[Vigilance disorders in intensive care patients. The central anticholinergic syndrome as a differential diagnosis of a brain stem lesion].

Four days after implantation of a biventricular assist device (Berlin heart) the 39-year-old patient showed a sudden loss of vigilance and tetraplegia. Clinical skills and neurophysiological states indicated a serious lesion of the brain stem. After a test application of Physostigmine 2 days later, the neurological deficits improved dramatically. The case demonstrates that neurological deficits can also be caused by or combined with an acute anticholinergic syndrome. The application of Physostigmine allows disorders caused by brain lesions to be differentiated from transitory syndromes.


[Acute jugular engorgement in liver transplantation].

A 56-year-old patient with chronic liver failure underwent liver transplantation; a Denver shunt had been placed 6 months previously. Following an initially uneventful operative course, during fashioning of the proximal caval anastomosis in the anhepatic phase, the patient developed very marked jugular engorgement. The central venous pressure rose to 45 mmHg and this lasted some 15 min. With the opening of the venous anastomosis and placement of the liver in its anatomical site, the central venous pressure returned to normal values once again. It can be concluded that during fashioning of the anastomosis, both the right atrium and distal superior vena cava were obstructed. While normally not haemodynamically significant, in this case, however, the superior vena cava became more narrow by the routinely placed venous lines and the Denver shunt. This in turn, gave rise to this particular clinical manifestation.


[Paravasal infusion over the proximal lumen of a Swan-Ganz catheter].

In a severe traumatized patient (34 years old, 182 cm tall, 90 kg body wt.), we inserted a Swan-Ganz catheter (110 cm, 5 lumina, Modell 93A-831-7.5F, Baxter Healthcare) via the right internal jugular vein. Infusion was started using the proximal lumen. Several hours later we observed a large swelling on the right side of the neck and the supraclavicular region due to paravasal fluid administration while recording normal pulmonary artery and wedge pressure curves. The reasons and consequences are discussed.


Complications of continuous spinal anaesthesia.

The practice of continuous spinal anaesthesia dates back to the beginning of the century. The history of the technique, and the problems which accompanied each method used, are reviewed. Complications encountered in current practice include post dural puncture headache; technical difficulties with insertion and removal of catheters; and a higher potential for nerve trauma, neurotoxicity, and method failure than seen with single-shot spinal anaesthesia. The question of the place of the technique in modern anaesthesia is addressed.


Anaesthesia and breast-feeding--the effect on mother and infant.

In this paper, we summarise the physiology of lactation and discuss the pathophysiology brought about by fasting, stress and anaesthetic drugs. Drug secretion into breast milk and subsequent absorption by the infant is considered. Maternal hydration must be well maintained with intravenous fluids, allowing an added 500 to 1000 ml for daily fluid loss in lactation. Maternal premedication, general anaesthesia and routine postoperative analgesics are also discussed as to the effects on the breast-fed infant. Drug side-effects may be avoided by timing breast feeding just before the next due dose. Sedatives with long half-lives should not be used. Endocrine and metabolic responses to anaesthesia and surgery are less with regional anaesthesia than with general, hence regional anaesthesia is preferred where it is a reasonable alternative technique.


Vasopressor therapy in cardiac resuscitation.

The standard 0.5 to 1.0 mg dose of adrenaline used in cardiac resuscitation may be inadequate on the basis of theoretical and experimental evidence. Well designed clinical trials are indicated to test the hypothesis that higher doses of adrenaline could be more effective in specific subgroups of people experiencing cardiac arrest. The success in resuscitation is related to the aortic diastolic pressure and the effectiveness of adrenaline relates to its peripheral vasopressor effect. Other catecholamines such as noradrenaline may be more efficacious, as could be non-adrenergic vasopressors. Clinical studies are required, however, to evaluate these potential alternatives.


Mortality prediction in infants with congenital diaphragmatic hernia: potential criteria for ECMO.

Over the last ten years the survival of infants born with congenital diaphragmatic hernia who reach the Intensive Care Unit of the Royal Children's Hospital, Melbourne has been constant at 56 +/- 6%. Experimental therapies such as extracorporeal membrane oxygenation, high-frequency oscillation and lung transplantation are now being considered as therapeutic options, and as such the ability to predict survival or death of these infants is increasingly important. The records of all infants with congenital diaphragmatic hernia admitted to the Intensive Care Unit between 1 January 1980 and 30 April 1989 were reviewed; blood gas, ventilatory details, and outcome information was obtained. Receiver operating curve analysis was used to determine the best predictor of death. An oxygenation index (MAP x FiO2/PaO2) > 0.3 or ventilation index (PIP x RR x CO2/1000) > 70 predicted a 94% mortality with a specificity of 96% and a sensitivity of 82%.


High-volume spinal anaesthesia. A dose-response study of bupivacaine 0.125%.

The clinical effects of high-volume spinal anaesthesia with bupivacaine 0.125% were studied in 30 patients presenting for postpartum sterilisation. Group A, B and C patients received 6, 8 and 10 ml of bupivacaine 0.125% respectively. Onset, duration and regression of sensory block and motor blockade, haemodynamic parameters and postoperative complications were studied. A sensory level of T10 was reliably obtained in Group B and C but not in Group A. Similarly motor blockade was unreliable in Group A compared with Group B (P < 0.05) and Group C (P < 0.05). Two segment regression times were similar in all three groups. L1 regression times were 47.9, 94.3 and 99.0 minutes in Groups A, B and C respectively. The corresponding times for complete recovery of motor power were 120, 212.3 and 182.7 minutes respectively (P < 0.01 when Group A compared to B and C). A significant incidence of high spinal anaesthesia occurred when 10 ml bupivacaine 0.125% was administered (P < 0.05 when compared with Group A). No patient experienced respiratory discomfort in spite of sensory levels of up to T1. Hypotension responded readily to intravenous fluids and small doses of ephedrine (three patients). Only one patient (Group A) developed a postdural puncture headache. In this study, high-volume spinal anaesthesia with bupivacaine 0.125% was found to be satisfactory for postpartum tubal ligation. The optimal volume of bupivacaine 0.125% was 8 ml.


Use of warm local anaesthetic solution for caudal blocks.

A double-blind study was undertaken to investigate the effect of prewarmed local anaesthetic solution on the latency of onset of caudal blocks. Forty-four (ASA I-II) patients were allocated into two equal groups. In Group A, the local anaesthetic solutions were injected at room temperature (25 degrees C), while in Group B, they were injected at 37 degrees C. All the caudal blocks were performed using 20 ml of lignocaine 1.5% with adrenaline 1:200,000. The speed of onset of perianal analgesia was found to be significantly faster (39%) with the prewarmed local anaesthetic solution (P < 0.05). No adverse effects were observed.


Oxygen dissociation curve in the adult respiratory distress syndrome.

The oxygen tension for half saturation (P50) was determined for venous blood in thirteen patients with the adult respiratory distress syndrome undergoing intensive therapy. The mean value for P50 was found to be significantly lower than the value found in ten normal control subjects (22.9 mmHg and 26.7 mmHg respectively; t = 3.03, P < 0.01). The extent of reduction in P50 was not related to serum phosphate level nor was it a predictor of short-term outcome. It is unlikely that the slight left-shifted oxygen-haemoglobin dissociation curve contributes in a major way to an oxygen delivery deficiency and its cause is unexplained.


Derived oxygen saturations are not clinically useful for the calculation of oxygen consumption.

In critically ill patients, oxygen consumption (VO2) and delivery (DO2) are used to determine optimal haemodynamic management and to grade severity of illness. VO2 may be measured by indirect calorimetry with metabolic gas monitoring systems or derived using the reverse Fick principle. Oxygen saturation (SaO2) may be measured directly by co-oximetry or derived by equations for incorporation into reverse Fick equations. A prospective study comparing VO2 measured by these methods was performed in 20 critically ill patients. The mean VO2 measured by the metabolic gas monitoring system (308 +/- 63.9 ml/min) was significantly greater than that measured by reverse Fick using measured SaO2 (284 +/- 72.0 ml/min) (P < 0.01). This difference may be due to intrapulmonary VO2. When SaO2 was calculated from three logarithmic equations and incorporated into the reverse Fick equations, calculated VO2's were significantly greater (P < 0.001) than those measured by indirect calorimetry. Correlation was poor and wide limits of agreement (-118 to +350 ml/min) were demonstrated. VO2 should ideally be measured by indirect calorimetry in the critically ill, or if reverse Fick is used, SaO2 should be measured by co-oximetry as the use of equations for clinical measurement of SaO2 is clinically suspect.


Fibreoptic bronchoscopy in the critically ill: a prospective study of its diagnostic and therapeutic value.

A prospective study was undertaken to assess the diagnostic value and therapeutic usefulness of fibreoptic bronchoscopy in the critically ill. Fifty-six bronchoscopies were performed in fifty patients. Biochemical, radiological, microbiological and clinical assessments were made before and after each procedure. Eighteen fibreoptic bronchoscopies were performed for therapeutic indications (32.1%) of which ten (55.6%) yielded a useful outcome. Thirty-eight bronchoscopies were for diagnostic purposes (67.8%) of which 22 (57.9%) were clinically useful. Broncho-alveolar lavage was performed in twenty-eight cases (50%) and it led to a clinically useful diagnosis in 17 (60.7%). There was no major complication. A subgroup of patients was defined (persistent left lower lobe collapse or consolidation following thoracic or abdominal surgery) in whom fibreoptic bronchoscopy usually did not yield a useful outcome. The use of fibreoptic bronchoscopy in the Intensive Care Unit, in combination with the technique of broncho-alveolar lavage, results in a clinically useful outcome in the majority of cases. Fibreoptic bronchoscopy is an effective and safe diagnostic and therapeutic tool in critically ill patients.


