Pharmaceutical characterization of corticosteroid suppository treatment for ulcerative colitis. The dose and method of administration of a corticosteroid given for the treatment of patients with ulcerative colitis are determined according to the range of the diseased area and its severity. In this study, we prepared a hydrophilic suppository consisting of water-soluble prednisolone sodium succinate (PSL-SS) and a hydrophilic base, polyethylene glycol (PEG), and a hydrophobic suppository consisting of water-insoluble prednisolone (PSL) and a hydrophobic base, Witepsol (WT). We determined the spread of the drugs after intrarectal administration and their therapeutic effect. When rats received the hydrophilic suppository, the drug spread farther oral than when they received the hydrophobic suppository. Moreover, more than half of the PSL-SS recovered was observed to have changed into PSL. A therapeutic effect on the colitis induced in rats by acetic acid was noted in the area up to 10 cm from the anus in the case of the hydrophilic suppository, while the effect of the hydrophobic suppository was seen only in the area up to 2.5 cm from the anus. In patients with ulcerative colitis, the hydrophilic suppository showed retrograde spread to a site 34.4 +/- 5.3 cm from the anus, while the hydrophobic suppository spread to a site 19.0 +/- 2.4 cm from the anus. These results suggest that a hydrophobic suppository should be used for patients in whom inflammation is confined to the rectum, and a hydrophilic suppository used for patients in whom inflammation reaches the rectum and the middle part of the sigmoid colon.


Focal hemorrhagic necrosis of the liver. A rare cause of hemoperitoneum. A 44-year-old white female developed hepatic hemorrhage due to focal hepatic necrosis. This is the only reported case of its kind we have found. No other underlying processes were identified except for the chronic use of oral conjugated estrogens. The possible role of steroids and a possible relationship to the pathogenesis of peliosis hepatis is discussed.


Fibrin ring granulomas in hepatitis A.

Fibrin ring granulomas in hepatitis A. Fibrin ring granuloma is characterized by a fibrinous ring surrounding a central fat vacuole. It has been found in the liver and bone marrow of patients with Q fever, and occasionally with visceral leishmaniasis, cytomegalovirus, Epstein-Barr virus, Staphylococcus epidermidis infections, Hodgkin's lymphoma, and hypersensitivity to allopurinol. We describe a case of serologically confirmed viral hepatitis A with this lesion in the liver biopsy. A false positive anti-hepatitis A virus IgM result has been excluded. This is, to our knowledge, the second reported case of type A hepatitis with hepatic fibrin ring granulomas. It confirms that hepatitis A should be included in the differential diagnosis of this lesion.


Esophageal hematoma and tear requiring emergency surgical intervention. A case report and literature review. Esophageal hematoma is a disorder characterized by the sudden development of pain, hematemesis, or dysphagia, commonly with minimal precipitant. We present the case of 59-year-old man with esophageal hematoma, precipitated by eating, with massive hematemesis requiring surgical intervention. A review of 31 additional cases in the literature since 1980 is discussed. The Mallory-Weiss syndrome and Boerhaave syndrome are distinct entities with some clinical similarities.


Intestinal carcinoid tumor and myotonic dystrophy. A new association? The occurrence of multiple carcinoid tumors of the small bowel with liver metastases is reported in a patient with a previous myotonic dystrophy. In addition to the association of myotonic dystrophy with multiple endocrine adenomatosis type 2A, hyperparathyroidism, and neurofibromatosis, this case report gives further evidence for the propensity of such patients to develop neuroendocrine tumors.


Effect of carbachol on intraocular pressure in small-incision cataract surgery. Sixty patients, who underwent phacoemulsification and implantation of a folded polyHema intraocular lens were assigned to two groups. Following wound closure 0.5 ml of 0.01% carbachol or balanced salt solution was instilled into the anterior chamber. Healon was used in all eyes but evacuated from the capsular bag behind the intraocular lens and the anterior chamber. Intraocular pressure was measured the day before as well as 6 and 18 hours postoperatively. At 6 hours the mean change of intraocular pressure from baseline was -2.8 +/- 5.3 mmHg in the carbachol group compared with +4.7 +/- 8.0 mmHg in the BSS group (p < 0.0001). At 18 hours the mean change from baseline was -3.0 +/- 4.6 mmHg in the treatment group and +2.3 +/- 8.5 in the control group (p < 0.0001). Intraocular pressure exceeding 25 mmHg at 6 hours was observed in 8 (27%) eyes of the control group but none of the treatment group. At 18 hours 4 (13%) eyes of the control group and 1 (3%) of the carbachol group still had an increase of intraocular pressure. Summarizing our results we conclude that the effect of Healon on the postoperative intraocular pressure is successfully counteracted by its aspiration from the capsular bag and the anterior chamber, especially when carbachol is used for intraoperative miosis.


Lens opacity in patients with hypercholesterolemia and ischaemic heart disease. Electronic lens opacity measurements. Lens opacity studies were performed using an electronic Lens Opacity Meter (Interzeag Opacity Lensmeter 701) in a population (n = 321) with ischaemic heart disease. These patients are participating in a trial targetting at the reduction of mortality and incidence of myocardial infarction using a cholesterol-lowering drug, simvastatin. A separate study to evaluate the reliability of the method showed good reproducibility. Repeated measurements after a short time-interval (2-10 days) gave statistically lower opacity values either due to a change in lens transparency or perhaps a change in pigment and cell dispersion in the aqueous caused by repeated mydriasis. Lens opacity values showed a highly significant positive correlation to age. Serum cholesterol, systolic blood pressure and smoking habits showed no significant correlations to the levels of lens opacity when adjustments for age were made.


Changes in the diagnostic parameters during keratoconjunctivitis sicca therapy. In 35 patients with mild, moderate and severe keratoconjunctivitis sicca, an association was found between treatment effect, break-up time value and Rose bengal score. Neither of these tests, used separately, was successful as a clinically valuable predictor of treatment effect as the scatter, in score points, was too large. Analysed together, however, as in a partial regression analysis, an adequate prediction is possible, which is clinically of some value.


Screening of diabetics who read incorrectly colour-dependent glucose test-strips. Forty-eight diabetic patients (82 eyes) were examined with four different colour vision tests and one blood glucose strip-test. The ages of the patients varied from 23 to 65 years (mean 44.3 years +/- 11.4, SD), the duration of diabetes from 13 to 41 years (mean 25.8 +/- 6.2), and the visual acuities from 0.2 to 1.0 (mean 0.8 +/- 0.2). Of the eyes, 77 had had photocoagulation, 25 had small peripheral lens opacities, and 55 had slight background retinopathy. The colour vision tests were: the Standard Pseudoisochromatic Plates part 2 (SPP2), the Lanthony Tritan Album, the Farnsworth Panel D 15 test and the box III of the Farnsworth-Munsell 100 hue (FM 100) test. The blood glucose test was Haemo-Glukotest 1-44. Of the 82 eyes, 38 incorrectly saw Haemo-Glukotest strips. The SPP2 test found 89% of the eyes, the Tritan Album 55%, the Panel D 15 71%, and the box III of the FM 100 test 76%. The strips were correctly interpreted in 44 of the eyes. However, 36% of them failed the SPP2, 16% the Tritan Album, 11% the Panel D 15 test and 18% the box III of the FM 100 test. The Panel D 15 test and the box III of the FM 100 test would be useful in screening those diabetics who cannot correctly interpret the colour-dependent glucose test-strips and would need a blood sugar meter for their blood glucose level testing.


The cornea in exfoliation syndrome.

The cornea in exfoliation syndrome. Exfoliation syndrome (EXS) is a disorder which affects some structures of the eye. We studied the changes of the cornea in patients with EXS and compared with those in normal persons. A prospective study of 96 consecutive patients more than 70 years of age was set up. 48 of them (70 eyes, group A) had exfoliation in one or both eyes and 48 (group B) had no ocular disease other than senile cataract. None of the patients had any systemic disease. The endothelium and thickness of the central cornea were studied. Endothelium of the eyes with EXS showed significantly (p < 0.05) lower cell density than those of group B. Cornea in group A was significantly thicker (p < 0.05) than in group B. The morphology of the endothelium in group A showed a decrease of hexagonal cells and a higher rate of polymegethism compared to group B. Corneal thickness and endothelium showed no significant differences between the eyes with EXS and normal fellow eyes. These results add another risk factor, the fragile cornea, in eyes with EXS, in cataract surgery.


The photopic hill: a new phenomenon of the light adapted electroretinogram. Utilizing a high intensity photographic flash unit, electroretinograms were recorded from normal adults under fully light adapted conditions over a 5 log unit range of stimulus luminance (-1.35 to 3.34 log cd-s/m2). At lower luminance levels b-wave amplitude increased with increased luminance until it reached a maximum (Vmax of the Naka-Ruston equation) in agreement with previous work. At higher luminance levels, the b-wave amplitude decreased to 33% of Vmax and then plateaued. This previously unreported phenomenon has been named the photopic hill. There was no appreciable change in b-wave amplitude with increased interstimulus intervals from 15 sec to 5 min and luminance-response functions serially recorded for increasing and for decreasing stimulus luminance were very similar. These latter results indicate that the photopic hill is not due to light adaptation. The reason for the photopic hill and possible clinical implications are discussed.


Reconsideration of Bell's phenomenon using a magnetic search coil method. The exact direction, amplitude and time course of Bell's phenomenon is still controversial. We evaluated the eye movements associated with spontaneous blinks, voluntary blinks and prolonged eyelid closure using a magnetic search coil method. Spontaneous blinks were accompanied by transient downward and nasalward eye movements, and similar movement accompanying voluntary blinks were often followed by upward movements. The eye positions occurring immediately after blinks often differed from the initial positions and were followed by corrective saccades, which disappeared when the subjects did not fixate. Prolonged eyelid closure was accompanied by tonic eye elevation and voluntary blinks were accompanied by marked transient eye elevation when eyelid closure was mechanically impeded. Under normal conditions Bell's phenomenon does not occur during blinks.


Cycloplegic refraction in children: single-dose-atropinization versus three-day-atropinization. A new scheme for refractive measurements under atropine cycloplegia was tested in 90 strabismic children aged two to several years. Refraction was determined by an autorefractor (CANON R 10) 90 minutes after application of two drops of atropine (0.5% atropine children < 2 1/2 years; 1.0% atropine children > 2 1/2 years) and compared with the results after 3 days of receiving 1 atropine eyedrop 3 times daily. In 86.5% the spherical equivalents differ not more than 1.0 diopter (p = 0.05); the correlation was 0.99. Astigmatic corrections were in agreement in 95.5%, the axis of cylinders in 93.0% (p = 0.05); the correlations were 0.95 and 0.97. The residual accommodation 90 minutes after 2 drops of atropine was not more than 1 diopter in all children. The additional cycloplegic effect of the three-day-atropinization was only 0.5 diopters. This new type of application allows a more rapid and less toxic assessment of refraction than the usual three-day-atropinization.


