Autologous blood transfusion today.

Autologous blood transfusion today. Autologous blood transfusion--the transfusion to a patient of his or her own blood--is increasingly being recognised as a useful adjunct to traditional transfusion practice. The reasons include fears of disease transmission, the potential adverse effects on the recipient's immune system of transfused donor blood, and logistical factors. The three main techniques of autologous transfusion are: (i) pre-deposit, in which patients donate blood over a period of time in preparation for elective surgery; (ii) pre-operative isovolaemic haemodilution, in which blood is removed immediately before surgery and volume replacement is given, the blood being reinfused post-operatively; and (iii) salvage transfusion--the collection of blood shed at surgery or in similar circumstances, which is reinfused immediately or after concentration and purification. All three techniques can help to improve the safety of transfusion and economise on scarce supplies of donor blood.


Babington's syndrome--setting the record straight. Mrs FM walked slowly to Guys Hospital on 5th July 1945. She had to walk slowly, for she had been increasingly breathless with exertion of late. She was to attend Ear, Nose and Throat Outpatients, and after some initial delays she was ushered in to see the consultant, Mr TB Layton. He had been appointed to the staff of Guys Hospital in 1912. He then served in the Great War, was twice mentioned in dispatches, and won the DSO. He claimed to be the first British officer to enter Jerusalem when it was taken by Allenby's forces. In a word he was a character; and much loved (Figure 1).


The value of serological tests for syphilis in atypical genital ulcer disease. A 45-year-old heterosexual man presented with phimosis three weeks after arriving in this country from India. Examination under anaesthesia and circumcision revealed a large ulcer on the ventral aspect of the penis around the fraenum. Histopathological examination of a biopsy taken from the ulcer revealed granulation tissue with inflammatory cell infiltrate. Specific and non-specific serological tests for syphilis carried out four weeks after the initial presentation showed high titres. The importance of serological tests for syphilis in genital ulcer disease, especially in atypical presentations, is discussed.


Unsuspected factors in 'self-limiting' ailments. An unsuspected subtotally perforated eardrum treated with wax softening drops shows how clinical findings do not always correlate with symptoms or history. Attention is drawn to the dilemma posed by delegating matters such as diagnosis and prescribing which have been considered to be purely in the medical sphere.


Steatorrhoea and sub-total villous atrophy complicating mefenamic acid therapy. We report a case of steatorrhoea and sub-total villous atrophy, occurring during therapy with mefenamic acid. The patient recovered on cessation of the drug while continuing a normal diet.


Ileal haemangiopericytoma and von Recklinghausen's disease. Haemangiopericytoma is an uncommon tumour of vascular pericytes which usually arises in deep subcutaneous tissues or the retroperitoneum. There are few reports in the English literature of haemangiopericytoma arising in the ileum. Von Recklinghausen's disease, a condition of autosomal dominant inheritance with a prevalence of 1 in 3000, is often associated with tumours of neural origin. Tumours of non-neural origin also occur in Von Recklinghausen's disease but haemangiopericytoma has not been described. We report on a patient with Von Recklinghausen's disease presenting with massive haemorrhage from an ileal haemangiopericytoma.


An unusual presentation of polymyalgia rheumatica with severe muscle weakness. An 83-year-old woman suddenly developed profound weakness of proximal and distal muscles in both upper limbs. Electromyography revealed abnormal changes but serum creatine kinase was normal. The weakness responded dramatically to steroid therapy. These unusual features of polymyalgia rheumatica are discussed.


Dressler's syndrome presenting as acute pneumonitis. An elderly man developed acute pneumonitis three weeks after a myocardial infarction treated with streptokinase. The differential diagnoses are discussed and a short review of lung disease in the post-myocardial infarction syndrome is presented.


Malignant melanoma of the parotid gland. We report a case which demonstrates pitfalls in the management of a parotid gland mass and highlights behaviour of malignant melanoma that is not widely appreciated. The danger of assuming a benign histological diagnosis of such a mass and the subsequent delay of definitive surgery is demonstrated. Metastases within the parotid gland are not uncommon, melanoma being one of the commonest sources. A search should always be made for a primary tumour in the head, neck and chest. This can be made exceptionally difficult by the uncommon phenomenon of spontaneous regression of the primary melanoma.


Impact of biologically closed electric circuits (BCEC) on structure and function. The basis of our physical world is electrical. The unified Electromagnetic field can appear to us as particles, i.e., matter, at certain densities of wavelengths. A close interrelation therefore exists between matter and electric energy. This knowledge is extensively utilized in technology. Various tools and instruments are electrically powered, utilizing the exceedingly important principle of closed electric circuits. Corresponding closed electric circuits and functions also exist in biology but are more sophisticated and complex. Unfortunately, these aspects are almost unrecognized. The principle of Biologically Closed Electric Circuits (BCEC) and some of their structural and functional effects are described. The Vascular-Interstitial Closed Circuit (VICC) is one specific BCEC system. It functions as a circulatory system in addition to the mechanical circulation. Its efficiency partly depends on its capacity to provide bidirectional transport of ions. The VICC is an in vivo electrophoretic-dielectrophoretic system that is powered by metabolic energy or injury currents. A VICC activation leads to transports of metabolites, new structuring and healing of an injured tissue. Examples are also presented of the process of healing. An abnormal, e.g., prolonged activation of VICC may also induce pathology. Neoplastic formation of cells and tissue can also be healed by the use of artificially applied electrophoresis or an artificially applied electric field as will be described. Our world once developed from electrical energy. This is probably the reason why the BCEC systems make primary differences between nonbiological and biological matter.


Low-dimensional chaos maps learning in a model neuropil (olfactory bulb). Quantification of a chaotic system can be made by calculating the correlation dimension (D2) of the data that the system generates (Packard et al., 1980). The D2 algorithm, however, requires stationarity of the generator, a feature that biological data rarely reflect (Mayer-Kress et al., 1988). So we developed the "point correlation dimension" (PD2), an algorithm that accurately tracks D2 in linked data of different dimensions (Carpeggiani et al., 1991). We now present a mathematical argument that, for stationary data, individual PD2s converge to D2 and we demonstrate that the algorithm rejects contributions made by bursts of noise. Data were obtained from the surface of the olfactory bulb of the conscious rabbit (64 electrodes, 640 Hz each, 1.3 sec epochs) before and after presentation of a novel or habituated odor. D2 could be calculated in only 1 of 10 novel-odor trials, whereas PD2 could be calculated in all. Both algorithms indicated that a novel odor evokes a spatially uniform dimensional increase. The PD2 uniquely exhibited the dimensional decreases that occur during inspiration and the gradients of mean dimension present during the nonstimulated control state. These control gradients remained unchanged without odor experience, but showed spatially specific PD2 increases following odor habituation. It is interpreted that, 1) the PD2 is sensitive, accurate, and appropriate for dimensional assessment of biological data, 2) that during analysis of unfamiliar information a single global process is transiently evoked in the neuropil, and 3) after experience multiple spatially specific processes tonically map the sites of learning.


Van Gogh and the life chart.

Van Gogh and the life chart. Adolf Meyer originally devised the life chart in order to chronologically document a person's major life events and significant illness experiences over his or her life span. It is the purpose of this report to update Meyer's life chart through the presentation of the life events and illnesses of the famous artist Vincent Van Gogh. Van Gogh's life illustrates significant early (predisposing) life stresses, as well as clusterings of stressful (precipitating) life events occurring proximal to the occurrence of his several illnesses. Through the use of a life chart an understanding of why an individual becomes ill at a particular time in their life is enlarged. In addition, a systematic basis for formulating prognosis becomes available.


Reflections on human Pavlovian decelerative heart-rate conditioning with negative tilt as US: alternative approaches. The negative-tilt preparation that has been reported since the late seventies is a specific form of Pavlovian conditioning that is of scientific interest and has potential applications. In this paper I reflect on the usefulness, to the development of this preparation, of two approaches to Pavlovian conditioning. One approach is the older S-R learning, stimulus-substitution paradigm exemplified by learning texts of the sixties. The other is the modern, Tolman-like view, according to which the phenomenon of Pavlovian conditioning is "now described as the learning of relations among events so as to allow the organism to represent its environment." The three assumptions encapsulated by this approach are: (a) that only CS-US contingency relations are learned; (b) that teleological modes of explanations are adequate; (c) that the representational theory of knowledge is sound. Concerning Pavlovian conditioning in general, questions been raised in the literature for all three assumptions; they have not been adequately answered. Regarding the specific problem of developing the human Pavlovian heart-rate decelerative conditioning with negative tilt as the US, I suggest that the cognitive approach has been much less helpful than the older, S-R, stimulus-substitution paradigm. Nevertheless, other literature clearly indicates that the cognitive, S-S approach has generated considerable interest and research, especially in preparations like the conditioned emotional response (CER), which are CS-IR ones in the sense that the effects on the CR are assessed indirectly through measuring an indicator or instrumental response (IR).(ABSTRACT TRUNCATED AT 250 WORDS)


Extinction instead of incubation following classical aversive conditioning in dogs. Two dogs received a single paired classical conditioning trial, with tone CS and 12 mA shock US. Both dogs then showed a conditioned blood pressure increase in response to the nonreinforced CS, which extinguished with additional nonreinforced presentations. The CR showed spontaneous recovery four days later, but reextinguished with additional nonreinforced presentations. The results were interpreted as not supporting Eysenck's theory of "incubation" following one-trial aversive conditioning.


Conditional reflexes as related to hypnosis and hypnotic techniques. Hypnosis has never been adequately explained in terms of conceptual framework of most schools of psychotherapy. The psychoanalytic concept that it consists of submission and surrender of important ego functions to the therapist does not explain all observed facts. During my wartime studies and since, I have been impressed by the observation that the patient's ego is by no means powerless and defenseless, even during a deep state of trance, i.e., in states of trance sufficiently deep to eliminate awareness of painful body injuries (1965). Erickson (1954) has shown on many occasions that in resistant subjects one of the best ways to induce trance is to encourage the patient to resist as much as he can. Haley (1963) has pointed out in detail that at the beginning of any hypnotic relationship there evolves a subtle battle for "one-upmanship." These observations certainly show that surrender in the psychological sense is by no means an aspect of even the most successfully induced trance states.


Nutrition and cancer: background and rationale of the European Prospective Investigation into Cancer and Nutrition (EPIC). The development of epidemiological research on diet and cancer during the last decades is discussed. Apart from some consistent data on the protection against several cancers conferred by a diet rich in fruits and vegetables, the results provided by retrospective case-control studies on diet and cancer remain contradictory on many important issues, and primarily on the relation between diet and breast cancer. The rationale is presented for setting up large prospective cohort studies combining epidemiological and laboratory methods in order to expand the presently limited knowledge of the role of nutrition and related factors in cancer etiology. The main features of the European Prospective Investigation into Cancer and Nutrition are outlined. The study is being carried out in seven European countries and it will collect data on diet, other lifestyle and environmental factors, anthropometry as well as biological samples in a cohort of about 400,000 healthy European adults. The subjects will be followed up to investigate the incidence of and mortality from cancer in relation to epidemiological data and biochemical markers.