Septic shock: does adrenaline have a role as a first-line inotropic agent?

Fifteen adult patients, admitted to Baragwanath Hospital ICU with septic shock after adequate fluid loading and on no other inotropic agents, were given adrenaline in incremental doses. Oxygen transport and haemodynamic variables were monitored with each dose increment until a systolic blood pressure of 120 mmHg was obtained. This was reached on an average dose of adrenaline of 0.16 +/- 0.02 micrograms/kg/min. Mean arterial blood pressure increased by 22 +/- 2 mmHg mainly due to an increase in cardiac index (1 +/- 0.2 l/min/m2) and systemic vascular resistance index (130 +/- 41 dyn.s.cm.-5m-2) with a small increase in heart rate of 8 +/- 3 beats per minute. Oxygen delivery was increased with no significant increase in oxygen consumption and lactate levels increased. Adrenaline is therefore an effective initial inotropic agent. Patients may respond to lower doses than when used concurrently with other inotropic agents but there was still a significant dose variation in response. We cannot, however, exclude a deleterious effect on oxygen utilization.


Total intravenous anaesthesia versus inhalational anaesthesia for dental day surgery.

Fifty young healthy and unpremedicated patients scheduled for removal of impacted teeth were randomly allocated to receive either total intravenous anaesthesia with propofol or conventional thiopentone/isoflurane/nitrous oxide anaesthesia. A double-blind postoperative assessment showed the former group to have a shorter reversal time and faster recovery of faculties, i.e. speech, memory as well as ability to sit up and walk without assistance (P < 0.01). There was no incidence of hypotension and of awareness in either group. The incidence of headache, nausea and vomiting was higher in the thiopentone/isoflurane/nitrous oxide group.


Propofol induction for laryngeal mask airway insertion: dose requirement and cardiorespiratory effects.

The dosage, haemodynamic and respiratory effects of propofol for laryngeal mask airway (LMA) insertion were investigated. Fifty patients (ASA I-II) were randomly assigned one of four induction doses of propofol (1.5-2.5 mg/kg) delivered over 30 seconds and the first attempt at LMA insertion was made at 90 seconds. The LMA was inserted at 90 seconds in 35 patients and by 300 seconds in 13 others (mean plasma concentration at 90 seconds was 7.7 mcg/ml (no delay) versus 5.2 mcg/ml (insertion delayed), P < 0.01). Insertion was less successful after 1.5 mcg/kg (failed at 90 seconds in 6 of 12 patients), but did not vary with the other doses. Additional propofol (0.5 mg/kg/30s) was required in 22 patients for LMA insertion or to prevent movement, resulting in propofol concentrations at 120-180 seconds above 7 mcg/ml. Respiratory effects were minor, but MAP decreased by 18 +/- 1.4 mmHg at 90 seconds. Cardiovascular effects did not differ significantly between dosage groups or with the use of additional propofol.


The incidence of bacteraemia following laryngeal mask insertion.

The incidence of bacteraemia following insertion of the laryngeal mask airway (LMA) was investigated in one hundred fit patients. Four cultures were positive: three represented contamination with skin flora; the other was a microaerophilic streptococcus grown from an anaerobic culture bottle. Although this organism can be pathogenic, it may also represent contamination. Our findings suggest that significant bacteraemia on insertion of the LMA is uncommon and is probably no more than with oral intubation. Antibiotic prophylaxis is of doubtful benefit in these circumstances.


The effect of epidural blockade on postoperative hypercoagulability following abdominal aortic bypass surgery.

The effect of epidural blockade on postoperative hypercoagulability was assessed in patients undergoing elective abdominal aortic bypass surgery. Twenty patients were randomised to receive general anaesthesia alone, or general anaesthesia plus thoracic epidural blockade with 0.5% bupivacaine. It was found that the addition of epidural blockade did not alter the postoperative increase in plasma fibrinogen, factor VIII coagulant, or alpha 1-antitrypsin. Similarly, epidural blockade did not affect the postoperative decrease in antithrombin III. The results suggest that epidural blockade with local anaesthetic agents does not prevent the postoperative hypercoagulability response following abdominal aortic bypass surgery.


Anaesthetic experience with cryotherapy for treatment of hepatic malignancy.

Hepatic cryotherapy is a relatively new technique, currently employed in the treatment of unresectable liver malignancy, which involves direct freezing of tumour deposits with liquid nitrogen. In a review of 26 patients undergoing this procedure, the anaesthetic considerations are defined. The total operation time ranged from 133 to 410 minutes. In spite of preventative measures, varying degrees of hypothermia occurred (range 33.7 degrees C to 36.5 degrees C), but no sequelae were encountered. Mean blood loss was 926 ml, and eleven patients required blood transfusion of between one and five units. There was a marked drop in platelet count associated with cryotherapy (mean fall of 123,000/mm3 by the second postoperative day). Following the procedure, fever and basal pulmonary atelectasis were common, while hypoglycaemia and renal impairment occurred on single occasions. Six patients underwent postoperative mechanical ventilation. Despite this, the mean hospital stay was under seven days.


A clinical evaluation of the Hemocue haemoglobinometer using capillary, venous and arterial samples.

The 'Hemocue' device for rapid estimation of haemoglobin concentration was evaluated in a clinical setting. Repeatable accuracy of capillary, venous and arterial samples was examined and then compared with standard laboratory venous haemoglobin estimates using a 'Coulter JT' analyser in 42 patients. The mean values for haemoglobin (g/l) and coefficient of variation were capillary 108.2 (8.0); venous 104.9 (2.2); arterial 105.9 (2.0); and laboratory venous 104.6 (1.3). Although the mean haemoglobin values were similar, capillary samples were significantly less repeatable than venous or arterial samples (Pitman test, P < 0.001). Comparison of variance between the laboratory sample and each sampling technique demonstrated that capillary samples were significantly more variable than venous or arterial samples. Peripheral skin temperature did not influence the accuracy of capillary samples. Hemocue estimations of venous samples were found to be as accurate as laboratory estimations. The lack of repeatable accuracy of capillary estimations was sufficiently large that their use cannot be recommended in clinical practice.


Fault in a Selectatec manifold resulting in awareness.

The Selectatec Vaporising System is a quick change system consisting of anaesthetic vaporisers of the Tec 3 and Tec 4 models and the compatibility manifold block on which these are seated on the anaesthetic machine backbar. There have been reports of difficulties with the seating and locking of the vaporisers which can cause a leak and failure of vapour delivery. The Faculty of Anaesthetists, Royal Australasian College of Surgeons (now Australian and New Zealand College of Anaesthetists) issued a hazard alert in March 1991 drawing attention to this potential fault. We present two cases of awareness associated with failure of internal seals within a Selectatec compatibility manifold block which did not have a detectable leak.


Elimination of electrooxidizable interferant-produced currents in amperometric biosensors.

Electrooxidizable ascorbate, urate, and acetaminophen that interfere with amperometric glucose assays are completely and rapidly oxidized by hydrogen peroxide in a multilayer electrode. The multilayer electrode is composed of an immobilized, but not electrically "wired", horseradish peroxidase (HRP) film coated onto a film of electrically "wired" glucose oxidase (GO). The "wired" enzyme is connected by a redox epoxy network to a vitreous carbon electrode. The current from the electrooxidizable interferants is decreased by their peroxidase-catalyzed preoxidation by a factor of 2500, and the glucose/interferant current ratio is increased 10(3)-fold. Undesired electroreduction of hydrogen peroxide can result when HRP is also "wired" to the electrode. Such unwanted "wiring" is prevented by incorporating an electrically insulating barrier layer between the wired GO film and the HRP film. The hydrogen peroxide necessary for elimination of interferants can be added externally, or when this is not possible, it can be generated in situ by means of a coupled enzyme reaction.


Influence of tyrosine on the dual electrode electrochemical detection of copper(II)-peptide complexes.

The bluret reaction makes peptides electrochemically active. This is the basis of an electrochemical method for the detection of peptides following their liquid chromatographic separation. This paper discusses the influence of tyrosine, an electroactive amino acid, on the detection of Cu(II)-peptide (bluret) complexes containing it. The dual electrode detector has an upstream anode and a downstream cathode. Tyrosine-containing peptides yield anodic signals that are approximately the sum of the tyrosine signal and the signal from the bluret complex of a nonelectroactive model peptide, phenylalanylglycyl-glycine (FGG). The cathodic signal is depressed in comparison to FGG. This is traced to the presence of an intramolecular reaction between Cu(III) and a reaction product resulting from the oxidation of the tyrosinyl residue. The rate constant for the corresponding intermolecular reaction is significant (10(6)-10(7) M-1 s-1), but in practical analytical situations, the concentrations of the reactants will be small, so the reaction will not be a major factor. Sensitivities for several bioactive peptides are reported. The dependence of the signals on the position of tyrosine in a tripeptide is also studied.


Determination of aluminum by chemical and instrumental neutron activation analysis in biological standard reference material and human brain tissue.

