Hemodynamic actions of guan-fu base A in anesthetized rats. Guan-fu base A (GFA) is a terpenoid alkaloid isolated from the tuber of Aconitum coreanum in this institute. GFA exhibited anti-arrhythmic effects in various experimental arrhythmia animal models, and bradycardic actions. In this paper, the hemodynamic action of GFA was investigated. GFA 20 mg.kg-1 iv decreased in heart rate from 420 +/- 51 to 305 +/- 60 bpm (P less than 0.05). The changes of SBP, DBP, LVSP, +/- dP/dtmax, and LVEDP were much smaller or insignificant. GFA (1, 3, 10, 30, 60 mg.kg-1 cumulative iv) increased the heart periods (HP) and QT-intervals in a dose-dependent manner, accompanied by a small increase in PQ-interval, but did not affect QRS complex. The increase in HP from 138 +/- 11 to 321 +/- 48 ms (P less than 0.01) was mainly due to a prolongation of the diastolic period from 22 +/- 12 ms to 156 +/- 46 ms (P less than 0.01). The triple product of HR x LVET x SBP was also decreased with every dose of GFA. This hemodynamic profile suggests that the bradycardic action of GFA can reduce myocardial oxygen consumption and improve myocardial blood supply, which may be of use in certain cardiac patients.


Effects of ketanserin on blood pressure variability in conscious spontaneously hypertensive rats. Computerized analysis of blood pressure (BP) was used to study for the effects of ketanserin (Ket) on BP and blood pressure variability (BPV). Rats were instrumented chronically and BP was sampled every 4 ms by a computer from 2:00 to 14:00. Then a single dose of Ket (3 mg.kg-1) was given iv. BP and heart period (HP) were recorded for the next 30 min. The results showed that Ket lowered systolic BP (26.7 kPa to 21.1 kPa), diastolic BP (20.5 kPa to 15.8 kPa), and systolic BPV (1.3 kPa to 0.94 kPa). Otherwise, a positive relationship was found between antihypertensive effects of Ket and BPV. These findings may be of importance in antihypertensive treatment.


Effects of microinjection of picrotoxin into posterior hypothalamus on ventricular electric stability. Ventricular fibrillation threshold (VFT), serum potassium, and monophasic action potentials (MAP) have been assessed before and after microinjection of picrotoxin (Pic) into posterior hypothalamus in rabbits. Pic (2 and 3 micrograms) brought about a biphasic effect on VFT, an initial decrease followed by a notable increase. Pretreatment with spinal cord transection almost abolished the descending phase, whereas pretreatment with vagotomy depressed the ascending phase significantly. Following the microinjection of Pic, serum potassium rose up to 5.0 mmol.L-1 at 30 min. The amplitude of MAP (MAPA) and Vmax were lessened in rabbits, while in vagotomized rabbits, the changes of MAP were aggravated, and the duration of MAP was shortened. Phentolamine counteracted the changes of MAP induced by Pic. These results suggested that the initial decrease of VFT caused by Pic derived mainly from the direct action and myocardial ischemia of sympathetic activation, while its subsequent elevation was caused by vagal activation and hyperkalemia.


Protective and anti-arrhythmic effects of dauricine and verapamil on acute myocardial infarction in anesthetized dogs. Dauricine (Dau) 5 mg.kg-1 and verapamil (Ver) 0.15 mg.kg-1 iv followed by infusions of 0.1 and 0.01 mg.kg-1.min-1, respectively, for 30 min, depressed the elevated coronary venous blood LDH and CPK after LAD occlusion. Dau produced antagonistic effects on acute myocardial ischemia-induced ventricular ectopic activities (VE) and ventricular tachycardia (VT). The incidences of VE and VT in Ver group and ventricular fibrillation (VF) in both groups tended to descend. The results suggested that Dau and Ver produced marked protective effects on myocardial infarction and antagonized the acute ischemic arrhythmia.


Cytotoxic activity of trewiasine in 4 human cancer cell lines and 5 murine tumors. Trewiasine (TWS) is a mytansinoid compound. It possessed a significant cytotoxic activity against various human cancer cell lines in vitro. U937 cells, which were more sensitive to the TWS, required TWS 1 microgram.ml-1 to inhibit cell growth over 90% (P less than 0.01). TWS also showed activities against murine tumors in vivo, such as the ascitic tumors S180, hepatoma, U14, and solid tumor Lewis lung carcinoma. Depression of leukocytes was not seen when mice were given ip TWS 10 or 50 micrograms.kg-1.d-1 x 7 d. TWS 0.1-1 micrograms.ml-1 caused no sister chromatid exchange induction in Chinese hamster cell line V79.


Effect of schisandrin B on lipoperoxidative damage to plasma membrane of rat liver in vitro. The effect of schisandrin B (Sin B) on oxygen free radicals--induced lipoperoxidative damage to plasma membrane of rat hepatocytes was investigated. When the plasma membrane of rat hepatocytes was incubated with iron/cysteine or Vit C/NADPH, the production of malondialdehyde (MDA) and consumption of NADPH increased, while the membrane fluidity reduced. Addition of Sin B (3-25 micrograms.ml-1) to the incubation mixture inhibited all these alterations of the plasma membrane induced by iron/cysteine and Vit C/NADPH. The results indicated that Sin B could maintain membrane stability of rat hepatocytes under oxidative stress.


Effects of cantharidin on interleukin-2 and interleukin-1 production in mice in vivo. After cantharidin (0.75, 1.5 mg.kg-1) was given ip 3 times every other day in mice, Con A-induced spleen lymphocyte proliferation, as measured by [3H]TdR incorporation assay, was enhanced from 7,978 +/- 1,780 to 36,631 +/- 8,467 and 29,997 +/- 3,788 dpm in both doses. Interleukin-2 and interleukin-1 production were also increased from 11 +/- 4 to 52 +/- 18, 23 +/- 6 U.ml-1 and from 7,628 +/- 1,477 to 14,532 +/- 2,272, 11,515 +/- 2,862 dpm, respectively. These results suggest that cantharidin potentiates immune response through the release of interleukin-2 and interleukin-1.


[Effect of habenular nucleus in 5-HT ascending pressor pathways]. The blood pressure was elevated by the electric stimulation of dorsal raphe nucleus in rats. Microinjection of 5-HT (6 micrograms, 3 micrograms) into habenular nucleus induced pressor effect too, but the heart rate was not much changed. Microinjection of procaine hydrochloride (300 micrograms.microliters-1) into both sides of habenular nuclei, the pressor effect induced by stimulation of dorsal raphe nucleus was alleviated obviously (85% blockade). The data suggested that habenular nucleus participates in the pressor effect caused by the excitation of dorsal raphe nucleus, and 5-HT may be one of the neurotransmitters in the action of habenular nucleus participating in cardiovascular regulatory function.


[Effects of benzyltetrahydropalmatine on rat portal vein and guinea pig myocardium]. In isolated rat portal vein, benzyltetrahydrophalmatine (BTHP) 0.3-100 mumol.L-1 dose-dependently increased the spontaneous mechanical activity. However, BTHP 300 mumol.L-1 showed an inhibitory effect on the spontaneous contraction. BTHP 200 mumol.L-1 reversed positive staircase phenomenon to negative ones in left atrium of guinea pig and inhibited the amplitude and Vmax and shortened the action potential duration (APD50) of the slow action potentials induced by high K+ (24 mmol.L-1) in guinea pig papillary muscles. BTHP reduced also the contractile force in papillary muscles of guinea pig. These results suggest that BTHP possesses calcium antagonistic effect in high concentration.


[Effect of hippocampal injection of oxytocin on shuttle-box avoidance behavior of rats]. Bilateral dorsal hippocampal injection of oxytocin (Oxy, 50 pg, on each side) in rats impaired the acquisition of conditioned avoidance behavior and accelerated the extinction of conditioned avoidance behavior in shuttle-box. The data suggested that the effect of Oxy on shuttle-box conditioned avoidance behavior of rats was at least partly accomplished via the hippocampus; Oxy affected short-term memory as well as long-term memory.


[Effects of 4-(4"-(2",2",6",6"-tetramethyl-1"-pipe-ridinyloxy) amino)-4'-demethylepipodophyllotoxin on nucleic acids, proteins, and DNA strand of L7712 cells in vitro]. The antitumor activity of GP-7, a new spin-labeled epipodophyllotoxin, was studied by liquid scintillation spectrometry. There were many similarities between GP-7 and etoposide. Both GP-7 and etoposide inhibited the incorporation of [3H]TdR, [3H]UR, and [3H]Leu into DNA, RNA, and protein synthesis in leukemia 7712 cells. The inhibition correlated with drug concentration and duration. IC50 of GP-7 and etoposide on DNA synthesis at 24 h were 0.21 and 0.37 micrograms.ml-1, respectively. The inhibition of GP-7 or etoposide on DNA synthesis retained even after the drug were washed out for 3 h. GP-7 and etoposide caused DNA single-strand breaks, with a well concentration-response relationship. These data suggest that the inhibition of DNA synthesis by GP-7 or etoposide is likely due to the damage of DNA template and breaking of single-strand DNA.


[Effect of artemether against Schistosoma japonicum]. Artemether (beta-methyl ether of artemisinin) first synthesized by Shanghai Institute of Materia Medica, Chinese Academy of Sciences(1), appears in colorless crystal and is more lipid-soluble than artemisinin. When artemether was given ig or im to mice infected with Schistosoma japonicum for 32-35 d at the dosage of 1/10-1/2 LD50. Its effects in the two administration routes were similar. After artemether 200 mg.kg.d-1 ig or 100 mg.kg-1.d-1 im for 1-2 d was given to mice infected with S japonicum cercariae at different intervals, d 7 schistosomules were more susceptible to the drug with worm reduction rates of 73.9-92.0%. The d 35 adult worms also exhibited susceptibility to the drug and the worm reduction rates were 47.0-70.1%, but less susceptibility to the drug in other developmental stages of schistosomes. The major morphological alteration of adult worms induced by artemether was sustained shrinkage accompanied by atrophy and degeneration of the worm's reproductive glands, eg, the testis in males and ovary as well as vitelline gland in females. The in vitro tests indicated that artemether showed apparent effects on different stages of schistosomes only when a higher concentration of 40 micrograms.ml-1 was used.


[Pharmacokinetics of puerarin in rats, rabbits, and dogs]. The puerarin was determined by HPLC with fluorescence detection. The plasma concentration-time course of puerarin in rats and dogs after iv was best fitted to a two-compartment open model, while that in rabbits was best fitted to a three-compartment open model. Species specificity was found among rats, rabbits, and dogs, calculated with compartment model program. The T1/2 beta after iv puerarin 9 mg.kg-1 in rats, rabbits, and dogs were 11, 21, and 67 min, respectively. There were no significant differences in pharmacokinetic parameters after iv 4.5-30 mg.kg-1 to rabbits and dogs.