Systemic acyclovir and penetrating keratoplasty for herpes simplex keratitis. Corneal graft survival in 13 patients (14 eyes) receiving oral acyclovir following corneal transplantation for herpes simplex keratitis was compared to that in nine patients (9 eyes) who underwent penetrating keratoplasty for herpes simplex keratitis without receiving postoperative acyclovir. Mean age, duration of disease, and time of follow-up did not differ in the two groups. There were no recurrences of herpes simplex keratitis in any patient receiving acyclovir during a mean follow-up of 16.5 months compared to a 44% (4/9) recurrence rate in patients without acyclovir during a mean follow-up of 20.6 months (p < 0.01). Graft failure occurred in 14% (2/14) of acyclovir treatment eyes and in 56% (5/9) of the grafts in patients not receiving acyclovir. Long term prophylactic oral acyclovir significantly decreased the recurrence of herpes simplex keratitis and reduced corneal graft failure in patients with a history of recurrent herpes simplex keratitis who underwent corneal transplantation.


Carteolol incorporated into FAT-MLV liposomes: prolonged and decreased reduction of IOP. Liposomes are used as carries providing a prolonged and improved drug action. They are capable of trapping beta-blockers such as Carteolol. In a randomized prospective double-blind clinical trial, Carteolol 2% suspended with frozen and thawed multivesicular large vesicles (FAT-MLV), FAT-MLV, and Carteolol 2% were applied to normal (slightly cataracterous) eyes and immediately after extracapsular cataract extraction or phakoemulsification with implantation of a posterior chamber lens in a standard procedure. Twenty-five patients were included in each group. Intraocular pressure (IOP) was measured for 3 days using applanation tonometry. In the normal eyes, a significant reduction of IOP was found for the patients receiving Carteolol and Carteolol MLV suspension. Moreover, an improved action and a prolongation of drug action was registered in the Carteolol/MLV group as compared to Carteolol treatment alone. After cataract operation, the control groups showed a significant increase in IOP. Carteolol produced a constant level of IOP but the Carteolol/MLV suspension showed a stronger decrease after ECCE and a still stronger decrease after phakoemulsification. Hence, Carteolol is suitable for the reduction of IOP but a Carteolol/MLV suspension is more effective, providing the possibility of a single application of a low-dose beta-blocker after cataract extraction with posterior chamber lens implantation.


Digital subtraction macrodacryocystography by videotechnique. Digital subtraction macrodacryocystography (DSMD) has proved to be the best imaging method for diagnosing situations of stenosis of the lacrimal system. The examination is performed with a computer-controlled X-ray unit with a C-arc coupled to an image intensifier TV system with a fluoroscopic control. All the findings were recorded on videotape thus allowing good dynamic flow documentation and contributing to improved scientific analysis.


Application of hyaluronidase after unsuccessful trabeculectomy. Trabeculectomy fails to control the intraocular pressure (IOP) adequately in some cases. The effect of the enzyme hyaluronidase--300 IU Hylase 'Dessau' (commercially available ampuls)--applied in subconjunctival injection in the region above the filtering bleb in case of postoperative rise in IOP following trabeculectomy was studied. Successful IOP control was defined as an IOP below or equal to 20 mmHg with or without medication. The investigation concerned 62 eyes (46 patients) with primary open angle glaucoma (POAG) divided in three groups: Group I--39 eyes with early postoperative rise in IOP (7-20 days postoperatively), group II--15 eyes with late rise in IOP (6 months-1 year after surgery), group III--8 eyes with one previous unsuccessful trabeculectomy. In all examined cases IOP was over 20 mmHg (mean IOP was 26.23 +/- 3.46 mmHg) postoperatively before application of hyaluronidase. The follow up period ranged from 6 to 34 months. We found statistically significant lowering in IOP in group I (p < 0.01), group II (p < 0.05) and group III (p < 0.05). Complications related to the use of hyaluronidase were not observed up to now. Postoperative subconjunctival injection of hyaluronidase appears to improve the prognosis following unsuccessful trabeculectomy in POAG patients.


Rapid increase of intracellular Ca2+ concentration caused by aminoadipic acid enantiomers in retinal Müller cells and neurons in vitro. The ability of the gliotoxic compounds D,L-, D- or L-2-aminoadipic acid (AAA) to increase selectively the intracellular concentration of free calcium ion ([Ca2+]i) was examined in Müller cells cultured with or without retinal neurons. The monitoring of [Ca2+]i following exposure to 0.06 to 6 mM AAA was performed by a microfluorometry using a fluorescent Ca2+ indicator, Fura-2 acetoxymethyl ester. A rapid increase of [Ca2+]i occurred in the Müller cells following exposure to a relatively low concentration of the L-isomer. This is compatible with the known strong gliotoxicity of this isomer. The D,L- and D-forms of AAA activated neurons at low concentrations and activated the Müller cells at higher concentrations. The D-isomer appears to act selectively on retinal neurons and may be an agonist of an excitatory amino acid receptor. These results indicate that the ability of AAA to elevate cytosolic [Ca2+]i depends on the stereospecificity of the AAA and on cell type.


The history of stereoscopy.

The history of stereoscopy. Ptolemy (127-148 AD) studied physiological diplopia, correspondence and the horopter. He had all the data to build a theory of depth perception through disparity detection, but left that undone. Alhazen (1000 AD) associated depth perception with the sensation of binocular convergence, just as Kepler (1611) and Descartes (1637). With the development of the concept of retinal correspondence and the fusion of the retinal images in the brain (Huygens 1667, Newton 1704) a cerebral mechanism of disparity detection became thinkable. The rise of Empiricism (Molyneux' Premise, the case of Cheselden) postponed the solution of the problem, finally reached by Wheatstone (1838). Physiological proof of Wheatstone's theory came from the experiments of Barlow et al. (1967).


A case of eye disease (Lippitudo) on the Roman frontier in Britain. A newly excavated Roman report, written in ink on wood, on the strength of the First Cohort of Tungrians at Vindolanda in northern Britain, registers 31 men unfit, 15 as sick, 6 as wounded, the remainder, 10, with eye-disease, 'lippientes'. The paper also comments on the prevalence of eye-disease in antiquity and some of the suggested causes thereof.


Some Byzantine chroniclers and historians on ophthalmological topics. Byzantine historians and chroniclers recorded events not only of national importance, but also of daily life. The authors present various aspects in relation to ophthalmology. A selection of subjects including eye disorders and injuries, as well as visual problems discussed in myths, narratives and religious dogmas are presented.


The penalty of blinding during Byzantine times. Medical remarks. This paper which is based on the works of Byzantine chroniclers examines the imposition of blinding as a penalty in Byzantium. Punishment by blinding, though of extremely ancient origin, was imposed on Christians in the Roman Empire under the rule of Diocletian (AD 303). This continued up to the time of Constantine the Great and blinding as a penalty reappeared in the Byzantine Empire (AD 705) under the rule of Justinian Rhinotmitos. The writers investigate the grounds for the imposition of the penalty, and the methods employed, and a series of examples are given as handed down by Byzantine chroniclers. Finally, the ethical background of the penalty is examined according to the legislature and common-law extant in Byzantium.


Miraculous ophthalmological therapies in Byzantium. A series of cures for ophthalmological diseases practised by saints are described, particularly the Saints Cosmas and Damian and the Saints Cyrus and John, the famous 'Anargyroi'. In the xenones of the Byzantine churches and in the hospitals connected to these, therapeutic regimes, cures and surgical interventions took place at night during incubation, following the example of the ancient Asclepieia. This conclusion stands in spite of the fact that the authors describing the lives of the saints were often clergy who frequently cloak the true therapeutical cures by presenting them in a supernatural manner in order to stress the divine intervention of the saints. From the operations mentioned, it is clear that cataract surgery was among the operations most frequently practised.


Christoph Scheiner's eye studies.

Christoph Scheiner's eye studies. Christoph Scheiner was born in 1573 or 1575. In 1595 he entered into the Order of the Jesuits; he died in 1650. In 1619 his book Oculus, dealing with the optics of the eye, appeared in Innsbruck. The invention of the telescope was of utmost importance for progress in astronomical and physical research. Scheiner himself built telescopes and discovered the sunspots. As a result, an unpleasant priority dispute with Galilei ensued. From 1624 onwards, Scheiner was in Rome, where his main work Rosa Ursina was published in 1630. A part of this book deals with the physiological optics of the eye as well. Some of his discoveries and experiments are taken from these two books: determination of the radius of curvature of the cornea, discovery of the nasal exit of the optic nerve, increase in the radius of curvature of the lens in case of accommodation, Scheiner's procedure (double images with ametropia), refractive indices of various parts of the eye, Scheiner's experiment. Without any doubt, Christoph Scheiner belongs to the foremost scientists of the first half of the 17th century.


The first Danish chairs of ophthalmology. In the last century German medical sciences made up the chief inspiration to the medical profession in Europe. The influence of German ophthalmology spread to Denmark, and accordingly the first Danish professor, Edmund Hansen Grut was trained in the Graefe clinic. His successor, Jannik Bjerrum grew up in southern Jutland, a district later on lost to the German Empire. The hitherto prevailing Danish sympathies with the neighbour in the south vanished after this. Bjerrum thus wrote all his papers in Danish and made no efforts to achieve an international reputation. In contrast, Marius Tscherning, received widespread recognition as a scientist. He spent many years in France. His scientific insights at last brought him to the Danish chair of ophthalmology. The history of the first three professors of ophthalmology, so different in their attitudes, has narrative value, but exemplifies as well the rapid development of the profession in the years 1886-1925.


Ophthalmology in Europe in the days of the French Revolution. The authors highlight the political and scientific landmarks in 18th century France; the Revolution of 1789 had positive effects, in that it marked the accession of the French middle-class to political power and enabled the promotion of young scientists without consideration of social class or fortune; it had negative effects, in that France lost the scientific edge it had gained when all existing chairs in ophthalmology were abolished. The status of ophthalmology and of physiological optics in the 18th century are discussed, with a brief mention of the most important innovators in the field.


[Electrophysiological effects of neferine against ischemic ventricular tachyarrhythmias]. The electrophysiological effects of neferine (Nef, 8mg/kg,i.v.) on ischemic ventricular tachyarrhythmias in both normal and ischemic myocardium were studied in open-chest dogs by programmed electrical stimulation (PES) with intimal surface anodal direct current at the circumflex coronary artery during 5-8 days after acute myocardial infarction. Its effects were compared with procainamide (PA). Both drugs lengthened the QTc interval and the effective refractory period (ERP) of normal and infarcted myocardium in both ventricles and decreased the dispersion of ERP in infarcted myocardium (IDR) as well as in left ventricle (VDR), increased the diastolic excitability threshold (DET) of normal and infarcted myocardium in both ventricles remarkably. The PES-induced VT or VF was prevented in all of Nef treated dogs and in 5 out of 6 PA treated dogs, Nef prevented spontaneous VF in 5 dogs (n = 6), PA prevented spontaneous VF in 4 dogs (n = 6). The results indicated that Nef may be effective in preventing the onset of reentrant ventricular tachycardias and sudden cardiac death after myocardial ischemic damage.