Since aluminum is an extremely difficult element to determine reliably in biological samples, no National Institute of Standards and Technology (NIST) biological standard reference material for tissue has yet been certified for aluminum. A chemical neutron activation analysis procedure employing anion-exchange chromatography was developed. The procedure proved successful in decontaminating radioactivatable sodium and chlorine and phosphorus which can produce aluminum via a fast neutron bombardment. For bovine liver (NIST SRM 1577 a) a value of 2.1 +/- 0.2 micrograms of aluminum/g of sample was determined, comparing favorably to the uncertified value 2 micrograms/g sample. For freeze-dried urine (NIST SRM 2670) a value of 0.18 +/- 0.01 micrograms of aluminum/mL of urine was observed. Its uncertified value is 0.18 micrograms of aluminum/mL of sample. Twenty three individual samples in three different human brains were analyzed for their aluminum content.


Organized media for fluorescence analysis of complex samples: comparison of bile salt and conventional detergent micelles in coal liquids.

Accurate quantitative determinations are often difficult to obtain from fluorescence analysis of complex samples due to sample matrix effects and intermolecular interactions between solutes. Organized media can be used to minimize these unwanted processes without physical separation or extraction of the analytes from the sample matrix by isolating the analyte molecules in a uniform microenvironment within the sample. The advantages of bile salt micellar media over conventional detergent micelles are demonstrated for analysis of coal liquids. The bile salt media is shown to increase the sensitivity and dynamic range of fluorescence measurements relative to simple ethanolic solutions, without promoting gound-state and excited-state interactions that occur in the detergent micellar media.


Integrated approach to surfactant environmental safety assessment: fast atom bombardment mass spectrometry and liquid scintillation counting to determine the mechanism and kinetics of surfactant biodegradation.

Fast atom bombardment mass spectrometry and liquid scintillation counting have been used to study the biodegradation of a novel cationic surfactant in live sludge. The rates of primary biodegradation and the extent of complete mineralization were determined. Furthermore, an intermediate degradation product was identified and its rates of formation and subsequent removal have been established. These data find utility in assessing the environmental safety of the surfactant and the accuracy of various environmental fate models.


Fast atom bombardment tandem mass spectrometric identification of diacyl, alkylacyl, and alk-1-enylacyl molecular species of glycerophosphoethanolamine in human polymorphonuclear leukocytes.

Fast atom bombardment ionization with tandem mass spectrometry of both positive and negative ions is a useful technique for the identification of intact glycerophosphoethanolamine (GPE) phospholipids, providing information as to polar head group and fatty acyl substituents. In the identification of GPE molecular species, positive ion neutral loss scanning for 141 units was attempted to confirm the presence of the phosphoethanolamine polar head group. This scan was found to discriminate against the abundant subclass of phospholipids having an 1-O-alk-1'-enyl linkage, termed plasmalogens, as well as 1-O-alkyl ether species. The neutral loss process is suggested to involve attack of a carbonyl oxygen from either sn-1 or sn-2 on the sn-3 methylene carbon with loss of neutral phosphoethanolamine. Using FAB/MS/MS alone, it is not possible to differentiate between plasmalogens and other 1-O-alkyl ether molecular species having the same molecular weight. The combination of mild acid hydrolysis, which selectively hydrolyzes the labile 1-O-alk-1'-enyl bond, with subsequent FAB/MS/MS distinguished species of these distinct subclasses. Using these techniques and precursor ion scans for the arachidonoyl carboxylate anion, m/z 303, the arachidonic acid containing glycerophosphoethanolamine molecular species were identified and the relative abundance of arachidonoyl plasmalogen, alkylacyl, and 1,2-diacyl GPE molecular species in the human polymorphonuclear leukocyte (neutrophil) was determined to be 75.4%, 12.1%, and 12.5%, respectively. These values were not significantly different from that reported in the literature using conventional methodology.


Separation of closely related large peptides by micellar electrokinetic chromatography with organic modifiers.

Large peptides with similar electrophoretic mobilities were separated by micellar electrokinetic chromatography (MEKC) with organic modifiers. [Leu13]motilin and [Met13]motilin differ by only one neutral amino acid residue. Because the electrophoretic mobilities of these peptides are almost identical, these peptides were not separated by capillary zone electrophoresis (CZE). Such large peptides have not been separated by conventional MEKC either, because they interacted strongly with the micelle. However, they were completely separated by MEKC when an organic solvent was added to the micellar solution. Some insulins, larger peptides than motilin, from different origins, which have very similar electrophoretic mobilities, were also successfully separated by the same technique. The size of peptides which were separated without organic modifiers was examined.


Microtiter plate binding assay for cholinergic compounds utilizing the nicotinic acetylcholine receptor.

A receptor-based binding assay for the determination of cholinergic compounds of the nicotinic acetylcholine receptor has been developed. By conducting the assay in a 96-well microtiter plate, the method is suitable for large-scale screening in drug development. Solid-phase extraction of the enzyme label significantly simplifies the assay protocol compared to earlier methods. The assay is based on immobilization of biotin-BSA on the microtiter which takes up avidin-labeled peroxidase due to avidin-biotin interaction. To perform the assay, a ligand (the analyte) and a biotin alpha-bungarotoxin conjugate (alpha Bgt-biotin) sequentially bind to a vesicle bound nicotinic acetylcholine receptor. This is done either in a test tube, assay I, or in a biotinylated microtiter well, assay II. Avidin-HRP is then added to this mixture; free alpha Bgt-biotin conjugate and immobilized biotin-BSA compete for the avidin sites. After the assay solution has been aspirated off, bound enzyme activity is determined which is directly related to the amount of alpha Bgt-biotin added. Dose-response curves of cholinergic compounds and Scatchard plots were generated to evaluate the apparent binding constants. Kinetic studies were conducted for the purpose of optimization. The final assay can be performed in under 4 h with a minimum of sample handling.


Chiral separation of leucovorin with bovine serum albumin using affinity capillary electrophoresis.

A method for the determination of the (6R)- and (6S)-stereoisomers of leucovorin using electrokinetic chromatography (EKC) in the affinity mode has been developed. Bovine serum albumin (BSA) is used as a run buffer additive to incorporate enantiomeric selectivity into the system. Protein-wall interactions are minimized by using a poly(ethylene glycol) (PEG) coated capillary. Chiral resolution is obtained in 12.5 min with efficiencies greater than 200,000 theoretical plates using BSA as an additive, while no resolution is obtained in the absence of BSA. A general equation is derived to calculate the free energy of interaction between the leucovorin isomers and the BSA molecule. This method represents a new means of obtaining thermodynamic data for substrate binding interactions and for the general study of drug cross-reactions and interactions of drugs with serum and other proteins.


Separation and identification of DNA-carcinogen adduct conformers by polyacrylamide gel electrophoresis with laser-induced fluorescence detection.

We have developed a separation protocol utilizing high-resolution polyacrylamide gel electrophoresis (PAGE) to isolate stable anti-benzo[a]pyrene diol epoxide adducts of oligodeoxynucleotides. Both enantiomers produced multiple adduct species. The distribution of adduct types could be quantitated by densitometry of autoradiograms or Cerenkov counting of eluted oligomers modified by anti-BPDE isomers. Laser-induced fluorescence (LIF) spectra of eluted adducts at 4.2 K (fluorescence line-narrowing spectroscopy) and 77 K revealed that bands corresponded to pure conformers of pyrene chromophore. Carcinogen-modified oligodeoxynucleotides were single-stranded, but there were often considerable stacking interactions between the pyrenyl residues and the oligonucleotide bases, indicating that electrophoresed oligomers were single-stranded but in a native, versus random coil, conformation. The ability to identify and quantitate adducts by PAGE-LIF, coupled with the high resolution and sensitivity of both techniques, makes PAGE and LIF in tandem a potentially powerful tool in the study of chemical carcinogenesis or other ligand-DNA interactions.


Quantitative determination of native proteins in individual human erythrocytes by capillary zone electrophoresis with laser-induced fluorescence detection.

Intracellular fluid within single human erythrocytes is analyzed by capillary electrophoresis with laser-excited native protein fluorescence. Good signal-to-noise is achieved, allowing even minor components to be quantified. Non-Gaussian distributions were found for total protein, fraction carbonic anhydrase, fraction hemoglobin A0, and an unidentified component. Variations among a group of 29 cells for each quantity are as much as 1 order of magnitude, even though erythrocytes are known to be fairly homogeneous in size distribution. Variations in fraction hemoglobin A0 reflect differences in in vitro oxidation rates to methemoglobin. A positive correlation was observed between carbonic anhydrase and hemoglobin A0 for individual cells. This is consistent with the presence of erythrocytes of different ages within the population, with the older cells being less capable of maintaining enzyme activity and preventing oxidative damage.


Secondary ion emission from solutions: time dependence and surface phenomena.

The temporal behavior of FAB mass spectra from glycerol solutions of tetradecyltrimethylammonium bromide (C14H29-N(CH3)3Br, TTAB) and tetraethylammonium iodide (TEAI) was investigated. FAB spectra of the TTAB solution displayed a continuous decrease in TTA+ with time. Spectra obtained from the TEAI solution were initially invariant for several minutes and then displayed a gradual increase in the relative abundance of TEA+ to a maximum, followed by a precipitous drop in ion intensity. Secondary ion images of droplets of TTAB solution showed that emission of both TTA+ and glycerol secondary ions was homogeneous across the sample. Secondary ion images of droplets of TEAI solution showed heterogeneous and segregated emission of both TEA+ and protonated glycerol. Results from the FAB spectra and the secondary ion images were correlated and rationalized on the basis of surface tension-induced mass transport and matrix evaporation.


[The effect of agonists and antagonists of opiate receptors on the activity of the kallikrein-kinin system in hemorrhagic shock].