Effects of graded restriction of perfusion on circulation and metabolism in the working leg; quantification of a human ischaemia-model. An experimental model used with the intention of mimicking the ischaemic condition in patients with arterial obliterative disease was evaluated. The influence of reduced effective perfusion pressure by increased external pressure on leg blood flow and metabolism was determined during exercise in 10 healthy subjects. Catheters were inserted into the right femoral artery and vein and into the left femoral vein. Supine one-legged (n = 5) or two-legged (n = 5) cycle exercise was performed with the subject's legs in a pressure chamber. Zero and three different levels of local supra-atmospheric pressure were applied over the legs: 30, 50 and 60 mmHg. Three submaximal work loads were used: 24, 48 and 72 W/leg. Leg blood flow was measured by the constant-infusion dye-dilution technique. Samples were also drawn from the femoral artery and vein for oxygen saturation and lactate determinations and arterial pressure was recorded. Exercise blood flow decreased progressively with increasing chamber pressure (P less than 0.001). Exposure to 50 mmHg over the working leg led to a mean reduction of blood flow by 16% and venous oxygen saturation by 12 percentage units (P less than 0.05). Lactate release increased with increasing pressure (P less than 0.05). In summary, local application of moderate positive external pressure over the working leg reduces blood flow in a 'dose-dependent' manner, and as a consequence, femoral venous oxygen saturation decreases and lactate release increases. Thus, this method makes it possible to induce graded ischaemia in human skeletal muscle during exercise in a controlled fashion.


Bio-energetic changes in human gastrocnemius muscle 1-2 days after strenuous exercise. [31P]magnetic resonance spectroscopy was used to study the metabolic sequelae of intense muscular activity in gastrocnemius of seven subjects 1-2 days after a 67-mile bicycle ride. The muscle was examined at rest, during a test exercise and during recovery from test exercise. Post-ride and pre-ride results were compared. At rest, the ratio of phosphocreatine to ATP (PCr/ATP) was increased post-ride; during test exercise PCr/(PCr+Pi) was lower post-ride; and the recoveries of PCr, Pi and PCr/(PCr+Pi) after test exercise were delayed, with decreased 'overshoot' of PCr/(PCr+Pi) (which is due to recovery of Pi to below its resting value). Mild mitochondrial damage (perhaps due to exposure to high cytosolic [Pi] during the bicycle ride) may explain some of these results. In contrast to reports of largely eccentric exercise there was no increase in resting Pi/ATP. We have thus demonstrated perturbations of muscle bio-energetics 1-2 days after strenuous exercise, in the absence of convincing enzymological evidence of muscle damage.


Influence of prostaglandins and a prostaglandin H synthase inhibitor on cervical secretion of the guinea-pig. The modulatory effects of several prostaglandins and a prostaglandin H synthase inhibitor (indomethacin) on basal as well as nerve stimulation induced secretion from the cervical glands of the guinea-pig were studied. Hypogastric nerve stimulation resulted in a secretory response of +113%. Indomethacin dose dependently inhibited this secretory response. Prostaglandins E2, F2 alpha and I2 inhibited and 19-OH prostaglandin E1 reduced nerve stimulation induced secretion. Prostaglandin I2 and 19-OH PGE1 markedly enhanced basal secretion, while indomethacin as well as PGE2 and PGF2 alpha did not induce any secretion of cervical glands. However, PGF2 alpha in combination with the alpha-adrenergic blocker phentolamine resulted in an increase in secretion. The inhibitory effect of prostaglandins on cholinergic secretory innervation might be due to stimulation of adrenergic nerves exerting an inhibitory influence on cholinergic secretomotor innervation. It is suggested that PGI2 and 19-OH PGE1 exert postjunctional stimulatory effects on the secretory lining and that a lack of secretory effect of PGF2 alpha at least in part may be due to stimulatory effects on adrenergic neurons, inhibiting cholinergic secretomotor transmission. Thus, in this in vitro study it is shown that metabolites of the arachidonic acid cascade and a prostaglandin H synthase inhibitor can modulate cervical secretion and thus maybe influence fertilization.


Protein kinase C activity in rat renal proximal tubule cells. The presence of protein kinase C (PKC) in proximal tubule cells of the rat kidney is established by means of immunodetection and by the demonstration of calcium- and phospholipid-dependent, staurosporine-inhibitable histone phosphorylation. The calcium-dependence of renal PKC is described. Maximal activation of the enzyme (178.2 and 258.8 pmol P1 mg-1 min-1 for cytosol and membrane respectively) was achieved with 5 microM of Ca2+. Phorbol 12, 13 dibutyrate (PDBu) translocated PKC from cytosol to membrane in a dose- and time-dependent fashion, while 4 alpha-phorbol 12,13-didecanoate produced no significant effect on translocation. Cytosolic PKC activity was compared in immature and mature tissues (10- and 40-day-old kidneys). Basal activity was found to be significantly higher (P less than 0.05) in immature cells (272.8 vs. 157.5 pmol Pi mg-1 min-1). PDBu at 10(-6) M for 15 min reduced immunoreactivity in the soluble fraction of both groups, which was accompanied by a significant decrease in kinase activity. We speculate that the high PKC activity in the infant kidney plays a role in cell growth.


Metabolic rates of minke whales (Balaenoptera acutorostrata) in cold water. Body temperature, blubber thickness and lung capacity (Vc) were recorded in newly killed minke whales, while respiratory frequency (f) was determined in free-swimming animals. Mean deep (thoracic) body temperature was 34.7 +/- 0.8 (SD) degrees C (n = 14). Weighted mean core/blubber interface temperature in animals caught in 2.5-5.5 degrees C water was 28.8 +/- 1.7 degrees C (n = 8). The minimum average rate of sensible heat loss (HLs) was 3.81 +/- 0.53 (SD) W kgw-0.75 (n = 8) in animals with body masses (w) in the range of 1840 to 5740 kg, HLs being inversely proportional to w (HLs = -2.98 10(-4) w +4.89 W kgw-0.75 (n = 8, r2 = 0.73, P less than 0.01)). The average rate of respiratory heat loss (HLr) was 0.26 +/- 0.04 (SD) W kgw-0.75, regardless of w, in the same 8 animals. Total rates of heat loss (HL = HLr+HLs) in 2.5-5.5 degrees C water ranged between 3.40 and 4.87 W kgw-0.75, with an average of 4.06 +/- 0.52 (SD) W kgw-0.75 (n = 8). Estimates of oxygen consumption based on records of f and Ve, and data on oxygen extraction from other cetaceans, yielded a range of metabolic rates which compared nicely with the calculated HL values.


Changes in high-energy phosphates in rat skeletal muscle during acute respiratory acidosis. We used 31P magnetic resonance spectroscopy to study changes in phosphorus metabolite concentrations in rat skeletal muscle during respiratory acidosis (14 and 20% inspired CO2) and recovery. As intracellular pH fell (from 7.05 to 6.75 after 20 min of 20% CO2), intracellular [P(i)] increased by up to 50% while phosphocreatine concentration decreased by up to 8%. The sum of all intracellular phosphates remained constant. [ADP] decreased by up to 40% in accordance with the creatine kinase equilibrium but the phosphorylation potential [ATP]/([ADP][P(i)]) was preserved as a result of increased [P(i)]. This adjustment may be a mechanism for maintaining mitochondrial ATP synthesis despite low pH. Eventually this increase in cellular [P(i)] could lead to slow efflux of P(i) from the skeletal muscle cell contributing to the hyperphosphataemia of acute respiratory acidosis.


Effects of Amrinone on shortening velocity, force development and ATPase activity of demembranated preparations of rat ventricular myocardium. This study analyses the effects of Amrinone (bipyridine derivative with phosphodiesterase inhibitor properties) on the myofibrillar apparatus of rat myocardium. Thin trabeculae were isolated from the right ventricle and chemically demembranated. Force development and shortening velocity were measured during maximal calcium activations (pCa = 4.45) in control conditions and in the presence of 1-3 mM Amrinone. Maximum shortening velocity was obtained both from extrapolation of the force-velocity curve and with the slack test method. Amrinone was found to significantly reduce maximum shortening velocity and force development. Myofibrils and myosin were prepared from rat ventricular myocardium and their ATPase activity was assessed in control conditions and in the presence of Amrinone (0.3-6 mM). Ca-Mg dependent myofibrillar ATPase activity which was determined at low ionic strength was depressed by Amrinone in a dose-dependent way. Ca-stimulated ATPase activity determined at high ionic strength in myofibril or myosin preparations was not affected. Furthermore, Amrinone did not influence the pCa-ATPase activity curve of the myofibrillar preparations. A comparison between the inhibitory effects of Amrinone on myofibrils prepared from euthyroid rats and myofibrils prepared from hypothyroid rats was carried out. The ATPase activity was significantly less depressed in myofibrils prepared from hypothyroid rats than in those prepared from euthyroid rats. These results provide the first evidence of an effect of Amrinone on ATP splitting and force generation in the myofilament system of cardiac muscle.


Force production in voltage-clamped human atrial muscle. Human atrial muscle preparations obtained during open heart surgery were mounted in a sucrose gap. Force and membrane currents were recorded during voltage clamp. After a 20-s rest, 10 clamps from a holding potential of -40 to 0 mV at 1.0 Hz were given. This was followed by a test clamp (called 1) of a varied duration and amplitude and two more test clamps (called 2 and 3) as during the priming period. Peak force of contraction 1 (F1) was independent of clamp duration from 2s to about 100 ms but declined at shorter durations. Peak force of contraction 2 (F2) and 3 (F3) increased with the duration and became potentiated. Increasing the clamp amplitude raised F1 to an optimum value at about +10 mV and there was a decline at higher voltages. Both F2 and F3 increased at higher amplitudes. A conventional bell-shaped current-voltage relation for the second inward current was obtained during clamp 1 with maximum inward current around -10 mV. In control experiments on isolated human myocytes peak current was recorded at somewhat more positive potentials. The relation between F3 and F2 was linear both when duration and amplitude of clamp 1 was varied. The slope of the line, interpreted as a measure of recirculation of activator calcium, was 0.4. It is concluded that force during voltage clamp in human atrial muscle is similarly related to membrane voltage as previously reported for guinea pig and ferret preparations.


Intra-neural electrical stimulation of cutaneous nociceptive fibres in humans: effects of different pulse patterns on magnitude of pain. A study was performed to elucidate how different impulse frequencies and impulse patterns in cutaneous nociceptive fibres influence the subjective magnitude of pain. Groups of nociceptive A delta and C fibres were co-activated by electrical intraneural stimulation at constant intensity in cutaneous fascicles of the peroneal nerve in healthy human subjects. The resulting pain sensations were rated on a modified visual analogue scale. Five-second trains were administered randomly at irregular intervals of at least 30 s. Five of the stimulus patterns had regular interpulse intervals, corresponding to frequencies of 1, 2, 4, 10 and 15 Hz, and three other patterns were constructed to mimic to some extent the initially phasic and subsequently slowly adapting discharge patterns which may be encountered in recordings from human nociceptors. The results from these experiments using stimulation frequencies within physiological discharge ranges for human nociceptors indicate that the subjective magnitude of pain increases monotonously as a function of stimulus frequency, and that patterns mimicking nociceptor discharges in response to natural stimuli give rise to greater peak magnitudes of pain than artificial regular patterns with a corresponding number of impulses.