[Reperfusion arrhythmias in acute myocardial infarction]. Twenty-seven patients with acute myocardial infarction (AMI), in whom infarct-related coronary artery was occluded and thrombolytic therapy or PTCA were performed, were studied. Reperfusion confirmed by immediate coronary angiography was achieved in 24 patients. Reperfusion arrhythmias (RA) occurred in 19(79.2%) of the patients, including ventricular arrhythmias in 13 (54.2%). Ventricular fibrillation (VF) and sustained ventricular tachycardia (VT) developed in 2(8.4%), and accelerated idioventricular rhythm in 5(20.8%); the latter showed a reliable indicator of coronary artery recanalization. Transient sinus bradycardia or AV block occurred in 10 (66.7%) of the 15 patients with inferior-posterior MI, which was an indicator of recanalization of coronary artery and salvage of myocardium in inferior-posterior MI. The occurrence of RA was not correlated with the duration of ischemia; ventricular RA was not related to the location of AMI and the occurrence and severity of ischemic arrhythmias before reperfusion. The patients with RA were treated with ordinary antiarrhythmic therapy, VF and sustained VT in 2 patients were converted by electric defibrillation. No death related to RA occurred. RA couldn't be prevented by lidocaine.


[Coronary heart disease and silent myocardial ischemia]. Silent myocardial ischemia was studied in 100 patients with coronary heart disease (CHD), proved by the coronary arteriogram (at least one major coronary artery narrowed by > or = 50%). The study demonstrated that 51 of 100 patients with CHD had episodes of myocardial ischemia by Holter monitoring. In the 51 patients, during daily activities, through 24-hour Holter monitoring, 239 transient episodes of ST depression were detected, 161 of the total were asymptomatic (67.4%). There were no statistically significant differences in the heart rate and the product of heart rate and systolic blood pressure before ST depression between asymptomatic and symptomatic episodes. The heart rate at the time of maximal ST depression during both asymptomatic and symptomatic ischemia increased by 13 and 22 beats/min, respectively, over those before ST depression (P < 0.01); whereas the increase in heart rate during symptomatic ischemia was more significant than during asymptomatic ischemia (P < 0.01). The increase of product of heart rate and systolic blood pressure at the time of maximal ST depression during asymptomatic and symptomatic ischemia were 22.2 and 35.4, respectively, over those before ST depression (P < 0.01). The incidence of silent ischemic episodes in patients with single vessel disease was 81.7% and those with multivessel disease was 61.3% (P < 0.01). The frequency of silent ischemic episodes was maximal (36% of total number of ischemic episodes) between 6 a.m. and 12 a.m. during 24-hour, whereas the incidence of silent ischemic episodes in patients with single vessel disease was similar to that in patients with multivessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)


[Assessment of plasma catecholamine and beta-endorphin contents in patients with silent myocardial ischemia and angina pectoris]. Thirteen patients with totally silent myocardial ischemia (group 1) and 15 patients with effort angina (group 2) were studied. The coronary angiography of both groups indicated coronary artery stenosis > or = 50%. In group 1, the beta-endorphin plasma level (beta-EPL) during rest was significantly higher than those in group 2 (15.639 +/- 1.258 pg/ml and 8.920 +/- 1.478 pg/ml, respectively, P < 0.01). There were significant increases in beta-EPL in both groups after exercise as compared with that before exercise (beta-EPL is 33.801 +/- 6.243 pg ml/in group 1, P < 0.01; 18.169 +/- 3.540 pg/ml in group 2, P < 0.01). The difference between two groups after exercise was also significant (P < 0.05). The plasma level of noradrenaline (NE) during rest was 0.267 +/- 0.035 ng/ml, adrenaline (E) was 0.112 +/- 0.018 ng/ml in group 1, and NE was 0.218 +/- 0.032 ng/ml and E was 0.110 +/- 0.015 ng/ml in group 2. After exercise, NE was 1.017 +/- 0.160 ng/ml (P < 0.001), E 0.276 +/- 0.076 ng/ml (P < 0.001), E 0.260 +/- 0.043 ng/ml (P < 0.01) in group 2. There was no difference between two groups both in rest and after exercise (P > 0.05). This study indicates that the high plasma beta-endorphin level might play a major role in the occurrence of totally silent myocardial ischemia.


[Clinical outcome of silent myocardial ischemia detected by bicycle ergometry study]. Seventeen patients with positive maximal or submaximal bicycle-exercise test accompanied by painlessness and 14 patients with susceptible coronary heart disease with negative exercise test were studied and traced for 36 months. The patients underwent repeated bicycle-exercise test of the same stress and compared with those before 36 months. The results showed that 7/17 patients (41.2%) had an increase in the depressed level of ischemic type ST segment induced by exercise test. 3 of them developed effort angina pectoris: 1 suffered from myocardial infarction, 1 had recurrent atrial flutter and left heart failure, and 1 suddenly died from cardiac disease. The cardiac event rate was 3/17 (17.6%) in this group. While 14 patients with negative exercise test had no cardiac events. It seems to mean that silent myocardial ischemia detected by exercise test might have potential danger of cardiac events.


[Electrophysiological effects of different dosage of adenosine triphosphate on normal sinoatrial and atrioventricular node]. In order to study the electrophysiological basis of smaller dosage that would terminate PSVT effectively and decrease side effects remarkably, we have observed the electrophysiological effects of ATP in different dosage (5mg, 10mg, 15mg) on the sino-atrial node (SAN) and atrioventricular node (AVN). Cardiac electrophysiological investigations were carried out in 62 patients with history of PSVT by using the method of trans-esophagus ECG and body surface ECG continuously and simultaneously, during the normal sinus rhythm and PSVT. The results showed that when the effect of 10mg ATP on SAN was not clinically significant yet, it did strikingly block the AVN conduction enough to terminate the PSVT with no severe arrhythmias. 37 cases of 62 patients were provoked PSVT during control electrophysiological study, the PSVTs of 33 cases out of these 37 patients (89.7%) were terminated by using 10mg ATP. There was no serious bradyarrhythmias after PSVT termination. We suggest that 10mg ATP is a reliable dose for PSVT termination.


Lung abscess in children in Harare, Zimbabwe. Despite the rarity of lung abscess in children, 24 patients were treated at Harare Central Hospital during the 10 year period (1979 to 1988). The bacteriology and clinical findings of the 24 patients are presented. Bacteria were isolated from 18 patients. The most frequent isolates were Staphylococcus aureus, group A beta haemolytic streptococci, and Pseudomonas aeroginosa. Most of the abscesses followed measles, empyema or an episode of aspiration. The patients were managed with bronchoscopy, physiotherapy, and appropriate antibiotics, and had a mortality of 25%. Efforts at controlling measles as well as early and appropriate management of empyema are likely to reduce the number of lung abscesses in children.


Epilepsy and retarded growth in a hyperendemic focus of onchocerciasis in rural western Uganda. An unusually high number of patients with epilepsy was observed in Kyarusozi sub-county, where infection with Onchocerca volvulus is hyperendemic. A preliminary survey was carried out in April 1991, when all patients with epilepsy and growth retardation were invited for medical examination. Two hundred and thirty one patients were screened, of whom, 91% were below the age of 19 years. The infection rate with Onchocerca volvulus in patients with epilepsy (61%) and retarded growth (70%) was significantly higher than in the general population of Kyarusozi sub-county. The prevalence of epilepsy in the study area was estimated to be at least 2%. Psychological impairment was more often observed among patients with a combination of onchocerciasis, epilepsy and/or growth retardation than the patients with onchocerciasis, epilepsy or growth retardation alone.


Emotional illness in a paediatric population in Nigeria. In a survey of 500 children aged between 5-15 years in a small rural community in Nigeria, 15.0% were found to suffer from mental morbidity. Disturbances of emotion and conduct disorder constituted 66.7% of total morbidity detected. Children from disrupted families (due to divorce, separation and widowhood) were found to be significantly more likely to suffer from psychiatric morbidity. The need to train primary health care worker and for them to work closely with families and school teachers in the provision of community mental health care services for children in the rural communities of developing countries was emphasized.


Risk indicators of nutritional status of households of a Kenyan semi-arid population. Assessments of nutritional status of semi-arid population in Kiambu District comprising 1042 persons from 260 households showed that 64.2% of the households had at least one malnourished person. The main aim of the study was to establish whether patterns of households malnutrition were distinguishable by specific risk indicators. Fourteen patterns of household malnutrition were established by classifying malnourished people according to age vis-a-vis nutritional status of other members of that household and six risk indicators were found to be related to malnutrition at the household level. Although partial relation was found between patterns and some indicators, no risk was found to be exclusively related to a specific pattern but failure to establish such a relationship was attributed to sample size.


Diagnostic challenges: lymphotropic sero-"questionables". During a sero-survey for lymphotropic retroviruses, seven screening tests were performed for the three lymphotropic retroviruses of relevance in Djibouti, East Africa (HIV-1, HIV-2 and HTLV-1). Of the 82 subjects whose sera reacted in at least one retroviral screening assay, about one third could be followed, and their sera were re-examined after a 5-month interval, and then after an additional 3-month interval. Six selected individuals are reported here, whose retroviral serologies presented important and often unexplained changes over an eight-month period. The six cases summarize prototypic situations and present serological results in a style appropriate to stimulate thought on the significance and interpretation of lymphotropic viral serologies. Each case study is followed by a set of questions that formulate pertinent serological concepts.


Aseptic necrosis of the head of the femur among sickle cell anaemia patients in Uganda. A number of HbSS patients presenting with aseptic necrosis of the femoral head have been seen at Mulago Hospital in Kampala, Uganda. A record review of the hospital's Sickle Cell Anaemia Clinic for the period 1985-1989 revealed that aseptic necrosis of the femoral head has been diagnosed in 2.9% (47/1611) of patients attending regularly. The largest number of diagnosed patients were in the 15-24 year old age group; peak incidence occurred in 20-24 year old women. Diagnosis in this series of patients was generally delayed and management was accordingly difficult. It is suggested that clinicians ask directly about pain in the hip of sickle cell patients rather than waiting spontaneous reporting. Such an approach may improve early detection of this potentially crippling problem.


Some factors contributing to protein-energy malnutrition in the middle belt of Nigeria. A number of risk factors leading to malnutrition were investigated among 400 mothers of malnourished children in the middle belt of Nigeria. Poverty, family instability, poor environmental sanitation, faulty weaning practices, illiteracy, ignorance, large family size and preventable infections are the main factors responsible for malnutrition. The strategies for intervention are in the area of health education emphasizing the importance of breastfeeding, family stability, responsible parenthood and small family sizes through culturally acceptable family planning methods. There is need to improve weaning methods through nutrition education, growth monitoring and food demonstration with community participation. Political will is needed to improve literacy status, farming methods and general living conditions.