Mean blood pressure and heart rate have been registered in the experiments on male Wistar rats. Kallikrein-kinin system (KKS) components have been evaluated in blood plasma: plasma kallikreinogen, kallikrein-inhibiting capacity, spontaneous esterase activity. The parameters were determined before and after hemorrhage in the volume accounting for 10, 20 and 30% of the circulating blood volume. The rats were administered enkephalin analogues--DAGO, DADL and naloxone. The administration of mu-agonist DAGO improved hemodynamics. DAGO effect was eliminated by naloxone. The administration of enkephalins did not affect KKS parameters, while naloxone potentiated KKS changes induced by hemorrhage. It has been shown that KKS is not involved into the mechanism of hemodynamic changes in response to enkephalin administration during hemorrhagic shock.


[Practical aspects of cardioplegia].

Concentrations of the ingredients have been analysed in a nonstandard cardioplegia solution (CS) and CS from St. Thomas Hospital at the outset before CS introduction into the coronary vessels of patients under cardioplegia. It has been shown that the use of nonstandard CS was accompanied by undesirable variability in ingredient concentration, which to some extent may be accounted for by the use of incompletely unfrozen CS. The use of CS from St. Thomas Hospital could be accompanied by moderate hypermagnesiumemia, which did not lead to the onset of vascular insufficiency. It is stressed that plasma magnesium content should be controlled when this CS is used.


[The clinical picture of non-traumatic apallic syndrome].

Clinical signs of non-traumatic apallic syndrome (AS) are caused by universal necrosis of the brain cortex, with the brain stem remaining intact. The reasons of AS are heart and respiration arrest, stable collapses of various genesis, vascular brain diseases. Management was ineffective. Strict AS prevention is necessary, i.e. timely and expert cardiorespiratory resuscitation. Intensive care and cardiorespiratory resuscitation are not recommended in patients with vast brain infarction secondary to brain vascular diseases.


[The use of ultra-high doses of insulin for the treatment of severe heart failure during cardiosurgical interventions].

The experience is reviewed on the use of superhigh insulin doses 1200 to 3800 U (31.4 +/- 5.3 U/kg) for the treatment of acute heart failure in 17 patients subjected to open heart surgery. Symptoms of heart failure refractory to catecholamines and vasodilators were accompanied by marked hyperglycemia (23.1 +/- 4.3 mmol/l). It was impossible to discontinue assisted circulation. In 82.3% of patients myocardial contractility upon insulin administration improved considerably, which led to discontinuation of assisted circulation with moderate inotropic support. Possible mechanisms ensuring the efficacy of massive insulin therapy in patients with acute heart failure are discussed.


[The role of humoral factors in the pathogenesis of the postoperative syndrome].

Blood plasma levels of "pain substances" (serotonin, histamine, prostaglandin F2 alpha, adrenaline /A/) and neuropeptides (beta-endorphin, somatostatin) have been evaluated in 39 patients during the early postoperative period after lung and mediastinum surgery. The studies have shown that the content of these biologically active substances increases considerably. Following stellate ganglion blockade A concentration decreased significantly, the uptake of narcotic analgesics used for postoperative analgesia reduced 1.7-fold, however the levels of "pain substances" and neuropeptides remained unchanged. It is believed that postoperative pain syndrome develops due to the elevation of the levels of the substances under study. Stellate ganglion blockade produces only sympatholytic effect, which shows the necessity of the elaboration of drug therapeutic techniques blocking "pain" receptors and using "pain substance" antagonists.


[The status of indices of immunity and hemostasis in patients with lung cancer and their changes due to general anesthesia and surgical trauma].

Phagocytosis, some factors of humoral immunity and hemostasis have been studied in cancer patients before and after surgery. Suppression of natural body resistance in the preoperative period, as well as significant inhibition of leukocyte phagocytic activity following surgery and anesthesia have been established. A correlation has been suggested between hemostasis damages in the postoperative period and an elevated IgM concentration.


[The status of intracellular metabolism during intensive therapy of severe surgical endotoxicosis].

Introduction of separation plasmapheresis and plasmasorption into intensive therapy of 60 patients with surgical endotoxemia ensured marked detoxication, which manifested in earlier improvement of the clinical symptoms and normalization of intracellular metabolism in cellular elements of the peripheral blood. The data obtained make it possible to recommend the use of the above treatment procedures for elimination of profound intracellular metabolic disturbances in the postoperative period.


[The use of fatty emulsions in the postoperative period in cardiosurgical patients with kidney failure].

The data are presented on the use of fatty emulsions for parenteral nutrition of 68 cardiosurgical patients with renal failure in the postoperative period. It has been established that intravenous administration of fatty emulsions ensures up to 50% of an overall daily calories uptake, with the infusate volume restricted considerably, helps stabilize energy and nitrogen body balance and reduces the risk of complications associated with hyperosmolality and hyperglycemia.


[A comparative evaluation of the efficacy of the traditional combination of high-frequency and intermittent high-frequency artificial ventilation of the lungs in patients with parenchymatous acute respiratory insufficiency].

Conventional controlled lung ventilation (CLV) with positive end expiratory pressure (PEEP) (Con CLV), combined high-frequency CLV (Com HF CLV) and intermittent high-frequency CLV with PEEP (Int HF CLV) have been performed in 43 patients with parenchymatous acute respiratory failure (ARF). It has been established that Int HF CLV significantly increases PaO2 in patients with focal damages of the lung parenchyma and effective compliance (Ceff) > 0.033 l/cm H2O. Com HF CLV increases significantly PaO2 and lung compliance in patients with disseminated lung damages and Ceff < 0.030 l/cm H2O and has marked consequences. Different efficacy of various types of HF CLV under study may be to some extent accounted for by different intraalveolar maximum pressure, which (as it has been shown on the lung model) is higher in Com HF CLV and lower in Con CLV and Int HF CLV.


[Auxiliary extracorporeal and hyperbaric oxygenation in the combination treatment of severe exotoxic shock].

Extracorporeal blood oxygenation makes it possible to stabilize blood circulation, improve gas exchange in severe exotoxic shock, perform blood replacement with small volume of donor blood and continue etio-pathogenetic treatment of patients with severe poisoning with acetic essence and methemoglobin-forming poisons. Hyperbaric oxygenation in the early postperfusion period decreases oxygen debt, improves intravenous glucose utilization, providing adequate energy supply. Extracorporeal and hyperbaric oxygenation added to the therapeutic complex improves by half the clinical efficacy of resuscitation and intensive care.


[The prospects of using dopamine as an antishock preparation].

The quantitative evaluation of the centralization reaction for shockogenic trauma has been experimentally established as an objective criterion of circulatory homeostasis failure severity and adequacy of its correction. The highest antishock effect of dopamine is reached when cardiac output fraction addressed to thoracic region vitals is supported by dopamine on the 43-45% level. Single infusion of the new synthesized prolonged dopamine (12.5 mg/kg) supplies hemodynamic stabilization for post-trauma hypovolemia during 4 hours.


[The effect of hemosorbents on the structure of polymorphonuclear leukocytes in man].

The effect of various hemosorbents (HS)--carbon and textile--on the structure of neutrophils has been studied in vitro. It has been shown that the mechanism of cell degranulation is universal on various HS and does not depend on the anticoagulant used or on blood donor diseases. The degree of degranulation both for primary and for secondary granules increases with the prolongation of blood contact with HS, directly depends on HS--blood ratio and is determined mainly by the type of HS: degranulation on textile HS is considerably greater than that on carbon HS. Degranulation was confirmed by elevated blood plasma concentration of lactoferrin, a specific marker of secondary neutrophil granules. It is suggested that cell degranulation on HS leading to a considerable posthemosorption increase in the blood plasma level of biologically active intracellular components is essential in the process responsible for correcting hemosorption effect in different diseases.


[General anesthesia during surgery of breast cancer].

In 1982-1989 intravenous anesthesia was performed to 1160 patients operated on for breast cancer. Intravenous analgesia has a number of advantages over endotracheal anesthesia. The analgesic techniques have been compared. Absence of complications in the operative and postoperative periods, prompt recovery of the patients' physical and psychic activity following intravenous anesthesia make it a method of choice for surgical treatment of cancer patients who require no myorelaxation.


[Functional disorders of the autonomic nervous system during severe poisoning by clophelin in children].

Disturbances in autonomic nervous system function have been studied during clofelin poisoning in children. A correlation has been established between changes in autonomic homeostasis and reduction in body temperature, bradycardia and arterial hypotension. The studies of cortisol blood level suggests two phases of poisoning: primary (specific) vagotonic phase and secondary (nonspecific) hypersympaticotonic phase. Changes in autonomic homeostasis accounted for the use of atropine sulfate for specific (antidote) therapy.


[Evaluation of the uptake of crystalline amino acid preparations based on the concentration of urea in the blood and tissues].

The assimilation of polyamine, levamine and "new" alvesin has been experimentally assessed by blood and tissue urea concentrations. It has been established that polyamine was best assimilated and was followed by levamine and "new" alvesin.


[Multifactorial surgical risk index of the development of respiratory complications].

Respiratory events are between the most frequent postoperative complications. The preoperative conditions associated with postoperative respiratory failure were evaluated in a prospective study of 1182 patients from six Italian Surgical Units. Multiple regression logistic analysis was employed for statistical evaluation and a predictive prognostic score was derived. Only the presence of the following conditions was significant in affecting postoperative respiratory outcomes: preoperative respiratory and cardiac failure, hypotransferrinemia, prolonged surgical procedures (above the 2 hours) and peroperative bacterial contamination. Advanced age did not appear as a major risk factor. Studies on the predetermination of the pulmonary complications have been widely published. Historical risk factors include the presence of respiratory disease, smoking habits, obesity and thoracic or upper abdominal surgical procedures. Although the results of the present study need a prospective confirmation, the predictive scoring system proves to be a usefull tool that can be employed in most of the General Surgery Units.