Chemotherapy-induced anemia in patients with primary lung cancer. To elucidate the factors which influence the value of hemoglobin, the nadir value of hemoglobin, frequency of blood transfusion and prognostic value of blood transfusion in patients with primary lung cancer during intensive chemotherapy, the hematological features of 124 patients entered into a randomized phase III study containing cisplatin were retrospectively analyzed. There was no difference in the percent nadir hemoglobin value of the first course of chemotherapy (% of pretreatment value) in any of the subgroups with respect to sex, body weight loss, performance status, age, stage, number of metastatic sites or treatment arms. The only predictive indicator for the nadir hemoglobin value in the first course of chemotherapy was the pretreatment value of hemoglobin. The equation for the regression line was y = 1.07 + 0.73x (R2 = 0.663, p < 0.001). The lowest nadir hemoglobin value (% of pretreatment value) during all chemotherapy courses was significantly lower in the subgroups older than 60 years and those with body weight loss. There was an inverse correlation between the accumulated dose of cisplatin and the lowest nadir hemoglobin value (p < 0.05). The frequency of blood transfusion in patients with more than two metastatic sites was significantly higher than in those with one or no metastatic sites (p < 0.05). Survival of patients who had required blood transfusion after chemotherapy was significantly shorter than that of patients who had not (p < 0.05).


A combination of mitoxantrone, etoposide and prednisone in elderly patients with non-Hodgkin's lymphoma. From January 1988 to December 1991, 55 elderly patients (14 pretreated and 41 previously untreated) with non-Hodgkin's lymphoma (NHL) entered a prospective study to evaluate the feasibility of a combination of mitoxantrone (7-9 mg/m2), VP 16-213 (150 mg, 2-hour infusion on day 1, and 200 mg per os on days 3 and 5) and low-dose prednisone (25 mg days 1-5) (MVP regimen), recycling every 21-28 days. The median age was 75 (range 64-93). All but 4 pretreated patients had intermediate- or high-grade lymphomas. Complete remissions were obtained in 22 of 40 (55%) evaluable previously untreated patients, and partial remissions in 10 (2 of these obtained complete remissions after radiotherapy), for an overall response rate of 80%. The median duration of response was 12 months. At 24 months the overall survival was 52% and the relapse-free survival was 31%. Of 14 pretreated patients complete remissions were obtained in 4 (29%) and partial remissions in 3. Granulocytopenia and fever were the most important side effects; two patients contracted bronchopneumonia and one of them died. Other toxicities were mild. We conclude that this combination chemotherapy is effective as first-line and salvage treatment in elderly patients with intermediate- and high-grade NHL, and that it is feasible on an outpatient basis, with manageable toxicity.


Adult lymphoblastic lymphoma: high incidence of central nervous system relapse in patients treated with the Stanford University protocol. Twelve adult patients with non-leukaemic lymphoblastic lymphoma were treated with combination chemotherapy and central nervous system prophylaxis according to the protocol developed at Stanford University. Despite strict adherence to the Stanford protocol, 4 of 12 patients relapsed in the CNS, all with meningeal disease. Only four of the 12 patients are in continuing complete remission 6 to 88 months from the completion of induction therapy. These results are inferior to those previously reported for this regimen, and fail to confirm the high rate of control of CNS disease.


Prospective study with combined low-dose chemotherapy and zidovudine in 37 patients with poor-prognosis AIDS-related non-Hodgkin's lymphoma. French-Italian Cooperative Study Group. The French-Italian Cooperative Study Group included patients with poor-prognosis AIDS-related non-Hodgkin's lymphoma (NHL), defined as those with performance status (PS) > or = 3 and/or opportunistic infections (OI), in a prospective study with a 50% reduced-dose combination chemotherapy regimen: CHVmP-Vincristine-bleo (cyclophosphamide 300 mg/m2 i.v. day 1, doxorubicin 25 mg/m2 i.v. day 1, teniposide 30 mg/m2 i.v. day 1, prednisone 20 mg/m2 per os days 1-5, vincristine 2 mg i.v. day 15, and bleomycin 10 mg i.v. day 15), given every 21 days for eight cycles, and concomitant zidovudine 500 mg per os per day. The aims of this combined treatment were to reduce bone marrow toxicity and infectious complications related to chemotherapy (with a low-dose chemotherapy regimen), and to control the HIV and related infectious complications (with zidovudine therapy). Thirty-seven patients entered this prospective study. At the time of the NHL diagnosis, 41% of the patients had asymptomatic HIV infection, 27% had ARC and 32% had already had CDC-defined diagnoses of AIDS. The median CD4+ cell count was 35 mm3. Only 29 patients are evaluable for response, since 8 received only one cycle of chemotherapy. Fifteen of 29 (52%) patients obtained objective responses, with only 4 (14%) achieving complete remissions (CR) of 1, 4, 14 and 29+ months. Three (16%) CRs were achieved in 19 evaluable patients included in the study because of poor PS, and only one CR was observed in 10 evaluable patients with histories of OI, either alone or with poor PS. The most common side effect was bone marrow toxicity with 2 related toxic deaths.(ABSTRACT TRUNCATED AT 250 WORDS)


Cyclophosphamide, doxorubicin and fluorouracil (CAF) plus depo-buserelin in the treatment of premenopausal women with metastatic breast cancer. A phase II study was undertaken to assess the effect of CAF plus depo-buserelin, as first-line treatment, in premenopausal women with breast cancer. Of 66 patients entered 60 are eligible and evaluable; their median age was 45, estrogen receptor (ER) was positive in 9, negative in 11 and unknown in 40. The median disease free interval (DFI) was 11 months. Metastatic sites were visceral in 14, bone in 34 and soft tissue in 37. Twenty-nine patients had metastatic disease of one site, while 31 had 2-4 sites. An objective response of 82% was documented (29 complete responders and 20 partial responders). Median time to treatment failure was 11.5 months and median survival 37 months. Most commonly encountered side effects attributable to CAF were alopecia, nausea and vomiting, leucopenia and thrombocytopenia. Side effects attributable to buserelin were hot flashes. After one cycle baseline mean serum estradiol fell from premenopausal levels to postmenopausal levels. This study showed that CAF plus buserelin is well tolerated, with a very high response rate in selected premenopausal patients with advanced breast cancer.


Feasibility and toxicity study of a high-dose chemotherapy regimen for autotransplantation incorporating carboplatin, cyclophosphamide and thiotepa. Sixteen patients received a high-dose chemotherapy regimen consisting of carboplatin (1600 mg/m2) and cyclophosphamide (6000 mg/m2) as daily two-hour infusions over four days (CC). All but two of them also received thiotepa (480 mg/m2) in eight 30-minute infusions given every 12 hours (CTC). Bone marrow and/or peripheral stem cell (PSC) reinfusions took place 72 hours after the last course of chemotherapy. The major toxicity was bone marrow suppression, the duration of which was markedly reduced in the patients receiving PSC reinfusions. Non-hematological toxicity was relatively mild and consisted of nausea and vomiting, minor mucositis and skin rashes. All but one patient had mild and completely reversible elevations of serum ALAT and/or LDH levels. One patient, who had received full-dose chemotherapy despite a creatinine clearance of 56 ml/min, developed significant toxicity consisting of transient cyclophosphamide-associated pancarditis, reversible neurotoxicity and partially reversible hearing loss and renal function impairment. There were no toxic deaths. In view of the high carboplatin dose, the CTC regimen may be particularly suitable for use in the salvage treatment of germ cell cancer. Since CTC causes no serious organ toxicity, further studies to determine its suitability for double or even triple transplantation programs are warranted.


Etoposide (E) + epirubicin (E) + cisplatin (P) combination chemotherapy (EEP) in advanced gastric cancer: negative impact on clinical outcome. Spanish Cooperative Group for GI Tumor Therapy (T.T.D.). One hundred nineteen patients with advanced gastric cancer were included in a study comparing EEP vs. FEM chemotherapy. The response rate was higher (30%) in patients on EEP than in those treated with FEM (p = 0.05). Severe leukopenia, anemia, alopecia and infection were significantly more frequent on EEP. In addition, because of its intrinsic toxicity, EEP chemotherapy has a negative impact on the performance status of patients treated with this regimen, more than half of whom presented at least one episode of severe symptomatic toxicity while on EEP chemotherapy. The median time to progression and median survival for EEP-FEM were 2.08-3.4 and 4.2-7.9 months, respectively. Our data do not support the use of EEP chemotherapy in patients with AGC.


Enantiomer-specific effects of an intravenously administered arrhythmogenic dose of bupivacaine on neurons of the nucleus tractus solitarius and the cardiovascular system in the anesthetized rat. This investigation was designed to determine whether the effects on the cell firing rate (CFR) at the nucleus tractus solitarius (NTS) and on the cardiovascular system, which are associated with a toxic dose of bupivacaine, have an enantiomer-specific component. Adult Sprague-Dawley rats were anesthetized with chloral hydrate, and a femoral artery and vein were cannulated. After the cranial surface was exposed, a 3-mm hole was drilled 2 mm caudal and 1.5 mm lateral with respect to lambda for placement of a 1-microns tungsten microelectrode. Cells of the NTS were located 6-6.5 mm from the brain surface, and CFR was continuously recorded. Lead II electrocardiogram and arterial blood pressure were also recorded. Twenty-four animals received either d- or l-bupivacaine (2 mg/kg) in random order. Cell firing rates decreased from 21 +/- 13 to 0 +/- 0 impulses/second (p < 0.001) at 34 +/- 15 seconds after the injection of d-bupivacaine. Cell firing rates decreased from 22 +/- 17 to 2 +/- 4 impulses/second (p < 0.01) at 68 +/- 45 seconds after injection of l-bupivacaine. In addition to the decreases in blood pressure and heart rate that were found, all animals exhibited an inversion in electrical axis beginning within 2-3 seconds after bupivacaine administration. Mild bradycardia was noted in four of the animals receiving the l-bupivacaine, whereas severe bradycardia was observed in all animals receiving d-bupivacaine. Most important, this severe bradycardia was accompanied by progressive hypotension. In addition, all animals receiving d-bupivacaine became apneic and died, whereas all animals receiving l-bupivacaine continued to breathe and all but two of the animals survived. Data in the current report support the hypothesis that effects of bupivacaine on neurons of the NTS and on the cardiovascular system have an enantiomer-specific component.