Drug quality control work in Daru: observations during 1983-1986. During a 4 year period (January 1983 to December 1986), 418 requests for drug analysis were received in the Drug Analysis and Research Unit, Department of Pharmacy, University of Nairobi. Of these requests, 212 were from Medical Supplies Coordination Unit, 190 from Government hospitals and health research institutions, 11 from the Ministry of Health Headquarters (Director of Medical Services and Chief Pharmacist) and 5 came from local pharmaceutical manufacturers. Of the samples analysed, 70.8% were from local manufacturers, 26.1% were imported and 3.1% were from undeclared sources. Failure to comply with test for quality, as set out in official compendia (B.P. Eur. ph. Ip, etc.) were observed at 45.8% for locally manufactured drugs and 31.4% for imported drug products.


Assessment of infants of diabetic mothers by a simple body mass index. Twenty-five infants of diabetic mothers were studied in three hospitals over a six month period to assess the value of mid-arm circumference/head circumference (MAC/HC) ratio in the evaluation of outcome of diabetic pregnancies. The quality of intrauterine growth of each infant was determined from the MAC/HC standard. The infants were grouped, and analysed, on the basis of control of maternal diabetes. For the identification of infants of poorly controlled diabetic mothers, the MAC/HC standard had sensitivity of 81.8% and specificity of 92.9%. The standard was useful in identifying infants of diabetic mothers most likely at increased risks for neonatal morbidity. The standard is simple to use and is suggested for routine evaluation of products of diabetic pregnancies especially in developing countries.


Estimation of plasma fibrinogen and its degradation products in uncomplicated cases of malaria with low parasitemia. There are four hypotheses which have been advanced to explain the pathophysiology of severe and complicated malaria such as cerebral malaria. However, none of them adequately explains all the features of cerebral malaria in man. One such hypotheses is Disseminated Intravascular Coagulation (DIC). To determine whether this condition occurs in patients with uncomplicated malaria, the authors conducted a study on fibrinogen and its degradation products, euglobulin lysis time and parasite counts in 30 cases of uncomplicated malaria. By spectrophotometric method, plasma fibrinogen in patients with uncomplicated malaria was found to be normal as compared to normal healthy adults. There were no fibrinogen degradation production (FDP) detected in either patients or healthy controls, using latex agglutination tests at a dilution of 1:5. This method for FDP estimation is significant in that a serum agglutination with 1:5 dilution indicates a concentration of FDP in the original serum in excess of 10g/ml, designated as positive results of experiment. High values of euglobulin lysis time (ELT) were noted in patients with low parasitaemia. Analysis of these results showed that disseminated intravascular coagulation did not occur in uncomplicated cases of malaria. In this study on cases of uncomplicated malaria and low parasitaemia the biochemical parameters relating to to DIC have been essentially normal, although DIC is thought to be a primary stage in the development of cerebral malaria. According to Reid, DIC is an important intermediate mechanism in the pathophysiology of severe and complicated malaria such as cerebral malaria.


Pathogens and antibiotic susceptibility profiles in the urinary tract. Of 2,780 specimens of midstream urine (MSU) collected from patients of Medical out-patient Unit of Lagos University Teaching Hospital (LUTH), and examined between March 1989 and February 1990, 780 (28.1%) had bacterial colony counts greater than 100,000 per ml. The commonest pathogens were E. coli, Klebsiella aerogenes, Proteus mirabilis, Pseudomonas aeruginosa. 9.8% of the infections were caused by Gram-positive bacteria while 6.0% were due to the fungus, Candida albicans and Candida species.


Sodium supplementation in very low birth weight infants fed on their own mothers milk I: Effects on sodium homeostasis. Sodium supplementation was done on 41 very low birth weight (VLBW) preterm infants with 25 other infants of similar weight status as controls. All the infants were fed on their own mothers milk whose sodium and potassium content was determined. Serum and urinary sodium, potassium and creatinine levels were determined in both groups during the study period of six weeks. Determination of weight gain, length gain and head circumference gain showed that these anthropometric parameters are significantly increased by sodium supplementation while sodium and potassium concentrations were not significantly affected. There were no cases of either hypernatraemia or hyponatraemia though renal excretion of sodium was very high in the supplemented group. Conclusions drawn from the study are that very little weight gain could have been due to fluid retention and that though sodium supplementation does not affect sodium profiles in these infants it has significant effect on their growth rate which may be due to its indirect/direct association with bone and protein metabolism.


Behçet's syndrome presenting with chronic periodontitis: a case report. Behçet's syndrome is a disease of uncertain aetiology characterised by recurrent oral and genital ulcerations, ocular lesions and skin lesions. Although cases of this syndrome have been reported almost worldwide, the literature did not reveal any reports from this region. Management of this disorder is mainly palliative. However several treatment regimens have been tried. Following are some of the treatments considered effective. Azathioprine, corticosteroids, chlorambucil, transfusions of fresh blood or plasma and fibrinolytic therapy with phenformin and ethyloestrenol. The importance of multi-disciplinary management of such patients is emphasized.


B-endorphin response to a low dosage of human corticotropin releasing hormone during metyrapone administration in depression. This study defines the pituitary B-endorphin (BE) secretory response to a low dosage (0.3 ug/kg) of human corticotropin releasing hormone (CRH) in depressed patients and normal controls pretreated with metyrapone. We find no difference in the B-endorphin response to CRH in depressed subjects without evidence of HPA overactivity, compared with controls. This finding is contrasted with other data demonstrating a blunted B-endorphin response to CRH in depressives. The influence of metyrapone pretreatment on the pituitary B-endorphin response to CRH through a mechanism that minimizes the impact of cortisol negative feedback is discussed. Future studies which include low dose CRH infusion both in the presence and in the absence of metyrapone pretreatment will help investigate alterations in the regulation of pituitary B-endorphin secretion in depression including the possibility of increased pituitary sensitivity to the negative fast feedback of cortisol.


Effects of physical exercise on sex hormone binding globulin, high density lipoprotein cholesterol, total cholesterol and triglycerides in postmenopausal women. This study was performed on 18 postmenopausal female volunteers in order to examine changes in sex hormone binding globulin (SHBG), high density lipoprotein cholesterol (HDLC), total cholesterol (TC) and serum triglyceride (TG) levels in a period of four months of moderate physical exercise. While SHBG decreased significantly (from 55.3 +/- 20.9 to 48.3 +/- 21.0 nM, P < 0.05), TG increased significantly (from 87 +/- 41.7 to 120.5 +/- 57.5 mg/dl, P < 0.001). These changes were accompanied by a significant decrease (P < 0.001) in body fat content. Other parameters such as HDL-cholesterol, TC and BMI did not change significantly. Plasma levels of SHBG were negatively correlated to serum TG both at the beginning (r = 0.492, P < 0.05) and at the end (r = 0.538, P < 0.05) of the period of moderate exercise. Also, changes in SHBG were negatively correlated with changes in BMI (r = 0.585, P < 0.05) and this could indicate that SHBG levels are more related to nutritional status than androgen/estrogen imbalance.


Quantitative analyses of urinary pyridinoline and deoxypyridinoline excretion in patients with hyperthyroidism. It is well established that bone turnover increases and bone resorption exceeds bone formation in patients with hyperthyroidism. Recently, urinary pyridinoline and deoxypyridinoline have been employed as indicators of bone resorption. In this study, urinary pyridinoline and deoxypyridinoline levels in fourteen female patients with untreated hyperthyroidism were measured and compared with levels in 134 healthy females. Values of urinary pyridinoline and deoxypyridinoline were significantly higher than in age-matched controls. Moreover, values of serum free triiodothyronine correlated with urinary pyridinoline (r = 0.769, p < 0.01), and urinary deoxypyridinoline (r = 0.799, p < 0.001) in patients with hyperthyroidism.


Alterations of thyroid parafollicular cell organization in aged rats neonatally treated with estradiol. Cellular and subcellular organization of parafollicular cells of aged male Wistar rats (180- and 365-day-old), neonatally (3rd day) treated with a single dose (1 mg) of oestradiol-dipropionate (OeDP), were studied. Based on argyrophil properties of parafollicular cells in control and treated group, two morphometrically distinct cell types were observed (under and over 50 microns 2 of cell area), reflecting distinct functional status of the same cell type. The first signs of hyperplastic changes in parafollicular cells were observed in 180-day-old rats and they were more severe in 365-day-old animals. Morphometric averages for the area of parafollicular cells and nuclei, as well as for the cell number in estradiol-treated animals were higher than in the controls, but these differences were statistically insignificant. However, subcellular organization of parafollicular cells showed that besides the cells with clearly visible characteristics such as control hyperplastic cells, there were parafollicular cells with progressively more abnormalities expressed as myelin-like figures, cytoplasmic cribriform structures and dilated endoplasmic reticulum (ER), demonstrating long-lasting effects of neonatally applied estradiol.


Effect of reserpine on the inhibition of prolactin released from different pituitary constructs in vitro by dopamine, bromocriptine and apomorphine. Hourly release of Prolactin by pituitary constructs 1 whole pituitary (PI), adenohypophysis (P-N) and pituitary-hypothalamus co-incubate (PHC) were compared. Adenohypophysis secreted significantly more prolactin than PI and PHC, while PHC secreted significantly less than PI. Co-incubation of (P-N) with posterior pituitary reduced the elevated secretion of prolactin. Addition of dopamine (10(-7) M), bromocriptine (10(-7) M) and apomorphine (5 x 10(-8) M) to these constructs did not affect the release of prolactin from PI but inhibited the same from (P-N) and PHC. Treatment with reserpine increased serum prolactin levels but intrapituitary prolactin contents were decreased. Hourly release of prolactin from pituitary constructs derived from reserpine-treated rats was significantly reduced as compared to ascorbic acid--treated controls. Inclusion of dopamine (10(-7) M), bromocriptine (10(-7) M) and apomorphine (5 x 10(-8) M) in these constructs inhibited prolactin secretion further. In vitro addition of perphenazine stimulated the release of prolactin by PHC but was without any effect on PI and (P-N). The data are interpreted to suggest that dopamine in posterior pituitary may be an important determinant of hypothalamic modulation of prolactin secretion.


