is frequently associated with clinical and laboratory characteristics and rarely occurs in children. Total surgical excision results in cure in all aspects. To make early diagnosis of mesenteric CD is not easy, especially for children. An 11-year-old Taiwanese boy was recently evaluated for anemia and delayed growth. His clinical findings included a syndrome of severe hypochromic microcytic anemia, neutropenia, thrombocytosis, hypoferremia, hypergammaglobulinemia, and growth failure. Radiological examinations (abdominal ultrasound, small intestinal series, and computerized tomography) identified hepatosplenomegaly, nephromegaly, and huge masses in the middle abdomen with precaval, celiac, and paraaortic lymph nodal enlargement. However, detailed physical examination failed to detect a mass. At laparotomy a double-fist-sized confluent mass was found arising from the mesenteric root. Most masses were discrete and were excised individually. The pathologic diagnosis was plasma-cell type angiofollicular lymph node hyperplasia (Castleman's disease). Seven weeks after surgery, he had an episode of acute hepatitis B. Postoperatively, he exhibited a dramatic growth spurt; the hemoglobin, red blood cell indices, serum iron, and immunoglobulins returned to normal in 2 months. Neutropenia, which has not been previously related to mesenteric CD, was an unexpected finding in our case; however, it resolved spontaneously 3 months after the surgery, suggesting its causal relationship with the tumor.


Synovial sarcoma associated with osteofibrous dysplasia. A case report and review of the literature.

We report on a 14-year-old boy who demonstrated an unusual association between osteofibrous dysplasia and synovial sarcoma. This case suggests that a patient who presents with osteofibrous dysplasia of the tibia can eventually develop a malignant musculoskeletal tumor in the same anatomical location (same limb). This experience suggests that a patient who presents with osteofibrous dysplasia should be followed up for the possibility of a coexisting synovial sarcoma in the same leg.


Multiple subcutaneous leiomyosarcomas in an adolescent with AIDS.

The case of 17-year-old boy with thalassemia major who contracted the human immunodeficiency virus (HIV) through multiple transfusions is described. Eight years after the onset of generalized lymphadenopathy, and 5 years after the documentation of HIV infection on serologic grounds, he developed the first of multiple, painful, subcutaneous nodules, which proved to be leiomyosarcomas of vascular origin. The histopathology and possible pathogenesis of these unusual tumors are discussed.


Disseminated Langerhans cell histiocytosis in identical twins unresponsive to recombinant human alpha-interferon and total body irradiation.

Monozygotic twin boys presented at 1 year of age with seborrheic skin rash, otorrhea, and hepatosplenomegaly. Skin biopsy confirmed Langerhans cell histiocytosis. Treatment with conventional antineoplastic drugs and with calf thymus extract was ineffective. The disease remained refractory to recombinant human alpha-interferon and to low-dose total body irradiation, and the children died between 3 and 3 1/2 years of age.


Alaska nursing home takes national role in addressing urinary incontinence.

Urinary incontinence affects over half of all residents in the nation's 25,000 nursing homes. While incontinence assessment, treatment and management techniques have been validated under "laboratory" conditions, the practicality of maintaining the systems pose difficulties for most nursing homes. An evaluation of a new automated system for managing urinary incontinence indicates that a nursing home in Anchorage, Alaska, has successfully implemented and maintained the new system for over ten (10) months. Researchers found that The Mary Conrad Center quickly reduced wetness rates in the target group from 25 percent prior to implementation of the program, to about eight percent and have been able to reduce wetness rates to even lower levels in subsequent months. The evaluation provides critical evidence that nursing homes can implement and maintain the comprehensive system. If further testing in other facilities result in similar findings, the system stands to impact the quality of care for over one million nursing home residents affected by urinary incontinence.


DNA flow cytometry of primary tumors and their skin metastases. Correlation of DNA histograms.

The purpose of this study was to determine whether quantification of DNA content would demonstrate conserved patterns in primary tumors and their metastases and to learn whether this technique would be useful in determining if a tumor was metastatic from a previous primary tumor or represented a new neoplasm. The study comprised of all cases nonmelanoma metastatic skin lesions in which the primary tumor was also resected at this hospital between the years 1984 and 1990 (22 cases). Both the primary and metastatic lesions were examined by the deparaffinized flow cytometric technique for DNA content. DNA-aneuploid tumors were considered to correlate if the DNA indices (ratio of aneuploid to diploid peak channels) were within 10%. Thirty-four tumors were DNA-aneuploid; eight tumors were DNA-diploid. We found agreement in 20 of 22 cases (agree--aneuploid: 16 cases; agree--diploid: four cases). In six of our cases the histograms of the primary and the metastatic lesions did not correlate when only one block was examined; however, when three blocks from each site were studied, we found concordance of DNA indices in four cases. There was disagreement in two of 22 cases (disagree--different DNA indices: two cases). In both of these cases, only one block of the primary tumor was available for examination, and the histograms were of marginal quality. This study demonstrates that the histogram pattern (aneuploid versus diploid) of DNA content is highly conserved between primary and metastatic tumors. There was 91% agreement between DNA indices of primary tumors and their metastases (20 of 22 cases) using a 10% correlation criterion.(ABSTRACT TRUNCATED AT 250 WORDS)


Body composition testing of athletes in the field using bioelectric impedance analysis.

Bioelectric impedance analysis was performed as part of the field testing of seventeen athletes competing in the 1990 Iditarod Sled Dog Race. The purpose was to measure initial body composition and the changes that occurred during this extended performance period under Arctic conditions. Four women and thirteen men aged 26-53 years were tested to measure changes in their lean body weight, total body water, total body fat and percent body water. Study results record average body fat losses of 2.14 kg in the male and 1.02 kg in the female racers. Total body water and lean body mass remained stable, while an increase in body water percentage (men: 4.31%, women: 2.78%) was recorded. Though questions remain, bioelectric impedance analysis demonstrates potential for use in future field research projects.


Dysplastic nevus syndrome among Japanese. A case study and review of the Japanese literature.

Three Japanese families with dysplastic nevus syndrome (DNS) are reported. Each family had at least two members with multiple dysplastic nevi (DN). Family members with DN or multiple moles had paler skin than average Japanese, usually sunburned, and tanned less than average, whereas members with darker skin almost never had DN. Each of two families had one cutaneous malignant melanoma (CMM) patient associated with multiple DN. Both CMMs were on the leg. In Japanese DNS, skin color and sun sensitivity seem to be closely related to DN. The locations of CMMs associated with DNS were unique: No CMMs were found on acral areas where they most frequently occur in Japanese.


Analysis of the rural medivac system in the Copper River area.