Thalamic nociceptive mechanisms in cats, influenced by central conditioning stimuli. Field potentials and single cell activity evoked by tooth pulp (TP) stimulation were studied in the ventrobasal (VB) complex of the cat. The experiments were performed using a conditioning-test paradigm. Evoked cell activity or field potentials following TP stimulation was used as a test. Conditioning stimulus was given to different regions of the thalamic central lateral nucleus (CL). Conditioning electrical stimulation in medial (ML 2.8-3.6 mm) parts of CL induced a depression of the TP evoked response in 10 cells. Stimulation sites in lateral CL (ML 3.6-4.2 mm) induced facilitation in eight cells and decreased activity in seven cells. Tooth pulp evoked field potentials in thalamus were facilitated by a preceding stimulation in lateral CL. Cells in the lateral parts of CL are suggested to induce an increased activity in cells in the VB complex which mediate nociceptive information. This effect is suggested to be mediated via a CL induced disinhibition at a reticular thalamic (RE) or at a VB complex level. The medial parts of CL seem to give a traditional feedback inhibition on VB cells. Such an effect is also suggested to be mediated via the RE complex. The importance of these findings are discussed with relation to changes in the thalamus that may occur following long lasting nociceptive stimulation.


Inefficiency of bilateral amygdaloid lesions to reduce the transient motor reactions exhibited by swine during exposure to CO2. The aim of the study was to evaluate from the ethical point of view the importance of transient muscular jerks commonly exhibited by swine at an early stage of pre-slaughter CO2-anaesthesia. The influence of 5 min restraint upon plasma concentrations of adrenaline (A) and noradrenaline (NA) was studied in swine (n = 6) before and after bilateral lesioning of the amygdaloid region of the brain, as were the motor reactions of the same and three other animals during 1 min exposure to 80% CO2. The A and NA responses to the restraint became almost extinguished after amygdaloid lesioning in three of the animals, were reduced by about 50% in one swine, whereas no reduction was seen in the other two animals investigated. The amygdaloid lesioning did not visibly influence the latency for, and the duration and intensity of the muscular jerks manifested by the swine during the CO2-exposure. The results do not favour the possibility that transient motor reactions exhibited by swine during pre-slaughter CO2-exposure are manifestations of emotional stress. Instead, the study indirectly supports the idea that the cause of the muscular jerks may be disinhibition of subcortical motor centres being inactivated by the CO2-anaesthesia somewhat later than neocortical cells normally exerting the inhibition.


IGF-I binding and IGF-I expression in regenerating muscle of normal and hypophysectomized rats. Binding of iodinated IGF-I to tissue sections from regenerating muscle was studied by autoradiography in normal and in hypophysectomized rats. Binding of IGF-I was low in control muscle in both groups of animals, but increased transiently about 10-fold during regeneration after injury. Maximal binding occurred later in hypophysectomized rats than in control rats, and there was also a slower regeneration process in these animals. IGF-I, as demonstrated by immunohistochemistry, and IGF-I mRNA, as demonstrated by in situ hybridization, were expressed by the regenerating muscle cells in both groups of animals. It is concluded that locally produced IGF-I is the most likely ligand for IGF-I receptors during muscle regeneration.


Power spectral analysis of heart rate and blood pressure variability in anaesthetized dogs. Short-term oscillation of heart rate and blood pressure are mainly regulated by the automatic nervous system. It has been proposed that non-neural factors, such as changes in intrathoracic pressure, can strongly modulate this rhythmicity. Our aim was to evaluate the effect of changing intrathoracic pressure and central autonomic nervous activity on heart rate and blood pressure variability. Evaluation was performed by using spectral analysis techniques with autoregressive modelling. The variability in heart rate and blood pressure remained in animals with open chest or paralysed respiratory muscles. After vagotomy, the variability in heart rate decreased, but not that of blood pressure. Total spinal anaesthesia elicited a decrease in the variability in blood pressure. The pharmacological blockade of alpha- and beta-receptors further decreased both variabilities. It was concluded that in anaesthetized dogs heart rate and blood pressure variability are mainly of central origin and non-neural factors have only minor effect on these central rhythms. High (> 0.15 Hz), medium (0.07-0.15 Hz) and, obviously low (0.00-0.07 Hz) frequency variations in heart rate are mostly mediated vagally. In blood pressure, medium and obviously low frequency variations are modulated by sympathetic nervous system, whereas high frequency variations are secondary to the heart rate variation.


The ethanol technique of monitoring local blood flow changes in rat skeletal muscle: implications for microdialysis. We have investigated the feasibility of monitoring local skeletal muscle blood flow in the rat by including ethanol in the perfusion medium passing through a microdialysis probe placed in muscle tissue. Ethanol at 5, 55, or 1100 mM did not directly influence local muscle metabolism, as measured by dialysate glucose, lactate, and glycerol concentrations. The clearance of ethanol from the perfusion medium can be described by the outflow/inflow ratio ([ethanol]collected dialysate/[ethanol]infused perfusion medium), which was found to be similar (between 0.36 and 0.38) at all ethanol perfusion concentrations studied. With probes inserted in a flow-chamber, this ratio changed in a flow-dependent way in the external flow range of 5-20 microliters min-1. The ethanol outflow/inflow ratio in vivo was significantly (P less than 0.001) increased (to a maximum of 127 +/- 2.8% and 144 +/- 7.4% of the baseline, mean +/- SEM) when blood flow was reduced by either leg constriction or local vasopressin administration, and significantly (P less than 0.001) reduced (to 62 +/- 6.4% and 43 +/- 4.4% of baseline) with increases in blood flow during external heating or local 2-chloroadenosine administration, respectively. Dialysate glucose concentrations correlated negatively with the ethanol outflow/inflow ratio (P less than 0.01) and consequently decreased (to 46 +/- 7.6% and 56 +/- 5.6% of baseline) with constriction and vasopressin administration and increased (to 169 +/- 32.5% and 262 +/- 16.7% of baseline) following heating and 2-chloroadenosine administration. Dialysate lactate concentrations were significantly increased (approximately 2-fold, P less than 0.001) during all perturbations of blood flow. In conclusion, this technique makes it possible to monitor changes in skeletal muscle blood flow; however, methods of quantification remain to be established. The fact that blood flow changes were found to significantly affect interstitial glucose and lactate concentrations as revealed by microdialysis indicates that this information is critical in microdialysis experiments.


Functional and stereologic estimations of myocardial capillary exchange capacity in treated and untreated spontaneously hypertensive rats. Myocardial capillary exchange capacity was investigated by stereologic and functional techniques in parallel during pressure-overload cardiac hypertrophy and after long-term antihypertensive therapy with the vasodilator felodipine. In 26-week-old female spontaneously hypertensive rats (SHR) blood pressure increased by 25% and left ventricular weight (LVW/BW) increased by 18% compared to Wistar-Kyoto rats (WKY). Myocardial capillary surface and volume densities normalized for organ weight were similar in both ventricles for both strains. Moreover, capillary surface density was higher sub-epicardially (EPI) than in the subendocardium (ENDO) in the left ventricle of SHR. Thirteen weeks of felodipine-therapy (SHR-Felo) normalized blood pressure without affecting LVW/BW although a transition from concentric to eccentric hypertrophy is known to occur. Myocardial capillary surface and volume densities and the left ventricular ENDO-EPI-gradient in surface density were similar to untreated SHR. However, felodipine-treatment increased right ventricular weight and capillary volume density. Functional capillary exchange was estimated in terms of permeability surface area products (PS) for Cr-EDTA and vitamin B12 and normalized for organ weight. PSCr-EDTA, PSB12 and the ratio PSCr-EDTA/PSB12 (an index of capillary permeability) were similar in SHR and WKY. Furthermore, the relation between functional and stereological indices of exchange capacity was investigated in a multiple linear regression analysis. However, no significant correlation between PS and neither capillary surface nor volume density was found. In conclusion, myocardial capillary exchange capacity was well adapted to the pressure overload cardiac hypertrophy present in female SHR. Despite induction of right ventricular hypertrophy, felodipine-treatment did not affect capillary exchange capacity. Furthermore, when functional and stereologic estimates were performed in parallel, the importance of dynamic factors for myocardial capillary exchange capacity (e.g. heterogeneity) was illustrated.


Lipid peroxidation capacities in the myocardium of endurance-trained rats and mice in vitro. The endurance-training programme in Experiment 1 (Exp. 1) consisted of a total swimming time of 149-159 h per male Han Wistar rat and in Experiment 2 (Exp. 2) the male NMRI-mice run on a treadmill at a speed of 25 m min-1 1 h per day, 5 days a week for 3 weeks. One group of the rat hearts was perfused with 0.3 mM cumene hydroperoxide (CumOOH) while the others were fractioned (mitochondria, sarcolemma and sarcoplasmic reticulum) and these cell fractions and homogenates were used to determine the total concentration of peroxidative lipids and the susceptibility to lipid peroxidation. The perfusion with CumOOH caused the release of thiobarbituric acid reactive substances (TBARS) into the perfusate. The release of TBARS from the trained hearts was smaller than that of the control hearts (P < 0.01). The concentration of TBARS was also smaller in the myocardium of the right ventricle of the trained rats (P < 0.01). The concentration of reduced GSH remained at a higher level after the CumOOH perfusion suggesting a better redox state in the hearts of trained animals. The concentration of the lipids susceptible to lipid peroxidation was lower in the homogenates of the trained rat hearts (P < 0.05). However, this decrease could not be explained by any of the tissue fractions used when studied in rat hearts. In Exp. 2 the total concentration of lipids susceptible to peroxidation remained unchanged in the mice hearts.(ABSTRACT TRUNCATED AT 250 WORDS)


Vasoconstrictor reactions in spontaneously hypertensive rats versus Wistar Kyoto can be increased or decreased depending on the conditions of perfusion. The reactions of resistance vessels in SHR and WKY hindquarters were compared during saline or blood perfusion. During saline constant-flow perfusion at all initial pressures (80-200 mmHg) sympathetic vasoconstrictor effects were greater in SHR than those in WKY. During perfusion at constant and equal pressure vasoconstrictor responses were greater in SHR vs. WKY only at high pressure--200 mmHg. On the other hand, under constant pressure conditions at lower pressures (80 and 120 mmHg) sympathetic stimulation induced weaker responses in SHR than in WKY, which at, for example, 80 mmHg was the case at every frequency of sympathetic stimulation used (2-20 Hz). Also, the responses to exogenous noradrenaline and vasopressin occurred during perfusion at low (80 mmHg) and for both equal constant-pressure conditions lower in SHR than in WKY. Comparison of sympathetic effects in SHR and WKY during blood hindquarter perfusion revealed similar results. Also, when SHR and WKY responses were compared at their ordinary levels of constant-pressure, sympathetic vasoconstrictor effects in SHR were lower than those in WKY.


