Activation of neutrophil function by recombinant human granulocyte colony-stimulating factor improves the survival of rats with peritonitis

We examined the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and cefmetazole sodium on survival, neutrophil count, and neutrophil function in rats with peritonitis produced by cecal ligation and puncture. Rats with peritonitis received either rhG-CSF (50 or 100 g/kg) with or without cefmetazole (50 mg/kg) for 3 days, cefmetazole alone, or no treatment and were evaluated as controls. The mortality rate of all treated rats was significantly lower than that of the untreated rats. The survival rate was 57.1% for the rats given both rhG-CSF and cefmetazole, but there was no significant improvement of survival as compared with cefmetazole therapy alone. Treatment with rhG-CSF at 100 |Gmg/kg caused the circulating neutrophil count to increase significantly. The phagocytic activity for latex beads and neutrophil H₂O₂ production showed a greater enhancement by phorbol myristate acetate (PMA) in the untreated rats, thus indicating that neutrophils from treated rats were more activated. These findings show that rhG-CSF can improve survival and neutrophil function in rats with peritonitis, while combined therapy with cefmetazole was also found to be beneficial.     

First experience in healthy volunteers with technetium-99m l,l-ethylenedicysteine,a new renal imaging agent

Animal studies have indicated that technetium-99m l,l-ethylenedicysteine (^99mTc-l,l-EC) may be a promising tracer agent for renal function studies. We have performed a paired study with ^99mTc-mercaptoacetyltriglycine (^99mTc-MAG₃) and ^99mTc-l,l-EC in six male volunteers. In both cases, iodine-131-labelled o-iodohippurate was co-injected as an internal biological standard. The analog images between 0 and 30 min p.i. were of identical diagnostic value for both tracer agents. The two renograms were similar in all volunteers. The mean 1-h plasma clearance for ^99mTc-MAG₃ and 99 mTc-l,l-EC was significantly different, respectively 382.9 ± 17.1 ml/min per 1.73 m² versus 460.2 ± 47.7 ml/min per 1.73 m² (P<0.003). The urinary excretion after 30 min p.i. was 69.4% ± 5.6% of the injected dose for ^99mTc-MAG₃ versus 66.5% ± 2.5% for ^99mTc-l,l-EC (P>0.05) and after 60 min p.i. respectively 83.1% ± 3.9% versus 79.8 % ± 4.3 % (P > 0.05). ^99mTc-l,l-EC has a very low plasma protein binding (31% ± 6.8%) as compared to ^99mTc-MAG₃ (88% ± 5.2%) and a larger volume of distribution. Although the exact mechanism responsible for the high plasma clearance of ^99mTc-l,l-EC is not yet fully known, we conclude that this new agent merits further clinical evaluation in patients to establish its value as a renal radiopharmaceutical. Correspondence to: A. Verbruggen     

Thyroidal handling of radioiodine in sea level residents exposed to hypobaric hypoxia

In the present investigation thyroidal accumulation of radioiodine and its release were assessed by direct testing of thyroid function using radioactive iodine, in vivo, in sea level residents intermittently exposed to hypobaric hypoxia. Thyroidal accumulation of radioiodine and its turnover were examined daily for 14 days. Twelve healthy human male volunteers were divided into three groups, with an equal number of individuals in each group. A decompression chamber was used to expose each group of subjects to hypoxic conditions at a simulated altitude of 3810 m for 8 h/day for 14 days. An oral dose of 25Ci iodine-131 was administered to each individual of the first group immediately before the initiation of intermittent hypoxia. The second group of subjects received a tracer dose at the beginning of the 4th day of the 14 days, intermittent exposure to hypoxia, while the third group received the tracer dose 1 week after the completion of the exposure. Control studies were carried out on the subjects before they were subjected to the experimental conditions. Thyroidal accumulation of¹³¹I in experimental subjects during the hypoxic state and in the post-hypoxic state was higher than in the control studies. The pattern of accumulation during exposure to hypoxia and in the post-hypoxic state showed multiple peaks of radioactive iodine uptake (PRAIU), a unique feature. The multiple PRAIU by the thyroid in experimental subjects were sharp and of short duration, reflecting an increased rate of¹³I release from the thyroid. Control subjects had a single PRAIU by the thyroid 24 h after the administration of tracer.     