A pattern of increasing use of aeromedical transport has been observed in the Copper River area of Central Alaska. A retrospective chart review was made to determine the reasons for these medivacs, and the outcome of the patients who were transferred by air ambulance from Cross Road Medical Center in Glennallen, Alaska. In this series there were no unexpected adverse outcomes. Additional or more accurate diagnoses were made on nearly one fourth of the patients. Ninety-two percent of those medivaced were hospitalized with 21 percent needing emergency surgery and 16 percent needing an ICU bed. All categories of patients showed benefit from transport to a higher level facility. There were no complications resulting from the transport.


Mutant p53 protein is expressed in Bowen's disease.

A total of 26 specimens of histologically determined, cutaneous Bowen's disease from 23 patients were investigated for the incidence of mutant p53 protein expression by an indirect immunoperoxidase technique using the monoclonal antiserum CM1 on paraffin-embedded formalin-fixed tissue sections. Its potential role as a label of cutaneous malignancy was also evaluated: 15 specimens (57.7%) showed nuclear positivity of dysplastic keratinocytes, whereas 11 specimens (42.3%) were immunonegative. Cytoplasmic labeling was never a feature. In general, labeling was predominantly diffuse in distribution although in a significant proportion it was focal. One of two concurrent basal cell carcinomas arising adjacent to plaques of Bowen's disease was immunopositive. Focal immunopositivity of "cytologically normal" adjacent epithelium was seen in six specimens (23%). The study confirms the presence of mutant p53 protein in the majority of nongenital Bowen's disease. Its identification within nuclei of the adjacent "normal" epidermis may represent a potential marker of early (visible) neoplastic transformation.


Granulomatous mycosis fungoides. Clinicopathologic study of two cases.

Granulomatous mycosis fungoides is a rare form of mycosis fungoides with controversial histogenesis. Early reports seemed to indicate a favorable prognosis for these patients. We report two cases of granulomatous mycosis fungoides, both of which had other unusual clinical features. The cases were studied with routine light microscopy, immunohistochemistry, electron microscopy, and gene probe studies. Despite some clinical and histopathologic similarities, the results of the immunohistochemical and molecular biologic studies were diverse. These results suggest that granulomatous mycosis fungoides does not define a single subset of cases, immunophenotypically or biologically.


Palisading granulomas caused by infectious diseases.

We recently encountered a palisading granuloma in which an infectious cause was not considered until special stains revealed hyphae and tissue culture revealed organisms of phaeohyphomycosis. A review of more than 2,500 cases of various granulomas revealed 11 cases of palisading-type granuloma caused by infection, including phaeohyphomycosis, nontuberculous mycobacteriosis, papulonecrotic tuberculid, tuberculoid syphiloderm, cat-scratch disease, sporotrichosis, cryptococcosis, and coccidioidomycosis. Infectious disease should be considered in the differential diagnosis of palisading granuloma. Special stains for bacteria, fungi, and acid-fast bacilli should be performed in biopsy specimens that have a palisading granuloma pattern with central necrosis, especially in immunosuppressed patients.


Clinicopathological correlation in chronic urticaria.

Except for urticarial vasculitis, histopathological studies on the different types of urticaria are scant in the medical literature. With the purpose of evaluating the histopathological changes that occur in chronic urticarial eruptions, and to correlate the histopathological findings with the clinical presentation of the patients, skin biopsy studies were done in 36 patients with chronic urticaria. Three well-defined histopathological patterns were found: namely neutrophilic, lymphocytic, and mixed type. No cases of vasculitis were found. No specific association to the clinical presentation of the patient was found.


Histopathologic differences in the photoaging process in facial versus arm skin.

We used clinical criteria to study skin biopsy specimens with mild to moderate photoaging taken from the face and dorsal forearms of 74 Caucasian volunteers between the ages of 30 and 50. Facial skin had a greater number of granular cell layers, a higher degree of keratinocytic atypia, and more often showed a compact stratum corneum than arm skin. Furthermore, the dermis of facial skin had a more extensive perivascular and perifollicular lymphocytic infiltrate, more perifollicular fibrosis, a greater number of mast cells and melanophages, and thinner vascular walls than forearm skin. This study demonstrated that the photoaging process is different for face and arm skin. Appreciation of these differences should permit more refined studies of photoaging and the development of more efficient therapies.


Relationship of tumor cell motility and morphologic patterns. Part 1. Melanocytic skin tumors.

In the diagnosis of melanocytic skin tumors, the assessment of the overall architectural pattern (silhouette) is often essential. We have previously shown by a computer simulation model that tumor patterns are likely to depend on the relative degrees of proliferation and motility of the tumor cells. In this study, we examined the morphological pattern of 12 cases each of nevocellular nevi, primary melanoma, and metastatic melanoma by image analysis. The patterns of the individual melanocytic skin tumors were compared statistically with patterns generated by computer simulation, which facilitates estimates of biological properties of the tumor cells. Additionally, mitotic counts were made to measure tumor cell proliferation. A comparison of the three diagnostic groups revealed that the cells of nevocellular nevi show a low degree of motility, which, however, still exceeds the very low degree of proliferation. Thus, an "invasive" pattern with numerous small nests and single cells at the base of the lesion is common. In primary malignant melanoma, tumor cell motility and tumor cell proliferation are significantly increased in various proportions, thus leading to varying morphological patterns. In metastatic melanoma, a strikingly elevated degree of proliferation exceeds the only slightly elevated degree of motility and leads to sharply demarcated, "expansive" lesions. To check the validity of the technical procedure, estimates of proliferation based on pattern analysis alone were compared with the results obtained by mitotic counts. There was a significant correlation, indicating that the assumptions of the computer model and the image analysis procedure are in fact applicable to real-life melanocytic skin tumors.(ABSTRACT TRUNCATED AT 250 WORDS)


Complex adnexal tumor of the primary epithelial germ with distinct patterns of superficial epithelioma with sebaceous differentiation, immature trichoepithelioma, and apocrine adenocarcinoma.

A 60-year-old man came for treatment of a sharply outlined erythematous plaque on the gluteal area (45 x 20 mm) of 20 years' duration. Eccentrically located on the plaque was a nodule, 20 mm in diameter. Histological study of the plaque showed a superficial platelike tumor with basaloid bland cytology and sebaceous gland differentiation. Histologic study of the nodule found an undifferentiated adenocarcinoma whose ductlike glandular structures opened to the skin surface and infiltrated the whole depth of the dermis. Study of other areas of the lesion detected two more neoplasms. A nodule of squamous cell carcinoma was found within the superficial band of the benign sebaceous tumor. The fourth neoplastic pattern consisted of epithelial islands composed of basaloid cells within a fibroblastic stroma. There was prominent palisading of epithelial cell nuclei at the periphery of the islands, which usually were surrounded by a sheath of mesenchymal cells. In this complex adnexal tumor of the primary epithelial germ, sebaceous and follicular differentiation both simulate neoplastic patterns recently described as separate entities: superficial epithelioma with sebaceous differentiation and immature trichoepithelioma. The undifferentiated adenocarcinoma may represent differentiation toward the third component of the germ, that is, the apocrine gland.