[Tumors of nerve sheaths of the peripheral nerves].

Objectives of this paper are the analysis of the confidence in the complementary investigation for the differential diagnostic between schwannoma and neurofibroma, and the retrospective evaluation of the therapy based on the consequent follow-up. The study has been conducted on 36 patients, most of them observed by University Clinic of Navarra (Pamplona), and the others by N. Picardi, all with preoperative diagnosis of schwannoma and neurofibroma, localized in 13 cases in peripheral nerves. Diagnostic iter, pathologic definition, therapy and evolution has been evaluated for all of them. In conclusion we feel that this pathology has to be suspected every time we find a tumor with neurologic symptomatology and that surgical indication of exeresis is the most correct in the majority of cases; moreover imaging investigations is rather useful, but if any doubt occurs we must proceed to biopsy or directly to exeresis of the tumor. Our experience shows that schwannoma, thanks to its anatomic patterns, can be treated less radically toward the nerve continuity than neurofibroma, and that the technique of nerve graft could be a useful alternative in this kind of surgery.


[Complications of gastroesophageal reflux: considerations on a non-selected case series].

According to the experience of the authors on a non-selected case report, pharmacologic progresses in the therapy of various aspects of peptic disease permit an ease management also of gastro-esophageal reflux disease. Moreover, endoscopy is the very modern pivot of conservative treatment of more severe complications as strictures are, through repetitive and progressive instrumental dilatations. The surgical treatment of the most severe and intractable eveniences must be chosen for only a low percentage number of patients, after a careful functional analysis of the single case. Very important is the endoscopic and histologic control of Barrett esophagus and severe dysplasia.


[Cholelithiasis after total gastrectomy for gastric cancer].

After gastric resection for peptic ulcer and total gastrectomy for Zollinger-Ellison syndrome, there is an increased prevalence of cholelithiasis. In order to assess whether this increased prevalence also exists after total gastrectomy for cancer, we evaluated the rate of cholelithiasis (echographic diagnosis) both before and after this operation. Between 1980 and 1990, 89 patients underwent total gastrectomy for cancer in the Surgical Department of our Institute. The pre-operative prevalence of gallstones was 5% in the males and 13.8% in the females. Seventy-four of the eighty-nine patients (83%) were examined post-operatively (7 patients with pre-operative cholelithiasis, 3 who died during the post-operative stay and 5 lost to follow-up were excluded from the study). The median post-operative follow-up was 24 months (range 3-115 months). The post-operative prevalence of cholelithiasis in the 74 patients was 39.6% in the males and 19% in the females. We also calculated the expected frequency of gallstones in both the pre- and post-operative groups from prevalence data in the population of the city where our Institute is based (taken from an echographic survey). We then compared the observed frequency of cholelithiasis with the expected frequency and we found that the difference in pre-operative frequencies, both in the males and females, was not statistically significant (p > 0.05). The same was true of the post-operative frequencies in the females (p = 0.48), but in the males there was a statistically significant difference between the observed frequency of cholelithiasis and that expected after total gastrectomy (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)


[Preoperative staging of gastric carcinoma using endosonography (EUS)].

Accurate staging of gastric malignancy can only be obtained at surgery and after detailed histological examination of the resection specimen. Endoscopic ultrasonography may provide accurate detection and staging of gastric cancer because of its ability to visualize both the intramural and extramural extent of the lesion and any adjacent lymph node involvement. From february 90 to april 91, 29 patients with a gastric carcinoma were studied endosonographically before surgery. All studies were performed with an Olympus EU-M3. Preoperative TNM classification and a prediction of the resectability of gastric cancer were done in every patient. The results were matched with those obtained with the histology of resected specimens according to the TNM classification 1987. Endoscopic ultrasonography was accurate in assessing the extent and depth of tumor infiltration. The overall accuracy rate was 90.5% (19 out of 21 patients). Overstaging occurred in 9.5% of the cases (2 patients); none understaging occurred. EUS was less accurate in assessment of lymph node metastasis; the overall accuracy rate was 57.1%. Distinction between reactive lymph node and small micrometastatic lymph node involvement could be hard. Local resectability was correctly diagnosed with EUS in each of 23 patients; in two patients an intramural mass with a deep infiltration into the surrounding tissue was correctly diagnosed. In our opinion EUS is an essential diagnostic procedure in the clinical staging of the gastric cancer.


[Ileal diverticula: apropos of a case].

The authors report a case of abdominal aortic aneurysm surgically treated. At surgical exploration an ileal diverticulum was discovered. A 15 cm ileum tract was hyperemic and oedematous. The abdominal aortic aneurysm was resected and an aorto aortic graft implanted. The retroperitoneal space was carefully closed and then the diverticulum resected and an end-to end intestinal anastomosis performed. An etiological review of this pathology was done identifying two possible causes: true and false diverticula. The true diverticulum is a congenital lesion involving the 3 layers of the intestinal wall. On the contrary the false diverticulum is acquired and generally develops on the mesenteric site due to a pulsion mechanism. The wall involves the mucosa and serosa layers only. Diagnosis is often done during abdominal exploration for other cause (as in our case) or for complicated diverticula. Preoperative radiologic diagnosis is rare and doesn't always require surgical treatment.


The simultaneous presence of primary lymphoma and adenocarcinoma in the stomach.

The authors describe a rare case, recently observed by them, of coexisting primary lymphoma and adenocarcinoma of the stomach. After illustrating the more salient aspects of the clinical and anatomopathological pattern, the Authors discuss the general issue of the simultaneous presence of the two pathologies, analysing in particular their classification and etiopathogenic aspects. They then discuss the peculiar aspects of the case considered, including the preoperative diagnosis of non-Hodgkin gastric lymphoma, and highlight the fact that, unlike what is more frequently reported in the literature, the carcinomatous component had been completely ignored. As a final consideration, they stress the importance of studying this rare combination of tumoral components in order to gain a better understanding of oncogenic mechanisms so far unknown.


[Carcinoma of the cecum: is early diagnosis possible?].

Between 1982 and 1989, a consecutive series of 34 patients with cancer of the cecum were operated in our hospital. Overall, at 5 years the survival was 50%. We did not notice any correlation among symptom duration and survival. Patients admitted in the asymptomatic phase had the best survival rate (66.6%). Our study suggest that only neoplasm diagnosed in asymptomatic patients and treated promptly are related to a good survival rate. We, therefore, emphasize the importance and the necessity to investigate all patients with a suspected cecum cancer by means of colonoscopy.


Actions of neurotensin: a review of the electrophysiological studies.

Three effects of NT were observed on midbrain DA cells. The modulatory effect of NT, that is, the attenuation of DA-induced inhibition, has been most extensively examined. Studies indicate that this effect of NT was not simply due to a nonspecific excitation. NT selectively attenuated DA-induced inhibition without affecting either GABA-induced inhibition or glutamate-induced excitation of the same cells, and the attenuation of DA-induced inhibition could be observed at the doses at which the basal activity of DA cells was not changed by NT. The attenuation of DA-induced inhibition by NT is also unlikely to result from the formation of a DA-NT complex, since neuromedin N, which competes with NT for the same receptor but does not bind to DA, mimicked the effects, and neurotensin(1-11), which forms a complex with DA but is inactive in competing for NT receptors, did not. The similarities between the effects of NT and those of 8-bromo-cAMP and forskolin suggest that intracellular cAMP and protein kinase A may be involved. This suggestion was supported by the findings that IBMX (an inhibitor of phosphodiesterases) potentiated the effect of NT; and SQ22536 (an inhibitor of adenylate cyclase) and H8 (an inhibitor of protein kinase A) antagonized it. Phorbal-12,13-dibutyrate (an activator of protein kinase C) did not mimic the effect of neurotensin, and H7 (an inhibitor of protein kinase C) did not reduce the effect, suggesting that protein kinase C is unlikely to be involved in the modulatory effect of neurotensin. Experiments in vitro indicated that the excitatory effect of NT on DA cells occurred at higher concentrations (> 10 nM) than those needed for producing the modulatory effect. Its persistence during DA receptor blockade by sulpiride suggests that this effect was not entirely mediated by an attenuation of the inhibition induced by endogenously released DA. At even higher concentrations (> 100 nM), a sudden cessation of cell activity preceded by an increase in firing rate was observed. Whether this effect of NT was due to depolarization inactivation or a toxic effect of the peptide at high concentrations remains to be determined. In most other areas studied, the excitatory effect of NT was most commonly observed. In many areas, this excitatory effect was apparently a direct postsynaptic effect of NT. However, different mechanisms may be involved (see Table 1). For example, in some areas NT acted through a decrease in membrane conductance, while in others no change or an increase in the membrane conductance was observed.(ABSTRACT TRUNCATED AT 400 WORDS)


[Intestinal recanalization 16 years after Hartmann's operation].

The authors report a case of a surgical intestinal recanalization after 16 years since a Hartmann's intervention. After some considerations on the results they obtained in similar cases, the Authors call attention on this specific clinical case. They come to the conclusion that a successful surgical recanalization--although the difficult availability of the remaining rectal stump--is possible even if a long period has passed since a Hartmann's intervention was performed. In fact the rectal stump and the sphincter apparatus, even if excluded from the fecal transit for a long while, retain largely their specific functional activities and show a marked ability for an effective sensitive-motor restoration.