口服Ⅱ号避孕药对血小板功能及血液凝固的影响

为了解口服Ⅱ号避孕药对血小板功能及血液凝固性的影响,本文对65名连续服药妇女进行了研究。她们的年龄为27～45(平均36.5)岁。服药期限1～17(平均6.7)年。测定项目有纤维蛋白原,血小板粘附率,血小板聚集率,Ⅷ因子相关抗原,抗凝血酶活力等。20例未服药妇女作对照。测定结果服药组血小板粘附率、聚集率及纤维蛋白原比对照组明显增高(P<0.001)。Ⅷ因子相关抗原略增高,但无统计学意义。抗凝血酶活力显著降低(P<0.001)。本文就急性心肌梗塞及血栓栓塞的潜在可能性等问题进行了讨论,并对预防此类并发症提出了建议。     

Hemispherectomy — 25 years later — findings and concepts

Summary In the first part the case of a then 27 year old female patient with right-sided infantile spastic hemiplegia after left-sided porencephaly is described, in whom hemispherectomy was performed 25 years ago. The postoperative state and the development are described as well as the social outcome and the present neurological status. A computer-tomogram shows the actual state of the brain.The second part is devoted to a scientific discussion of the supplementary motility after pyramidal lesions which is defined as the action of descending subcortico-spinal pathways starting probably in the mesencephalon, whereas an ipsilateral pathway is unlikely. Comparative neurological experiments serve to support such a concept as well as similar observations in traumatic cerebral lesions in man. In the light of the far more skilled motility in cerebral lesions of the young as well as the possibility of a shift of neuropsychological functions of the dominant to the contralateral hemisphere in children up to the age of 8–10 the possibility is discussed that plasticity — the concept of Albert Bethe — could form the mechanism of auxiliary function.Furthermore the surprising sensory performances in some of the patients with hemispherectomy are emphasized and the possibilities of anipsilateral substratum are discussed; however, this contrasts with the concepts formulated for the auxiliary motility after pyramidal lesions. Clarification of these problems will probably follow only after further experimental work.

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Zusammenfassung Im ersten Teil der Arbeit wird der Fall einer damals 27-jährigen Patientin beschrieben, die eine rechtsseitige infantile spastische Hemiplegie nach linksseitiger Porencephalie hatte. Bei ihr war 25 Jahre zuvor eine Hemisphärektomie durchgeführt worden. Der postoperative klinische Status und die Entwicklung der Syndrome wird beschrieben und über die soziale Situation berichtet. Schließlich wird der derzeitige neurologische Status genau wiedergegeben. Erstmalig zeigt ein Computer-Tomogramm den Zustand des Hirns nach diesem Zeitraum.Im zweiten Teil der Arbeit wird die Entstehung der Ersatz-Motilität diskutiert, die als eine Aktion deszendierender subkortiko-spinaler Bahnen definiert wird, die wahrscheinlich vom Mittelhirn ihren Ausgang nehmen, während die Tätigkeit ipsilateraler Systeme für unwahrscheinlich gehalten wird. Vergleichende Tierexperimente am Hirn unterstützen eine solche Auffassung, ebenso wie auch die Beobachtung bei umschriebenen Hirnverletzungen des Menschen.Dann wird die Möglichkeit von Ersatzfunktionen durch Plastizität diskutiert — ein Begriff von Albert Bethe. Dies erscheint im Lichte vieler Beobachtungen wichtig, da die Ersatz-Motilität bei Hirnläsionen junger Menschen sehr viel höhere Geschicklichkeit ermöglicht als bei Läsionen von Älteren; weiter ist zu beachten, daß neuropsychologische Funktionen bei einer Hirnläsion vor dem 8. bis 10. Lebensjahr von einer dominanten Hemisphäre noch auf die andere Seite verlegt und dort lokalisiert werden können. Schließlich wird bei diesen Patienten auf die erstaunlichen Fähigkeiten der sensiblen Systeme nach Hemisphärektomie hingewiesen und hier die Möglichkeit eines ipsilateralen anatomischen Apparates diskutiert. Jedoch können bei der Sensibilität so genaue funktionell-morphologische Vorstellungen noch nicht formuliert werden, wie sie sich z. Zt. schon für die Ersatz-Motilität nach Pyramidenbahnläsion ergeben. Erst genauere Experimente im Tierversuch können weitere Aufklärung bringen.