Actinic granuloma of the conjunctiva.

Few cases of actinic granuloma of the conjunctiva have been reported. A 39-year-old woman developed a pinguecula. A biopsy study revealed actinic granuloma histopathologically. This case is an example of the interface between dermatology and other fields, and helps to confirm the existence of actinic granuloma of the skin as a distinct entity.


Malignant Triton tumor. A case with protean histopathological patterns.

A case of malignant Triton tumor occurring in the leg of a 48-year-old woman with neurofibromatosis (von Recklinghausen's disease) is presented. The neoplasm was composed mainly of spindle-shaped cells forming interlacing fascicles with areas of massive necrosis. The important feature in this neoplasm was the presence of rhabdomyoblastic cells admixed with other cellular components. In addition, variable histologic features including solid, myxomatous, hemangiomatous, hemangiopericytomatous, epithelioid, and lymphomatous areas were identified. This variety has been recognized in malignant schwannomas, but not in malignant Triton tumors. There were discrete foci with each predominant histologic feature shown in a map of the neoplasm in which the distribution of those components is demonstrated based on the histology and immunohistochemistry. Satisfactory biopsy specimens are necessary for accurate diagnosis of malignant Triton tumor.


Carcinoid tumor with skin metastasis.

An 80-year-old male patient presented with a 4-month history of nine extremely painful cutaneous nodules located on his forehead, neck, thorax, arms, and thighs. Biopsies of two nodules were performed. Routine histology, immunohistochemistry for chromogranin, as well as electron microscopy demonstrated that the nodules corresponded to cutaneous metastases of a carcinoid tumor, probably originated in the gastric antrum. The present description is, to the best of our knowledge, the first one to correlate the spontaneous and pressure-induced pain in the nodules with perineural invasion and neural sectioning by tumoral cells. S-100 protein and electron microscopy demonstrated numerous Langerhans cells among the tumoral cells.


Sex differences in skin pigmentation illustrated in art.

In different cultures of the world, many artists have made their female models lighter skinned than male models. There exists a biologic truth behind these observations. Several spectrophotometric studies have found that female skin reflectance is 2-3 percentage points above (that is, paler skin) that of males in diverse populations in Europe, Asia, Africa, and North and South America. The sex difference in skin pigmentation is, however, subtle and often difficult to appreciate. Probably artists have used pigmentation to emphasize sexual differences between men and women in the same way they use body size and musculature.


Detection of airborne reindeer epithelial antigen by enzyme-linked immunosorbent assay inhibition.

Hypersensitivity reactions to reindeer epithelial (RE) allergens have been recently demonstrated among reindeer herders. To determine the concentration of airborne RE antigens a method based on inhibition of the enzyme-linked immunosorbent assay (ELISA) was developed. Dust samples were collected in workshops where reindeer leather was processed and the workers had inhaled dry epithelial dust during their working shifts. Specific IgE to RE allergen could be detected in one of 5 workers. RE antigen concentrations varied from 0.01 microgram to 3.9 micrograms/m3 in the air of the workshop. All workers except one claimed work-associated respiratory symptoms.


Allergic symptoms up to 4-6 years of age in children given cow milk neonatally. A prospective study.

In a previously published prospective study, we followed the development of allergic symptoms in term infants with a slightly reduced birthweight (-1 SD to -2 SD). These children received, according to local routine, early feeding with cow milk formula in order to diminish such neonatal problems as hypoglycemia and hyperbilirubinemia. Of 216 infants 207 were observed for allergic symptoms up to 18 months of age. One group (F) received cow milk formula during the first days of life before the mother's breastmilk production started and was then breastfed; the other (B) was not given any formula before normal breastfeeding started. Unexpectedly, we found fewer allergic symptoms, in particular allergic skin problems, in the group fed cow milk, the difference being concentrated to children with a family history of allergic symptoms. At 5 years of age 183 of the 207 children have been reinvestigated. Mild symptoms of allergy (suspected and obvious) were found in 22% (F) and 27% (B) respectively (NS). Moderate and severe symptoms of allergy (obvious) were found in 4.2% (F) and 4.5% (B). In the subgroup with a double family history of allergic symptoms, 28% (7/25, F) and 59% (10/17, B) had symptoms of allergy (p less than 0.05). This difference was even more pronounced when laboratory tests in favour of atopic diagnosis were included, 14% (F) and 53% (B) respectively (p less than 0.05). Thus at 5 years we still find a significantly lower frequency of allergic symptoms in the subgroup fed cow milk formula early with a family history of allergic symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of the Phadebas RAST with the Pharmacia CAP system for insect venom.

Determination of specific IgE by RAST is a well-established method in the diagnosis of immediate allergic reactions. In this study, we have compared the RAST with the ImmunoCAP, a novel test system which is based on a new type of solid phase. A total of 123 sera from 111 insect venom-allergic patients (74% female) were investigated. All patients had their diagnosis confirmed on the basis of their history and skin tests with insect venom. The patients' age showed a mean +/- S of 44.2 +/- 14.6 years. The total serum IgE levels ranged from 4-1712 kU/l, with a median of 108 kU/l. The results of specific IgE, as determined by RAST and CAP, showed a significantly higher sensitivity, by almost one class, with the CAP compared with the RAST system. The quotient of specific IgE to total IgE, determined with the CAP system, could not be shown to be an expression of sensitization, compared with the severity of sting reactions (Müller classification (16)). A conversion factor for vespid venom RAST to CAP was calculated from the present data by subtracting the RAST from the CAP values. The mean delta value +/- SD was found to be 0.9 +/- 0.65, with a range from -0.8 to 2.7 and a median of 0.9. The data clearly show the differences between RAST and CAP-RAST classes, indicating that the CAP-system has a higher sensitivity and that patients with a low level sensitization are missed by the RAST method.


Prospective estimation of IgG, IgG subclass and IgE antibodies to dietary proteins in infants with cow milk allergy. Levels of antibodies to whole milk protein, BLG and ovalbumin in relation to repeated milk challenge and clinical course of cow milk allergy.