Effects, release and disposal of endothelin-1 in conscious dogs. Cardiovascular and renal responses to a step-up infusion of endothelin-1 (ET-1) (1, 5, and 15 ng kg-1 min-1) were investigated in conscious dogs. In addition, the disappearance of ET-1 in arterial and central venous plasma after an infusion of 10 ng kg-1 min-1 was quantified, and the effects of vasopressin (AVP, 10 ng kg-1 min-1) and angiotensin II (AII, 2, 5, and 10 ng kg-1 min-1) on plasma ET-1 were investigated. The step-up infusion of ET-1 increased the plasma level from 3.6 +/- 0.3 to 243 +/- 23 pg ml-1. Concomitantly, arterial blood pressure increased and heart rate (HR) decreased dose-dependently. Diuresis, sodium, and potassium excretion did not change significantly. However, free water clearance increased during the infusion. Clearance of creatinine and excretion of urea decreased (39 +/- 4 to 29 +/- 3 ml min-1 and 87 +/- 16 to 71 +/- 14 mumol min-1, respectively). Decay curves for ET-1 in venous and arterial plasma were identical, and initial t1/2 was 1.1 +/- 0.1 min. Vasopressin increased arterial blood pressure (107 +/- 4 to 136 +/- 3 mmHg) beyond the infusion period and increased plasma ET-1 (85%). An equipressor dose of AII tended to decrease plasma ET-1. It is concluded that the lung is apparently not important in the removal of ET-1, that the disappearance of ET-1 follows a complex pattern, and vasopressin--in contrast to angiotensin II--is able to increase the plasma concentration of ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)


Polyamines in nerve terminals and secretory granules isolated from neurohypophyses. In isolated nerve terminals from ox neurohypophyses the following concentrations of polyamines [pmol (microgram protein)-1 (mean +/- SEM)] were found: spermine: 2.07 +/- 0.14 (n = 3), spermidine: 0.22 +/- 0.01 (n = 4), putrescine: 0.20 +/- 0.01 (n = 4). In secretory granules isolated from the same tissue, the concentrations were: spermine: 0.57 +/- 0.02 (n = 3), spermidine: 0.07 +/- 0.04 (n = 3), putrescine: 0.13 +/- 0.04 (n = 3). After incubation of isolated nerve terminals with the polyamines, they were taken up as a function of time and concentration, approaching saturation at high concentrations. The kinetic parameters of their synthesizing enzyme, ornithine decarboxylase, in ox neurohypophyseal nerve terminals (apparent Km 0.75 mM and Vmax 22.5 pmol mg protein-1 h-1) were comparable to those previously found in cerebral cortex of rats. When isolated, hemilobes from rat neurohypophyses were incubated in a medium which contained spermidine (5 mM), and were stimulated by 56 mM K+, release of vasopressin was smaller than in control experiments. However, after removal of spermidine and after restimulation, 50 min after initial stimulation, the release was significantly elevated. It is suggested that polyamines may take part in modulation of vasopressin release.


Luminal and basolateral uptake and degradation of insulin in the proximal tubules of the dog kidney. In order to determine the major routes of insulin degradation in the body, insulin was labelled with a 'trapped' or 'residualizing' label: [125I]tyramine-cellobiose ([125I]TC) and injected intravenously in dogs. In contrast to conventional iodine-labelled insulin (131I-insulin), the [125I]TC-insulin allows measurements of total uptake in specific organs in vivo because the radioactive degradation products do not leave the cells. One h after the injection of trace doses, the amount of radioactivity recovered in the kidney from [125I]TC-insulin was nine times higher than when conventional [131I]insulin was used. In the blood, the amount of acid-precipitable radioactivity was the same for both labelled preparations, indicating similar clearance rates. A comparison of the uptake of insulin in filtering vs. non-filtering (ureter-occluded) kidneys indicated that the uptake of insulin is twice as high through the luminal than through the basolateral cell membrane; after 60 min, 8.9 +/- 0.8% of the injected [125I]TC-insulin dose remained in the filtering kidney and 3.2 +/- 0.2% of the dose was accumulated in the contralateral kidney, with occluded ureter but normal blood perfusion. In both filtering and non-filtering (ureter-occluded) kidneys, the subcellular distributions of [125I]TC-insulin were studied after various times by isopycnic sedimentation in sucrose gradients. No difference between peritubular and tubular uptake was discernible. The intracellular transport was rapid, leading to accumulation of radioactive label in dense lysosomes within 10 min.


Changes in muscle fibre type from adolescence to adulthood in women and men. Age-related changes in muscle fibre characteristics have been presented in cross-sectional studies previously. The aim of the present study was to investigate longitudinally whether the muscle fibre type composition and muscle fibre area change from adolescence to adulthood. Fifty-five men and 28 women were studied at the age of 16 and again at the age of 27. Biopsies were taken from the vastus lateralis muscle and analysed for fibre types (I, IIA, IIB, IIC) and fibre areas. Different development of fibre type composition with increased age were seen in women and men: the type I percentage tended to increase in the women (51 +/- 9 to 55 +/- 12) and decrease significantly in the men (55 +/- 12 to 48 +/- 13). The fibre areas remained unchanged in both sexes. It is suggested that there is a sex-related fibre adaptation to increased age.


Neuro-effector characteristics of sweat glands in the human hand activated by irregular stimuli. Intraneural electrical stimulation of cutaneous fascicles in the median nerve was performed in 24 normal subjects and the effects on sweating within the innervation zone were monitored as changes of skin resistance and water vapour partial pressure (wvpp). The aims were: (1) to investigate the response variability between repeated stimulation sequences in the same skin site and between different sites and (2) to compare quantitative effects of regular and irregular stimulation on skin resistance and wvpp. Regional axillary anaesthesia of the brachial plexus eliminated spontaneous and reflex sympathetic activity. With repeated irregular stimulation sequences skin resistance responses from the same skin site varied only slightly between trials. Differences between response curves from two skin sites in the same subject or from different subjects were also small but significantly greater (P < 0.01) than differences between responses to repeated stimulation in the same site. Irregular stimulation with average frequencies of 0.49 Hz and 3.51 Hz gave greater resistance responses than if the same number of stimuli were delivered regularly (P < 0.01). The difference was most pronounced at 0.49 Hz. At an average frequency of 0.49 Hz the stimulation usually evoked no changes of wvpp whereas an average frequency of 3.51 Hz caused an increase of wvpp which was greater with irregular than with regular stimulation in all subjects. We conclude that: (1) sweat responses to sudomotor nerve traffic vary slightly due to local factors in the skin or the terminal nerve endings and (2) irregular sudomotor nerve traffic evokes more sweat than if the same impulses occur regularly.


In vivo and in vitro studies on effects of beta-endorphin and naloxone on sex steroids in the water frog, Rana esculenta. The effects of beta-endorphin and its receptor antagonist, naloxone, on progesterone, androgens, and oestradiol-17 beta release in male and female Rana esculenta were studied in vivo and in vitro. In the in vivo experiments the frogs underwent hypophysectomy, gonadectomy or both, or were left intact; the animals were injected with beta-endorphin or naloxone and killed after 15, 30, 90 and 240 min. In the in vitro experiments inter-renal, testis and ovary, all with and without added pituitary, were incubated with beta-endorphin or naloxone for 10, 20, 40 and 80 min. The in vivo and in vitro data from males and females were in agreement. In vivo beta-endorphin increased progesterone in all experimental groups and oestradiol in intact and hypophysectomized frogs, while it decreased androgens in all experimental groups. In vitro beta-endorphin increased progesterone in inter-renal and gonadal tissue, and oestradiol in gonads only, while it decreased androgens in inter-renals and gonads. In vivo and in vitro naloxone induced opposite effects to beta-endorphin. These data suggest that in Rana esculenta, opioids are involved in the modulation of hypothalamo-pituitary-inter-renal and gonadal axes. In particular, the data indicate a direct effect of opioids on inter-renal and gonadal sex steroid production.


In vivo and in vitro release of indomethacin from water-soluble and fatty base suppositories. The plasma concentration of indomethacin was measured after the rectal administration of water-soluble and fatty base suppositories in rats. The results were compared with the in vitro indomethacin release from suppositories determined by Paddle method using three different types of membranes: cellulose membrane, artificial sausage membrane and natural sausage membrane. The plasma concentrations of indomethacin during the first 4h after the rectal administration were higher in rats that received water-soluble base suppositories than in those that received fatty base types. When either a cellulose membrane or an artificial sausage membrane of cow protein was used in the Paddle method, the amount of indomethacin released from fatty base suppositories was significantly higher than that from water-soluble base ones. However, the results were reversed when a natural sausage membrane of pig colon was used. The discrepancy in the in vitro experiments using water-soluble base suppositories seemed to be due to the difference of pore size of membrane used. Careful consideration should be given to the membrane used in the Paddle method especially when this method is employed to examine the release of poorly soluble drugs like indomethacin in both water-soluble and fatty base suppositories.


Histochemical detection of lipid peroxidation in human gastrointestinal, mammary and renal carcinomas. Constitutional lipid peroxidation in randomly selected 32 cases of clinically advanced carcinoma from human gastrointestinal tract (20 cases), breast (8 cases) and kidney (4 cases) was examined histochemically in frozen sections using cold Schiff's reagent. Only two cases of gastrointestinal carcinoma were positive by the reagent. Non-cancerous parenchymal cells were negative. These findings suggest that detectable constitutional lipid peroxidation seldom occurs in either cancerous or normal tissues. The capacity for normal and neoplastic tissues to undergo lipid peroxidation was also studied by incubation with an iron-NADPH pro-oxidant system. Normal parenchymal cells showed, to various degrees, a positive reactivity. In gastrointestinal carcinoma, 6 out of 7 cases of well differentiated adenocarcinoma reacted positively, whereas 2 out of 8 cases of moderately to poorly differentiated adenocarcinoma disclosed weakly positive reactions. Mucinous adenocarcinomas (4 cases) were all negative. Signet-ring cell carcinoma (1 case) was positive. One out of 8 cases of breast cancer also showed positive reaction. Four renal cell carcinomas were all negative. Cancer cells have lower capacity to undergo lipid peroxidation than normal cells, when the iron-NADPH pro-oxidant system was employed. In gastrointestinal carcinoma, the ability to undergo lipid peroxidation by the iron-NADPH pro-oxidant seems to be correlated with their histological differentiation. This fact may suggest that differences in lipid composition or the NADPH enzyme system exist between well differentiated and poorly differentiated gastrointestinal malignancies.