Effect of local anesthetic concentration on capillary blood flow in human skin. The objective of this study was to evaluate and compare the effect of lidocaine, mepivacaine, and bupivacaine on capillary blood flow in humans over therapeutic and subtherapeutic concentrations. The effect of each treatment in eight unmedicated male volunteers was measured in a randomized, controlled, double-blind comparison. Each participant received subcutaneous injections (total, 14), at separate sites on the abdomen, consisting of 0.2 ml lidocaine (0.05%, 0.5%, 1%, and 2%), mepivacaine (0.05%, 0.5%, 1%, and 2%), bupivacaine (0.025%, 0.25%, 0.5%, and 0.75%), saline, or saline with epinephrine (5 micrograms/ml), and at an additional site a needle stick was performed and no injection made. Cutaneous blood flow was measured with a laser Doppler capillary perfusion monitor before and for 60 minutes after these interventions. The maximum increase in cutaneous blood flow was 277 +/- 141% to 511 +/- 136% (mean +/- SE) after lidocaine, 124 +/- 110% to 316 +/- 155% after mepivacaine, and 242 +/- 193% to 725 +/- 198% after bupivacaine. The increase in blood flow depended on local anesthetic concentration: low concentrations induced minimal changes, whereas higher concentrations caused great increases in cutaneous blood flow. Injection of saline or needle stick alone increased cutaneous blood flow 285 +/- 237% and 260 +/- 121%, respectively. Our findings indicate that the trauma of needle stick or saline injection produces a significant increase in cutaneous capillary blood flow. Injection of clinically useful concentrations of bupivacaine and lidocaine produced even greater increases in capillary blood flow, indicating a vasodilatory effect. Injection of the lowest concentrations of lidocaine and bupivacaine caused flow to increase to a magnitude similar to that after injection of saline. In contrast, clinically useful concentrations of mepivacaine do not increase capillary blood flow to a greater extent than saline, and lower concentrations tend to blunt the increase in blood flow, indicating a mild vasoconstrictor effect.


Skin blood flow after intradermal injection of ropivacaine in various concentrations with and without epinephrine evaluated by laser Doppler flowmetry. Skin blood flow changes after intradermal injection of ropivacaine in various concentrations with or without epinephrine were investigated using laser Doppler flowmetry. Twenty-three non-smoking, healthy, young male volunteers participated. Four test sites were used on each forearm (volar surface) in a randomized, double-blind study. Recordings were made at 20, 40, 60, and 90 minutes after intradermal injection (0.1 ml, 30-gauge needle). Injections of saline and 1% lidocaine and an untreated area served as controls. In Series 1, various concentrations of ropivacaine (1%, 0.5%, 0.375%, 0.125%, and 0.063%) were injected. The data from this series showed a dose-response relationship: 1% ropivacaine provoked an increase in skin blood flow similar to saline; 0.5% and weaker concentrations of ropivacaine showed a reduction in flow compared to saline, this being more pronounced with the weakest solutions (0.125% and 0.063%). In Series 2, injection of 1:200,000 (5 micrograms/ml) epinephrine alone and injections of ropivacaine in various concentrations (1%, 0.5%, and 0.25%) with addition of epinephrine were carried out. Injection of epinephrine alone showed a flow almost as low as at the untreated control sites. Ropivacaine epinephrine injections were followed by a lower skin blood flow compared to saline, but the flow was significantly larger compared to the effect of epinephrine itself at the 20-minute recording. The combination of ropivacaine and adrenaline did not accentuate but instead diminished the vasoconstrictive effect of epinephrine.


Patient-controlled analgesia with epidural meperidine after elective cesarean section. We report the first controlled analysis of the use of patient-controlled epidural meperidine. This randomized, prospective study compares the efficacy and safety of patient-controlled epidural meperidine to conventional intramuscular meperidine for the management of postoperative pain after elective cesarean delivery. After delivery, 60 patients were randomly assigned to receive either conventional intramuscular meperidine therapy or epidural meperidine by a patient-controlled analgesia pump, which was programmed to deliver bolus doses in addition to a continuous background infusion. Patients in the patient-controlled epidural analgesia group used significantly less meperidine in the first 24 hours after surgery (p < 0.05) and had significantly lower visual analog pain scores (p < 0.05) from three hours postoperatively until study completion at 24 hours. Patients in the patient-controlled epidural analgesia group ambulated sooner (19 +/- 7.8 versus 29.2 +/- 2.2 hours, p < 0.005) and cared for their infants earlier (4.6 +/- 0.9 versus 8.1 +/- 6.8 hours, p < 0.05) than patients receiving intramuscular meperidine. One patient developed a respiratory rate of four breaths per minute, 25 minutes after receiving 75 mg epidural meperidine in the operating room. This was treated with intravenous naloxone. No other serious side effects occurred in either group. Both groups were similar with regard to minor intraoperative and postoperative side effects. Patient-controlled epidural meperidine after cesarean delivery more effectively manages postoperative pain than conventional intramuscular use. The technique is preferred by both patients and nursing staff and can be used in the ward setting with appropriate organization and education. Respiratory depression, if it occurs, should present early after epidural bolus administration.


Distribution of 3H-morphine after lumbar epidural administration in unanesthetized rabbits. This study focused on the distribution of 3H-morphine in the spinal cord, roots, urine, and blood, after epidural administration in rabbits. Under nitrous oxide, halothane, and oxygen endotracheal anesthesia, the cisterna magna of New Zealand albino rabbits was cannulated for cerebrospinal fluid sampling, and catheters were placed in the lumbar epidural space. Through the epidural catheter, 200 pmol of 3H-morphine contained in 500 microliters of 1.3 mM (0.21 mg) morphine was injected. Arterial blood and cisternal CSF were sampled at 0, 5, 15, 30, 45, 60, 90, and 120 minutes after injection. Animals were killed with intravenous pentobarbital at the end of 120 minutes (n = 3), 6 hours (n = 4), and 12 hours (n = 2). In each animal the brain, spinal cord, spinal roots, liver, kidneys, and urinary bladder were removed. The injection site over the cord was identified and all tissues were immediately frozen at -70 degrees C. Two-mm thick cross-sections, were taken from every centimeter of the spinal cord. Radioactivity in the series of sections was determined by scintillation spectroscopy. At 2 hours, 4.2% +/- 1.1% of the injected radioactivity was recovered, and at 6 hours 1.6% +/- 0.6% was recovered. Radioactivity was concentrated mainly around the lumbar injection site, and it decreased as the distance increased from the injection site and coincided with elapsed time after the injection. Multiple linear regression analysis of radioactive labels showed the significant effect of time, distance from the injection site, and the time-distance interaction on the distribution of 3H-morphine in the spinal cord (p < 0.0001 for time and rostral and caudal distance from the injection site; and p < 0.0001 for interaction between time and distance.) A major portion of the injected radioactivity was recovered in the urine and a small amount in other tissues and body fluid: bladder, liver, spinal roots, kidney, plasma, and cerebrospinal fluid.


Thoracic paravertebral block in chronic postoperative pain. Chronic postoperative pain in thoracic dermatomes is common. The most frequently used methods of pain relief in this area are posterior multidermatomal intercostal nerve or thoracic epidural blocks. Compared with these methods, thoracic paravertebral block may have some advantages. Usually only one injection is needed, and the use of larger volumes of local anesthetic (up to 25 ml) results in widespread unilateral analgesia including sympathetic block without the potential risk of hypotension and motor block associated with epidural block. We retrospectively analyzed 281 thoracic paravertebral blocks performed for chronic postoperative pain (post-thoracotomy and postmastectomy) from 1986 to 1990 in our pain clinic. In post-thoracotomy group, patients were without pain for at least a month after 58% of the blocks; in 30%, the effect lasted for at least two months; in 8%, more than four months and, in 3%, more than five months. In 88% of patients with postmastectomy pain, the achieved pain relief with thoracic paravertebral block was less than a month. No severe complications occurred. Thoracic paravertebral block proved to be a reliable and safe technique for unilateral pain relief in chronic post-thoracotomy pain.


When to remove an epidural catheter in a parturient with disseminated intravascular coagulation. Pain from labor and delivery is often attenuated with epidural anesthesia. A complication of indwelling epidural catheters is intraspinal hematoma. The development of a bleeding diathesis can worsen complications markedly. Frequent assessment of neurologic status is important until the underlying cause of the coagulopathy can be treated and the bleeding resolves. If there is no indication of intraspinal bleeding, we recommend removing the catheter because of potential catheter migration. If bleeding is occurring around the catheter insertion site and possibly in the epidural or subarachnoid space, the catheter may be left in place to tamponade the insertion site. In cases of intraspinal hematoma, which can cause neurologic deficits, immediate decompression surgery is needed.


Self-reactive T cells are present in the peripheral lymphoid tissues of cyclosporin A-treated mice. Cyclosporin A (CsA) prevents most immature thymocytes from progressing to a mature phenotype and blocks the deletion of T cells that express self-specific TCR in the small population of cells that achieve maturity. The latter effect may explain the paradoxical observation that this immunosuppressive drug can induce autoimmunity in irradiated rodents and humans if administered while new T cells are developing in the thymus. This study shows that the repopulation of the periphery with mature T cells is delayed in irradiated CsA-treated mice, presumably because CsA blocks T cell development in the thymus. The peripheral repertoire of these mice contained self-reactive IL-2 producing T cells that could be detected in a sensitive limiting dilution assay. In addition, self-reactive T cell hybridomas were isolated from the IL-2 receptor+ population present in CsA-treated mice. One of these hybridomas expressed a TCR V beta chain that is normally expressed on thymocytes that are deleted via recognition of self-antigens. Despite the presence of self-reactive T cells that had escaped clonal deletion, CsA-treated mice rarely developed lethal autoimmune disease, implying that a peripheral mechanism of tolerance can prevent the onset of autoimmune disease.


Activation of B lymphocytes by NK cells. The ability of NK cells to induce differentiation of B lymphocytes to IgM secretion in vitro has been investigated. Homogeneous preparations of NK cells obtained from IL-2 propagated splenocytes from SCID mice were found to have the ability to induce resting B lymphocytes to proliferate and secrete significant amounts of IgM. The induction is greatly enhanced by the presence of both IL-2 and IL-5 and does not require T lymphocytes or adherent cells in the responding population. Cell contact between the two populations is not necessary suggesting that the effect is mediated by soluble factor(s) which can be produced even by irradiated NK cells. Because the activity cannot be replaced by either r-tau-IFN or tumor necrosis factor-alpha or inhibited by antibodies to these lymphokines, a novel NK cell-derived factor(s) may be involved. The implications of this interaction between NK cells and B lymphocytes are discussed.