Prospectively, serum levels of IgE, specific IgE antibodies (AB) to whole cow milk protein (CMP), bovine se-albumin, bovine immunoglobulin, bovine lactoferrin, bovine lactalbumin and beta-lactoglobulin (BLG), IgG and IgG subclass antibodies to ovalbumin (OA) and BLG, and IgG4 RAST to CMP (bovine whey) were measured in 39 infants with cow milk protein allergy (CMPA) at birth (cord blood), at time of diagnosis and before and after milk challenge at the age of 12 months. Immunological measurements were also undertaken in 33 control infants without CMPA at birth, at 6 months and at 18 months. At no time, were differences found between the levels of IgG and IgG subclass AB to OA and BLG in control versus infants with CMPA. In the 39 infants with CMPA no correlation was found between the levels of IgE, IgG and IgG subclass AB in cord blood and subsequent levels of these values, irrespective of the type of CMPA (IgE-mediated (CMA) or non-IgE-mediated (CMI)), and irrespective of whether remission had occurred. In cord blood 25/33 (76%) of the infants with CMPA had specific IgE-AB to one or more of the bovine milk proteins indicating a prenatal intrauterine sensitization to cow milk protein. At 6 months the frequency of specific IgE-AB to bovine milk proteins was significantly (p less than 0.05) higher in infants with CMA versus CMI, and at 12 months total serum-IgE and the increase of these specific IGE-AB and RAST to CMP were significantly higher (p less than 0.05) in infants with persistent CMA. From 6 to 12 months withholding milk resulted in a significant fall in specific IgE-AB to CMP, and IgG, IgG1 and IgG4 anti-BLG followed by an increase after milk challenge. Decreasing levels of IgG anti-OA from birth to 6 months reflect passive maternal transfer of IgG through the placenta, and increasing levels of IgG anti-BLG, already from birth to 6 months, may represent an early exposure to CMP in all infants. Significantly higher levels (p less than 0.05) of IgG anti-OA AB, IgG1 and IgG4 anti-BLG AB were found in infants with persistent CMA, indicating a close relation between the synthesis of IgE and IgG and between IgE and IgG subclasses (IgG1 and IgG4) in symptomatic cow milk-allergic individuals.(ABSTRACT TRUNCATED AT 400 WORDS)


Immunologically induced purulent anterior segment inflammation of the guinea pig eye.

A single conjunctival application of ovalbumin to inbred guinea pigs (IMM/S 209) immunized with the same antigen in Freund's complete adjuvant provoked an acute purulent inflammation of the anterior segment of the eyes with a duration of up to 1 week. Intense conjunctival injection and chemosis were followed by a purulent discharge. A corneal haze was observed regularly, and a considerable proportion of the animals developed a pronounced pannus and corneal ulcers. Tear fluid cytology revealed a rapid increase in cell concentration, from the normal level (less than 10(8)/l) to greater than 10(11)/l. Seventy to 95% of the cells were polymorphonuclear leukocytes. Histological examination revealed an acute inflammatory reaction which radiated from the conjunctival fornices to the entire anterior segments of the eyes. The process was characterized by an intense oedema, vasodilation and perivascular aggregations of polymorphonuclear leukocytes, and to a lesser extent eosinophilic granulocytes which characteristically infiltrated and penetrated the epithelial layers. Neovascularization could be observed early after challenge in the stroma of all parts of the outer eye. Ulcerations of the conjunctival and corneal epithelia were observed frequently. After a number of reiterations of the antigenic challenge, a marked infiltration with lymphocytes and basophils/mast cells was observed, and significant scarring of the conjunctival mucosa developed. In several animals, a slight, but significant co-reaction of the contra-lateral, non-challenged eye was observed.


Prevalence of atopic disorders among adolescents in Turku, Finland.

A study of the prevalence of atopic disorders among 15-16-year-old teenagers was carried out in a coastal urban town in south-western Finland. Altogether, 1712 children were found in that age group, all previously examined by a pediatrician. Each child who had present or previous allergic diseases was invited for a detailed study, a total of 434 (25%) pupils. Of these patients 416 (95.8%) participated in clinical examination and skin testing. The prevalence of atopic diseases was 21% in the studied group; atopic eczema was found in 9.7%, allergic rhinitis in 14% and asthma in 2.5%. Of subjects who had rhinitis, 38% also had atopic eczema, while rhinitis--as the only symptom--was found in 8.8%. Figures obtained from this survey suggest that the prevalence rates of atopic diseases are about the same as found 10 years ago in Finland and they correspond also with other recent reports.


Immunotherapy in patients allergic to cat and dog dander. I. Clinical results.

Twenty-four asthmatics allergic to cat and/or dog dander were included in a study to examine the efficacy and safety of immunotherapy (IT) with partially purified, standardized extracts of cat or dog dander. In the first placebo controlled, double-blind part of the study, 10 patients were treated with extracts of both cat and dog, 12 with cat extracts and 2 with dog extracts. Fifteen patients received active IT and 9 placebo injections. Patients treated with both extracts received active extracts only, or placebo only. Bronchial allergen challenge after 5 months demonstrated a significant fall in sensitivity to cat (P = 0.04) in patients treated with cat extracts. No significant changes were found in sensitivity to dog after treatment with dog dander extract or in the placebo groups. During this period, bronchial sensitivity to histamine did not change significantly in any of the groups. To examine the effect of more prolonged IT, 19 patients allergic to cat (17) and/or dog (9) were treated for 12 months. Bronchial sensitivity to cat decreased further (P = 0.003), while no significant change was found in dog extract-treated patients. In cat extract-treated patients a significant decrease in bronchial histamine sensitivity developed (P = 0.02). Systemic side effects were few, but in some cases, local side effects were a dose-limiting factor. This study demonstrated that IT with cat extract may benefit cat-allergic asthmatics, whereas no influence of IT with dog extract was detected in dog-sensitive asthmatics.


Flow cytometric analysis of intraepithelial lymphocytes in the human nasal mucosa.

Recently, much research has been carried out on phenotypes and the function of intraepithelial lymphocytes of the intestines. However, only few studies have been made of nasal intraepithelial lymphocytes (nIEL), and the results have been controversial. We examined the population of different subsets of the human nIEL by means of 2-color flow cytometry after culturing lymphocytes isolated from the inferior turbinates of hypertrophic rhinitis in incubation media with monoclonal antibody against CD3. As a result, CD8+ cells (suppressor/cytotoxic T cells) and double negative T cells (CD8- CD4- T cells) were the most predominant. The CD4+ cells (helper/inducer T cells) to CD8+ cells ratio was 0.6. Cytotoxic T cells predominated over suppressor T cells in CD8+ cells and helper T cells predominated over inducer T cells in CD4+ cells. Double positive T cells (CD8+CD4+ T cells) were nil and natural killer cells and CD8+ killer cells few. CD8+ cells and CD4+ cells were activated during cell culture. alpha beta receptor bearing T cells predominated over gamma delta receptor bearing T cells in CD8+ cells and CD4+ cells but gamma delta receptor bearing T cells predominated over alpha beta receptor bearing T cells in double negative T cells. To investigate the effect of cell culture on the population of each phenotype of nIEL we also examined peripheral blood lymphocytes by flow cytometry before and after culture, and found that activated T cells markedly increased and suppressor T cells, gamma delta bearing T cells and natural killer cells slightly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)


Immediate adverse reactions to immunotherapy in allergy.