Effect of taurine concentration on platelet aggregation in gestosis patients with edema, proteinuria and hypertension. To elucidate the relationship between the high concentration of taurine in platelets and platelet aggregation in patients with EPH gestosis (gestosis with edema, proteinuria and hypertension), platelet aggregation and the platelet release response (release of ATP and beta-thromboglobulin) were studied in the washed platelet suspension (PS) obtained from normal pregnant or non-pregnant women and EPH gestosis patients. Platelet aggregation and platelet release response were significantly lower in EPH gestosis patients than in normal pregnant and non-pregnant women. Platelet aggregation, platelet release response induced by ADP and collagen and the aggregation induced by A23187 were inhibited in taurine-loaded PS from non-pregnant women. These results suggest that the decrease of platelet aggregation in EPH gestosis patients was caused by high concentrations of taurine in platelets, which may inhibit the intracellular Ca2+ movement and platelet release response. Therefore, taurine appears to have a protective effect against the hyper-coagulative state in EPH gestosis.


Comparison of antitumor activity of new anthracycline analogues, ME2303, KRN8602, and SM5887 using human lung cancer cell lines. In an attempt to predict the clinical activity of newly developed anthracycline analogues, ME2303, KRN8602, and SM5887 in the treatment of lung cancer, we compared antitumor activity of these drugs with that of adriamycin, using six human lung cancer cell lines and two drug-resistant human lung cancer sublines. Taking the pharmacokinetic data into consideration, we evaluated the relative antitumor activity: the ratio of area under the concentration-time curve of each drug to the 50% inhibitory concentration of the drug. Regarding this ratio, ME2303 was more potent than adriamycin, SM5887, and KRN8602. Cross-resistance of the new analogues to adriamycin was investigated using an adriamycin-resistant small cell lung cancer subline, SBC-3/ADM100 and an etoposide-resistant subline, SBC-3/ETP. SBC-3/ADM100 being 106-fold more resistant to adriamycin than the parent SBC-3 showed less resistance to the analogues: 1.80-fold to KRN8602, 3.80-fold to SM5887, and 8.60-fold to ME2303. SBC-3/ETP which was 52.1-fold more resistant to etoposide and 39.5-fold more resistant to adriamycin were also less resistant to the new analogues: 3.27-fold to KRN8602, 9.07-fold to SM5887, and 17.3-fold to ME2303. In conclusion, ME2303 was found to be the most potent agent among drugs tested for the treatment of lung cancer, and KRN8602 can be expected to be beneficial for the treatment of drug-resistant small cell lung cancer.


Clinical study of malignant tumors originating in the pelvic region. We evaluated the surgical problems encountered during treatment of 14 patients with malignant tumors originating in the pelvic region at our department. The tumor involved the iliac bone in 6 patients, the ischial bone in 2, the pubic bone in 2, and the gluteal region in 4. Invasion to the sacrum was observed in 7 patients. Twelve patients underwent surgical procedures consisting of intralesional resection in 6, marginal resection in 3, and wide margin resection in 3. Six of the 7 patients with sacral invasion developed local recurrence. Two patients with chondrosarcoma and one with parosteal osteosarcoma survived for 4 or more years, but the mean survival period in those with high grade malignant tumors was 11 months. These findings indicate the difficulties encountered in the treatment of malignant pelvic tumors.


Indications and timing of surgery for cholelithiasis associated with valvular heart disease. Twenty patients with cholelithiasis associated with valvular heart disease were studied to assess the need and the optimal time for cholecystectomy. Twelve patients (11 symptomatic and 1 asymptomatic patients) underwent cholecystectomy. The remaining patients were asymptomatic. The levels of the total bilirubin in 9 patients, and of LDH in 15, were higher than normal. In most of the patients, the serum transaminase levels were higher than normal, but in few cases, the levels were higher than 200 IU/l. These abnormal values, however, were not consistently observed in these patients. No clear association between the type and form of valvular heart disease was demonstrated. The type of prostheses used for valve replacement in these patients were ball, tilting disc and leaflet. No significant differences in efficacy were observed among different types of prostheses. The incidence of silent stones is high in patients with valvular heart disease and heart surgery often causes deterioration in patients with cholelithiasis. The recovery of the patients who underwent cholecystectomy before valve replacement were better than those who underwent cholecystectomy after heart surgery. In conclusion, therefore, patients showing any abnormal results in liver function tests should be assessed in detail by abdominal echography and should receive surgical treatment of biliary tract before heart surgery if necessary.


Laparoscopic cholecystectomy: report of 42 cases. Our initial experience with laparoscopic cholecystectomy for cholecystitis and cholelithiasis was reviewed in 42 patients and the data were compared with those of 21 patients who underwent conventional open cholecystectomy previously. Only one patient required conversion to an open operation. Three of the 42 patients had minor complications without death in laparoscopic cholecystectomy. The mean time for the laparoscopic cholecystectomy was 100 +/- 40 min, as compared with 79 +/- 21 min for the open cholecystectomy. The average postoperative hospital stay was 11.4 +/- 7.1 days for the laparoscopic procedure and 35.5 +/- 15.4 days for the conventional procedure. The laparoscopic cholecystectomy offers the patients shortened hospitalization and lower complications and can replace the conventional open cholecystectomy in large degree, at least in the uncomplicated cases.


Asthma classification by a score calculated from clinical findings and examinations in subjects sensitive to inhalant allergens. Twenty-one patients with atopic asthma were classified into three types according to their symptoms (clinical diagnosis): Ia, simple bronchoconstriction; Ib, bronchoconstriction + hypersecretion; and II, bronchiolar obstruction, and this classification was compared with a classification made according to clinical findings and examinations (score diagnosis). Type Ib asthma was characterized by the increased incidence of eosinophils in bronchoalveolar lavage fluid (BALF), while type II was characterized by ventilatory dysfunction in small airways and the increased incidence of neutrophils in BALF. Four patients, whose expectoration was between 50 and 99ml/day, of the 12 with type Ia assessed by clinical diagnosis were evaluated as type Ib by score diagnosis. One patient with type II by clinical diagnosis was assessed as questionable type II by score diagnosis. In the other 16 patients, the clinical and score diagnoses were the same.


Hemodynamic performance of the biventricular bypass system operated in an independent variable rate mode. The present study was undertaken to determine whether a biventricular bypass system operated in an independent variable rate (VR) mode can maintain the entire circulation. Two pusher-plate pumps which incorporated the Hall effect position sensors were used to bypass the right and left ventricles in 10 sheep under fibrillation. The flow distributions of the pump output to the carotid and renal arteries were investigated every 6 h using ultrasonic blood flow meters for 24 h in 5 animals, and the controllability of the VR mode was evaluated in 5 long-term experiments. The carotid artery flow ratio to the pump output decreased significantly from 4.7 +/- 0.8% before the bypass to 2.7 +/- 0.9% after 24 h. However, the renal artery flow ratio did not change throughout the experiments. In the long-term experiments, the animals were kept alive from 3 to 48 days (mean 15.6 days). The mean pump output had been maintained at more than 90 ml/min/kg for the first 7 days. After the surgery, the pump driving conditions were not readjusted in any experiment. The results indicate that the biventricular bypass system operated in the independent VR mode automatically maintains the entire circulation at a satisfactory level.


NG-nitro-L-arginine attenuates flow debt repayment in the reactive hyperemic response of the open-chest dog coronary artery: contribution of endothelium-derived relaxing factor. To test the hypothesis that the endothelium-derived relaxing factor (EDRF) contributes to coronary vasodilation induced by myocardial ischemia, we examined the effect of NG-nitro-L-arginine (a potent and selective inhibitor of EDRF release) on the coronary reactive hyperemic response in the open-chest dogs. Intracoronary infusion of NG-nitro-L-arginine at a coronary plasma concentration of 5 x 10(-5) M had no effect on hemodynamics and myocardial oxygen metabolism, but attenuated repayment of the flow debt by an average of 20.4% and 20.0% following coronary occlusion for 10 sec and 20 sec, respectively. Concomitant infusion of NG-nitro-L-arginine at the same concentration and 8-phenyltheophylline (a potent adenosine receptor blocker) at a coronary plasma concentration of 10(-5) M further attenuated flow debt repayment following 10 sec and 20 sec of coronary occlusion by 47.7 and 59.4%, respectively. These results indicate that EDRF plays a significant role in the coronary reactive hyperemic response and may cause vasodilation independently of adenosine-mediated vasodilation following coronary occlusion.


The role of Kupffer cells in complement activation in D-Galactosamine/lipopolysaccharide-induced hepatic injury of rats. To investigate the role of Kupffer cells in complement activation, we used a rat model of acute hepatic injury induced by D-Galactosamine (GalN) and lipopolysaccharide (LPS). In in vivo study, minimal histological changes were observed after i.p. GalN (200 mg/kg) single administration. Complement hemolytic activity (CH 50) decreased to 70% of its initial value 2-3 h after i.p. LPS (1.5 mg/kg) single administration. Massive hepatic necrosis was induced by simultaneous administration of GalN and LPS. After 2-3 h, CH 50 decreased to 70% of its initial value, and deposition of C3 fluorescence (C3) was observed in Kupffer cells. After 4 h, GPT was greatly increased (1286 +/- 240 IU/l), CH 50 was further reduced, and C3 was observed on hepatocyte membranes and in the cytosol. In in vitro study, we used hepatocyte cultures and co-cultures of hepatocytes and Kupffer cells to investigate the participation of GalN, LPS, complement, and Kupffer cells in hepatic cell necrosis. We found no increase of LDH (% leakage) when LPS and complement were added to the medium (22.7 +/- 5.7%). A moderate increase was observed with the addition of GalN (33.2 +/- 2.6%). A remarkable increase was observed only with the addition of GalN, LPS, and complement to the co-culture (50.0 +/- 8.8%). These results suggest that Kupffer cells activated by LPS are very important in promoting acute hepatic injury by complement.


Frequency of gamma delta T cells in peripheral blood, synovial fluid, synovial membrane and lungs from patients with rheumatoid arthritis. The percentages and absolute numbers of gamma delta T cells per CD3 positive cells (T cells) in four different compartments, namely peripheral blood, synovial fluid, synovial membrane and lungs from patients with rheumatoid arthritis (RA) and in peripheral blood from healthy controls were studied by two color flow-cytometric analysis. The percentages (mean +/- SEM = 6.3 +/- 0.8%, n = 22) and absolute numbers (70 +/- 11/microliters, n = 22) of gamma delta T cells in peripheral blood from RA patients were not different from those of 22 age-matched healthy controls (7.5 +/- 0.9%, 81 +/- 17/microliters, respectively). The gamma delta T cells in peripheral blood from 50 RA patients were, however, significantly decreased in negative correlation with the value of CRP as a marker for inflammation, although they had no correlation with the titer of rheumatoid factor as an autoantibody. The percentages of gamma delta T cells in synovial fluid from 10 patients (3.3 +/- 0.5%, n = 10) or in synovial membrane from 5 patients (4.2 +/- 1.9%, n = 5) and in bronchoalveolar lavage fluid from 6 patients (3.6 +/- 0.8%, n = 6) were not different from those in peripheral blood from the same patients. Thus, gamma delta T cells are not the dominant infiltrating T cell subset in the inflammatory sites of RA patients.