Induction of acute hyperglycemia, hyperlactemia and hypocalcemia in fed and fasted BALB/c mice by intravenous amylin injection. Amylin has been reported to influence carbohydrate metabolism in rats, dogs and cats. We report here that intravenous injection of 50 micrograms amylin (640 nmol/kg) induced hyperglycemia, hyperlactemia, and hypocalcemia in both fed and 5-hour fasted mice. Peak glucose and lactate increments occurred within 15 minutes of treatment, followed by a slower decline of plasma calcium levels. To determine dose-response characteristics of these effects, fasted animals were given amylin doses ranging from 0.005 micrograms to 500 micrograms (64 pmol/kg to 6.4 mumol/kg). Median effective doses (ED50) for the hyperglycemic, hyperlactemic, and hypocalcemic effects were 155, 16.9 and 190 nmol/kg, respectively, with maximum increases of 6.27 mM for glucose, 1.85 mM for lactate and maximum decrease of 0.37 mM for calcium. The estimated half-life (t1/2) of exogenous amylin in the circulation was 5.0 minutes in fasted mice. These results indicate that amylin is bioactive in mice. The kinetic data predict that biologically effective doses of exogenous amylin result in plasma concentrations comparable to pathophysiological concentrations of endogenous hormone previously reported.


Colposcopic pictures of Abnormal Transformation Zone (ANTZ): colpocytological and histological findings. The Authors have examined the correlation between the colposcopic pictures of the Abnormal Transformation Zone (ANTZ), in its varying degrees, and the colpocytological and histological examinations in order to seek a better definition of the indications of carrying out aimed biopsies. From our results a good agreement has been observed from the colpocytological and histological examination and the colposcopic pictures of the ANTZ. In patients with colposcopic images of ANTZ G2 the colpocytological examination diagnosed a CIN 3 in 80.6% of cases, invasive carcinoma in 6.4%, and in histologic examination CIN 3 in 71% and microinvasive carcinoma in 10.7%. Instead in the ANTZ G1, CIN 3 was revealed colpocytologically in 7.9% of the cases and histologically in 7.3%. Among these last, in half of the cases, the focuses of CIN 3 were present at the level of third inferior of the cervical canal. Finally, in ANTZ G0 there was cytological evidence in 6.6% of cases of CIN 3 with a histological correspondence of 3.9%. In particular the focuses of CIN 3, small and limited, had resulted from biopsies carried out on some glandular openings not clearly attributable to ANTZ G1. With regard to the opportuneness of carrying out aimed biopsies, mandatory in the cases of ANTZ G2, we feel it would be useful to carry them out also for ANTZ G1, above all if alterations are diagnosed at the colpocytologic examinations, and in ANTZ G0 if colpocytological alterations are present. Therefore integrating colposcopic and colpocytologic examinations and aiming the biopsies would seem to lead to good diagnostic reliability and adequate successive personalized treatment.


Phenotype of lymphocyte in ovarian tumor peritoneal fluid. A preliminary study. Phenotype of lymphocytes was estimated in 16 peritoneal fluids obtained from 9 ovarian cancer patients. Peritoneal fluids contained predominantly T cells (more than 80%) while B cell content was relatively low. Approximately 50% lymphocytes carried T-helper cell marker (CD4). Percentage of T-cytotoxic/suppressor cells (CD8+ cells) differed between patients with progression and those showing no tumor progression (19.0 +/- 7.5 vs 32.7 +/- 18.5). CD4/CD8 ratio was higher in the group of patients with progression than in the group with no progression of the tumor (3.4 +/- 2.1 and 2.0 +/- 1.5). Chemotherapy did not affect the parameters. Estimation of CD8 and CD4/CD8 ratio in peritoneal fluid cells could be helpful in monitoring of disease progression.


Carcinoma of the vulva: critical analysis of survival and treatment of recurrences. Survival analysis of 181 vulvar cancer patients shows that stage and lymph nodal spread remain the most important prognostic factors. Other prognostic elements are: depth of stromal infiltration, thickness and site of the lesion, vascular space invasion. Precise definition of these pathological prognostic elements may be obtained only after appropriate surgical pathological evaluation of the primary lesion and regional nodes. Treatment must be adequate in the cost-benefit balance and surgery is the cornerstone in vulvar cancer management. Risk of relapse is statistically correlated with site of primary tumour, depth of infiltration, lymph nodal invasion and vascular space invasion. The treatment of recurrence is personalized for different sites but surgery is the elective treatment of the local recurrences.


Prospects for preneoplasia immuno-detection and cancer immuno-prevention. The three traditional modalities of cancer treatment: surgery, radio- and chemotherapy, even when applied in optimal fashion, leave over 50% of incurable patients, because of the metastatic disease. Hence the importance of preventive methods in cancer, by directing attention to the detection and treatment of preneoplasia. Focal preneoplastic lesions have been observed prior to the appearance of malignant epithelial tissues. The phenotypic patterns of preneoplasia seem to be as varied as those of neoplasia. In the frame of persistent multicellular hyperplasia, the appearance of enzyme-altered foci is supposed to be related to the origin of neoplasia, and in this sense these lesions can be considered pre-neoplasia. If there is any immune reaction to the non-self promoted by these lesions, their detection and their enhancement or induction by a vaccine would be a cancer immuno-prevention. Preliminary experiments and clinical pilot studies have shown a specific host-resistance to a pharmaceutical placental suspension (PS), when injected intradermally (DTHS-reactivity test) in patients with clinical conditions having, as histopathological substratum, a cellular adaptive (reactive) or neoplastic proliferation. Boosting this reaction by an adjuvant (BCG, corynebacterium parvum, etc.) would be an immunotherapeutic approach to cancer, as adjunct to standard treatments and in preneoplastic-bearing patients an immuno-preventive method in cancer. In vitro studies have shown that a glycoprotein of MW 40 kDa (P40), from an extract of placental suspension (PS) is recognized by patients' serum, (Ouchterlony's technique). The monospecific rabbit antiserum (MRA) raised to P40 glycoprotein also reacts with the serum of patients with positive DTHS reactions to PS.(ABSTRACT TRUNCATED AT 250 WORDS)


Invasive cervical carcinoma in patients aged 35 or younger. There has been concern that invasive cervical carcinoma is more aggressive in young women. We studied retrospectively 36 patients who were less than 35 years old (mean age 30.8 years, range 22-35 years, SD 3.6), and 36 controls (mean age 59.4 years, range 40-72 years, SD 9.5), treated for invasive cervical carcinoma between 1976 and 1986. Histologically 31 (86%) were squamous cell carcinomas and 5 (14%) were adenocarcinomas both in the patients aged 35 years or younger and in the control group. Clinical findings and rates of pelvic lymph nodes metastases were comparable in both groups. Compared to controls, patients aged 35 or younger had longer intervals from diagnosis to recurrence (20.3 months vs. 9.0 months), longer intervals from recurrence to death (15.3 months vs. 7.0 months), and longer intervals from diagnosis to death (39.6 months vs 20.0 months). There was no difference between the groups in the 5-year survival (75% vs. 81%). In conclusion, we found no evidence that the overall clinical behaviour of invasive cervical cancer is more aggressive in young women.


Local immunosuppression determined by class II HLA antigen expression in patients with preclinical cervical carcinoma. Class II HLA antigen expression was investigated in biopsy material from patients with preclinical cervical carcinoma. Class II molecules were determined immunohistochemically by MoAb against HLA-DR antigens. A significant reduction of class II positive cells was established in the tumor tissue compared to the normal cervical epithelium. A correlation between the tumor progression and the inhibition of the class II antigen expression was found.


Fertility after ovarian cancer treatment. Considering the important improvement of surgical techniques and chemotherapy in the last few years, it is possible today, in selected cases of patients previously treated for ovarian cancer, to support their desire for motherhood, thus improving the quality of life for them. The major problem for the Gynecologic Oncologist in treating young women for ovarian tumour is the lack of statistically significant experience world-wide, because of the very few cases in which the reproductive function is preserved, and pregnancy is subsequently possible. In this report the problem is discussed, and the results obtained in our Institute are presented.


Rational use of cryosurgery and cold knife conization for treatment of cervical intraepithelial neoplasia. In recent years a variety of conservative treatment modalities are being used to remove Cervical Intraepithelial Neoplasia (CIN). A series of 568 cases of patients affected by CIN, detected in our Department over a period of 10 years and treated following a balanced use of colposcopy guided cryosurgery and cold knife conization, has been reviewed. One-hundred-fifty-three patients, 111 with CIN 1 and 42 with CIN 2, were treated by the use of a nitrous oxide cryoprobe. The remaining 415 patients underwent cold knife conization, under general anesthesia and hospitalization. Routine follow-up for all cases included cytology, colposcopy and aimed biopsy when required. Cryotherapy had a success-rate of 90.1% (CIN 1-CIN 2 only) and "complete" conization 94.6% (included CIN 3 cases). Complications of conization, such as late haemorrhage and cervical stenosis, were more frequent with the "open technique" than the "suture technique". Nine pregnancies after cryotherapy and 34 after conization have been reported, no significant differences were noted in the pregnancy outcome following either treatment.


Immuno-biologic integration for therapeutic approach in ovarian carcinoma. The "in vitro" cell growth of 14 ovarian carcinomas was evaluated and related with the clinical-pathologic stage (FIGO) and grade of histologic differentiation of disease, with the patients' immunological pattern and with the relapse and survival rates. We identified 4 different patterns of "in vitro" cell growth (P1, P2, P3 and P4). Their correlation with the clinical-pathologic stages of disease as well as with the recurrence and survival rates was strong: 75% of recurrences in pattern P3 and 100% in pattern P4, while tumours with patterns P1 and P2 did not relapse. Similar results were obtained for survival, in fact 2 of the 3 patients who died from disease had cell growth pattern P4, and the other a P3. A significant correlation was found with basal natural killer cell activity of peripheral blood lymphocytes too: in patients with P1 neoplasia the basal NK cell activity was significantly higher (p < 0.05) while it was significantly lower (p < 0.05) in patients with P4 neoplasia in comparison with the others. We conclude that the "in vitro" biological behaviour of ovarian neoplasia can be regarded as prognostic factors even if patients' basal NK activity represents the most significant prognostic element, directly related to the recurrence rate (p = 0.002).


Phase II trial with 5-fluorouracil and high-dose folinic acid, using new sequential dosing schedule, in pretreated advanced breast cancer patients. In this study, 30 patients with metastatic breast cancer were treated with 5-Fluorouracil (5-FU) and high-dose Folinic acid, using a new sequential dosing schedule. Our treatment consisted of one day i.v. infusion of 500 mg/m2 of Folinic acid over two hours. One hour after the beginning of Folinic acid infusion, 5-FU (500 mg/m2) was given by i.v. bolus injection. The complete and partial response rates achieved (CR+PR) were 21% in a population of patients pretreated with chemotherapy including 5-FU. Cutaneous and bone metastasis responded best to our treatment. There were no treatment related deaths or withdrawals from the study. The drug related toxicities observed in this study were usually mild to moderate and easily controllable. Thus preliminary results of our study suggest that response rate, quality of life and time to disease progression for the responders improved by this sequential treatment.