We report our experience of adverse reactions to immunotherapy (IT) in patients with insect venom allergy and inhalant respiratory allergy. Adverse reactions included large local reactions, generalized cutaneous reactions or systemic reactions. Among 87 patients treated for venom allergy, 43% had adverse reactions during the course of IT, averaging 2.5 reactions per patient and per course of IT. Nine had systemic reactions, of which 7 required adrenaline administration. Among 52 patients treated with inhalant allergen extracts, 40% had adverse reactions averaging 3 reactions per patient per course of treatment. Ten patients had systemic reactions but only 2 required adrenaline administration. There was no difference between the rate of adverse reactions in the venom and the inhalant treatment groups. IT has an inherent risk which has to be weighed against its benefits.


Different effects of physical training on the morphology of motor nerve terminals in the rat extensor digitorum longus and soleus muscles.

The morphology of nerve terminals in the rat extensor digitorum longus and soleus muscles was studied with light microscopy in 13-week-old male animals after 6 weeks of treadmill running and compared with data from untrained controls. The terminals were stained with methylene blue. Physical training tended to increase the area and length of the nerve terminals in relation to the corresponding muscle fiber diameter, and to reduce the density of nerve terminal varicosities, but significant differences between the trained group and the control group were obtained only in the extensor digitorum longus muscle. The different degrees of effect on the nerve terminals in the two muscles may be due to different abilities to respond to the training, but may also be due to differences in work load caused by the training. The effect of training on extensor digitorum longus junctions may reflect some transformation from fast to slow morphological characteristics.


The membranous skeleton: the role of cell condensations in vertebrate skeletogenesis.

Elements of the vertebrate skeleton are initiated as cell condensations, collectively termed the 'membranous skeleton' whether cartilages or bones by Grüneberg (1963). Condensations, which were identified as the basic cellular units in a recent model of morphological change in development and evolution (Atchley and Hall 1991) are reviewed in this paper. Condensations are initiated either by increased mitotic activity or by aggregation of cells towards a centre. Prechondrogenic (limb bud) and preosteogenic (scleral ossicle) condensations are discussed and contrasted. Both types of skeletogenic condensations arise following epithelial-mesenchymal interactions; condensations are identified as the first cellular product of such tissue interactions. Molecular characteristics of condensations are discussed, including peanut agglutinin lectin, which is used to visualize prechondrogenic condensations, and hyaluronan, hyaladherins, heparan sulphate proteoglycan, chondroitin sulphate proteoglycan, versican, tenascin, syndecan, N-CAM, alkaline phosphatase, retinoic acid and homeo-box-containing genes. The importance for the initiation of chondrogenesis or osteogenesis of upper and lower limits to condensation size and the numbers of cells in a condensation are discussed, as illustrated by in vitro studies and by mutant embryos, including Talpid3 in the chick and Brachypod, Congenital hydrocephalus and Phocomelia in the mouse. Evidence that genes specific to the skeletal type are selectively activated at condensation is discussed, as is a recent model involving TGF-beta and fibronectin in condensation formation. Condensations emerge as a pivotal stage in initiation of the vertebrate skeleton in embryonic development and in the modification of skeletal morphology during evolution.


Computer-assisted 3D-reconstruction and statistics of the limbic system. 1. Computer-assisted 3D-reconstruction of the hippocampal formation, the fornix, and the mamillary bodies.

The hippocampal formation of eight perfusion-fixed human brains was examined using new methods according to stereotactic and morphometric principles (macrovibratome and computer-aided 3D reconstruction). The reconstructions form part of a neuroanatomical reference system (NeuRef). This reference system allows for 3D visualisation of the brain and its components on a computer graphic workstation, as well as for the presentation of the union set based on a neuroanatomical structure taken from this sample of brains. This retrievable knowledge of neurofunctional systems is important for the preoperative planning of neurosurgeons and the adjustment of radiotherapy.


Computer-assisted 3D-reconstruction and statistics of the limbic system. 2. Spatial statistics of the hippocampal formation, the fornix, and the mammillary bodies.

A statistical method is described to show the distribution of neuroanatomical structures within a Cartesian coordinate system from any given number of examinations. The algorithm is based on polygons derived from the outlines of neuroanatomical structures in parallel canthomeatal-orientated cutting planes. These polygons are transformed in virtual voxels, rotated into the bicommissural coordinate system, and projected onto the three main planes of this coordinate system. Areas with the same probability for the structures examined are given in these planes. As an example this method is applied to the hippocampal formation and the results attained are shown.


Morphological observations on the harderian gland of the North American opossum (Didelphis virginiana).

The Harderian gland of the North American opossum (Didelphis virginiana) is large and well developed, despite the absence of a nictitating membrane in the adult of this species. The elongate glands are surrounded by a delicate connective tissue capsule from which thin septae extend, subdividing the gland into numerous lobules. The secretory units of the opossum Harderian gland are drained by a well defined but not extensive intralobular and interlobular duct system. Most of the secretory end pieces consist of tubulo-alveolar units with widely dilated lumina filled with secretory product. Numerous intact lipid vesicles suspended within an amorphous material constitute the luminal contents. Cells lining the tubulo-alveolar secretory end-pieces are usually columnar in shape, and characterized by numerous lipid-containing secretory vesicles and aggregations of poly-tubular complexes 40-60 nm in diameter. In addition, these cells contain numerous large irregularly shaped mitochondria, whose matrix is of considerable electron density. Intralobular and interlobular ducts are lined by electron-lucent epithelial cells that lack both the lipid-containing vesicles and the large mitochondria, although typical smaller mitochondria are found scattered within the cytoplasm. Both secretory end-pieces and ductal elements are invested by an abundance of myoepithelial cells. A second, smaller serous type of secretory unit may occur near the centre of some Harderian gland lobules. In these units secretory tubules and acini are compactly arranged surrounding a narrow lumen. Serous cells are pyramidal in shape and the cytoplasm is characterized by numerous electron-dense secretory granules and scattered profiles of rough endoplasmic reticulum.(ABSTRACT TRUNCATED AT 250 WORDS)


Regeneration in Salaria pavo (Blenniidae, Teleostei). Histogenesis of the regenerating pectoral fin suggests different mechanisms for morphogenesis and structural maintenance.