Asthma classification by pathophysiology and IgE-mediated allergic reaction: new concepts for classification of asthma. Bronchial asthma was classified by the pathophysiology and by the mechanism of onset of the disease. Forty asthmatics who had serum IgE levels lower than 200 IU/ml were evaluated by two classification methods. 1. In asthma classified by a score based on clinical findings and examinations, the characteristics of the findings and examination results were compared among three asthma types, i.e., Ia. simple broncho-constriction type, Ib. bronchoconstriction+hypersecretion type, and II. bronchiolar obstruction type. Type Ib patients, in addition to manifesting hypersecretion, had a significantly higher proportion of eosinophils in the bronchoalveolar lavage (BAL) fluid compared to other asthma types. Significantly decreased values for ventilatory parameters and an increased proportion of BAL neutrophils were found in type II compared with other asthma types. 2. In a new classification by mechanism of onset, asthma was classified into three types according to the degree of participation of IgE-mediated reactions associated with specific IgE antibodies and serum levels of total IgE: asthma induced by definite IgE-mediated reaction (atopic asthma), possible IgE-mediated reactions (asthma), and asthma induced by non-IgE-mediated reaction (asthma syndrome).


A case of trans-sternal bilateral thoracotomy for bilateral lung cancer. Trans-sternal bilateral thoracotomy was performed to resect the right upper lobe and the left S1 + 2 + S3, and to complete lymphadenectomy in a 35-year-old female case of lung cancer in whom multiple lesions were suspected. Trans-sternal bilateral thoracotomy was considered to be useful for one-stage surgery in patients in whom bilateral lung cancer is suspected or confirmed, because it provides a sufficient surgical field enabling the resection of lung and lymph nodes. This may be the first case report of trans-sternal bilateral thoracotomy to treat multiple primary lung cancer.


Pituitary and ovarian suppression after early follicular and mid-luteal administration of a LHRH agonist in a depot formulation: decapeptyl CR. In order to study its effect on pituitary and ovarian function, a single dose of triptorelin depot (Decapeptyl CR, Ferring) was administered to 12 women in the early follicular (EF,n = 6) or mid-luteal phase (ML,n = 6) of a normal cycle. In all 12 women the initial pituitary and ovarian responses were similar. Luteinizing hormone (LH) and follicle stimulating hormone (FSH) rose to peak values within 48 h, and declined to hypogonadotropic levels within 2 weeks' time. Steroid levels showed a slight to marked rise after injection and fell to hypogonadal values within 1 week. LH suppression was maintained until the 8th week after the injection, while FSH levels rose to normal between the 3rd and 4th week. Estrogen secretion started to be restored in the course of the 7th and 8th week. Menses occurred between the 11th and 13th week after the injection of the drug. This study demonstrates the possibility of rapid induction of a hypogonadotropic and hypogonadal condition in regularly cycling women by administration of a single triptorelin depot. Suppression of pituitary and ovarian function appears to be continued until the 8th week after the injection.


The GnRH 10 micrograms test promotes a maximal gonadotropic response in normal women. The authors have compared the results of gonadotropin stimulation with a gonadotropin releasing hormone (GnRH) intravenous bolus of 100 micrograms and of 10 micrograms in a group of eumenorrheic women. They conclude that there are no differences between the responses of the two dosages in normal women. Therefore the authors clarify that the dosage of 10 micrograms of GnRH as a bolus test may be used currently in clinical practice in order to assess gonadotropic function.


Auricular acupuncture in the treatment of female infertility. Following a complete gynecologic--endocrinologic workup, 45 infertile women suffering from oligoamenorrhea (n = 27) or luteal insufficiency (n = 18) were treated with auricular acupuncture. Results were compared to those of 45 women who received hormone treatment. Both groups were matched for age, duration of infertility, body mass index, previous pregnancies, menstrual cycle and tubal patency. Women treated with acupuncture had 22 pregnancies, 11 after acupuncture, four spontaneously, and seven after appropriate medication. Women treated with hormones had 20 pregnancies, five spontaneously, and 15 in response to therapy. Four women of each group had abortions. Endometriosis (normal menstrual cycles) was seen in 35% (38%) of the women of each group who failed to respond to therapy with pregnancy. Only 4% of the women who responded to acupuncture or hormone treatment with a pregnancy had endometriosis, and 7% had normal cycles. In addition, women who continued to be infertile after hormone therapy had higher body mass indices and testosterone values than the therapy responders from this group. Women who became pregnant after acupuncture suffered more often from menstrual abnormalities and luteal insufficiency with lower estrogen, thyrotropin (TSH) and dehydroepiandrosterone sulfate (DHEAS) concentrations than the women who achieved pregnancy after hormone treatment. Although the pregnancy rate was similar for both groups, eumenorrheic women treated with acupuncture had adnexitis, endometriosis, out-of-phase endometria and reduced postcoital tests more often than those receiving hormones. Twelve of the 27 women (44%) with menstrual irregularities remained infertile after therapy with acupuncture compared to 15 of the 27 (56%) controls treated with hormones, even though hormone disorders were more pronounced in the acupuncture group. Side-effects were observed only during hormone treatment. Various disorders of the autonomic nervous system normalized during acupuncture. Based on our data, auricular acupuncture seems to offer a valuable alternative therapy for female infertility due to hormone disorders.


The effect of combined estrogen/progestogen treatment in women with hyperprolactinemic amenorrhea. Eleven women with hyperprolactinemic amenorrhea were treated with a combined estrogen/progestogen preparation (Loestrin 30) for 3 months as hormone replacement therapy because of estrogen deficiency, with a view to protection against osteoporosis. Serum prolactin levels rose during the 1st month of treatment (p < 0.05) but did not rise significantly further during the 2nd and 3rd months. The levels rose in proportion to pretreatment levels by 28% (median), and fell significantly but not completely during the 1-week treatment-free intervals. After the study period, prolactin values appeared to remain stable in those women who continued longer on treatment, and returned to around pretreatment values in those who stopped. In one woman there was radiological evidence of pituitary tumor growth during treatment. This study shows that estrogen/progestogen treatment in standard contraceptive dosage usually leads to only moderate and non-progressive stimulation of pituitary activity in women with hyperprolactinemic amenorrhea, but occasional excessive growth of a prolactinoma can occur and treatment needs to be monitored. Women with relatively high prolactin levels seem to be at particular risk. Safer variations of estrogen therapy such as lower dosage or combination with a protective low dose of a dopamine agonist should also be considered.


Symptom-free interval after triptorelin treatment of uterine fibroids: long-term results. An increasing number of publications document regression of fibroids under treatment with gonadotropin releasing hormone (GnRH) agonists. However, recurrence after stopping treatment regularly counterbalances its benefit. We now report on 28 patients with intramural myomas, treated with triptorelin for 4-6 months and followed for 42-56 months. During or shortly after treatment, six patients entered menopause. In this group, a volume reduction of 71% was achieved and no surgery was needed thereafter. In 22 premenopausal women, a 64% decrease of uterine volumes was obtained at the end of treatment; the long-term reductive effect was 31%. When compared with initial values, a significant decrease was observed at the end of treatment (p = 0.0001) and of follow-up (p < 0.0005). In 13 (of 22) premenopausal patients, surgery was needed after triptorelin treatment for permanent control of fibroids. The remaining nine patients were free of symptoms after 42-56 months, having uteri in situ. These two groups differ significantly in pretreatment uterine volume (p < 0.001) and in reduction rate after therapy (p < 0.01), both parameters being higher in patients who finally needed surgery. In conclusion, triptorelin treatment is definitely beneficial in perimenopausal women and in nearly half of premenopausal women, in whom hysterectomy can be prevented. In the other half, surgery is necessary, despite significant volume reduction. These results need to be corroborated on larger groups of patients. More research is needed to explain different responses to treatment in premenopausal patients.


Calcitonin gene-related peptide, the menstrual cycle and premenstrual syndrome. Calcitonin gene-related peptide plasma levels were measured during four different phases of ovulatory menstrual cycles, in eight women suffering from the premenstrual syndrome and in eight controls. No significant fluctuations in calcitonin gene-related peptide levels occurred during the menstrual cycle. Neither were there significant differences in calcitonin gene-related peptide levels between the premenstrual syndrome and control groups.


Developmental and strain-specific heterogeneity of rat adrenal chromaffin cells recognized by a monoclonal antibody against intact chromogranin B. We have raised a monoclonal antibody (MAB-1E10) reactive with the intact forms but not the processing products of the chromaffin cell vesicle protein chromogranin B (CgB). The antibody recognizes rat and human, but not bovine and chick adrenal chromaffin cells. In addition, MAB-1E10 immunoreactivity was detected in rat PC 12 pheochromocytoma cells and in pituitaries. Several other tissues, including pancreas, small intestine and superior cervical ganglia, which are known to contain CgB in endocrine cells or neurons, respectively, were found not to be reactive with MAB-1E10. Using short-term cultures of dissociated adrenal chromaffin cells from Hannover-Wistar rats, we found that the expression of intact CgB is developmentally regulated. Between embryonic day 19 and postnatal day 40, about 80% of adrenal chromaffin cells--identified by their reactivity with an antibody against the enzyme dopamine-beta-hydroxylase--were found to be reactive with MAB-1E10. The proportion of positive cells subsequently decreased to about 5% at postnatal day 90. In the presence of glucocorticoids, this decrease was reduced to about 45% CgB-positive cells at postnatal day 90. In another rat strain, Sprague-Dawley rats, the proportion of MAB-1E10-immunoreactive chromaffin cells (about 50%) remained constant from birth to adulthood. Our results indicate that CgB is differentially expressed and/or processed in different rat tissues, strains and during development, and furthermore, that expression or processing in rat chromaffin cells might be regulated by glucocorticoids. Intact CgB appears to be a marker for a subpopulation of chromaffin cells, but its function(s) remains to be clarified.


Effects of combined pre- and postnatal ethanol exposure (three trimester equivalency) on glial cell development in rat optic nerve. This study evaluated the effects of a combined gestational and 10 day postnatal alcohol exposure (human three trimester equivalency) on the development of glial cells in the rat optic nerve. Pregnant rats were exposed to alcohol via a liquid diet, then their pups were artificially reared and further exposed to alcohol for 10 postnatal days via a gastrostomy fed liquid diet. Control animals, born of pair fed dams, were artificially reared on pair fed isocaloric diets. Optic nerve tissues were prepared for light and electron microscopic studies from animals on gestational days (G) 15 and 20 and postnatal days (P) 5, 10, 15, 20 and 90. There were fewer glial cells per cross-section on day 15 and the cross-sectional areas of optic nerves were smaller on days G20, P15 and P90 in the ethanol exposed animals. There was an alcohol-induced delay in the appearance of immature cells within the oligodendroglia lineage and a decrease in the number of oligodendroglia present at 15 and 20 days, indicating a delay in the maturation of oligodendroglial cells. These effects were compensated for by 90 days. Maturation of the astrocytic cell lineage was generally unaffected by the alcohol although there was evidence of increased numbers of cells in the lineage. There was no consistent indication of alcohol-induced degeneration of glial cells or their organelles. Thus, alcohol exposure for all of gestation and 10 postnatal days in the rat causes a delay in oligodendrocyte maturation but appears to have no long-term effects on the glial cell population of the optic nerve. Such a delay, by contributing to delays in myelin development, could help to explain some of the neurological dysfunctions associated with developmental alcohol exposures.