     

Electrophysiological determination of the refractive state of the eye of the opossum

The refractive state of the eye of the South American opossum Didelphis marsupialis aurita was investigated with electrophysiological techniques. Using adult specimens, trapped from the wild, averaged cortical evoked responses were recorded from the region of projection of the central visual field. Stimuli consisted of a phase reversal of a square wave grating generated on a CRO screen, with luminance of 2.4 cd/m2 and contrast 0.84. The refractive state of the eye was altered by means of trial lenses and the amplitude of the cortical responses thus obtained compared to those obtained with no lens (control values). Refraction "tuning curves" were determined for each animal. The average refractive state was found to be -2.27 D indicating that this species when raised in its habitat shows, at low ambient luminosity, some degree of myopia. Determination of the Contrast Sensitivity Function indicate that induced ametropias lead to a reduction of the cut-off value of the spatial frequency and a loss of contrast sensitivity.     

lontophoretic Delivery of a Series of Tripeptides Across the Skin in Vitro

The iontophoresis of eight tripeptides, of the general structure alanine–X–alanine, has been measured across hairless mouse skin in vitro. The peptides were blocked (a) at the carboxyl terminus using the mixed anhydride reaction with t-butylamine and (b) at the amino terminus by acetylation with ¹⁴C-acetic anhydride. The nature of the central residue (X) was varied by selecting one of five neutral amino acids, two negatively chargeable moieties (aspartic and glutamic acids), and a positively chargeable species (histidine). Constant current iontophoresis at 0.36 mA/cm², using Ag/AgCl electrodes, was performed for 24 hr in diffusion cells, which allowed both anode and cathode to be situated on the same (epidermal) side of a single piece of skin. Due to a combination of osmotic and electroosmotic forces, the anodal iontophoretic flux of neutral peptides was significantly greater than passive transport. Steady-state fluxes were not achieved, however, suggesting that time-dependent changes in the properties of the skin barrier may be occurring. Limited, further experiments confirmed that, on a 24-hr time scale, these changes were not fully reversible. The cathodal delivery of anionic permeants was well controlled at a steady and highly enhanced rate by the current flow. This behavior closely paralleled earlier work using simple negatively charged amino acids and N-acetylated amino acid derivatives. It appears that the normalized iontophoretic flux of these anionic species is independent of lipophilicity but may be inversely related to molecular weight. The positively charged peptide, Ac–Ala–His–Ala–NH(Bu^t), showed greater anodal iontophoretic enhancement when delivered from a donor solution at pH 4.0 than from a solution at pH 7.4. This was consistent with (a) the corresponding behavior of histidine alone and (b) the existence of a pK _a for these compounds at 6. Steady-state delivery was not achieved, although the levels of enhancement, especially at pH 4, were the largest observed. A preliminary investigation of tripeptide stability to either (i) electrolysis in the donor compartment or (ii) cutaneous metabolism revealed very little degradation under the conditions of the experiment. Overall, this research supports the principle of enhanced peptide delivery across the skin by iontophoresis and indicates a number of areas (e.g., mechanism and extent of current-induced changes in skin barrier function, molecular size dependence, pathways of current flow) on which further work should be focused.     