The pectoral fin of blennies is differentiated into a dorsal field and a ventral hook field. A histogenetic analysis of the regenerating pectoral fin was related to two questions. First, are histological specializations of the hook field responsible for the impairment of the regenerative capacity of pectoral fins of blennies? Second, can analysis of the temporal sequence of histogenetic events be used to make testable predictions about the tissue interactions required to re-establish the adult pattern? Regeneration of pectoral fins was examined in Salaria pavo (Blenniidae, Teleostei). Approximately 80% of the length of the fin rays was amputated. Fin ray stumps were evaluated 7, 14, 24, 48 and 72 h after amputation, regenerates 4, 5, and 6 days after amputation and at length of about 30%, 50% and 60% regeneration of the original fin length. The regeneration process is subdivided into four stages: wound healing, blastema formation, fin ray formation and distal outgrowth and differentiation of hook characters. Analysis of the early events of regeneration, wound healing, blastema formation and distal outgrowth, yielded no profound differences from those of conventional fins in general. Impairment of regenerative capacity becomes manifested before histological differentiation of hook characters, and it is thus unlikely that their presence is the proximate cause of heteromorphic regeneration. The sequence in which the anatomical specializations characteristic of fin hooks (lepidotrichal cord, cuticle, fin web regression) appear was variable. Detailed analysis of older regenerates revealed a more regular pattern. In the first phase the characters appear to be largely independently organized, while they become locally correlated later. It is concluded that the anatomical differentiation passes through two stages, initiation of anatomical differentiation, and then mutual adjustment of character expression leading to spatially correlated expression of the lepidotrichal cord, the cuticle and the fin web regression.


Silver impregnability of ischemia-sensitive neocortical neurons after 15 minutes of cardiac arrest in the dog.

The development of postischemic neuronal argyrophilia and the subsequent fate of argyrophilic neurons were studied in dogs after 15 min of complete cerebral ischemia and survival varying from 1 h to 7 days. Histopathological examination of the vulnerable neocortical region was performed using the Nauta degeneration method, and the time course of cellular changes was described. Clear-cut neuronal argyrophilia was found to precede cell body shrinkage and gradual disintegration corresponding to selective neuronal death. To clarify this initial stage of neuronal impregnability, the samples from the animals surviving 8 h postarrest were stained with toluidine blue or processed for electron microscopy, and the distribution of argyrophilic cells was confirmed to be identical with that of hyperchromatic or electron-dense cells. On the other hand, infrequently observed "tissue infarctions" exhibited no silver affinity in spite of apparent cellular damage. These findings indicate that enhanced impregnability is related to cytochemical processes incidental to the phenomenon of "selective neuronal death", which can be readily detected by the Nauta method.


The generation and changing retinal distribution of displaced amacrine cells in Bufo marinus from metamorphosis to adult.

The generation and retinal distribution of displaced amacrine cells (DAs) were studied from metamorphosis to adult in the cane toad Bufo marinus. Displaced amacrine cells were identified by inducing chromatolytic changes in ganglion cells (GCs) following optic nerve section. Cells that did not chromatolyse in the ganglion cell layer (GCL) of the retina were regarded as DAs. The number of DAs increased considerably from an estimated 10,000 at metamorphosis to 211,000 in the adult toad, and was accompanied by a substantial decrease of average cell density. In contrast to the reported 6:1 cell density gradient of all cells of the GCL in adult toad (Nguyen and Straznicky 1989) only a shallow 1.6:1 density gradient of DAs from the visual streak to the dorsal and ventral retinal margins was detected. Consequently, the incidence of DAs increased from 15% of all cells of the GCL in the visual streak to 30% in the dorsal and ventral peripheral retina. These results indicate that the ratio of the newly generated DAs and GCs at the ciliary margin must be changing during development. More GCs are generated before and around metamorphosis then DAs, in contrast to the relative increase of the percentage of DAs generated after metamorphosis. The possible control of the numbers of DAs in the GCL is discussed.


Types of callosally projecting nonpyramidal neurons in rat visual cortex identified by lysosomal HRP retrograde labeling.

Callosally projecting neurons, labeled following injection of horseradish peroxidase (HRP) into the 17/18a border of the contralateral hemisphere, have been examined by light and electron microscopy. These neurons exhibit two types of horseradish peroxidase labeling: either a diffuse, Golgi-like labeling, or a granular, punctate labeling. The punctate type of HRP-labeling is the predominant form in nonpyramidal neurons, while pyramidal neurons frequently display either diffuse or punctate labeling. Only punctately labeled neurons have been examined in this study. Light microscopic analyses of 1-microns sections show that in the heavily labeled zone at the area 17/18a border approximately 9% of all of the cells in layer II/III are callosally projecting nonpyramidal cells, and 70% of them are callosally projecting pyramidal cells. Light and electron microscopic examinations indicate that the nonpyramidal neurons are a heterogeneous group which consists of small multipolar neurons, large multipolar neurons, small bipolar neurons, and large bipolar neurons. To investigate the ultrastructural appearance of the punctate HRP labeling, selected neurons have been examined in thin sections. In the electron microscope, the tetramethylbenzidine (TMB) reaction product appears as electron-dense crystals, while the diaminobenzidine (DAB) reaction product appears as dark, electron-dense material which fills the lysosomes. These lysosomes occasionally have a halo of reaction product, but often they are not morphologically distinguishable from dark lysosomes present within neurons from control animals in which the darkening results from staining the thin sections with lead citrate and uranyl acetate. However, labeled neurons possess more dark lysosomes than neurons from control animals. These additional dark lysosomes presumably contain the HRP reaction product visible by light microscopy.


Communication compartments in the axial mesoderm of the chick embryo.

Intracellular microinjection of the fluorescent tracer Lucifer Yellow into mesoderm cells along the rostrocaudal axis of the early chick embryo has revealed compartments where the intercellular diffusion of dye, presumably via gap junctions, is restricted at the borders between groups of cells. Cells in the segmental plate were dye-coupled, as were cells forming the epithelial somites. However, dye-coupling was not observed between different somites, nor was it observed between the outer epithelial cells and the cells in the somitocoele. On dispersal of the somite, dermatome cells were dye-coupled. However, sclerotome cells were found to be divided into rostral and caudal compartments separated by a group of cells bordering the intrasclerotomal fissure (of von Ebner) that also exhibited dye-coupling, restricted primarily to cells along the fissure. Some of these compartment borders can be accounted for by the presence of a morphological barrier which reduces cell-cell contact, but others are more difficult to explain, as there appears to be extensive cell-cell contact across the border. This would be analogous to some compartments found in insects. Some of the compartments also have borders similar to those described by cell lineage studies. The results also indicate that dye-coupling becomes restricted in a spatial and temporal manner as the mesodermal cells mature.