Effects of acetyl-L-carnitine on the survival of adult rat sensory neurons in primary cultures. Acetyl-L-carnitine produces a significant increase in the survival time-course of adult rat sensory neurons maintained in primary cultures up to 40 days. The analysis of our data suggests that 200 microM acetyl-L-carnitine added to the medium, slows down neuronal decay especially in the first 10 days in vitro, sparing a fraction of cells which would otherwise be lost. Patch-clamp recordings from these neurons show that superfusion with acetyl-L-carnitine (100-1000 microM) does not induce any membrane current. In addition an agonist muscarinic effect particularly concerning high-voltage activated calcium channel modulation appears to be ruled out. In conclusion our data favour the role of acetyl-L-carnitine in the trophism of sensory neurons in adult rats. In agreement with other in vivo experiments our data reinforce the hypothesis that this substance might be involved in reducing neuronal loss observed in nervous system aging.


Synaptic ribbons, spheres and intermediate structures in the developing rat retina. The present study was conducted to investigate the qualitative and quantitative development of synaptic bodies in retinae of Wistar rats during postnatal days 4-28. In addition, the effects of different light regimens and of eye pigmentation on SB numbers were studied. Synaptic bodies were counted and measured in the outer plexiform layer of retinal tissue fixed and processed by routine electron microscopical techniques. At postnatal days 4 and 5, retinae showed only few synaptic bodies. The main numerical development of synaptic bodies occurred between postnatal days 4 and 9, numbers remaining more or less constant thereafter. The intracellular location of synaptic ribbons changed from predominantly cytoplasmic sites to positions at the membrane. In Wistar rats of postnatal day 15 held under a light/dark regimen, synaptic ribbon numbers and lengths were found to be significantly larger at night than at daytime. This was not observed in animals kept under constant darkness. In retinae of a pigmented rat strain, Brown Norway, total numbers of synaptic bodies were similar to those of Wistar rats, whereas the relative proportions of synaptic ribbons and spheres or sphere-like structures, respectively, differed between strains. These results are discussed with regard to synaptic body formation and regulation under the influence of light and eye pigmentation.


Correlation between P19 presence and MHC class II expression in human fetal astroglial cells cocultured with HTLV-I donor cells. The possibility of a direct infection of human brain by HTLV-I, has been studied using an in vitro model. Human fetal astroglial cells were cocultivated with irradiated HTLV-I donor cell line MT-2, and assayed for the presence of HTLV-I core protein p19 after 1 week. Fifty-six per cent of GFAP positive astrocytes showed the viral core protein p19 and increased expression of Class II MHC antigens. Electron microscopy of astroglial cells exposed to HTLV-I revealed the presence of vacuoli-like structures containing viral core protein p19. Cell intermediate filament cytoskeleton was also disorganized. Even if this study does not provide direct evidence for virus replication inside astroglial cells, all these findings suggest that HTLV-I can indeed enter the cell and exert a cytopathic effect. Therefore the results of the present study are consistent with the hypothesis that astroglial cells could be involved in demyelination processes occurring in the HTLV-I associated neurological disorders, such as human associated myelopathy and tropical spastic paraparesis.


Mechanoluminescence: an assay for lymphocyte analysis in neoplasia. We have studied the mechano-electrochemical activation of optical emission (mechanoluminescence, ML) from the surface of lymphocytes. In C57BL/6 mice with B16 melanoma at the terminal stage of tumour growth and after immunotherapy with thymic agents, there is a correlation between light emission and the value of lymphocyte surface charge and titres of thymic serum factor (FTS).


Luminescence from the yeast Candida utilis and comparisons across three genera. Weak luminescence was detected from oxygenated liquid cultures of the yeast Candida utilis during two stages of its growth cycle. The first period of emission occurred during the exponential phase of growth and comprised an ultraviolet band (270-390 nm; ca 19 photons s-1 cm-2 of culture surface) and a visible band (450-620 nm; ca 68 photons s-1 cm-2). The second period of emission occurred late in the stationary phase of growth and was comprised almost entirely of a visible region band (450-620 nm; 6.8 x 10(2) photons s-1 cm-2). No luminescence was observed when the yeast was grown anaerobically. These observations are compared with those previously obtained for two other yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe. The ratios of the intensities of the blue/red emissions in the stationary phase luminescences correlated with the ratio of the saturated/unsaturated lipid content for the three yeasts. This result provided further support for the claim that the stationary phase luminescence arises from the reactions associated with lipid peroxidation. A number of previously suggested sources of the exponential phase luminescence are discussed and rejected. Oxidative side reactions accompanying protein synthesis remain a possible source of that emission.


Transcriptional induction of H2 (class I) antigens and beta 2 microglobulin by interferon-gamma in interferon-sensitive and interferon-resistant Friend leukemia cells. The effect of interferons (IFNs) type I (alpha/beta) and type II (gamma) on the stimulation of H2-Dd (class I) and beta 2 microglobulin genes transcription was analysed in IFN-sensitive (w.t.) and IFN-resistant Friend erythroleukemia cells (FLC). Type I IFN enhances the expression of H2-Dd and beta 2 microglobulin genes in w.t. FLC but does not modulate the expression of these genes in clones resistant to IFN-alpha/beta. IFN type II treatment of w.t. and IFN-alpha/beta resistant cell lines results in an increased expression of H2-Dd and beta 2 microglobulin genes, while being ineffective in the cell clone resistant to both types of IFNs. In this cell system the effect(s) of IFN type II is in part mediated by the induction of IFN-beta. The results reported in the present paper suggest that the IFN-gamma is able per se to increase the expression of H2-Dd and beta 2 microglobulin genes; since a reduced but clearly evident stimulation of the expression of these genes was observed in the FLC clone totally resistant to type I IFN.


[Assessment of iron requirements during treatment of anemia with recombinant human erythropoietin in patients with chronic renal insufficiency under hemodialysis]. Iron deficiency occurs often in patients with recombinant human Erythropoietin (rhEPO) therapy in chronic renal failure (CRF) associated anemia. We have studied 10 patients with CRF on regular hemodialysis (HD), female = 8, male = 2, average age = 49 [32 to 72], time on HD 44.2 +/- 25.0 months. Before starting rhEPO, the mean hemoglobin value was 7.36 +/- 1.29 gr/dl, the mean ferritin 695.4 +/- 276.0 ng/ml, the mean serum iron 160.3 +/- 49.5 micrograms/dl and the mean transferrin saturation 55.3 +/- 12.6%. Transfusional requirements in the 12 months Pré-rhEPO were 10.9 +/- 3.2 units. The rhEPO dose level was 80 U/kg body weight (3 times a week, after HD) in the Correction Period (mean time = 46.7 +/- 18.6 days), being reduced afterwards in order to remain target Hb stable between 10 and 11 gr/dl. Iron deficiency was detected (transferrin iron saturation less than 16% or serum ferritin less than 30 ng/ml) in 5 of the 10 patients. Patients have been divided into two Groups (GI--patients which developed iron deficiency; GII--patients which remained iron replete). There were no significant differences between GI and GII in the serum iron, transferrin and transferrin saturation values of the Pré-rhEPO. Serum ferritin in the Pré-rhEPO was lower in GI than GII (GI = 489.2 +/- 23.6 ng/ml; GII = 901.6 +/- 96.4 ng/ml; p less than 0.01). Falls in the transferrin iron saturation during the Correction Period and 3, 6 and 12 months and in the serum ferritin at 3, 6 and 12 months versus Pré-rhEPO have occurred.(ABSTRACT TRUNCATED AT 250 WORDS)


[Skin pathology in kidney transplant recipients]. Since 1990, 82 unselected renal allograft recipients were evaluated in order to establish the incidence of cutaneous disorders. This pathology was related to the period of immunosuppression according to time of transplantation: 0-3 months; 3-12 months; 12-36 months and beyond 36 months. Most of them were on triple immunosuppression (cyclosporine A, azathioprine and prednisone)--(51); Twenty-two also associated anti-timocyte globulin five days after transplantation; 7 were on Azathioprine and Prednisone and two of them associated Cyclosporine with Prednisone. Iatrogenic manifestations were the most common (80.5%) followed by infections in 63.4% and pre-malignant and malignant cutaneous lesions in 13.4%, other types of manifestations were found in 20.7% of patients. A significant incidence of pre-malignant and malignant lesions confirms other reports, making a dermatological surveillance advisable.


[Carcinoma of the lung. Review of a caseload of 12 years at a service of internal medicine]. The authors present a retrospective study of medical records of patients with lung cancer, admitted at the Service 1 of Internal Medicine of Santo António dos Capuchos Hospital during a 12 year period (1978-1989). Of the 112 selected patients, 50% had histologic diagnosis, the remaining had strong clinical radiographic, endoscopic and/or autopsic evidence of pulmonary malignancy or malignant cytology in sputum, bronchial secretions or pleural fluid. The clinical symptoms and means of diagnosis are presented and the advanced stage of the disease, at admission, the problems concerning the histologic diagnosis and the high mortality rate (55.4%) are emphasized.


A macrophage derived blastogenic factor -MBF- induces cytokines and cytotoxic effectors in human peripheral blood mononuclear cells. A soluble macrophage-derived blastogenic factor, previously reported as MBF, is secreted from macrophages activated with galactose oxidase. It was previously shown that MBF is able to induce IFN-gamma production and proliferation of T lymphocytes. In this study we found that MBF is able to induce in human peripheral blood mononuclear cells (PBMC) production of interleukin 1 (IL-1) beta, interleukin 2 (IL-2) and tumor necrosis factor (TNF) alpha and generation of MHC-unrestricted cytotoxic activity. The induction of killer cells is likely to rely on IFN-gamma production in that in PBMC treated with a monoclonal antibody (Mab) against IFN-gamma, the MBF induced cytotoxic activity was drastically reduced. A comparison of MBF induced cytotoxic effectors with those induced by IL-2 showed that both cytotoxic effectors pertain to NK lineage, in that they were CD3- and CD16+. On the contrary, the precursors of MBF and IL-2 induced killer cells were different; MBF cytotoxic precursor cells were highly sensitive to L-Leucine methyl ester (Leu-OME), a drug able to eliminate monocytes and NK cells, whereas IL-2 cytotoxic precursors were unaffected by this drug.


[Neurologic manifestations of Behçet disease. Review of the caseload of the Neurology and Dermatology services at the Santa Maria Hospital]. Neurological involvement in a series of patients with Behçet's disease, evaluated at the Departments of Neurology and Dermatology, St. Maria Hospital is reported. Meningoencephalytic or encephalytic were the most common clinical forms, while headache, cerebellar and pyramidal signs were the most prevalent symptoms/signs. On follow-up (range 2-13 years) the majority of the patients had either a progressive or a remitting-progressive course. Magnetic ressonance imaging was the most valuable method of detecting central nervous system lesions.