Modulatory influences of estrogen and progesterone on cervical dysplasia in mice model system. The effectiveness of estrogen and progesterone on the different types of cervical dysplasia are poorly documented compared to their effects on the total process of cervical carcinogenesis. In the present study, an attempt has been made to evaluate the influences of estrogen and progesterone on the different types of cervical dysplasia which are believed to be the antecedents of cervical carcinoma induced by chemical carcinogen (20-Methy cholanthrene) in the mice model system. It was observed that moderate dysplasia is less aberrant than that of marked dysplasia which could not be modified by either of the hormones.


Value of AgNOR counts in cervical pathology. Nucleolar organizer regions (NORs) were counted on normal tissue, condylomata, CIN 1, 2 and 3, to verify the possibility of a differentiation between the various grades of CIN and between them and condylomata. Counts were performed on the full thickness of the tissue, layer by layer (stratified counts). A significant difference (p < 0.05) was found between the mean of normal tissue in relation to condylomata and CIN 2 and 3 and between CIN 1, and CIN 2 and 3. There was no significance (p > 0.05) between normal tissue and CIN 1, between CIN 2 and 3 and between condylomata and CIN 2 and 3. The range of variations in the counts was associated with overlapping between the various cases. Our data showed also a progressive rise in mean NOR values from normal tissue to CIN 3. The stratified counts showed in all the groups a rise from basal to parabasal cells. Counts on parabasal and intermediate layers distinguished two groups of cases. In one there was either the same number of dots or a further rise while in the other a definite decrease was seen. The former pattern may be related to a potential for malignant evolution of the lesion. NORs should be counted in all cases of CIN and condylomata to treat more aggressively those lesions which present the patterns of a progressive rise of NORs from basal to intermediate cells.


Recent advances in the pathogenesis of atopic dermatitis. Atopic dermatitis (AD) is an inflammatory skin disorder affecting 5%-10% of children. Although basic mechanisms remain largely speculative, recent studies on the pathogenesis have elucidated new insights, pointing to the importance of food and inhalant allergens. The pathogenesis of AD can be more easily explained by the model of late skin reaction occurring after mast cell activation. The present report highlights some of the more recent developments in the mechanisms of AD which can be important in understanding and treating this troublesome disease.


Streptococcal pharyngitis and epiglottitis in a newborn infant. We describe a newborn infant with Streptococcus sanguis septicaemia and concomitant upper airway obstruction due to epiglottitis and pharyngitis. This rare infection of the supraglottic region was treated with endotracheal intubation and antibiotics. Full recovery occurred within 4 days.


A comparison of ceftazidime and aminoglycoside based regimens as empirical treatment in 1316 cases of suspected sepsis in the newborn. European Society for Paediatric Infectious Diseases--Neonatal Sepsis Study Group. We report a prospective, non-blind, randomised, multicentre, parallel group, multinational investigation to compare ceftazidime to aminoglycoside based regimens as empirical treatment in 1316 cases of suspected sepsis in the newborn. In each of the 15 study centres either ceftazidime alone (CAZ) or ceftazidime + ampicillin (CAZ + AMP) was compared to an amino-glycoside/ampicillin combination (AG + AMP). In all cases treatment was based on "an intention to treat". Bacteria considered to be pathogenic were isolated from 176/1316 (13.4%) patients. The incidence of proven infection varied from 39% in a Yugoslav centre to 6% in a British centre; a further 489/1316 (37.1%) patients fulfilled the criteria for clinically suspected sepsis. A total of 210 bacterial isolates from 197 infection sites in 176 patients were considered to be clinically significant. The cure rate for evaluable patients with proven infection who were treated with CAZ + AMP (97%, 30/31) was significantly higher than that for the corresponding patients treated with AG + AMP (66%, 26/39), (P < 0.002). The difference in cure rate between CAZ monotherapy (79%, 34/43) and AG + AMP (86%, 32/37) was not significant. Treatment failed in 28/150 (18.7%) evaluable patients. There were significantly fewer failures (P < 0.001) with CAZ + AMP than with AG + AMP therapy. There were 55 staphylococcal infections. Treatment was successful in 16/19 evaluable patients treated with CAZ or CAZ + AMP and in 16/29 evaluable patients treated with AG + AMP. None of the study centres encountered problems with ceftazidime resistant bacteria. The cure rate for patients with only clinical and radiological evidence of sepsis was greater than 94% in all treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Deletion of the short arm of the X chromosome: a hereditary form of Turner syndrome. In the mothers of two girls with Turner syndrome due to a deletion of the short arm of an X chromosome, the same chromosomal anomaly was detected. Both mothers and daughters had short stature but normal pubertal development. Short parents and normal pubertal development do not exclude Turner syndrome in a girl with small stature.


Family studies of the steroid 21-hydroxylase and complement C4 genes define 11 haplotypes in classical congenital adrenal hyperplasia in The Netherlands. Two steroid 21-hydroxylase genes are normally present within the human major histocompatibility complex near the genes encoding the fourth component of complement (C4A and C4B). Steroid 21-hydroxylase is encoded by the CYP21 gene, while the highly homologous CYP21P gene is a pseudogene. We studied steroid 21-hydroxylase and complement C4 haplotypes in 33 Dutch patients (29 families) suffering form classical congenital adrenal hyperplasia (CAH) and in their 80 family members, and also in 55 unrelated healthy controls, using 21-hydroxylase and complement C4 cDNA probes. Eleven different haplotypes, defined in terms of gene deletions, gene duplications, conversions of CYP21 to CYP21P, and "long" and "short" C4 genes, were found. In 23% of the patients' haplotypes, the CYP21 gene was deleted; in 12%, it was converted into a CYP21P pseudogene. In the remaining 65%, the defect was apparently caused by a mutation not detectable by this method. The most common haplotype (with one CYP21 and one CYP21P gene) was significantly more often observed in patients with simple virilizing CAH than in those with salt-losing CAH. Comparison of the 21-hydroxylase haplotypes found in CAH patients from several countries shows evidence for considerable genetic variation between the groups studied.


Hartnup syndrome, progressive encephalopathy and allo-albuminaemia. A clinico-pathological case study. Clinical, biochemical, neuropathological and neurochemical findings in a case of Hartnup syndrome are reported. After initially normal development, the affected girl suffered progressive neuropsychiatric decline with statomotor and mental retardation and intractable seizures and died at the age of 2 years. Postmortem neuropathological and neurochemical investigations showed a combination of extensive neuronal degeneration and cerebral dysmyelination. Pathogenetic hypotheses and the relationship between neuropsychiatric disease and Hartnup syndrome are discussed. Additionally, a fast type bisalbuminaemia present in the girl and her mother is described.


Decreased incidence of extra-alveolar air leakage or death prior to air leakage in high versus low rate positive pressure ventilation: results of a randomised seven-centre trial in preterm infants. Two different ventilation techniques were compared in a seven-centre, randomised trial with 181 preterm infants up to and including 32 completed weeks gestational age, who needed mechanical ventilation because of lung disease of any type. Technique A used a constant rate (60 cycles/min), inspiratory time (IT) (0.33s) and inspiratory: expiratory ratio (I:E) (1:2). The tidal and minute volume was only changed by varying peak inspiratory pressure until weaning via continuous positive airway pressure. Technique B used a lower rate (30 cycles/min) with longer IT (1.0 s). The I:E ratio could be changed from 1:1 to 2:1 in case of hypoxaemia. Chest X-rays taken at fixed intervals were evaluated by a paediatric radiologist and a neonatologist unaware of the type of ventilation used in the patients. A reduction of at least 20% in extra-alveolar air leakage (EAL) or death prior to EAL was supposed in infants ventilated by method A. A sequential design was used to test this hypothesis. The null hypothesis was rejected (P = 0.05) when the 22nd untied pair was completed. The largest reduction in EAL (-55%) was observed in the subgroup 31-32 weeks of gestation and none in the most immature group (< 28 weeks). We conclude that in preterm infants requiring mechanical ventilation for any reason of lung insufficiency, ventilation at 60 cycles/min and short IT (0.33 s) significantly reduces EAL or prior death compared with 30 cycles/min and a longer IT of 1 s. We speculate that a further increase in rate and reduction of IT would also lower the risk of barotrauma in the most immature and susceptible infants.


The possible risk of bilirubin encephalopathy as predicted by plasma parameters in neonates with previous severe asphyxia. The study group consisted of nine mature newborn infants with a previous history of severe asphyxia and a control group of 18 mature, healthy newborns with the same postnatal age and sex. The object of the investigation was to compare the possible risk of development of bilirubin encephalopathy between the two groups as estimated by plasma parameters. The asphyxia group had a significantly lower reserve albumin concentrations for binding of monoacetyldiaminodiphenyl sulphone (P = 0.008), a measure of binding of unconjugated bilirubin, and significantly lower total albumin concentrations (P = 0.02). No significant difference was observed in unconjugated bilirubin concentration. It is suggested that mature newborns with previous severe asphyxia are at a slightly increased risk of developing bilirubin encephalopathy over and above the well-known risk associated with increased permeability of the blood brain barrier.


Plasma endothelin-1 like immunoreactivity levels in neonates. We attempted to determine the plasma endothelin-1-like immunoreactivity (ET-1) levels and to evaluate its physiological significance in 29 neonates: 5 with respiratory distress syndrome (RDS), 3 with transient tachypnoea of the newborn (TTN), 4 with neonatal asphyxia, 5 with bronchopulmonary dysplasia (BPD) following RDS, 7 healthy preterm infants and 5 healthy full-term infants. Plasma ET-1 levels in infants with RDS were significantly higher than those in healthy full-term infants through the 1st week of life. Plasma ET-1 levels in infants with neonatal asphyxia were high on the first 2 days of life and then gradually decreased to those of healthy full-term infants. Plasma levels in infants with TTN were the same as those in healthy full-term infants. Plasma ET-1 levels in infants with BPD were high when compared with those in healthy preterm infants during the first 2 months of life. This study showed that plasma levels were markedly elevated for a long time in the infants with respiratory distress. We speculate that plasma ET-1 may be a specific marker for pulmonary endothelium injury in infants with respiratory distress.