Cardiac function in congenital hypothyroidism: Impairment and response to L-T4 therapy

Summary Electrocardiograms (heart rate, QRS voltage, QRS axis in the frontal plane, Q-Tc interval), echocardiograms [left ventricular fractional shortening (LVFS); preejection period (PEP); PEP/left ventricular ejection time (PEP/LVET) ratio; end-diastolic left ventricular free wall and interventricular septum thickness; presence of pericardial effusion], and thyrotropin (TSH), thyroxine (T₄), and triiodothyronine (T₃) serum levels were evaluated before and 1 week, 1 and 2 months after the start ofl-thyroxine (L-T₄) therapy in 11 infants with congenital hypothyroidism (CH), aged 16–59 days when first seen.Before the start of therapy, infants with CH had significantly lower QRS complexes and LVFS and significantly higher values for Q-Tc, PEP, and PEP/LVET than normal infants of the same age. The QTc interval, PEP and PEP/LVET ratio of infants with CH were significantly greater before than 1 week after L-T₄ therapy, and LVFS was significantly lower before than 1 month after L-T₄ therapy. Four of the infants with CH had small pericardial effusions, which disappeared within the first week of therapy.QRS axis in the frontal plane, Q-Tc interval, and PEP were negatively correlated with logT₄ and logT₃ serum levels. PEP/LVET ratios were negatively correlated with logT₄ serum values. The QRS voltage values were positively correlated with logT₄ and logT₃ serum values. The frontal-plane QRS axis, Q-Tc interval, and PEP/LVET ratio were positively correlated with logTSH serum levels. The QRS voltages were negatively correlated with TSH serum levels.Our data show that before therapy infants with CH have the same functional, but not morphological, abnormalities as older hypothyroid ones and that one third of them have small pericardial effusions. L-T₄ therapy rapidly reverses these changes.     

The role of PGE2 in the sensitization of mechanoreceptors in normal and inflamed ankle joints of the rat

Summary The role of PGE₂ in the sensitization of highthreshold tarsal joint mechanoreceptors (putative nociceptors) has been investigated in 11 arthritic and 16 normal rats. Injections of a low dose of Freund's complete adjuvant at multiple sites into the tissues surrounding the ankle joint induced a chronic unilateral monoarthritis in the injected limb. Measurements of both spontaneous activity and responses of tarsal joint mechanoreceptors to repeated graded mechanical stimuli were made. All of the mechanoreceptors examined had afferent fibres with conduction velocities in the C or A- range. Using this new model of joint inflammation we have shown that lysine acetylsalicylate reduces the mechanical sensitivity of these joint mechanoreceptors and reduces the spontaneous activity in afferent nerve fibres. Prostaglandin E₂ is unable to restore either the spontaneous activity in the afferent axon or the mechanical sensitivity of tarsal joint mechanoreceptors after lysine acetylsalicylate in the arthritic rat. Similarly, PGE₂ does not sensitize or excite tarsal joint mechanoreceptors in the normal rat. In the normal rat, however, PGE₂ potentiates the excitatory action of bradykinin and enhances the sensitizing effect of bradykinin on the responses of joint mechanoreceptors to mechanical stimulation when both substances are injected simultaneously. These results indicate that PGE₂ is not important in the sensitization of these joint mechanoreceptors in this model of chronic joint inflammation but that in other circumstances PGE₂ may be able to contribute to a sensitization of joint mechanoreceptors by enhancing the action of bradykinin.     

Extravascular chest wall technetium 99m diethylene triamine penta-acetic acid: implications for the measurement of renal function during renography

Measurement of individual kidney glomerular filtration rate (IKGFR) from the gamma-camera technetium 99m diethylene triamine penta-acetic acid (^99mTc-DTPA) renogram requires a continuous measurement of arterial activity. This is usually based on a region of interest (ROI) placed over the cardiac blood pool on the posterior view, with the assumption of negligible contamination from activity in the extravascular space of the chest wall. By injecting a small dose of technetium 99m human serum albumin (HSA) before the^99mTc-DTPA in 12 patients undergoing routine renography, the contribution of extravascular activity to the total signal recorded over the cardiac blood pool was calculated to be 11.0% (SE 2.1%) 1.5 min after DTPA injection, rising to 35.1% (SE 2.5%) at 15 min. Subtraction of the time-activity curve recorded from a ROI of the same size over the right lung generated a pure blood signal as shown by almost identical HSA/DTPA signal ratios recorded in blood samples taken 5 min after HSA and 15 min after DTPA and from the gamma-camera at the corresponding times. The effect of using a cardiac blood pool time-activity curve uncorrected for extravascular activity was to overestimate IKGFR by an average factor of 1.17 (SE 0.03). Offprint requests to: A.M. Peters