[Incidence of and mortality from malignant tumors inthe municipality of++Vila Nova de Gaia: 1981-1987]. Data from the population based Cancer Registry of Vila Nova de Gaia for the 1981-1987 period are presented. Cancer is becoming a disease increasingly frequent in Portugal, causing progressively higher mortality rates. Population and geographic characteristics of Vila Nova de Gaia country is presented. Information sources of this Registry are hospitals, pathology labs, Health Authority files and death certificates. Net (229.2, 216.6) and standardized for european population (369.9, 245.9) incidence rates are presented for respectively men and women. Comparisons with registries from other countries (e.s.) are made.


[Diagnosis of Lepore hemoglobinopathy with DNA analysis]. We illustrate the application of recombinant DNA methods (namely Southern blotting) for the genotype diagnosis of haemoglobin Lepore Boston: the use of the restriction endonucleases PstI and XbaI along with a beta globin gene specific probe make it possible to detect a deletion of approximately 7kb which typically characterizes the delta beta Boston gene. The impact of using such methods in the prenatal diagnosis of major haemoglobinopathies is discussed.


[Chronic disease, the chronic patient and his family. Psychosocial impact of diabetes mellitus]. Concerning a revision about the mutual influence between the diabetes, the diabetic and his family, the author reviews the literature about the psychosocial area of the Family Physician content's work. It is also confirmed the high prevalency of the chronic disease and the importance of the family ecosystem, not only as support but also as problem to the bearing person of such type of disease. Studies of chronic disease indicate that family dysfunction is associated with poor health outcomes. The areas which more and better have been studied in this scope are reviewed. Thus, having as backdrop the diabetes management, the family's diabetic influence in general is reviewed, as well as the parental attitudes, the family organization and the family life events. Finally, the health care team role is reviewed and particulary the role of the family physician in the management of this type of patients. It is pointed out, as example of the Family Medicine specific contribution, the improving cooperation with medical treatment from the diabetic.


[Research on psychosomatic disease. Various theoretical and methodologic aspects]. This article mentions ther present main lines of psychosomatic research either in what concerns the elimination of the concept of psychosomatic illness, or in what concerns its etiological understanding of the peculiar ways of therapeutic approach. We specify some methodological problems resulting from using several instruments to collect data and measure them. We analyse the theoric relevance of the constructs: depressive equivalents and, specially, the alexithymia one. Starting from the consensual phenomonological description of this construct, we explain its psychodynamic understanding, its neurophysiologic basis and sociocultural determination. We question the relationship between alexithymia and psychosomatic illness. We point out the pertinency of its utilization as a risk or maintainance factor and the possibility of its modelling by ambiance factors. We clarify the main heuristic contributions of this construct to psychosomatic investigation and we analyse, critically and concisely, the validity and fidelity of some instruments of measure built to measure it. It is necessary to pay prior attention to psychosomatic investigation in the health area. We propose lines of investigation to be developed in our country that should have a multidisciplinary perspective.


[Gastrinoma localized in the pylorus in a patient with recurrent peptic ulcer]. We report a clinical case of a woman, 56 years old, with a history of duodenal ulcer and esophagitis, under medication with H2 receptors blockers during 3 years. Plasma basal gastrin was near normal levels. A stimulation test with secretin was compatible with gastrinoma. CT scan and selective angiography didn't localize the tumor. At laparotomy we found a pyloric nodule that prove to be the gastrinoma. Eighteen months after surgery the patient is asymptomatic and with a normal endoscopic examination and secretin stimulation test.


[Neodymium--Yag laser in the recanalization of arterial occlusions]. Failure of the guide-wire to recanalize some arterial total occlusion does not preclude balloon angioplasty. Nowadays there are recanalization devices such as the mechanical atherectomy and Lasers. The following report describes the successful use of the Nd: YG Laser in the recanalization of a common iliac artery total occlusion in a patient with claudication, rendering possible balloon angioplasty and a Palmaz Stent implantation, which is the first case performed in our country.


[Ileoanal pouch for the treatment of adenomatous polyposis and ulcerative colitis--clinical and functional results]. The results of the first 9 patients with proctocolectomy and ileal pouch operated on between 1983 and 1990 were analysed. This procedure was carried out in 8 patients with adenomatous polyposis. Three of these patients had an associated rectal cancer and one a degenerated sigmoid polyp. One patient had ulcerative colitis and was previously submitted to a colectomy related with perforated fulminant colitis. Three types of pouches were constructed: 3 S, 3 J and 3W, all with a temporary ileostomy. A circular stapler was used in 2 cases for ileoanal anastomosis. Three postoperative complications were observed: two patients with pouchitis during the presence of a diverting ileostomy and an ileal fistula following ileostomy closure, all medically treated. Clinical and functional results were evaluated 1 to 7 years after the procedure. The average daytime stool frequency was 4 with 1 nocturnal. All patients indicated normal continence. One patient had her professional life affected due to the increased number of defecations. Differences in the clinical results of the patients with S, J and W pouches were not statistically different. The functional results expressed as median and range were as follows: resting and pressure 45 cm H2O (20-60), voluntary anal pressure 70 cm H2O (34-120), compliance 3.70 ml/cm H2O (1.14-11.40), maximal tolerated volume (MTV) 320 ml (110-48) and threshold volume 95 ml (40-170). The MTV values of the groups with J and W pouches were 190 ml (180-200) and 370 ml (340-480), respectively (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


[Spinal brucellosis. 4 years of experience]. The Authors retrospectively studied 17 patients who have been admitted to the Infectious Diseases Clinic of Coimbra University Hospital during a four year period and whose final diagnosis was brucellar spondylitis. Clinical, epidemiological, laboratory and imaging features are analyzed, as well as those related to the therapeutic schedules and outcome. Females were more often affected (70.58%) and the mean age was 53.35 +/- 13.82 years. Lumbar spine was most frequently involved and an unusual elevated incidence of paravertebral soft tissue swelling was noticed (23.52%). Two patients were also suffering from neurobrucellosis (11.76%). The preferred therapeutic schedule was rifampin and doxycycline and surgery was performed in one patient. Finally, several comments are made regarding basically the incidence, laboratory and imaging diagnosis, therapeutic aspects and evolution of the disease. The imaging similarities and differences between tuberculous, pyogenic and brucellar spondylitis are briefly approached.


[Surgical and trauma patients in a medical intensive care unit]. to characterize and to assess in terms of severity the surgical and trauma patients admitted to a medical intensive care unit (ICU). retrospective study base on clinical records and the ICU computerized database. the medical ICU of a tertiary hospital. of the 2468 patients admitted to the ICU in 1989, 289 (11.7%) were surgical or trauma ones. The more frequent reasons for admission were: the need for mechanical ventilation, metabolic problems, and depression of consciousness. Of these 289 patients, 48.1% required mechanical ventilation, 14.9 hemodialysis; 4.8% had a pulmonary artery catheter inserted. Mean APACHE II, TISS and MOF scores were high (20.09 +/- 9.29, 24.17 +/- 11.45 and 5.4 +/- 3.59); they were determined in 79.2, 88.2 and 43.9% of patients respectively. Both APACHE and TISS scores were correlated with mortality. When compared with medical patients, surgical/trauma ones although younger (52.9 +/- 20.7 years versus 55.9 +/- 20.2, p = 0.00152), had a longer mean stay in the ICU (7.63 +/- 12.7 days v. 3.64 +/- 7.61, p = 0.0001), and a higher mortality (also in the ICU) (28.7 v. 16.7, p = 0.0005. these are seriously ill patients, who are frequently referred to the ICU in late stages of clinical evolution. We propose they should be closely followed, from the earliest possible stage, by medical-surgical teams, in order to benefit from a multidisciplinary approach.


[Comas in the emergency room of a central hospital]. The aim of the present prospective work was to study the etiologic diagnosis and prognosis of the comatose patients for whom a neurologic examination is requested. It included 148 consecutive cases admitted to the emergency room of a general hospital. Coma was caused by supratentorial lesions in 38%, subtentorial lesions in 10%, diffuse or metabolic brain dysfunction in 49%, and psychiatric disorder in 1% of the patients. CT scan was the most valuable ancillary exam, modifying the initial etiologic diagnosis in 42% of the cases on whom it was performed. Seventy percent of the patients died. Coma caused by structural lesions had a worse outcome than coma caused by diffuse or metabolic brain dysfunction (intoxications excluded), and this type of coma had a worse outcome than drug-induced coma. The presence of anisocoria, the number of brainstem reflexes present and the pattern of motor response, as well as the Glasgow Coma Scale score, predicted the outcome.


Percutaneous splenic embolization of the splenic artery in the treatment of hypersplenism. Percutaneous splenectomy was performed in 6 patients with hypersplenism. Peripheral blood cell counts improved in 5 of the patients. The authors review the indications, technique and complications of percutaneous splenic embolization. It is concluded that medical splenectomy is an effective method particularly to alleviate symptoms of hypersplenism.


[Solar radiation--physicochemical aspects]. The solar radiation spectrum and the properties of its components are studied in the present paper. The history of the sun rays before reaching earth surface is analysed. A simplified analysis of the interaction mechanisms of these components with molecules, the energy absorption capabilities of the latter and the expected biological consequences are considered. Special emphasis are given to the properties of ultra-violet and infra-red radiations and their production considered.


[Anorexia nervosa and a psychosomatic investigation]. The paper begins with a revision of diagnostic criteria of Anorexia Nervosa (AN), stressing the importance of early diagnosis and transitional forms between AN and Bulimia Nervosa. A retrospective study of 13 female patients with AN, treated during 1990 in Lisbon Psychiatric University Clínica (Hospital de Santa Maria, Lisboa) is then described. The Authors outline some common characteristics of the sample, many difficulties in the early relationship mother-child, shown by maternal unsatisfaction on feeding the baby and with changing of food. Concluding, the Authors point out some directions for eating disorder's investigation, starting with a multidisciplinary work including biological and cultural factors and understanding of individual development and family dynamics.


[Pulmonary emphysema in a patient with Turner's syndrome]. Turner's Syndrome was first described in 1938 by Henry Turner and has an incidence of 1:3000 live female births. The authors present an unusual case of a 48-year-old woman with late diagnosed Turner's Syndrome. Whose karyotype was (46,X,i(Xq)), associated with a pulmonary emphysema and pulmonary hypertension. The case and the methods of study are presented. Some aspects of this case, namely the hypothesis of an association between the pulmonary emphysema and Turner's Syndrome are discussed.


[Emphysematous cholecystitis].

[Emphysematous cholecystitis]. Emphysematous cholecystitis (EC) is a rare and dramatic disease that requires prompt therapeutic procedures. The authors report a case of a 70-year-old-woman, admitted to the Intensive Care Unit for Infectious Diseases of the Santa Maria Hospital, with the diagnosis of EC. The literature on EC is also reviewed.