Characterization by photoaffinity labelling of the human platelet thromboxane A2/prostaglandin H2 receptor: evidence for N-linked glycosylation. Thromboxane A2 (TXA2) and prostaglandin H2 (PGH2) are potent proaggregatory and vasoconstrictor lipids acting through a receptor referred to as the TXA2/PGH2 receptor. The receptor was purified using a modification of a previously described method from human platelet membranes solubilized using the detergent (3-[(3-cholamidopropyl)-dimethylammonio]-1-propane-sulfonate (CHAPS) and a combination of affinity chromatography and wheat germ lectin chromatography. This procedure resulted in a 1075 +/- 375-fold purification and a specific activity of 1.45 +/- 0.55 nmol/mg protein (n = 5). Repeating these chromatography steps on this partially purified receptor resulted in a preparation with a specific activity of 21 +/- 3 nmol/mg protein (n = 5). This represents the theoretical specific activity if one assumes a molecular weight of 50,000 for the receptor. The fold purification was 11,750 +/- 1250 based on crude membranes and an overall yield of 24%. To further the characterization of this receptor, we synthesized a new radioiodinated photoaffinity probe, 7-[(1R,2S,3S,5R)-6,6-dimethyl-3-(4-azido-3-iodobenzenesulfonylamino++ + )- bicyclo[3.1.1]hept-2-yl]-5(Z)-heptenoic acid (I-SAP-N3). [125I]l-SAP-N3 irreversibly incorporated into the purified receptor yielding a single band by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) autoradiography and indicated a molecular weight for the receptor of 50-51 kDa. The incorporation of the ligand could be inhibited by a variety of TXA2/PGH2 analogues. In addition, photoaffinity labelling was inhibited in a stereoselective manner as demonstrated by the pair of enantiomers (d)- and (l)-S145. Digestion of photoaffinity labelled receptor with N-glycosidase F demonstrated the presence of at least two N-linked glycosylation sites.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of S-adenosyl-L-methionine on brain muscarinic receptors of aged rats. The number of muscarinic receptors in the striatum and hippocampus of aged rats is significantly lower than the number measured in young animals. The treatment of aged rats for 30 days with S-adenosyl-L-methionine (SAM) restored the number of muscarinic receptors to levels found in the striatum and hippocampus from young animals. We did not observe a clear-cut difference between the dissociation constants of untreated young and untreated or SAM-treated aged rats, whereas the binding capacity varied. Moreover, in vitro addition of SAM to hippocampal membranes from aged rats resulted in a significant increase in the number of binding sites. This in vitro effect was antagonized by S-adenosyl-L-homocysteine, a specific in vitro inhibitor of methyltransferase activity. The reduction in the muscarinic receptor density could be related to a decrease in neuronal membrane fluidity induced by aging, while its increase after SAM treatment might be ascribed to the ability of this methyl donor to increase the fluidity of cell membranes by stimulating phospholipid synthesis.


Prolonged in vitro exposure of rat brain slices to adenosine analogues: selective desensitization of adenosine A1 but not A2 receptors. Agonist-induced desensitization of adenosine A1 and A2 receptors was studied in rat striatum slices maintained in carbo-oxygenated Krebs buffer. Slices were exposed to adenosine analogues (either cyclo-pentyl-adenosine or N-ethyl-carboxamido-adenosine) for selected time periods (15-60 min) and repeatedly washed at the end of agonist exposure. Agonist-induced changes of adenosine receptors were then evaluated in P2 fractions prepared from slices by measuring A1 and A2 receptor-regulated adenylate cyclase. A1 receptors were rapidly desensitized by agonist exposure, as shown by a gradual loss of A1 receptor-mediated inhibition of basal cyclase activity and cAMP formation, which was evident within 15-30 min after addition of the adenosine analogue. Agonist-induced desensitization of A1 receptors was dose- and time-dependent, and seemed quicker in onset with cyclo-pentyl-adenosine, according to the higher A1 selectivity of this receptor agonist, with respect to N-ethyl-carboxamido-adenosine. Binding of the A1-selective agonist [3H]cyclo-hexyl-adenosine was unaffected by the desensitization procedure at any of the exposure periods utilized, suggesting that an uncoupling of A1 receptors from their transduction system is indeed responsible for the loss of functional activity. Loss of A1 receptor function was accompanied by a time-dependent amplification of A2 receptor-mediated stimulation of adenylate cyclase activity, likely due to an 'unmasking' of A2 stimulatory receptor function as a consequence of the desensitization of A1 inhibitory receptors. All these effects could be completely counteracted by the concomitant exposure to an adenosine receptor antagonist, and specifically involved the coupling mechanisms of adenosine receptors with their effector system.(ABSTRACT TRUNCATED AT 250 WORDS)


Histamine activates phosphorylase and inositol phosphate production in guinea pig hepatocytes. In guinea pig hepatocytes, histamine increased phosphorylase activity and inositol phosphate production. Similar effects were obtained with 2-(2-aminoethyl)-thiazole, a histamine H1 receptor agonist, but not with dimaprit or impromidine, H2 receptor agonists. These effects of histamine were dose-dependently inhibited by the H1 antihistamines, (+)-chlorpheniramine and mepyramine (pyrilamine) but not by cimetidine or ranitidine, H2 antagonists. (+)-Chlorpheniramine and mepyramine had similar potencies (apparent Ki values approximately 3 nM) when incubated with the cells for 1 min (phosphorylase a assays) but the former was 15-20-fold more potent than the latter at longer incubation times (apparent Ki values approximately 3-4 nM and 45-90 nM, respectively) indicating that mepyramine is actively metabolized by guinea pig hepatocytes. Histamine increased cytosol calcium approximately 2-fold, an effect also mediated through H1 receptors. The actions of histamine were not affected by in vivo ADP-ribosylation by pertussis toxin. Our data clearly indicate that histamine modulates the metabolism of guinea pig hepatocytes via activation of H1 receptors. These receptors are coupled to the phosphoinositide turnover-calcium mobilization signalling pathway through a pertussis toxin-insensitive process.


Protein kinase C activity in blood vessels from normotensive and spontaneously hypertensive rats. This study investigates the effects of phorbol dibutyrate (PDB) on protein kinase C (PKC) activation, as assessed by the translocation of PKC activity from the cytosolic to the particulate fraction, in aortas and mesenteric arteries from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The basal distribution of PKC activity between the cytosolic and particulate fractions of SHR and WKY aortas, and mesenteric arteries, was not significantly different. PDB induced a concentration-dependent decrease in cytosolic PKC activity in SHR and WKY aortas. PDB (0.01 microM) decreased cytosolic PKC activity to a greater magnitude in SHR aorta as compared to WKY aorta, while 1.0 microM PDB decreased cytosolic PKC activities to similar magnitudes in SHR and WKY aortas, and mesenteric arteries. These results suggest that the increased sensitivity of SHR vessels to contraction by phorbol esters may be due, at least in part, to the greater sensitivity of PKC in these vessels to phorbol ester activation.


Nucleotide sequence of estrogen receptor cDNA from Sprague-Dawley rat. The cDNA of the Sprague-Dawley rat estrogen receptor was sequenced. With respect to the published Wistar rat estrogen receptor sequence, a single amino acid difference (tryptophan instead of asparagine) was found in the hormone binding site. Since tryptophan was found at the same position in chicken, human and mouse estrogen receptors, it is proposed that the Wistar rat could represent an interesting natural mutant for estrogen receptor studies.


Evidence for the presence of 5-HT1B receptor messenger RNA in neurons of the rat trigeminal ganglia. In situ hybridization histochemistry and receptor autoradiography were used to determine the presence of 5-HT1B receptor messenger RNA (mRNA) and 5-HT1B receptor proteins, respectively, in rat trigeminal ganglia. Receptor autoradiography on rat trigeminal ganglia, using appropriate 5-HT1B radioligands, did not demonstrate any specific labelling. In contrast, in situ hybridization showed that many ganglion cells contain 5-HT1B receptor mRNA, suggesting the presence of presynaptic 5-HT1B receptors on trigeminovascular neurons.


5-HT4 receptors, present in piglet atria and sensitive to SDZ 205-557, are absent in papillary muscle. Putative 5-HT4 receptors were investigated in isolated piglet left atria and papillary muscles. In atrial tissues, 5-hydroxytryptamine (5-HT) was a potent positive inotropic agent with a pD2 of 6.7. Its effects were antagonised in a selective and competitive manner by the 5-HT4 receptor antagonist, SDZ 205-557, with a pA2 of 7.3. In contrast to atrial tissues, piglet papillary muscles were virtually unresponsive to 5-HT 10(-8)-10(-3) M, suggesting that functional cardiac 5-HT4 receptors are not present in ventricular tissue.


Ischemia-induced impairment of 2-deoxyglucose uptake and CA1 field potentials in rat hippocampal slices: protection by 5-HT1A receptor agonists and 5-HT2 receptor antagonists. Various in vitro models have been developed to study ischemia and/or hypoxia. In the present experiment, we examined whether hypoxia/hypoglycemia (ischemia) in rat hippocampal slices reduced the 2-deoxyglucose (2-DG) uptake and CA1 field potentials evoked by stimulation of Schaffer collaterals. Autoradiograms revealed that ischemia for 15 or 20 min reduced 2-DG uptake in the stratum radiatum of the CA1 and the dentate gyrus. Similarly, the CA1 field potentials of slices exposed to ischemia for 15 and 20 min decreased by about 70 and 90% after a 6-h washout. In the second experiment, we evaluated the neuroprotective effect of the 5-HT1A receptor agonists 8-OH-DPAT and buspirone, and the 5-HT2 receptor antagonists cyproheptadine, mianserin and ketanserin on deficits of 2-DG uptake and Schaffer-CA1 field potentials induced by ischemia. The 5-HT1A receptor agonists and 5-HT2 receptor antagonists exhibited significant neuroprotective actions against ischemia-induced deficits. Therefore, impairments of 2-DG uptake and CA1 field potentials induced by ischemia may be good markers of ischemia-induced functional deficits. The attenuating action of 5-HT1A receptor agonists and 5-HT2 receptor antagonists were assessed using this model of ischemia.


p-methylthioamphetamine is a potent new non-neurotoxic serotonin-releasing agent. p-Methylthioamphetamine (MTA), was compared to p-chloroamphetamine (PCA) in a number of pharmacological assays. MTA was about 2-fold more potent than PCA at inhibiting synaptosomal uptake of [3H]5-hydroxytryptamine ([3H]5-HT), and about 7-fold and 10-fold less potent than PCA at inhibiting synaptosomal uptake of [3H]dopamine and [3H]norepinephrine, respectively. In drug discrimination assays, MTA was nearly equipotent to PCA in animals trained to discriminate saline from 3,4-methylenedioxymethamphetamine (MDMA), or two related analogues S-(+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (S-MBDB) or 5-methoxy-6-methyl-2-aminoindan (MMAI). MTA caused dose-dependent increases of tritium efflux from superfused rat frontal cortex slices preloaded with [3H]5-HT, comparable to that induced by an equal molar concentration of PCA. The potential neurotoxicity of MTA was examined by measuring monoamine and metabolite levels at one week following an acute dose. A 10 mg/kg dose of PCA caused a 70-90% decrease of cortical, hippocampal and striatal 5-HT and 5-hydoxyindoleacetic acid (5-HIAA) levels, while twice the molar dose of MTA (21.3 mg/kg) had no effect. Thus, MTA is a potent, selective, serotonin releaser, apparently devoid of serotonin neurotoxic effects. This work also supports the idea that catecholamine systems may play a critical role in the neurotoxicity of PCA-like compounds.