[Ogilvie's syndrome: clinical reality or nosographic error?].

The authors report their experience in the management of Ogilvie's syndrome, a rare form of large bowel acute pseudo-obstruction. The study includes fifteen cases of the disease. There were ten males and five female, with a mean age of sixty-two years (range 45-92). Three patients were only treated with medical and conservative measures, one with unsuccessful colonoscopy and twelve (two with colonic perforation) underwent laparotomy. The surgical procedures performed were tube cecostomy (40%), colonic resection with primary anastomosis (27%) and exploratory laparotomy with decompression (13%). The overall morbidity and mortality rate were respectively 0 and 13%. Our epidemiological, clinical and therapeutic results are similar to those reported in the international literature. The pathophysiology of the syndrome is still unknown. It can be "idiopathic" or can complicate other diseases or surgical procedures (urological and gynaecological procedures mostly). Plain abdominal roentgenogram is the most useful diagnostic test, but colonoscopy may be an alternative diagnostic (and therapeutic) weapon. Conservative treatment is the method of choice but when the cecal diameter is more than 12 cm. (impending perforation), when the colon is perforated or when medical measures are unsuccessful, surgical procedure is compulsory. The age of the patient, cecal size, delay in colonic decompression are the most important prognostic factors. Even with a proper management, the prognosis is severe and the mortality rate is high (3-50%).


[Rare colonic occlusions: volvulus of the splenic flexure].

Authors report a case of perforated splenic flexure volvulus, treated with resection, end colostomy and closure of the distal stump. From the revision of literature it comes out the case reported is the 30th recorded till now, the 6th with ischemic complications, and the only one with perforation. Actual pathogenetic trends and various therapeutic options are reported.


[Radical excision and primary suture of pilonidal sinus: our experience].

Various operations could be used for pilonidal sinus disease. The authors report their experience, discuss the etiopathogenesis (acquired or congenital origin) describe their method of treatment and results and compare them with those of the other reviews.


Control of anterior pituitary hormone secretion by neurotensin.

Neurotensin is localized in discrete populations of neuronal cell bodies with terminals in the hypothalamus and median eminence. High-affinity binding sites for neurotensin have been demonstrated not only in the hypothalamus but also in the pituitary gland. These studies suggest a role for neurotensin in control of hypothalamic-pituitary function. We initially demonstrated that neurotensin could block the release of prolactin in conscious, ovariectomized and male rats after its injection into the third ventricle, whereas intravenous injection of the peptide significantly elevated plasma prolactin and increased prolactin release by pituitaries incubated in vitro. These results suggested that neurotensin had opposite actions on prolactin release, an inhibitory effect at a hypothalamic site and an excitatory one at the pituitary. Further studies employing dopamine receptor blockers and inhibitors of catecholamine synthesis indicated that the action of the peptide to block prolactin release was probably mediated by release of dopamine, which then inhibited prolactin release by the pituitary gland directly. We have evaluated the physiological significance of the peptide in control of prolactin release by intraventricular injection of highly specific antiserum against neurotensin. The antiserum evoked dose-related elevations in plasma prolactin in intact males that were significant but smaller in magnitude than those seen in females, actions opposite to those of the peptide itself, which indicates that the inhibitory action of the peptide within the brain is physiologically significant. Intravenous injection of this antiserum produced a significant suppression of plasma prolactin in females but not males, which indicates that the previously demonstrated stimulatory effect of the peptide on prolactin release by the gland is also physiologically significant because immunoneutralization of the peptide resulted in a decline in plasma prolactin. Our earlier experiments revealed that neurotensin had a dose-related ability to inhibit LH release in ovariectomized and ovariectomized, estrogen progesterone-treated rats. Since it had no effect on the release of LH in vitro, we assigned a hypothalamic site for this action. It appears that this inhibitory effect of the peptide to suppress LH release is also physiologically significant since the intraventricular injection of the antiserum against the peptide produced a dose-related stimulation of LH release in ovariectomized and ovariectomized, estrogen progesterone-blocked rats. The mechanism by which endogenous neurotensin inhibits the release of LHRH has yet to be evaluated.(ABSTRACT TRUNCATED AT 400 WORDS)


Antibodies against a 30 kilodalton cochlear protein and type II and IX collagens in the serum of patients with inner ear diseases.

Collagen molecules are major extracellular matrix proteins involved in the development and support of delicate auditory sensory organs. Type II collagen is widely distributed within inner ear tissues, while type IX is found only within the labyrinthine membrane and dense fibers of the tectorial membrane. Antibody specific for type II collagen has been shown to be elevated in some patients with hearing loss due to several presumably autoimmune illnesses (including Meniere's disease, otosclerosis, chronic progressive sensorineural hearing loss, and relapsing polychondritis). Purified human type II and IX collagens and an extract of human cochlear tissue were subjected to isolation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to nitrocellulose. The sera of 21 patients with inner ear disease were examined for the presence of anticollagen and anticochlear antibodies; the sera were used to probe Western blots of purified human collagens II, IX, and XI, and cochlear protein extract with peroxidase-conjugated goat anti human polyvalent immunoglobulin as the second antibody. Anti-type II collagen antibodies were seen in 12 of 21 (57%) patients, while 13 of 21 (62%) had anti-type IX antibodies detectable by Western blot. A previously unreported 30 kd (probably noncollagen) protein was 21 (62%) had anti-type IX antibodies detectable by Western blot. A previously unreported 30 kd (probably noncollagen) protein was found by SDS-PAGE of human cochlear tissue extracts, with 3 patients, all with Meniere's disease, having antibody activity to this protein detected by Western blot.(ABSTRACT TRUNCATED AT 250 WORDS)


Spontaneous remission in experimental autoimmune labyrinthitis.

We investigated the time course of hearing impairment and cellular infiltration into the inner ear after systemic sensitization of guinea pigs with a single intradermal injection of bovine inner ear antigen (IEAg) in complete Freund's adjuvant (CFA). Lymphocytes and polymorphonucleocytes appeared mainly in the scala tympani on days 7 to 14, and in addition there was thickening and cellular infiltration of the round window membrane at day 14. These cellular infiltrations resolved after day 28. The auditory brain stem response thresholds from IEAg-sensitized animals were significantly elevated after day 7. Some sensitized animals (n = 5) had spontaneous remissions after day 28; however, the hearing thresholds did not completely recover. These results demonstrate that experimental autoimmune labyrinthitis can be induced by a single inoculation of IEAg-CFA and that remission, as evidenced by clearing of the cochlear cellular infiltration and improved hearing thresholds, can occur spontaneously.


Nonsquamous carcinomas of the larynx.

Nonsquamous carcinomas make up fewer than 1% of all epithelial malignancies of the larynx. The majority are subsurface in origin and arise from seromucous glands of the larynx. Adenoid cystic carcinoma is not only representative of this group, it is the most prevalent. All other salivary-type carcinomas are rare. Rarer still are surface adenocarcinomas. Neuroendocrine carcinomas appear to constitute the majority of so-called laryngeal adenocarcinomas.


Indium 111-labeled leukocyte scintigraphy in evaluating head and neck infections.

This retrospective study looked at the role of indium 111-labeled white blood cell (111In WBC) scintigraphy in head and neck infections. The efficacy of 111In WBCs was compared to gallium 67 citrate (67Ga) and technetium Tc99m methylene diphosphonate (99mTc MDP) scintigraphy in detecting and monitoring the resolution of infection. For 22 active infections, the sensitivities for 111In WBC, 67Ga, and 99mTc MDP scintigraphy were 94%, 56%, and 86%, respectively, and the specificities for 111In WBC, 67Ga, and 99mTc MDP scintigraphy were 100%, 43%, and 0%, respectively. For 8 successfully treated infections, all seven 111In WBC studies became negative after therapy, in as short an interval as 1 month. In contrast, all seven 99mTc MDP images remained positive for as long as 6 months after therapy. The seven 67Ga studies had variable results, with four (57%) remaining positive, including two (28%) positive at 6 months after therapy. These results suggest that 111In WBC scintigraphy should be the initial radionuclide imaging tool in detecting active head and neck infections because of its greater accuracy, and its ability to revert to normal much sooner than 67Ga or 99mTc MDP scintigraphs when applied to a subset of patients with resolved infections.


Combined effects of noise and cisplatin: short- and long-term follow-up.

The combined effects of noise exposure and intravenous cisplatin injection on electrophysiologic hearing thresholds in guinea pigs were studied with short-term and long-term follow-up. The combined effects on the permanent threshold shift were dependent on the order of exposure. A potentiation was achieved when noise exposure preceded cisplatin injection by 30 minutes or by 3 days. Cisplatin injection 2 or 3 days before noise exposure produced no significant potentiation or inhibition. The combined effects on the temporary threshold shift were not influenced by the sequence of exposure.


Maxillary sinus atelectasis.

Two patients are presented with maxillary bone loss and atelectasis of the sinus walls in association with chronic subclinical maxillary sinusitis. Maxillary sinus atelectasis results in a mild cosmetic deformity, but may also cause diplopia by involving the orbital floor. Ostial obstruction and inflammation-mediated osteopenia are postulated to be the responsible mechanisms. Surgical treatment of the sinusitis may prevent progression of the bone loss.


Ultrastructural changes in human nasal cilia caused by the common cold and recovery of ciliated epithelium.