Interleukin 10 inhibits allogeneic proliferative and cytotoxic T cell responses generated in primary mixed lymphocyte cultures. The effects of IL-10 on the generation of alloreactivity in primary mixed lymphocyte cultures (MLCs) were investigated. IL-10 inhibited in a dose-dependent fashion the alloantigen-induced proliferative responses. The suppressive effect was maximal when IL-10 was added at the beginning of the cultures, suggesting that it acts on the early stages of T cell activation. The proliferative responses were enhanced in the presence of a neutralizing anti-IL-10 mAb, indicating that endogenously produced IL-10 suppresses proliferation in primary MLC. The inhibitory effects of IL-10 were observed irrespective of whether irradiated allogeneic peripheral blood mononuclear cells, purified monocytes or freshly isolated B cells were used as stimulator cells. The proliferation of both the CD4+ and CD8+ T cell subsets was inhibited to a similar extent. The reduced proliferative responses were only minimally restored by high concentrations of exogenous IL-2, indicating that the effects of IL-10 are not exclusively due to inhibition of IL-2 synthesis. Furthermore, the production of IL-2, interferon (IFN)-gamma, IL-6, granulocyte macrophage colony stimulating factor, and tumor necrosis factor-alpha in primary MLCs was diminished by IL-10 and enhanced in the presence of anti-IL-10 mAb. The strongest effects were observed on the production of IFN-gamma. Although IL-10 reduces the proliferative responses, the ratios of CD3+CD4+ and CD3+CD8+ T cells remained the same in IL-10 treated and control cultures, yet the percentages of activated CD3+ T cells, as judged by CD25 and HLA-DR expression, were consistently reduced.(ABSTRACT TRUNCATED AT 250 WORDS)


Identification of single amino acid substitutions in the staphylococcal nuclease protein that enhance and diminish T cell clone recognition of naturally processed peptides. It has been inferred that residue changes that affect T cell recognition of synthetic peptides will have a similar effect in the intact protein. However, since small peptides do not require antigen processing it is possible that residue changes in synthetic peptides will not have an equivalent effect in the intact protein. Mutant proteins of staphylococcal nuclease (Nase) and 15mer synthetic peptides with corresponding substitutions were compared to determine if residue changes within an immunodominant epitope have an effect on the generation of naturally processed peptides. Five different substitutions in the synthetic peptide resulted in loss of reactivity of individual Nase-specific clones. When the same single amino acid changes were made in the intact protein, the naturally-processed peptides were also unable to stimulate the Nase-specific clones. However, two other substitutions in the synthetic peptide were stimulatory for a T cell clone even though the same changes in the intact protein were non-stimulatory. These results suggest that certain residue changes affect recognition of the naturally processed peptide but not the synthetic peptide with the same amino acid change. In addition, these results demonstrate that the effects of amino acid substitutions in synthetic peptides on T cell recognition may not always reflect the effects of these substitutions in the intact protein. Substitutions located outside Nase-specific T cell epitopes were also examined. Thirty different mutant proteins were all stimulatory. Moreover, a number of these mutants proteins were 50- to 100-fold more efficient in their stimulatory capacity than the native Nase protein.(ABSTRACT TRUNCATED AT 250 WORDS)


Induction of protective CD8+ T lymphocytes by an attenuated Listeria monocytogenes actA mutant. We tested the ability of an attenuated actA mutant of Listeria monocytogenes to induce protective immunity in mice. This mutant can enter and multiply in the cytosol of the infected host cell, but is deficient in actin-dependent cell-to-cell spread. It was found to be of attenuated virulence for inbred C3H mice: the LD50 after i.v. injection was 1000-fold higher than that of the wild-type strain. Mutant bacteria multiplied up to the fourth day in the liver, but only for 1 day in the spleen. A single infection with the maximum sublethal dose of the actA mutant induced long-lasting immunity; the LD50 of virulent wild-type L. monocytogenes increased 100-fold and growth of wild-type L. monocytogenes was controlled in liver and spleen of these mice. The presence of Listeria-reactive T cells in spleen of C3H mice infected 7 days previously with the actA mutant was monitored, through their ability to protect naive syngeneic recipients against wild-type L. monocytogenes. Protection was mainly conferred by Thy-1+ CD8+ T lymphocytes; depletion of CD4+ T cells had no significant effect on the level of transferred protection. Such attenuated mutants may be used to develop live vector vaccines for delivery of heterologous proteins into the cytosol, thereby favoring the induction of a CD8+ T cell response.


Threshold tolerance in H-2Kb-specific TCR transgenic mice expressing mutant H-2Kb: conversion of helper-independent to helper-dependent CTL. To evaluate the role of the structure of the class I molecule and associated peptide(s) in intrathymic selection and tolerance, mice expressing as a transgene (tg) a TCR specific for the H-2Kb alloantigen were crossed with mice expressing the mutant class I molecule H-2Kbm1 or H-2Kbm8. In H-2k/k TCR tg mice (in a situation of exclusive positive selection), peripheral tg TCR expressing (Ti+) CD8+ T cells showed high, suboptimal, and an absence of reactivity for H-2Kb, H-2Kbm1, and H-2Kbm8, respectively. In the peripheral lymphoid organs of TCR tg H-2k/k, H-2k/bm8, H-2k/bm1, and H-2k/b mice respectively, the tg TCR was expressed on T cells with decreasing intensity of surface CD8. Thymic subpopulations of TCR tg mice presented a pattern of negative selection with decreasing intensity from H-2k/b to H-2k/bm1 and H-2k/bm8. This suggests that a weak interaction between the TCR and H-2Kbm8 exists which partially results in negative, but not in positive, intrathymic selection. Results further indicate that expression of H-2Kbm8 does not induce tolerance to H-2Kb. In H-2k/bm1 mice, the peripheral Ti+ CD8lo cells express two distinct types of 'threshold' tolerance in vitro: (i) they generate cytotoxic T lymphocytes (CTL), in the presence of exogenous IL-2, which fail to respond to H-2Kbm1 but remain reactive to H-2Kb; and (ii) they do not make significant titers of IL-2 and do not significantly proliferate in response to H-2Kb, unlike the Ti+ CD8+ T cells from H-2k/k TCR tg mice which respond efficiently. These results show that tolerance is induced up to a level of non-reactivity within a given MHC environment: for the same TCR, CTL reactivity to H-2Kbm1 is totally lost, whereas CTL reactivity to H-2Kb is only slightly reduced. Additionally, proliferation and IL-2 production by Ti+ CD8+ cells in response to H-2Kb were strongly affected in H-2k/bm1 mice. Thus, in H-2k/k mice the Ti+ CD8+ cells behave as helper-independent, whereas in H-2k/bm1 mice CD8+ cells expressing the same TCR behave as helper-dependent CTL.


Inhibition of tumor growth by histoincompatible cells expressing interleukin-2. Murine tumor cells engineered to express IL-2 have been shown to be rejected by the syngeneic host, which is then protected against a subsequent tumorigenic challenge. To assess whether IL-2 has to be produced by the tumor cells themselves, or whether its local delivery would be sufficient to promote such beneficial effects, the syngeneic tumor cells were co-inoculated with allogeneic or xenogeneic cells secreting IL-2, selected after gene transfection. In several murine systems, it was observed that this is an efficient approach for controlling the growth of the syngeneic tumor. However, animals which rejected the tumor were not protected against a subsequent challenge. Several lines of evidence indicate that NK cells play a major role in tumor rejection induced by the IL-2 expressing histoincompatible vector cells. Thus, while local delivery of IL-2 in the vicinity of a tumor might not be sufficient to promote a systemic long-term specific antitumor immune response, it can control the growth of the primary syngeneic tumor. These experiments demonstrate the feasibility of using genetically engineered histoincompatible cells (which are rejected by the host's immune system) as a transient delivery system in vivo.


Treatment of burns with skin substitutes. More than 2 million persons sustain thermal injuries in the United States annually (Monafo and Crabtree, 1985) and more than 10,000 burn victims die (Collini and Kealey, 1989). The principal factors affecting mortality are the total area burned and the area of third degree (full thickness) burns (Tompkins et al., 1985) with wound sepsis being the leading cause of mortality. Early aggressive excision and immediate covering of the wounds improve survival (Herndon and Parks, 1986). Various biological and synthetic substrates have been employed to replace the injured skin. Most of these provide a permeability barrier which substitutes for the epidermal function of the lost skin. An ideal skin replacement should also provide a substitute for dermis, which provides both support and stability for the epidermal replacement and prevents wound contraction. The dermal and epidermal replacement should be firmly integrated by a complete basement membrane zone (BMZ).


Contact hypersensitivity reaction to ovalbumin in newborn guinea pigs from maternally sensitized animals. An animal study was conducted to elucidate the role of ovalbumin (OA) in the development of eczematous lesions in intrauterine sensitized newborns. Four groups of pregnant guinea pigs were used: group A, immunized by oral administration of 1% OA in drinking water until parturition; group B, immunized by intradermal injection of OA with Freund's complete adjuvant; group C, immunized by both methods; and group D (control), not immunized. The newborn guinea pigs of each group were patch tested with 10% OA in white petrolatum. Positive reactions were seen in the newborns of groups B and C, but not in those in groups A and D. By enzyme-linked immunosorbent assay and passive cutaneous anaphylaxis, a high titre of OA-specific IgG was detected in the group B and C newborns. The number of positive patch test reactions decreased concomitantly with the decline of specific IgG. Histologically, eczematous changes were observed in the positive reaction sites. Many OA antigen-bearing Langerhans cells were found by the immuno-double labelling technique. Immuno-electron microscopic findings revealed the presence of OA antigens as well as IgG molecules on the cytoplasmic membranes of Langerhans cells. Our studies demonstrated that maternal sensitization with OA can induce an eczematous reaction in the newborns to OA patch testing under the presence of high levels of OA-specific IgG in the serum. From these findings it is suggested that IgG plays an essential role in the development of contact hypersensitivity reaction to OA.


Genetic nature of vitiligo.

Genetic nature of vitiligo. Four hundred vitiligo patients and 100 non-vitiliginous controls were studied to find out the prevalence of vitiligo in relatives of patients and controls. The difference was found to be statistically highly significant. The data reflected that there is some genetic mechanism involved in the etiology of vitiligo. Respective relatives of all forms of the disease in the vitiligo group showed a clear preponderance compared to controls. There was clustering of affected relatives in vitiligo cases compared to controls. The ratio of affected and unaffected siblings with unaffected parents or one parent affected, the ratio in the children of probands, the ratio in children of affected paternal and maternal grandparents of probands, suggest the polygenic nature of vitiligo.