Effect of aspirin on the fibrinolytic response in perfused rat hindquarters. The role of aspirin on tissue plasminogen activator (t-PA) release was studied in rats after experimental venous occlusion. For this purpose, we developed a new experimental model which combines a vascular perfusion system (isolated rat hindquarters) with vascular stimulation, namely the application of venous stasis. Application of venous stasis for 30 min induced the release of t-PA from the vascular endothelium into the perfusate (from 0.19 +/- 0.05 to 0.39 +/- 0.05 UI/ml), reaching a peak 90 s after reperfusion. Aspirin administered to rats 60 min before the experiments (100 mg/kg i.v.), or dissolved in Tyrode solution (100 microM), suppressed 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) synthesis (0.38 +/- 0.09 in control and < 0.01 and 0.15 +/- 0.09 ng/ml, respectively, in aspirin-treated groups) but did not prevent the increase in fibrinolytic activity after venous occlusion (from 0.20 +/- 0.04 to 0.38 +/- 0.06 and from 0.07 +/- 0.03 to 0.27 +/- 0.03 IU/ml, respectively, in the aspirin-treated group). Our results suggest that the increase in fibrinolytic activity after experimental venous occlusion in isolated rat hindlegs is modulated by mechanism(s) other than the cyclooxygenase pathway in the vascular wall.


Blockade of the pacemaker current by intracellular application of UL-FS 49 and UL-AH 99 in sheep cardiac Purkinje fibers. UL-FS 49 (Zatebradine) and its quaternary derivative, UL-AH 99, were injected by iontophoresis in shortened sheep cardiac Purkinje fibres. The i(f) pacemaker current changes were analyzed using the two-microelectrode voltage-clamp technique. Injection of either drug resulted in a decrease of the maximal diastolic depolarization rate as a consequence of a reduction in i(f) amplitude, with no changes in the kinetics of this current or in voltage dependence. The i(f) blockade was proportional to the total charge injected. After drug iontophoresis under conditions where no i(f) current was activated, an exponential use-dependent decline in i(f) tail current was observed during the application of a voltage-clamp pulse train activating i(f). A slow recovery from blockade, measured after prolonged hyperpolarizations, followed exponential kinetics. Recovery rate and extent of steady state recovery increased with more negative potentials. This suggests that bradycardiac agents interact with the i(f) channel in cationic form from the inside of the cell.


Comparison of the anticonstrictor action of dihydropyridines (nimodipine and nicardipine) and Mg2+ in isolated human cerebral arteries. The isometric tension recorded from ring segments of branches of human middle cerebral artery was the parameter used to study the inhibition of spasmogen-induced contractions as model for cerebral vasospasm. Concentration-response curves to 5-hydroxytryptamine (10(-9)-3 x 10(-5) M) and prostaglandin F2 alpha (10(-7)-3 x 10(-5) M) were inhibited in Ca(2+)-free medium and in Ca(2+)-free medium to which EGTA (1 mM) had been added, respectively. Nimodipine (10(-7), 10(-5) M), nicardipine (10(-7), 10(-5) M) and Mg2+ (magnesium sulfate 10(-4), 10(-2) M) inhibited the 5-HT-elicited contractions, and this inhibition was similar for the highest concentrations tested. In contrast, nimodipine and nicardipine were more effective than Mg2+ to inhibit the prostaglandin F2 alpha-elicited contractions. Nimodipine (10(-9)-10(-5) M), nicardipine (10(-9)-10(-5) M) and Mg2+ (10(-5)-3 x 10(-2) M) relaxed the arteries precontracted with PGF2 alpha (10(-5) M), but nicardipine was the most potent relaxant drug. Because 5-hydroxytryptamine and prostaglandin F2 alpha may be involved in the pathogenesis of cerebral vasospasm, nimodipine, nicardipine, and Mg2+ could be used in the pharmacological treatment of this disorder. However, dihydropyridines (particularly nicardipine) are more potent anticonstrictors than Mg2+.


Effect of 5-HT1C and 5-HT2 receptor stimulation on excessive grooming, penile erection and plasma oxytocin concentrations. Serotonin (5-HT) receptor agonist-induced excessive grooming, penile erection and oxytocin secretion were studied in chronically cannulated freely moving rats. The 5-HT1C receptor agonist, m-chlorophenylpiperazine (m-CPP), which also binds to other 5-HT receptors, produced dose-dependent excessive grooming, penile erection and increases in circulating oxytocin concentrations. Maximal responses for excessive grooming and penile erection occurred at 0.3-0.6 mg/kg i.v. m-CPP. Higher doses (0.9-2.5 mg/kg i.v.) caused further increases in oxytocin concentrations, but attenuated both behavioral responses. All three responses to m-CPP (0.6 mg/kg) were attenuated by antagonists with high affinity for the 5-HT1C receptor site (mianserin, LY-53857 and metergoline), but not by the 5-HT2 receptor antagonist ketanserin. The 5-HT2/5-HT1C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), increased plasma oxytocin concentrations only. After ketanserin pretreatment, DOI caused penile erection and diminished the oxytocin response. All responses to DOI were blocked completely by pretreatment with LY-53857 plus ketanserin. Excessive grooming and penile erection showed significant bimodal correlations with the oxytocin response. These data suggest that stimulation of 5-HT1C receptors induces excessive grooming, penile erection and increased oxytocin secretion. Stimulation of 5-HT2 receptors causes a further increase in plasma oxytocin concentration, but inhibits both behavioral responses.


Pro-arrhythmic effect of nicorandil in isolated rabbit atria and its suppression by tolbutamide and quinidine. Nicorandil, a potent vasodilator substance which exerts its effects through complex mechanisms including KATP channel activation, has so far been reported to exert antiarrhythmic but not pro-arrhythmic cardiac activity. We now examined the effects of 10(-4) M nicorandil on spontaneously active or electrically driven isolated rabbit atria. Nicorandil (a) significantly reduced the action potential duration at both 50% (by approximately 45%) and 80% (by approximately 30%) repolarization and the effective refractory period (by approximately 25%) and (b) reproducibly induced short periods of tachycardia either in normal Tyrode solution after a single extra-stimulus or in low-potassium media in the absence of extra-stimulation. Quinidine (10(-5) M) or the KATP channel inhibitor, tolbutamide (10(-5) M), suppressed the nicorandil-induced arrhythmias. It is suggested that the pro-arrhythmic effect of nicorandil results from its KATP channel opener activity and occurs essentially when the underlying conditions facilitate re-entry.


The effect of stress factors on the spontaneous photon emission from microorganisms. The results of recent work on the photon emission from three yeasts and a bacterium is presented. Both visible region and ultraviolet photon emission is observed; however, no luminescence is observed in the absence of oxygen. The visible region emission is attributed to excited carbonyl groups and excited singlet oxygen dimers formed during the decomposition of lipid hydroperoxides. Possible sources of the ultraviolet photon emission are also examined. The use of microorganisms in the study of ultraweak photon emission and its relation to oxidative, temperature and chemical stress is reviewed and the applications and (or) functions of this photon emission are also discussed.


Stress-induced photon emission from perturbed organisms. This paper reviews an ultraweak luminescent response of selected biological systems (lower and higher plants, insects and spermatozoa) to certain kinds of detrimental mechanical, temperature, chemical and photochemical stress and to lethal factors. The enhancing effect of white light and formaldehyde on the ultraweak luminescence of yeast and spermatozoa cells is described for the first time. An increase in the percentage of long wavelengths (lambda > 600 nm) with an increase in reaction time, and a significant influence of the suspending medium on the ultraweak luminescence, were observed. The vitality and motility of bull spermatozoa and the vitality of yeast cells were drastically decreased by treatment with white light, water, formaldehyde and iron-ions. Successive irradiation of intact bull spermatozoa cells with white light caused an increase in the intensity of delayed luminescence. An attempt has been undertaken to find stochastic models of non-stationary photon emission. The quasi-relaxation descending stage of non-stationary processes can be modeled as the Integrated Moving Average process IMA (0, 1, 1), and memory and transfer functions can describe the degree of perturbation in the yeast Saccharomyces cerevisiae. The relation of the ultraweak luminescence response to perturbations of homeostasis is discussed in the framework of biochemical and physical models.


Time-resolved luminescence of perturbed biosystems: stochastic models and perturbation measures. Measures of biosystem perturbation using a cybernetic approach based on stochastic models of photon emission processes are presented, and compared with classical measures. Perturbation phenomena reflected in non-stationary emission processes are represented by means of filtering theory.


Nonlinear response of biophoton emission to external perturbations. By considering an exciplex system consisting of collective molecules in interaction with both the 'pumping' fields and the biophoton fields, the two-level exciplex model and the three-level exciplex model are presented. They are useful for the investigation of the quasi-stationary behaviour of biophoton emission, and biophoton emission as a dynamic process in the presence of external perturbations. Our theoretical results predict a series of nonlinear effects, such as chaos, fractal behaviour, and non-equilibrium phase transition. These effects characterize the coherence nature of living systems. In our approaches, there are two important quantities f and x, which can be used to mark the working points of the two-level and three-level exciplex systems. All the influences of external perturbations on the exciplex systems, e.g. change of temperature, the addition of agents, exposure to light, etc., can be interpreted as shifts of the working points of the systems, leading to a diversity of nonlinear response of biophoton emission. In addition, the agreements of the theoretical results and the corresponding experimental observations on biophoton emission from biological systems in the presence of external perturbations are demonstrated.


Photon emission in tumor biology.

Photon emission in tumor biology. Photon emission from mammalian cells has been subject of study for many years. Growing research activity is directed on the photon emission within the field of tumor biology. These studies, applying high-sensitivity photon counting methods, have paid attention to several aspects, including photon emission from serum of tumor-bearing animals, photon emission of tumors and of isolated tumor cells. In addition, research activity is increased with respect to the photon emission induced by white light from cultured tumor cells. In this review we report on the different aspects of spontaneous and induced photon emission of tumor cells as compared to normal cells. Throughout these studies the question of a functional biological role of this spontaneous and light-induced photon emission has been raised and some different points of view will be discussed.


Photon emission of phagocytes in relation to stress and disease. Phagocytes, the first-line cells of the body's defence mechanisms against invading pathogens, kill microorganisms by means of lysosomal degradative enzymes and highly toxic reactive oxygen intermediates. The reactive oxygen compounds are produced, in a process called the 'respiratory burst', by the NADPH oxidase complex in plasma membranes, and by myeloperoxidase in phagolysosomes after degranulation. These processes generate electronically excited states which, on relaxation, emit photons, giving rise to phagocyte chemiluminescence (CL). This paper describes the conditions for the measurement of CL, and reviews the activity of phagocytes from individuals undergoing stress or disease. The capability of phagocytes to emit photons reflects remarkably well the pathophysiological state of the host. In many cases even the magnitude of the stress, the presence of a pathogen in the body, or the activity of the disease can be estimated. Physiological changes, e.g. in the reproductive cycle, can also be predicted.