Adenosine for controlled hypotension: systemic compared with intracoronary infusion in dogs.

We hypothesized that either through local myocardial or systemic effects, adenosine could be used to control hypotension during ischemia. Therefore, we compared the effects of systemic with intracoronary infusion of adenosine on myocardial hemodynamics and metabolism during ischemia in 27 dogs. Left anterior descending artery (LADa) flow was measured and the LADa constricted by a micrometer to restrict resting flow by 50%, 75%, and 100%. Adenosine was infused either systemically (n = 9), to maintain mean aortic pressure at 50-60 mm Hg, or directly into the LADa (n = 9), to create maximal coronary hyperperfusion; no adenosine was infused in the control group (n = 9). With systemic adenosine, during each constriction aortic pressure, left ventricular first derivative (LV dP/dt), and heart rate (HR) decreased: aortic pressure by 56.1% +/- 2.9% (mean +/- SEM), LV dP/dt by 36.2% +/- 2.2%, systemic resistance by 42.7% +/- 5%, and HR by 38.7% +/- 3% during 50% constriction (P less than 0.05 for each variable). Intracoronary adenosine decreased only aortic pressure, LV dP/dt, and HR, all to a lesser extent: aortic pressure by 5% +/- 2.8%, LV dP/dt by 15% +/- 1.2%, and HR by 4.6% +/- 1.7% (P less than 0.05, compared with systemic adenosine for each variable). With systemic adenosine only in the nonischemic area, regional myocardial blood flow increased and remained high, from 224.6 +/- 65.2 to 342 +/- 46.2 mL.min-1.100 g-1 during 50% constriction (P less than 0.05); with intracoronary adenosine, ischemic zone regional myocardial blood flow increased, but not consistently. In the ischemic area, O2 consumption was less with than without systemic adenosine; also, lactate flux production was less positive (-60.2 +/- 37.6 compared with 80.3 +/- 20.2 mmol.min-1.100 g-1 x 10(-3) during 50% constriction; P less than 0.05). Systemic infusion of adenosine during coronary hypoperfusion improves regional metabolism during ischemia and, thus, may mitigate myocardial ischemia. The mechanism by which systemic infusion improves metabolic status may be by decreases in both systemic pressure and systemic vascular resistance.


Effect of thoracic epidural anesthesia combined with general anesthesia on segmental wall motion assessed by transesophageal echocardiography.

Patients scheduled for vascular surgery are considered at risk for perioperative cardiac complications. Choice of anesthetic in such patients is guided by a desire not to adversely affect myocardial function. On the basis of data from laboratory studies, thoracic epidural anesthesia (TEA) has been advocated to prevent myocardial ischemia. The aim of this study was to assess whether TEA combined with general anesthesia has any effect on segmental wall motion (SWM) monitored by transesophageal echocardiography in these patients. Patients received alfentanil, midazolam, vecuronium, and 50% N2O in oxygen, and ventilation was controlled after orotracheal intubation; 12.5 mL of 2% lidocaine HCl was injected through an epidural catheter placed at T6-7 or T7-8. Hemodynamic measurements and transesophageal echocardiographic recordings were obtained before and 10, 20, 30, 40, and 60 min after lidocaine injection. Segmental wall motion was graded a posteriori by two independent experts on a predetermined scale (from 1 = normal to 5 = dyskinesia). A decrease greater than or equal to 2 grades was considered an SWM abnormality indicative of ischemia. Thoracic epidural anesthesia induced a decrease in systemic arterial blood pressure, heart rate, and cardiac index. The SWM score decreased slightly from 1.34 +/- 0.68 to 1.27 +/- 0.64 (mean +/- SD) (at 10 and 20 min, respectively) (P less than 0.05). Patients were a posteriori analyzed according to whether they had documented coronary artery disease or not. The SWM score before TEA was significantly higher in patients with documented coronary artery disease (1.51 +/- 0.88 vs 1.17 +/- 0.51, respectively; P less than 0.05) and did not change significantly after TEA.(ABSTRACT TRUNCATED AT 250 WORDS)


Role of systemic arterial pressure, heart rate, and derived variables in prediction of severity of myocardial ischemia during acute coronary occlusion in anesthetized dogs.

The present study examined the postulate that the quotient of mean systemic arterial pressure and heart rate predicts the severity of myocardial ischemia during occlusion of the left anterior descending coronary artery. Studies were performed in open-chest fentanyl-anesthetized dogs before and during halothane (n = 8) or isoflurane (n = 8) anesthesia. The pressure-rate quotient (PRQ) decreased significantly in both groups during incremental increases in halothane or isoflurane to 68% and 57% of control values at 0.5 MAC and to 41% and 38% at 1.5 MAC for halothane and isoflurane, respectively. Myocardial lactate production was unchanged from the ischemic region, and no correlation between the PRQ and myocardial lactate production was observed. In contrast, heart rate correlated significantly (r = 0.376; P less than 0.05) with lactate production. The product of systolic systemic arterial pressure and heart rate (rate-pressure product) correlated with blood flow (r = 0.493; P less than 0.001) and with oxygen consumption (r = 0.571; P less than 0.001) in the normal myocardium. A weak correlation (r = 0.330; P less than 0.05) of rate-pressure product with myocardial lactate production from the ischemic region was observed. There were no correlations between the PRQ and myocardial lactate production from the ischemic region or indices of blood flow distribution (i.e., inner/outer ratio in the ischemic region or ischemic/normal ratio). The relationship of hemodynamic variables to measurements of regional myocardial metabolism was independent of background anesthetic agent of depth of anesthesia. The current data suggest that heart rate changes are weakly predictive of severity of myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)


Should all children with suspected or confirmed malignant hyperthermia susceptibility be admitted after surgery? A 10-year review.

Children otherwise suitable for same-day discharge may be admitted to the hospital solely because they are known or suspected to be malignant hyperthermia-susceptible (MHS). To determine whether their hospitalization is necessary, the medical charts of 303 children labeled MHS who had undergone surgery with anesthesia free of malignant hyperthermia-triggering agents on 431 occasions between 1981 and 1990 were reviewed. Eighteen of these patients (25 cases) who were subsequently identified as biopsy-negative were excluded from the study. We recorded the reason for the MHS label and the perioperative management and outcome of the cases. Fifty-eight percent of procedures were followed by hospital admission solely because of the patient's MHS label. None of the 25 children (33 cases) with biopsy-proven malignant hyperthermia developed intraoperative or postoperative pyrexia. Ten children suspected to be MHS developed pyrexia greater than 38.5 degrees C. These episodes were not considered to be malignant hyperthermia and were not treated with dantrolene. None of the remaining 275 patients exhibited any features of malignant hyperthermia, although one had an adverse reaction to radiologic contrast medium. On the basis of our retrospective analysis, postoperative admission to the hospital solely on the basis of the MHS label is not warranted.