Malignant blue nevus: a report of eight cases. Malignant blue nevus is uncommon compared to its benign counterpart and is regarded as a rare form of malignant melanoma. We report the clinical and histological findings in eight cases. Histologically, all eight specimens showed no epidermal involvement and had contained within or were adjacent to portions of blue nevus or cellular blue nevus. Proliferation of bundles of bipolar spindle shaped cells with marked cellular atypia, mitotic figures, foci of necrosis, and inflammatory cell infiltrate were noted. Two of the cases were studied by DNA flow cytometry and the populations of tumor cells were found to be diploid. Two cases have died secondary to metastasis. Although malignant blue nevi may not behave as aggressively as nodular malignant melanoma, they have definite potential to do so and therefore should be removed by wide surgical excision.


Flow cytometric analysis of pig epidermal keratinocytes: effects of tape stripping. Tape stripping is a dynamic in vivo model for the induction of synchronized keratinocyte proliferation. We investigated the cell kinetics of pig epidermis by DNA-flow cytometric analysis, which was compared with [3H]thymidine incorporation mitotic counts and 2-[3H]-deoxy-D-glucose uptake. The stripping was standardized and confirmed histologically by the observation of complete removal of horny layer. Following the stripping, the proportion of cells in S-phase showed no remarkable change until 12 h. This was followed by a spike-like increase in the S-phase cells, the peak of which was reached at 24 h. This gradually decreased and returned to basal levels by 48 h. The cells in G2/M fraction initially decreased; the lowest value was obtained at 12 h. This was followed by a marked increase in the G2/M fraction, the peak of which was at 36 h. The keratinocytes in G2/M fraction gradually returned to basal levels by 96 h. [3H]Thymidine uptake and mitotic counts were mostly parallel with the data of the flow cytometric analysis, suggesting the latter as being a reliable system for cell kinetic analysis. The glucose uptake initially decreased (at 6 h following the stripping) and then increased at 24 h. Histologically the stripped epidermis regained its horny layer almost completely by 72 h following the stripping; this was occasionally accompanied by a moderate acanthotic change thereafter.


Mathematical assessment of the spatial distribution of Langerhans cells in guinea pig epidermis. Two mathematical indexes, Hopkins-Skellam index (HSI) and Morisita index (MI), were applied to assess the distribution of ATPase-stained epidermal Langerhans cells (ELC) in the guinea pig skin. To our knowledge, this is the first report in which the degree of regularity has been expressed numerically by computation based on theoretical equations. The regularity of ELC in the normal skin was confirmed by the value of HSI (P < 0.0001). In the topical steroid applied skin, the number of ELC decreased significantly but the value of HSI was similar to that of the normal skin; while in the ultraviolet B (UVB) exposed skin, both number of ELC and regularity of ELC distribution decreased significantly. The graph of MI for the UVB exposed skin clearly showed that the distribution of ELC had local clumps. The two indexes, HSI and MI have been quite useful for determining the regularity of ELC. These indexes may have a wide application to other cells.


Influence of phenobarbital on ECoG phenomena induced by metrazol in rats during ontogenesis. Effect of phenobarbital (PhB, 20 and/or 40 mg/kg) on epileptic ECoG phenomena induced by metrazol was studied in acute experiments in rats aged 7, 12, 18, 25 and 90 days. Fractionated administration of metrazol (20 mg/kg i.p. each 300 s) was used to quantify the effects of PhB. First signs of metrazol action (sharp elements and/or rhythmic metrazol activity) were not reliably influenced by PhB. On the contrary, the latency of the first EEG seizures as well as of the first generalized EEG seizures was prolonged and thus a dose necessary for their elicitation was increased in all age groups. These differences reached statistical significance in 12-, 18- and 25-day-old rats. A lack of effect of PhB against the rhythmic metrazol activity supports the adequacy of this activity as a model of human absences. Differences between the development of antiepileptic and hypnotic effects of PhB (described earlier) suggest two different mechanisms of action.


Sensitivity of the generator of spontaneous motility in chick embryos to the acute and chronic administration of MPTP. The acute and chronic effect of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) on spontaneous motor activity and its development was studied in chick embryos. 1. From the 13th day of incubation, the acute effect of MPTP (30 mg/kg e.w., up to 60 min after administration) consisted in significant depression of spontaneous motility. From the 17th day, the effect of MPTP in supraspinal compartments of the CNS also began to participate in this depression. 2. The subacute effect of MPTP (up to 24 h after a single dose) was lethal for 11-day-old embryos. Conversely, in older embryos resting motility partly recovered, with signs of an inverse correlation to the embryo's age. The final effect, however, consisted in absolute failure of the hatching process 3. The chronic effect of MPTP (3.57 mg/kg e.w./24 h, from the 4th to the 16th day of incubation) led to a developmental reduction of spontaneous motor activity, chiefly from the 8th to 12th day of incubation. 4. The interaction of nialamide (25 mg/kg e.w.), a blocker of monoaminooxidase produced disparate results with the effect of MPTP in young and old embryos.


Antidiuretic activity of terlipressin (triglycyl-lysine vasopressin)--role of pressure natriuresis. Terlipressin (triglycyl-lysine vasopressin TP), a "hormonogen" analogue, was introduced in gastroenterology for its low and protracted vasopressor action, reducing bleeding from gastrointestinal tract. Its antidiuretic activity, estimated originally in ethanol-anaesthetized rats (Sawyer's method) was claimed to be equally low and protracted. We performed several series of antidiuretic tests on conscious rats (Burn's method) with the following results. TP in low doses of 0.05-1.0 micrograms/kg exhibited typical dose-dependent antidiuretic effect. In the dose of 0.2 micrograms/kg, the dynamics of urine and sodium excretion did not differ from that after equivalent dose of lysine vasopressin and equipotent dose of DDAVP. The antidiuretic potency of TP (estimated by parallel line assay) was 175.0 U/mg. TP in doses of 5.0 and 20.0 micrograms/kg exhibited limited diuresis and marked natriuresis. High osmolality and sodium content were present in all portions of excreted urine. The discrepancy between previous and our results concerning antidiuretic activity of TP and the role of pressure natriuresis for overall renal action of TP are discussed.


Effect of cisplatin, carboplatin and stobadine on lipid peroxidation of kidney homogenate and phosphatidylcholine liposomes. The effects of the nephrotoxic, anticancer agents cisplatin (CDDP) and carboplatin (CBDCA), and the free radical scavenger, stobadine, were investigated on lipid peroxidation (LPO) of rat kidney homogenates and phosphatidylcholine (PC) liposomes. Kidney homogenates were incubated in air at 37 degrees C for 6-48 h and lipid peroxidation was detected spectroscopically as absorbance (533 nm) of the thiobarbituric acid-malondialdehyde (TBA-MDA) complex. CDDP (0.3-10 mmol.l-1) increased LPO of the homogenate. CBDCA decreased the TBA-MDA absorbance, yet was found to interfere with MDA, TBA and/or with the TBA-MDA complex. Thus when CBDCA is involved, the TBA-MDA method for detection of LPO is not suitable. Stobadine (0.1 mmol.l-1 and 1 mmol.l-1) inhibited LPO either in the control homogenate and in the homogenate where peroxidation was increased by CDDP. The effect of CDDP and CBDCA on peroxidation of PC liposomes was monitored as oxygen consumption using a Clark-type oxygen electrode. CDDP increased but CBDCA decreased the rate of oxygen consumption during the peroxidation of liposomes induced by FeSO4. The results suggest that the effects of CDDP and CBDCA on LPO may be linked with their nephrotoxicity.


Effect of propylthiouracil on liver regeneration in rats after partial hepatectomy. The effect of propylthiouracil (PTU) on the growth activity of intact liver and liver regenerating after partial (65-70%) hepatectomy (PH) was studied in rats. PTU (Propycil, Kali-Chemie, FRG) was dissolved in drinking water (1 g PTU per litre) and this was given to the rats, as their sole source of fluids, three days before PH and then up to the end of the experiment. In rats given PTU, marked inhibition of liver DNA synthesis and the mitotic activity of hepatocytes was found after PH. This effect was potentiated to some extent by partial inanition of the experimental animals given PTU, as demonstrated in a paired feeding test in control rats. PTU inhibition of DNA synthesis in intact and regenerating liver also took effect in thyroidectomized rats, even with substitution (thyroid hormone) therapy. The experiments demonstrated that the effect of propylthiouracil on DNA synthesis in the liver is mediated primarily by way of its direct effect on the liver.


Acute pneumonia reversibly inhibits hypoxic vasoconstriction in isolated rat lungs. Pneumonia was induced in rats by instillation of carrageenin (0.5 ml of 0.7% solution) into the trachea. Three or four days after instillation, the lungs were isolated, perfused with blood of healthy rat blood donors, and ventilated with air + 5% CO2 or with various hypoxic gas mixtures. Pulmonary vascular reactivity to acute hypoxic challenges was significantly lower in lungs of rats with pneumonia than in lungs of controls. The relationship between O2 concentration in the inspired gas and Po2 in the blood effluent from the preparation was shifted significantly to lower Po2 in lungs with pneumonia compared to control ones. These changes were not present in rats allowed to recover for 2-3 weeks after carrageenin instillation. We suppose that blunted hypoxic pulmonary vasoconstriction may contribute to hypoxaemia during acute pulmonary inflammation. Decreased Po2 in the blood effluent from the isolated lungs with pneumonia implies significant increase of oxygen consumption by the cells involved in the inflammatory process.


Effect of recombinant bovine somatotropin (somidobove) in a sustained release vehicle on plasma somatotropin level and lactational performance of dairy cows. The effects of administration of recombinantly derived bovine somatotropin (somidobove) in a sustained-release vehicle on the profiles of concentrations of bovine somatotropin (bST) in the blood plasma and on the milk yield of dairy cows of three herds were examined. Cows (36-87 days post partum) were treated subcutaneously with recombinant bST at 28-day intervals. In control animals, basal concentrations of bST averaged 1.4 ng.ml-1 in first-calf heifers and 1.5 ng.ml-1 in multiparous cows. In somidobove treated first-calf heifers, the concentration of bST was increased to 10.7, 14.5, and 27.0 ng.ml-1 at 24 h postinjection and in multiparous cows to 6.6, 11.0, and 11.7 ng.ml-1 on day 2 postinjection of 320, 640, and 960 mg of somidobove, respectively. On day 8 postinjection the average plasma bST levels of both parity groups are similar (on the average 3.4, 8.6, and 12.5 ng.ml-1 for three doses of somidobove respectively) and for the two highest doses being still significantly increased. During the 2nd week postinjection plasma bST concentration declined returning to control levels on day 15 postinjection. Somidobove-treated first-calf heifers produced 10.9, 16.7 and 17.9% and multiparous animals 25.5, 24.2 and 32.5% more milk than the controls when given 320, 640 and 960 mg somidobove, respectively. The cyclic pattern in milk yield within each 28-day injection interval was observed consistently in all herds. The milk yield increased to a maximum between day 4 to 8 postinjection and then slowly declined. Milk composition was not affected by somidobove treatment.