Changes in the ultrastructure of human respiratory cilia caused by the common cold were studied in 12 patients. The nasal mucosa was studied three times: on the first or second day after the beginning of symptoms, and 1 week and 3 weeks after the first biopsy. The damage was most severe at 1 week. The most remarkable finding was the loss of cilia and ciliated cells. However, the ultrastructure was usually normal, without any increase in tubular anomalies, as compared with the normal material of the previous reports. Three weeks after the beginning of the disease the number of cilia and ciliated cells had increased to nearly normal. However, as a sign of regeneration, immature short cilia (0.7 to 2.5 microns in length) were often seen. The ciliary orientation was uniform, dynein arms were normal, and there was no increase in the number of tubular anomalies. The results suggest that the impaired mucociliary function during viral infections is due to the loss of cilia and ciliated cells, rather than to ultrastructural anomalies in the cilia. The development of tubular anomalies and random ciliary orientation may require more extensive exposure to factors affecting ciliary function.


Diameter of the cochlear nerve in deaf humans: implications for cochlear implantation.

Although the parameters that are most important for postoperative speech perception in cochlear implantation have not been identified, it is assumed that the numbers of remaining cochlear neurons and spiral ganglion cells in the implanted deaf ears are critical. In this study, we evaluated the correlation of the maximum diameter of the cochlear and vestibular nerve trunks with the number of spiral ganglion cells in horizontal sections of the temporal bone of 42 patients who were profoundly deaf during life, and in 5 patients with normal hearing. The maximum diameters of the cochlear, vestibular, and eighth cranial nerves were significantly smaller in the deaf population as compared to normal-hearing controls. In addition, the counts of the remaining spiral ganglion cells were significantly correlated with the maximum diameter of the cochlear (p = .0006), vestibular (p = .001), and eighth cranial nerves (p = .0003). The regression equation estimated that 25% of the variance of the spiral ganglion cell count was predicted by the maximum diameter of the eighth nerve. Although the results of this study suggest that preoperative radiographic imaging of the diameter of the eighth nerve may be helpful in predicting the residual spiral ganglion cell count, the wide variability of diameters of the eighth nerve in hearing and deaf subjects militates against this theoretic usefulness.


Influence of general anesthesia on transiently evoked otoacoustic emissions in humans.

The influence of general anesthesia (GA) on transiently evoked otoacoustic emissions (TEOAEs) was studied in 19 normally hearing women undergoing surgery. Emissions were measured on the day before the operation, after premedication but before the beginning of the operation, and during and after the operation. There were no significant differences in TEOAE amplitude or in reproducibility between results obtained the day before the operation and after premedication. Ten patients received nitrous oxide (N2O) during GA (N2O group), and 9 patients did not (non-N2O group). The amplitude of TEOAEs was reduced during GA in 9 of 10 patients in the N2O group and in 7 of 9 patients in the non-N2O group. However, the average decrease of amplitude after the first 10 minutes was greater in the N2O group (4 +/- 3.4 dB) than in the non-N2O group (0.18 +/- 1.4 dB). The corresponding mean reproducibility of the response decreased in 9 of 10 patients of the N2O group (29% +/- 24%) and was nearly unchanged in the non-N2O group (2.3% +/- 7.2%). The time course of the amplitude reduction was similar in both groups. The smallest amplitudes were reached on an average by 19.3 +/- 11.4 minutes in the N2O group and by 17 +/- 13.6 minutes in the non-N2O group. Preoperative and postoperative TEOAEs were comparable in level and reproducibility. Differential frequency effects imply a middle ear effect for the greater reduction of TEOAE amplitudes in the N2O group due to gas diffusion into the middle ear.(ABSTRACT TRUNCATED AT 250 WORDS)


[Insulin therapy using a portable pump in children. Apropos of a pediatric experience].

Experience accumulated with 17 pediatric patients with insulin-dependent diabetes mellitus treated with an insulin pump is reported. Follow-up exceeds four years in seven patients. A significant improvement in metabolic control was seen in only four patients and was confined to the first year of use of the pump. Overall, the improvement in control was not significant. Severe hypoglycemia was uncommon (0.27/patient-year). Ketoacidosis was rare (0.08/patient-year). Transient ketosis was the most common adverse event and was often related to technical problems which should immediately lead to appropriate action by patients who have received proper education. Use of an insulin pump remains an alternative which deserves to be considered when conventional therapies fail.


[Idiopathic pericerebral swelling (external hydrocephalus) of infants].

Benign enlargement of the subarachnoid spaces was diagnosed in 41 infants on the basis of ultrasound and/or CT scan findings. 10 MHz transfontanellar ultrasonography is without doubt the most reliable investigation in this condition (skull-to-cortex distance greater than 5 mm). Patients with extracerebral collections due to a clearly identifiable pathologic process (e.g., prematurity, IUGR, neonatal distress, malnutrition) were excluded from the study. Macrocrania developed rapidly in 72% of patients, either as the single manifestation (30%) or with delayed motor development and hypotonia (30%). Other clinical patterns included evidence of intracranial hypertension (15%) and hypotonia without macrocrania (20%). The two main findings of this study were the high rate of familial forms and the severity of early hemorrhagic complications, i.e., spontaneous subdural hematoma (5/41 cases), with permanent neurologic impairment in some instances (2/5 cases). These complications call into question the benignity of this syndrome whose long-term outcome, particularly in terms of cognitive function, is as yet unknown.


[Peptic esophagitis and scoliosis in children].

Four pediatric cases of peptic esophagitis in patients with severe dorsolumbar scoliosis including three with a history of neurological disease provide the opportunity to point out that curvature of the spine fairly often causes development of gastroesophageal reflux. By displacing the anchoring points of the stomach and stretching the lower esophageal sphincter, scoliosis can be responsible for malposition of the cardia and fundus and for gastroesophageal reflux. Furthermore, plaster corsets increase intraabdominal pressure and may therefore promote gastroesophageal reflux.


[Donath-Landsteiner hemolytic anemia. Physiopathological, diagnostic and therapeutic aspects].

Donath-Landsteiner hemolytic anemia accounts for one third of all immunologic hemolytic syndromes in pediatric patients. Diagnosis is suggested by results of the direct Coombs test which is positive with anti-C3d, evidence of erythrophagocytosis on admission blood smears, and results of the Donath-Landsteiner test. Anti-P specificity should be routinely looked for. Management, required once the diagnosis is established, is symptomatic. Warmed red blood cell concentrates should be used for blood transfusions. Exposure to cold should be avoided. Use of maintenance corticosteroid therapy is no longer acceptable.


[Cantrell syndrome or the "shagreen skin" pentalogy. Apropos of 3 cases].

Three patients with incomplete forms of Cantrell syndrome underwent surgical therapy at the Department of Infantile Surgery in Strasbourg, France, between 1979 and 1990. One patient had a giant omphalocele. Another had a ventricular septal defect. Two of the three patients are alive and doing well. The nosology and prognostic factors in Cantrell syndrome are discussed.


[Neonatal streptococcus group B infection in Yaoundé (Cameroon). Epidemiologic and clinical aspects].

This study was designed to investigate epidemiologic and clinical features of neonatal group B streptococcal infections. Sixty cases seen over a 60-month period were reviewed. Incidence was 0.8% of admissions. Most affected infants were from low-income families (86.7% of mothers were unemployed and 73.5% of homes were without running water). Neonatal infection was delayed in most instances (76.67%). Fetid vaginal discharge (60%) and premature rupture of the membranes (35%) were the main findings upon history taking. Abnormal body temperature regulation (76.7%) was the most prominent clinical manifestation. Respiratory distress developed in 25% of patients. Meningeal involvement occurred in 73.3% of patients. Serotype B III was recovered in 31 of the 34 cases (91%) in which serotype was determined. Mortality rate was 21.7% and permanent sequelae occurred in 8.3% of patients.


Griseofulvin in the treatment of oral lichen planus: adverse drug reactions, but little beneficial effect.

An open trial was conducted of systemic griseofulvin in the treatment of oral lichen planus. Eleven patients completed the trial. Symptomatic benefit was noted in 21% of the twenty-three patients starting the trial, but there was no clinical improvement, and about one half of the group starting the trial suffered adverse drug reactions.


Recurrent aphthous stomatitis: the efficacy of replacement therapy in patients with underlying hematinic deficiencies.

A group of thirty-four patients with recurrent aphthous stomatitis (RAS) and single hematinic deficiencies were given replacement therapy after any reason for the deficiency had been sought and excluded. The response of the RAS was assessed in an open trial. The aphthae in 70% of patients subjectively improved with hematinic replacement therapy, a benefit exceeding the defined placebo response in recurrent aphthous stomatitis.


Radiographic study of mandibular nutrient canals.

This study was undertaken to determine the correlation between the presence of nutrient canals in the mandibular anterior region and sex, age, edentulous mandible, periodontal disease, and high blood pressure. The periapical roentgenograms taken from the mandibular anterior region of 1040 patients were examined. According to the data obtained from the present study, the occurrence of nutrient canals in the mandibular anterior region seemed related to age, edentulous mandible, periodontal problems, and high blood pressure. However, no relation to sex was found.


Effects of restorations and carious lesions on the periodontium in humans.

The objectives of the present study were to examine the effects of dental restorations, crowns and fillings, and carious lesions on the periodontal tissues. One hundred and one clinic patients were selected on the basis of each having one or more teeth with either carious lesions or restorations, and having contralateral teeth without restorations or carious lesions. Debris, calculus, gingivitis, pocket depths, and bone loss were evaluated using objective criteria of assessment for each condition. The results showed significantly greater gingivitis, pocket depth, and bone loss around teeth with restorations and carious lesions than around their controls.