Metoclopramide reduces the incidence of vomiting after tonsillectomy in children.

The efficacy of intravenous metoclopramide in controlling vomiting in children after tonsillectomy was determined in a prospective randomized, double-blind investigation. One hundred two unpremedicated, ASA physical status I or II children between the ages of 1 and 15 yr who were undergoing surgical removal of the tonsils, with or without adenoidectomy, were studied. Anesthesia was induced either with halothane, nitrous oxide, and oxygen by mask or by intravenous thiopental and was maintained with halothane, nitrous oxide, oxygen, and intravenous morphine (0.1 mg/kg). Each child randomly received either 0.15 mg/kg of metoclopramide or saline solution placebo intravenously after transfer to the postanesthesia care unit. All episodes of vomiting were recorded for 24 h after completion of surgery. The incidence of vomiting in the saline solution group was 70%, compared with 47% in the metoclopramide group (P = 0.026). The authors conclude that the administration of intravenous metoclopramide in a dose of 0.15 mg/kg on arrival in the postanesthesia care unit significantly decreases the incidence of vomiting in children after tonsillectomy.


Comparative effects of laryngeal mask airway and endotracheal tube insertion on intraocular pressure in children.

Intraocular pressure (IOP) measurements in children are frequently performed under halothane-nitrous oxide anesthesia; however, anesthesia face masks may limit access to the eyes, and tracheal intubation is associated with transient increases in IOP. Use of the laryngeal mask airway (LMA) permits the maintenance of a patent airway without the need for laryngoscopy and tracheal intubation. In a randomized study of 41 children, we compared the IOP, hemoglobin oxygen saturation, and hemodynamic responses to the insertion of an LMA or tracheal tube during a standardized steady-state anesthetic technique consisting of 1 MAC halothane and 66% nitrous oxide. Baseline measurements of IOP, hemoglobin oxygen saturation, heart rate, and arterial blood pressure were recorded and repeated within 15-30 s after insertion of the airway device and at 1-min intervals for 5 min. Insertion of the LMA required significantly less time (26 +/- 16 vs 39 +/- 17 s [mean +/- SD]) and was associated with higher hemoglobin oxygen saturation values compared with the tracheal intubation. The LMA did not increase IOP, heart rate, or arterial blood pressure above baseline values. In contrast, tracheal intubation was associated with significant increases of IOP, heart rate, and arterial blood pressure. We concluded that the laryngeal mask offers advantages over tracheal intubation and the face mask for airway management in patients undergoing IOP measurements.


Epidural test dose and intravascular injection in obstetrics: sensitivity, specificity, and lowest effective dose.

The authors studied the sensitivity and specificity of several epidural test doses as markers of intravascular injection in laboring patients in a prospective double-blind, randomized study. Fifty-nine parturients were assigned randomly to receive an intravenous injection of either normal saline solution (3 mL, NS group) or 1.5% lidocaine with epinephrine 1:200,000 (1 mL, EPI-5 group; 2 mL, EPI-10 group; or 3 mL, EPI-15 group). The EPI-5 and EPI-10 doses were diluted to 3 mL volume with normal saline solution. All injections were given during uterine diastole. Maternal heart rate was monitored with a pulse oximeter. An observer who was unaware of the study treatment recorded the baseline and the peak maternal heart rate within the first minute after the injection and questioned the patient about tinnitus, dizziness, metallic taste, and palpitations. He then recorded his opinion as to whether the patient had received the saline or the test solution. Analysis of the maternal heart rate showed an average increase (baseline-to-peak criterion) of 8 +/- 10 beats/min (mean +/- SD) in the NS group. In the other groups, the increase was 21 +/- 8 (EPI-5 group), 31.5 +/- 13 (EPI-10 group), and 29 +/- 9 beats/min (EPI-15 group). A baseline-to-peak criterion of greater than 10 beats/min identified all intravascular injections in the EPI-15 (by design) and EPI-10 groups (15 of 15 and 14 of 14, respectively) with a sensitivity of 100%. Specificity was 73% (11 of 15 true negatives).(ABSTRACT TRUNCATED AT 250 WORDS)


Headache after spinal anesthesia for cesarean section: a comparison of the 27-gauge Quincke and 24-gauge Sprotte needles.

A high incidence of postdural puncture headache (PDPH) occurs after spinal anesthesia for cesarean section. To examine this problem, a study was conducted with the recently developed 24-gauge Sprotte and 27-gauge Quincke needles in patients undergoing elective and emergency cesarean section (n = 298). The needle to be used was assigned in a random manner: group I, 27-gauge Quincke (n = 147); group II, 24-gauge Sprotte (n = 151). During the postoperative period, patients were visited daily and asked specifically about the presence and severity of headache. The overall incidence of PDPH was 2% (n = 6), five in the Quincke group (3.5%) and one in the Sprotte group (0.7%). There was no significant difference in the incidence of PDPH between the two groups. Five headaches were classified as mild, and only one was moderate to severe. All headaches resolved quickly with conservative management and without blood patch. The authors conclude that the choice between a 27-gauge Quincke and a 24-gauge Sprotte needle does not influence the incidence of PDPH after spinal anesthesia for cesarean section.


Interscalene brachial plexus block for shoulder surgery: a proximal paresthesia is effective.

This study was designed to determine whether the location of paresthesias is related to the success of interscalene blocks in providing anesthesia for shoulder surgery. Interscalene blocks were performed in 45 patients presenting for elective shoulder surgery. Interscalene injections of 33-55 mL of 1.5% mepivacaine with epinephrine were performed after the first elicited paresthesia to the shoulder, arm, forearm, or hand. In 20 patients (45%), the initial elicited paresthesia was to the shoulder, whereas in 25 patients (55%), the first paresthesia was reported as distal to the shoulder. All patients developed brachial plexus anesthesia adequate for shoulder surgery. The time-course of onset of motor block as evaluated at the shoulder and elbow was not different between patients with shoulder paresthesias and those with more distal paresthesias. Handgrip strength was quantitatively evaluated with a dynamometer, and both paresthesia groups showed similar decrements in hand strength except at the end of the measurement period, when patients with distal paresthesias had a significantly weaker handgrip than patients with shoulder paresthesias. We recommend that paresthesias to the shoulder be accepted in performing interscalene blocks for patients undergoing shoulder surgery.