Low survival of mice following lethal gamma-irradiation after administration of inhibitors of prostaglandin synthesis. An impairment of the survival of mice subjected to whole-body gamma-irradiation with a lethal dose of 10 Gy and treated with a repeated postirradiation administration of prostaglandin synthesis inhibitors (PGSIs), indomethacin or diclofenac, was observed. Morphological examination of the gastrointestinal tract and the estimation of blood loss into its lumen in animals treated with diclofenac did not show serious damage such as haemorrhages or perforation, but revealed structural injury to the intestinal mucosa indicating inflammatory processes. The lesions found are supposed to be connected with increased intestinal permeability which leads to endotoxin escape from the gut and a subsequent increased mortality rate of irradiated animals. It may be concluded that PGSIs are not suitable for the management of radiation sickness after an exposure to lethal doses of ionizing radiation.


Effect of acute alcohol treatment on dopamine concentration in corpus striatum of rats: a voltammetric study. A voltammetry technique has been used to determine changes in dopamine release in the rat corpus striatum after two doses of ethanol administration. The dopamine oxidation current reached a maximal value at 30 min after the first alcohol dose with a subsequent decrease towards the initial level at 60 min and kept to the basal level with a statistically insignificant oscillation. When a second dose of alcohol was applied at 60 min, it was followed by a decrease of the dopamine oxidation current peak to 50% of the initial value after another 60 min observation. The results resemble the known effect of alcohol on human behaviour (excitation followed by depression).


Effects of clonazepam on picrotoxin-induced convulsions. The convulsant effects of four doses of picrotoxin (PX)-2, 3, 4, and 6 mg/kg s.c.-were evaluated in the first part of the study. The 4-mg/kg dose, which elicited minimal seizures in all animals, generalized tonic-clonic (major) seizures in 75% of rats and fatal outcome in 69% of rats, was chosen for the second part, i.e. for testing the anticonvulsant action of clonazepam (Rivotril Roche, 0.1 or 1 mg/kg i.p.). Clonazepam exhibited a dose-dependent action against PX-induced seizures, being more efficient against major than against minimal seizures.


Morphometric analysis of coated vesicles in developing rat muscle spindles. The incidence of coated vesicles under sarcolemmal surfaces of equatorial, juxta-equatorial and polar regions in developing and adult spindles of the rat soleus muscle was examined by quantitative morphometry of transverse ultrathin sections. Coated vesicles were more numerous: 1) under primary sensory endings than under other types of neuromuscular contacts; 2) under the appositional sarcolemma between neighbouring intrafusal fibres than under free surfaces of the sarcolemma; and 3) in developing than in mature spindles. Factors such as location and age of the animal often interacted to produce an additive effect on the incidence of coated vesicles. Although there was a high incidence of coated vesicles at the postsynaptic surface under sensory terminals of bag2 fibres in 18 and 19 day gestational embryonic rats, it peaked in 4 day postnatal animals. The high incidence of coated vesicles at sensory endings supports the view that coated vesicles mediate neurotrophic interactions between afferents and intrafusal fibres during the critical late gestation and early postnatal time period, as sensory axons first contact their target fibres and exert a maximal directing influence on the differentiation of intrafusal fibre types. In addition, the preferential localization of coated vesicles under appositional rather than free surfaces of developing intrafusal fibres in 0-4 day rats suggests that they play a role in the transport of active substances among intrafusal fibres exhibiting different stages of maturity.


Voltammetrically determined differences in changes evoked by KCl microinjections on catecholamine levels in the reticular formation and corpus striatum of the rat. Using a microelectrode with carbon filaments and the voltammetric technique, changes evoked in the catechol oxidation current (CA.OC) and multiple unit activity (MUA) by microinjection of 3-5 microliters 0.5 mol.l-1 KCl were studied in the reticular formation (RF) of the medulla oblongata of anaesthetized rats; the effect of KCl stimulation of the RF and corpus striatum (S) on the CA.OC in these structures was compared. The microinjection of KCl in the vicinity of the working electrode in the RF caused depression of MUA which began 2-3 s after administration, persisted for up to 6 min after and then diminished, reaching control values within 9 min. The voltammetric signal was first recorded in the 1st min after microinjection, when there was an evident decrease in the CA.OC value (59% of the control value); this effect reached its maximum 7 min after administration (a mean drop to 23% of the control), while at the end of the experiment (i.e. after 24 min) CA.OC values had risen to 45-80% of the control value. The response in the S had a biphasic character, however. Immediately after the microinjection (1st min), the mean CA.OC value rose to 626% of the control, while in the second phase (3-10 min) it was seen to fall below the control values (means 21-63% of the control). The differences in the changes evoked by K+ depolarization in the concentration of catecholamines in the RF and S microenvironment are discussed from the aspect of the existence of different pools of the transmitter and other regional differences.(ABSTRACT TRUNCATED AT 250 WORDS)


Vestibular system galvanization in man: the effect of stimulation field changes on the angle of body mass centre displacement. During monopolar monoaural galvanization the absolute value of body mass centre displacement angle did not depend on the stimulation electrode position. The angle value was always close either to 0 degrees or to 180 degrees (i.e. in the latero-lateral direction). However, some fine angle differences between different electrode positions occurred and they were statistically significant in two cases. During monoaural bipolar stimulation the body mass centre moved practically in all directions (for all four used electrode positions) and the angles formed a more or less coherent rosette in the range of 0 degrees-360 degrees.


Different degrees of lipid peroxidation in the CNS of young and adult rats exposed to short-term hypobaric hypoxia. The authors studied the effect of short-term (20 min) hypobaric hypoxia at simulated altitudes of 7000 and 9000 m on the peroxidation of lipids in the cerebral cortex, subcortical formations, medulla oblongata and cerebellum of the laboratory rat. In 5- and 21-day-old rats, increased lipoperoxidation was recorded in all the studied regions of the brain. Differences were observed in sensitivity to the degree of hypoxia. In 5-day-old rats the response to both exposures was the same, but in 21-day-old animals exposure at 7000 m stimulated peroxidation in the cerebral cortex only (at 9000 m in all the parts of the CNS examined). In 35-day-old and adult rats, changes in the malondialdehyde concentration were likewise found after exposure at 9000 m, but not in every compartment (in 35-day-old rats in the cerebral cortex and subcortical formations and in adult rats in the cerebral cortex). In young rats, 30 and 60 min after exposure to hypoxia the malondialdehyde concentration was still higher than in older animals.


Transformation of blood monocytes to multinucleated giant cells in vitro: are there any differences between malignant and nonmalignant states? Blood monocytes (BMs) from 139 subjects (70 malignant melanoma patients, 31 breast cancer patients, 38 healthy controls) were cultured for at least 7 days. The formation of multinucleated giant cells (MGCs), which was checked during the whole time of culture, was observed in all cases. By the seventh day MGCs represented 25-50% and during the second and third month more than 90% of all cells. Lymphokines and/or concanavalin A stimulation (16-34 cases respectively) of BMs was performed as well. This stimulation greatly accelerated MGC formation. There were no differences either in spontaneous or in stimulated fusion between the different groups compared.


The human thermoregulation range within the neutral zone. A mathematical and physical model of thermoregulatory mechanisms has been derived and experimental data are presented for the elements of the model. The thermoregulatory range within the neutral zone has been analyzed by regression analysis of the experimental data. The optimal globe temperature and the adaptational shifts in temperature for winter and summer are also given.


Contribution to the problems of volume parameters of the left heart ventricle of patients with ischaemic heart disease. The authors studied some methodological questions associated with evaluation of the X-ray of the left ventriculogram (VTG). On the basis of their results they suggest that, in addition to the usual comprehensive volume parameters of the left ventricle (EDVI, ESVI, and EF), further indices, obtained either by drawing the cardiac contour frame-by-frame (norm dV/dtmin), or by dividing the diastole into halves or thirds (the indices norm FF 1/2 or norm FF 1/3), should be used. These indices allow more sensitive differentiation of patients with impaired left ventricular function.


Age dependence of the utilization of different quality proteins in animal experiments. Male rats aged 45, 85, 145 and 270 days (daily body mass increments on an optimal diet containing casein were 6.73, 2.88, 0.53 and 0.31 g respectively) were fed 15 days ad libitum on a diet with a nutrient content physiological for their age, in which the protein source was milk casein (ratio of essential to nonessential amino acids E/N = 0.79, compensation coefficient K = 14) or wheat gluten (E/N = 0.30, K = -8). In the case of gluten, net protein utilization (NPU) fell markedly in rapidly growing animals aged 45 and 85 days (33 and 30% more than with casein), indicating that without essential amino acid compensation, gluten is inadequate for animals of this age, whose organism requires fully ensured proteosynthesis for growth and development. In adolescence and adulthood (145 and 270 days), the utilization of proteins is not dependent on their quality (the decrease in NPU 13 and 12%--is nonsignificant). That means that a smaller amount of essential amino acids, including the limiting amino acid in uncompensated protein, is sufficient for the maintenance and renewal of organs and tissues, i.e. for proteosynthesis. The activation of gluconeogenesis (phosphoenolpyruvate carboxykinase activity in the liver) after the intake of plant protein confirms the effect of proteins on catabolic processes.


Comparison of two approaches to measurement of electrical impedance of glass microelectrodes designed for evaluation of temperature changes in biological tissues. We proposed a temperature sensitive microelectrode for rapid measurements of temperature at the cellular level. In principle, the electrical impedance of the tip of the microelectrode changes with temperature. We designed an impulse measurement system (STEP) sensitive to the above changes of impedance. The system is based on a presettable negative input impedance of the current to a voltage converter. We compared the efficiency of the new STEP with the currently used RAMP system. We found following advantages of the STEP system: i) the danger of high voltage oscillations which could mechanically destroy the microelectrode tip is eliminated; ii) this system provides the opportunity to set the maximum sensitivity of the system according to the measured temperature interval. Moreover, the STEP method makes it possible to measure the resistance by using a sinusoidal stimulation signal which has to be preliminarily compensated by a rectangular signal. The shortest sampling period of the new system represents 0.1 ms with a resolution higher than 0.1 K and sensitivity better than 30 mV/K.


Effect of short-term ethanol intake on antibody-dependent cell-mediated cytotoxicity (ADCC) in rats. The present study was designed to evaluate the effect of short ethanol intake on ADCC activity in blood and spleen mononuclear cells. Wistar rats were fed a standard diet and drank 0.1 M ethanol solution for three days. Glucose and water controls were used in this experiment. Increased ADCC activity was found in ethanol consuming rats in the blood and spleen as compared to both controls. Our findings support the assumption that ADCC may play an important role in liver disease of alcoholics.


Effect of tubocurarine on the central generator of embryonic spontaneous motility. The continuous administration of d-tubocurarine (6.5 +/- 0.4 mg/kg e.w./24 h) to chick embryos from the 4th to the 12th day of incubation had a positive effect on defects produced in the development of spontaneous motility either by decentralization of the spinal cord or by chemical phenobarbital depression, or by a combination of both experimental factors. In normal embryos, d-tubocurarine had no effect on the development of spontaneous motility.


High sensitivity of PHHC rat to dietary cholesterol. The Prague Hereditary Hypercholesterolaemic (PHHC) rat is a strain of the Wistar rat very sensitive to dietary cholesterol. The dynamics of changes in serum and liver lipids and lecithin: cholesterol acyltransferase (LCAT) were studied immediately after the switch to a high cholesterol diet. Immediate cumulation of free and esterified cholesterol in the liver after the increase in alimentary cholesterol intake is supposed to be the regulating step leading to a subsequent increase in serum cholesterol concentration. Activity of LCAT was negatively correlated to the concentration of free cholesterol in the liver, very early after the cholesterol diet was introduced, a possibility of a down regulation of enzyme synthesis similarly to the regulation of synthesis of cholesterol in hepatocytes was observed.


Biliary amino acid excretion in rats before and after bilateral nephrectomy. In previous studies it could be shown that after bilateral nephrectomy (NX) the excretory function of the liver is disturbed. To further clarify whether or not this "renohepatic syndrome" is caused by toxic effects of uremia or by competition phenomena between various uraemic toxins an additional aspect was investigated: the biliary excretion of endogenous amino acids. Furthermore, previously it could be shown that renal and hepatic excretory functions overlap. Therefore, the renal excretion of effectively biliary eliminated amino acids (glutamic acid, alanine, tyrosine, isoleucine) is very low and vice versa. That means, that the renal excretion of amino acids with low hepatic elimination (tryptophan, citrulline, lysine, taurine) dominates. The hepatic excretion of amino acids is hardly altered after NX. Remarkably, the removal of both kidneys is followed by a distinct reduction in amino acid plasma concentrations, especially if these concentrations are relatively high in the controls. Interestingly, there is no correlation between plasma concentrations and biliary excretion of amino acids. But the calculation of the bile to plasma concentration ratios of amino acids makes it possible to differentiate three groups of amino acids: Amino acids excreted actively into bile (ratio > or = 1), amino acids with ratios below 1, indicating effective retention, and amino acids with ratios of about 1, whose hepatic handling is passive. After NX these ratios tended to approach 1; low ratios increased and high ratios decreased. That means, active processes involved in excretion or retention are obviously disturbed. These changes could indicate uraemic liver damage as proved regarding influence of NX on hepatic excretion of other endogenous substances and xenobiotics.


Increase of slow periodic modulation of EEG in a patient with Alzheimer's disease. The recently described slow oscillations of amplitude of theta and alpha waves of the EEG (with a frequency below 0.08 Hz) in healthy subjects are attributed to the autonomic nervous system with control at the brain stem level. In the present pilot study, the slow brain rhythms were analyzed in a patient with Alzheimer's disease and were compared to a healthy subject. Dynamic analysis of the EEG was performed using time-frequency mapping which gives simultaneous time and frequency representation of the brain signal. This method comprises a transform of the filtered EEG signal into its analytic form and application of the Wigner distribution modified by time and frequency smoothing. It has been shown that the envelope of both theta and alpha activities oscillates at 0.04 Hz and 0.07 Hz in the healthy subject and at 0.03 Hz and 0.06 Hz in a patient with Alzheimer's disease. The amplitude of the slow oscillations of theta activity was substantially higher in the patient with Alzheimer's disease as compared with the healthy subject. It is being proposed that the increase of slow brain rhythms in the patient with Alzheimer's disease reflects an abnormal activity of the autonomic nervous system. However, the underlying pathophysiological mechanisms need to be further studied.


Single potassium channels of human glioma cells. Single potassium channels in the membrane of human malignant glioma cells U-118MG were studied using the technique of patch clamp in cell-attached and inside-out configurations. Three types of potassium channels were found which differed from each other under conditions close to physiological in their conductance and gating characteristics. The lowest-conductance channel (20 pS near the reversal potential) showed a mild outward rectification up to 45 pS at positive voltages and spontaneous modes of high and low activity. At extreme values of potentials its activity was generally low. The intermediate conductance channel had an S-shaped I-V curve, giving a conductance of 63 pS at reversal, and a low and voltage independent opening probability. The high-conductance (215 pS) channel was found to be activated by both membrane potential and Ca2+ ions and blocked by internal sodium at high voltages. The current-voltage curves of all three channel types displayed saturation.


Influence of light regimen and time of year on circadian oscillations of insulin and corticosterone in rats. Male SPF bred Wistar rats were adapted to natural light (N) and to a 12:12 h (light-dark) artificial light (A) regimen in the course of the year. The rats were analyzed at 3 h intervals during 24 h approximately at the time of the vernal and autumnal equinox and at the winter and summer solistice. Serum insulin circadian oscillations depended on the season, being different in various light regimens. The mesors were the highest during summer, the lowest during winter in both regimens. The external acrophases of insulin in the N differed from those in the A group, contrary to the computative ones. The annual mean of serum insulin concentration was lower in the N than in the A group. The circadian oscillations of corticosterone were influenced primarily by the time of year. The mesors were the highest during summer, lower in winter and spring in N and A group. The computative acrophases were similar in both groups in all seasons except spring. The external acrophase was similar in both regimens during the year. The response of insulin, a major anabolic hormone, to various light regimens during the day and year was different from that of corticosterone, a major hormone of the stress reaction.


The effect of various photoperiods on daily oscillations of serum corticosterone and insulin in rats. The effect of various photoperiods on circadian rhythms of chosen parameters was investigated in laboratory rats. SPF male Wistar rats were adapted for six weeks to artificial light-dark cycles (LD 8:16, 12:12, 16:8). The light was switched on at 07.00 h in all regimens. The rats were killed at 3-hour intervals within 24 h, the serum concentration of corticosterone, insulin, glucose, food and water intake was determined. The external and computative acrophases of corticosterone varied in every photoperiod being dependent on the duration of light, the mesor values decreased in LD 16:8 in comparison with other photoperiods. The external acrophase of insulin was located 4 h after light onset in LD 8:16 and 12:12, in LD 16:8 one hour before light onset. The mesor values were approximately equal in all photoperiods. The circadian rhythms of glucose were similar in all regimens. Circadian variation of food and water consumption culminated at the same time in all regimens, the amount of food consumed in light increased with the light duration. Various photoperiods remarkably influenced circadian oscillations of corticosterone and in part food and water intake which could be considered as photoperiodic traits.


Effect of prostaglandin E2 on the ductus arteriosus in the newborn rat. An ultrastructural study. A patent ductus arteriosus (DA) was maintained in newborn rats (Wistar strain) by administering prostaglandin E2 (PG E2) in doses of 15 micrograms.kg-1 at 30 min intervals up to 300 min after birth. In the control animals, the DA was functionally closed 300 min after birth. The lumen was blocked by clustered endothelial cells at various stages of degeneration. Elastic membranes of the media had disintegrated into irregular fragments and the smooth muscle cells were contracted. Cytoplasm excrescences formed on their surface as a result of contraction protruded as hernias into adjacent muscle cells and into endothelial cells. The smooth muscle cells degenerated. The administration of PG E2 inhibited contraction of the smooth muscle cells and so also the development of degenerative changes; 300 min after birth the DA was fully patent, the elastic membranes were structurally intact, regularly organized and continuous. The smooth muscle cells had the character of synthesizing cells with richly developed granular endoplasmic reticulum. The intima and its endothelial lining were likewise free from structural changes. The ultrastructural image of the wall of the DA correspondent to the state 10 min after birth, when the DA was fully patent. The administration of PG E2 did not induce any ultrastructural changes indicative of injury to the wall of the DA.


Critical quantum content for shortening of endplate currents in the frog skeletal muscle. The decay time of endplate currents was followed during progressive lowering of quantum content of endplate responses by reduced Ca2+. A certain critical value of about 100 quanta was found, when the decay of endplate currents remained constant even though the quantal content was reduced further.


Non-quantal acetylcholine release after cholinesterase inhibition in vivo. After anticholinesterase treatment in vivo, depolarization of the postsynaptic muscle fibre membrane by about 4 mV develops due to non-quantally released acetylcholine from the motor nerve terminal. This conclusion was supported by experiments with the curarization of diaphragm slices from anticholinesterase treated mice during intracellular microelectrode recordings.


Resetting of the mammalian circadian clock through lowering of the amplitude: rat pineal N-acetyltransferase rhythm as a model. During resetting of the mammalian circadian clock, not only phase of the clock is shifted, but amplitude of overt rhythms driven by the clock may be temporarily reduced or even abolished. The present paper is aimed to elucidate the mechanism of amplitude reduction of the overt circadian rhythm in the rat pineal N-acetyltransferase (NAT). The rhythm has two phase markers, namely the time of the evening NAT rise and that of the morning decline. When the phase relationship between both markers is compressed drastically, the NAT rise may occur just close to or at the time of the decline and consequently the NAT rhythm with a full amplitude cannot be expressed. Such a compression may occur in two ways: either animals are subjected to a considerable advance in the light onset which phase advances the morning NAT decline and at the same time phase delays the evening NAT rise, or they are subjected to a considerable delay in the light offset, which primarily phase delays more the NAT rise than the decline. While in the former case the phase markers move in opposite directions, in the latter case they move in the same direction, but to a different extent. The data suggest a complex structure of the underlying clock.


Differential sensitivity of the brain ATP-dependent and GTP-dependent succinyl-CoA synthetase to vanadium ions. Developmental aspects. We have recently found that both vanadate and vanadyl inhibit ATP-dependent succinyl-CoA synthetase (A-SCS) solubilized from the rat brain mitochondria. Aim of the present study was to estimate a proportion of A-SCS to G-SCS in adult and 5-day-old rat brain and their susceptibility to vanadium ions. The G-SCS to A-SCS ratio of 5-day-old brains was by 196% higher than that in adults. This is in accordance with previous observation that G-SCS is high in tissues metabolizing ketone bodies. Both G-SCS and A-SCS differ in their susceptibility towards vanadium ions. A-SCS of adult brain was more sensitive to vanadate (IC 50 1.6.10(-5) mol.l-1) than was G-SCS (IC 50 6.2.10(-5) mol.l-1). On the contrary G-SCS was more sensitive to vanadyl (IC 50 3.5.10(-4) mol.l-1) than was A-SCS (IC 50 9.0.10(-4) mol.l-1). Also autophosphorylation of G-SCS a-subunit was more resistant to vanadate than A-SCS. In contrast to the adult SCS forms, almost equal susceptibility of A-SCS and G-SCS to vanadyl and vanadate was observed in infant brains. The results suggest some structural (functional) differences between two SCS forms in adults and also between infant and adult G-SCS.


Morphological changes of the presynaptic and postsynaptic element in excitatory synapses during kindling. In a previous study of a kindling model using stimulation of the entorhinal cortex we found a redistribution of synaptic vesicles into the close vicinity of the active zone of synapses of Type I (Gray 1959) in the hippocampal gyrus dentatus. In this paper, ultrastructural studies of the same model are being continued using planimetry of the synaptic apparatus. A significant increase of the postsynaptic apparatus, area enlargement by 53%, increase of the perimeter by 28% and shape irregularity are being reported. No changes in shape or in size have been demonstrated in presynaptic structures or in the morphology of presynaptic mitochondria. These findings are discussed in relation to increased functional readiness of the synapses as signs of active reconstruction of the synaptic apparatus.


Evaluation of endothelium loss by in vitro vessel perfusion using millipore filters. Endothelial loss of isolated rabbit femoral artery and renal artery was evaluated during in vitro vessel perfusion. Desquamated endothelial cells were captured on millipore filters from the perfusion solution outflow of the vessel in 3 intervals lasting 5 minutes each. In the first 5 minutes of perfusion the endothelial loss was 1,289.2 +/- 166.5 cells: in the interval after a 30 minute perfusion 4,967.9 +/- 1,428.3 cells were caught on the filters, 3.9 times more than in the first interval. During and after the 2 minutes air bubble perfusion the endothelial catch was 5.5 times greater as compared to the second interval with the average of 27,473 +/- 6,209.6 cells. The present method of quantification of the endothelial cell loss in the in vitro vessel perfusion experiment makes it possible to obtain informations about the actual state of the endothelial lining and to contribute to more precise evaluation of the modulatory effect of the endothelium on vessel reactivity to pharmacological agents.


Hypoxia and fatty acids in immature nervous tissue in the rat. In experiments on 2-day-old rats (Wistar strain, our own breed), we studied the effect of altitude hypoxia (9000 m, 60 min) on the proportion of individual fatty acids in the brain (the cortex+the diencephalon+the cranial third of the mesencephalon). We found that hypoxia significantly altered the proportion of the various fatty acids, with a significant increase in the proportion of group n-3 polyenoic fatty acids at the expense of saturated and monoenoic acids. The results fully confirm the conception that one of the most important mechanisms responsible for the high resistance of new born mammals to oxygen deficiency is the ability of immature nervous tissue to activate, in particular, elongation (the elongation of fatty acids) and/or lipogenetic processes.


Motion-reversal visual evoked responses. Motion-reversal visual evoked responses (VERs) have remarkable waveform variability. In our opinion this is caused by the alternative predominance of either motion or pattern-onset/offset related components. The motion dependent component of motion-reversal VER closely resembles motion-onset VER (main negative peak with the latency of about 170 ms), the first positive peak (with the latency of about 100 ms) corresponds to the pattern-onset component and the second non-constant positive peak (with the latency of about 130 ms) seems to be identical with the pattern-offset positivity. The differences in expression of these components are dependent on some stimulus characteristics (mainly on the contrast of a structure, velocity of motion, retinal localization of the stimulus) and on substantial differences in the sensitivity of subjects to motion stimulation.


Hypoventilation after acute phrenicotomy of the urethane anaesthetized rats. The aim of this study was to explore the mechanism resulting in hypoventilation in rats with denervated diaphragm. Bilateral cervical phrenicotomy (PX) was performed in 15 male rats anaesthetized with urethane (1.3 g/kg i.p.); other 8 rats were sham operated (SX). Ventilation, PaCO2 and the integrated EMG of the external intercostal muscles (iEMG) were measured before and after the surgery, at regular intervals, up to 4 hours postoperatively. During the 4 hours after PX there was a progressive decrease in minute ventilation and an increase in PaCO2 compared with the control values and with that in the SX rats. The increase in PaCO2 was accompanied by an increase in the peak amplitude of the iEMG to 155 +/- 18% of control values after PX and to 228 +/- 33% 4 hours later. Despite the augmented EMG activity tidal volume gradually decreased. The iEMG of the intercostal muscles, however, did not reach a maximum because the shortlasting stimulation of breathing by acute hypercapnia and hypoxia as the result of added dead space (0.5 ml) increased the iEMG still further. These results indicate that both the central and peripheral mechanisms contribute to hypoventilation in anaesthetized rats with denervated diaphragm.


Effect of sialoadenectomy on stomach lesions induced by indomethacin and ethanol in relation to gastric vascular permeability, the gastrin level and HCl secretion in rats. Stomach lesions induced by indomethacin (20 mg.kg-1 i.p.) and ethanol (1 ml 95% intragastrically) were studied after a 24 hour fast in rats which had undergone sialoadenectomy. The size of the lesions was correlated with gastric HCl secretion, with gastric vascular permeability (determined from the Evans blue concentration in the stomach tissue after its i.v. administration) and with the serum gastrin level. These parameters were also studied in sialoadenectomized rats and in animals given epidermal growth factor (EGF) (50 lg.kg-1). It was found that sialoadenectomy significantly (p < 0.01) raised the incidence of stomach lesions after the administration of indomethacin and also after ethanol (p < 0.05). A significant increase in both basal and stimulated HCl secretion was found after sialoadenectomy. Both indomethacin and ethanol also increased gastric vascular permeability in rats not subjected to sialoadenectomy, but sialoadenectomy raised it significantly compared with the non-sialoadenectomized group. The serum gastrin levels fell after sialoadenectomy and the decrease was significant after the subsequent administration of indomethacin or ethanol. The administration of EGF to sialoadenectomized rats lowered the incidence of stomach lesions, inhibited HCl secretion and reduced vascular permeability. The lowered susceptibility of the gastric mucosa to the formation of lesions in sialoadenectomized rats given indomethacin or ethanol can be regarded as the outcome of the uptake of EGF.


The effect of administration of estradiol and testosterone on body growth of young male rats. The influence of estradiol and testosterone on body growth of young male Wistar rats was investigated. In the first experiment, estradiol was given to intact ad libitum fed male rats at 32, 37 and 42 days of age. Moreover, two untreated groups of animals were used: one was fed restrictedly according to the food intake of animals receiving estradiol and another was fed ad libitum. The animals were sacrificed at 47 days of age. Both untreated groups of animals achieved significantly higher body weight and length of tibia than estradiol treated animals. Also the growth of the tail of untreated animals was more intensive than that of estradiol treated animals. In the second experiment, estradiol was given to intact ad libitum fed male rats at 30, 35 and 45 days of age. Moreover, testosterone was given to a half of these animals at 45, 50 and 55 days of age. The animals were sacrificed at 60 days of age. Administration of testosterone significantly increased the growth of the tail and tibia in comparison to the animals which did not receive testosterone after estradiol administration. The results of the present study show that the inhibitory effect of estradiol on body growth of young male rats is not only the result of decreased food intake and that testosterone can improve the skeletal growth of male rats altered by previously given estradiol.


Different effects of oestradiol benzoate and norethisterone on the blood flow and mineral content in rat bones. In three experiments (2 on females, 1 on males), we determined the blood flow in the tibia and the distal part of the femur, together with cardiac output (by means of 85Sr-microspheres), tibial bone density and tibial ash weight related to bone volume. We found that 1) the bone blood flow always fell significantly after oestradiol benzoate, 2) no change occurred after norethisterone in doses corresponding to those of oestradiol benzoate, but the blood flow showed a tendency to fall after doses one order higher (it decreased significantly in one case only), 3) the density of the tibia and tibial ash weight related to bone volume rose nonsignificantly after oestradiol benzoate, but fell (mostly statistically significantly) after norethisterone. The lowering of the bone mineral indexes in rat bones after norethisterone is a surprising and potentially significant finding requiring further verification.


Acute toxicities of 2-dialkylaminoalkyl-(dialkylamido)-fluoro-phosphates. Toxicities expressed as LD50 values of 2-dialkylaminoalkyl-(dialkylamido)-fluorophosphates for rats and mice (i.m. administration) were determined. Rats were more sensitive to these compounds than mice: LD50 values varied from 17 (rats) to 1222 (mice) micrograms/kg. LD50 values at different routes of administration (i.v., i.m., s.c., p.o. and p.c.) for one derivative of this group, 2-dimethylaminoethyl-(dimethylamido)-fluorophosphate, were determined. Depending on the route of administration, LD50 values varied from 11 (i.v.) to 190 (p.o.) micrograms/kg for rats and from 27.6 (i.v.) to 222 (p.o.) micrograms/kg for mice, respectively. Percutaneous toxicity in rats only (LD50 = 1366 micrograms/kg) was determined.


Protective effect of ascorbic acid in high altitude hypoxia in the rat. Control (physiological saline treated) and ascorbic acid (AA) treated (1 mg.g-1 b.w. one hour before exposure) 18-day-old rats were exposed for 1 hour to high altitude in a hypobaric chamber and the mean lethal altitudes were calculated. AA displayed a protective effect, so that in two identical experiments the mean lethal altitude was 10,900 and 10,150 m in controls, while it was 11,500 and 11,450 m in AA treated animals.


The role of maternal syphilis, gonorrhoea and HIV-1 infections in spontaneous abortion. The role of the human immunodeficiency virus (HIV) and other sexually transmitted diseases (STDs) as risk factor for spontaneous abortion was investigated in a case-control study in Nairobi, Kenya. Cases (n = 195) were women admitted with clinical signs and symptoms of spontaneous abortion, before 20 weeks of gestation. Patients with induced or clinically septic abortion were excluded. Controls were unselected pregnant women in their second or third trimester (n = 195). Spontaneous abortion was independently associated with maternal HIV-1 antibody (14.4% versus 6.2%; adjusted odds ratio, 2.3; 95% confidence interval, 1.1-4.8), with maternal syphilis seroreactivity (6.8% vs 2.1%, adjusted odds ratio, 4.3; 95% confidence interval 1.2-15.6), and with vaginal colonization with group B streptococci (15.6% vs 5.2%; adjusted odds ratio, 3.2; 95% confidence interval, 1.5-6.7). No significant association was found between maternal infections with gonococci and genital mycoplasmas, and spontaneous abortion.