Herniation of an antral polyp through an oroantral fistula.

This paper reports a case of herniation of an antral polyp through an oroantral fistula, appearing as a polypoid lesion of the alveolar ridge. The patient was a 24-year-old female, and her upper molar had been extracted two months previously. The lesion was asymptomatic, and was a soft tissue mass, red in color and nontender to palpation, involving the alveolar ridge in the maxillary molar area. Review of the literature yielded only a few other such cases.


Dental disease in the differential diagnosis of fever of unknown origin.

A patient with a one-year history of fever of unknown origin is presented. Extensive work-up failed to reveal the source of the fever. Treatment of periodontal infection resulted in complete cure, suggesting a cause-effect relationship. A possible role of Interleukin 1 (IL-1), universal pyrogen, in periodontal disease is suggested.


Ehlers-Danlos syndrome: a case report.

A 13-year-old male patient classified as Type VIII, Ehlers-Danlos syndrome, in which the typical periodontal findings are not seen, is presented. The patient has many partially erupted deciduous teeth and partially erupted mandibular permanent incisors. It is suggested that Type VIII has two subdivisions. In subdivision A there is periodontal involvement with a normal eruption pattern; subdivision B has no periodontal involvement, but the teeth do not erupt.


[The metastatic liver: a rare cause of hepatocellular insufficiency].

Liver metastases are frequent, often large and sometimes very late in skin or choroid metastatic melanoma. Hepatic failure is a rarely described complication in metastatic liver melanoma. We report a case of liver failure in a metastatic liver melanoma in a woman 76 years old, treated 16 years before for a choroid melanoma. About this case, we discuss the frequency, the location of primitive tumors and mechanism of liver failure in metastatic liver.


[A new case of collagenous colitis associated with rheumatoid polyarthritis].

The authors describe a case with concomittant chronic polyarthritis and collagenous colitis. The sub-epithelial band-like collagenous deposit may be the result of fibroblastic production with autoimmune stimulation.


[Management of a focal hepatic mass: propositions of a workshop].

Focal hepatic masses are a common problem, due to the expansion of ultrasound. Individuals engaged in the four disciplines involved (hepatogastroenterology, digestive surgery, radiology and pathology) met to summarize the information available, to compare their experience and to make synthetic proposals. The method consisted of an expert report, discussion of the clinical cases, workshop discussion for each discipline around synthetic proposals, reporting of these proposals in full session and discussion. The results, i.e. the synthetic and consensual proposals concerned diagnosis, treatment and monitoring of focal hepatic masses are presented for each discipline.


[Description of a new disease: pancreatic lithiasis with radiolucent calculi].

118 patients presenting with pancreatic lithiasis were consecutively observed in our service. They underwent both an endoscopic pancreatography and god plain films of the abdomen. Calculi were classified in 3 groups: 1) Radiolucent calculi (17 cases, 5 females; 4 hereditary cases) are build up of amorphous residues of lithostathine S. They are not related to either alcohol, diet or tobacco. 2) Target calculi (27 cases, 4 females; 3 hereditary cases) have a radiolucent core as in 1 and a peripheral calcification. They are a late evolutionary stage of radiolucent lithiasis. The frequency of females and of hereditary cases is significantly greater in form 1 + 2 than in form 3. These two forms are a newly described disease without relationship with nutrition, alcohol or tobacco but the peripheral calcification of radiolucent calculi is favoured by alcohol and tobacco. This disease could be hereditary. 3) Calcic lithiasis (74 cases, 8 females, 2 hereditary cases) is the most frequent form of pancreatic lithiasis. Its cause is nutritional.


[Antibiotic residues and digestive microflora].

Can antibiotic residues modify the human gut flora, and select drug resistant bacteria? In volunteers given ampicillin (1.5 mg/d) or oxytetracyclin (2 mg/d), the fecal excretion of resistant enterobacteria was not changed significantly. However a possible effect would be hidden in human beings by the huge day to day fluctuations in the resistant bacterial populations. Heteroxenic mice (i.e. germfree mice associated with the flora of a human donor) and dixenic mice (i.e. mice harboring 2 isogenic strains, one of which carries an R-plasmid) are possible models to study the gut flora in vivo without contaminations and interfering factors. Minimum selecting doses in these models are between 0.5 and 10 mg antibiotic per liter of drinking water. These doses are smaller than what a consumer could ingest in food. Last, fecal resistant enterobacteria directly come from contamined food, as shown by their clearance from stools of volunteers eating a sterile diet. Hence antibiotic residues do not modify meaningfully the gut flora.


Estrogen suppresses hepatitis B virus expression in male athymic mice transplanted with HBV transfected Hep G-2 cells.

Hormones are known to regulate both viral and cellular genes. It has been shown previously that estrogen has an effect on liver gene transcription and mRNA stability. Sex hormones might have a role in the chronic persistence of hepatitis B virus (HBV) infection. In fact, there is a male preponderance in the incidence of chronic HBV infection, and HBsAg expression was reported to be much higher in male transgenic mice than in the females. We investigated the effect of estrogen on HBV gene expression and regulation in athymic mice bearing 2.2.15 cells, a human hepatoblastoma cell line derived from Hep G-2 transfected with HBV sequences. Both male and female mice were treated with estradiol after tumors could be observed. Episomal DNA was extracted from the tumors and hybridized with 32P-labelled HBV DNA. Southern blot and slot blot analyses demonstrated that male mice had higher expression of HBV DNA. Estrogen treatment suppressed HBV DNA expression in males, but had only a minor effect on females. HBeAg production in male mice was also inhibited by estrogen treatment. HBV RNA extracted from 2.2.15 cells showed 2-3-fold reduction following beta-estradiol treatment. Moreover, inhibition of HBV transcription by estrogen was demonstrated by an RNA pulse-labelling experiment. These data indicate that estrogen inhibits HBV expression in the in vivo model presented in this study. These results might contribute to a better understanding of the effect of sex hormones on the pathogenesis of HBV-induced liver disease.


The influence of dextran sulfate on influenza A virus fusion with erythrocyte membranes.

Dextran sulfate suppresses the low pH-induced fusion of influenza virus A/Brazil 11/78 with erythrocyte membranes, as shown by fluorescence dequenching assay, using the fluorophore octadecylrhodamine B chloride (R18). Inhibition of fusion was maximal at pH 5.0, while at higher pH values (> 5.6) fusion was not affected. Hemolysis of intact red blood cells by influenza A virus at low pH values is also prevented by dextran sulfate. The inhibiting effect of the polymer is mainly ascribed to repression of virus attachment. Evidence is given that the conformational change of the virus envelope protein hemagglutinin (HA) responsible for triggering fusion is not affected by the polymer.


Antiviral effects of recombinant human tumor necrosis factor-alpha in combination with natural interferon-beta in mice infected with herpes simplex virus type 1.

The protective effects of combination therapy utilizing recombinant human TNF-alpha (rTNF-alpha) and natural murine interferon-beta (IFN-beta) in mice infected with herpes simplex virus type 1 (HSV-1) was investigated. Mice treated with rTNF-alpha alone at all of the doses tested (a single i.v. administration, 2.3-2,300 micrograms/kg; multiple i.p. administrations 0.4-250 micrograms/kg) as well as mice that received IFN-beta alone at doses of 16 x 10(4) U/kg or less resulted in a 0% survival rate. Combination therapy consisting of a single administration of rTNF-alpha (230 and 23 micrograms/kg) and multiple administrations of IFN-beta (4 x 10(4) U/kg) resulted in a 40% and 60% survival rate. Multiple treatments of infected mice with rTNF-alpha (50 and 10 micrograms/kg) in combination with IFN-beta (4 x 10(4) U/kg) resulted in 50% and 70% survival rates, respectively. These results suggest that the combination therapy of rTNF and natural murine IFN-beta produce synergistic protective effects in mice infected with a lethal amount of HSV-1.


Project team investigates how the Association's organizational structure can be improved to meet future changes, challenges.

The members of the Project Team realize that this is a very different concept than that to which members are accustomed. The details of such a change would be developed with member input, and the new structure would be phased in over a period of several years to be fully implemented by the year 2000.


Award for Excellence in Perioperative Nursing--AORN's ultimate prize.

Excellence should be part of our daily practice. Through sharing of knowledge, ideas, and information, private excellence is transformed into public excellence and deserves recognition. AORN recognizes that many individuals have and do make a difference in their individual practice settings as well as by their national influence. The importance of recognizing members for their contributions to perioperative nursing is evidenced by the addition of the two new awards and the many other individual awards given by the Association. The importance of peer recognition and participation in the selection process for the awards cannot be underestimated. The Award for Excellence Committee encourages your continued involvement in the nomination process. Excellence is not just for a chosen few! It is something each of us is capable of doing each day. What we need to do now is to recognize it in ourselves and others and to accord those who display this quality the recognition they deserve.


[Current status of research on cancer metastasis].

Metastasis is the most critical problem for the oncologists to treat cancer patients. The processes of cancer invasion and metastasis consist of a long series of sequential, interrelated, and complicated steps. Understanding the mechanisms responsible for cancer invasion and metastasis is, therefore, a primary goal of cancer research and will produce new approaches to control and inhibit cancer metastasis. Massive investigations are being carried out for cancer metastasis. Recently many investigations on the research fields other than cancer result in being related with metastasis research. We reviewed the current findings, including our data, on the research for cancer metastasis and discussed the current status of the research.


[Epidemiology of pancreatic cancer].

Pancreatic cancer has been increasing in recent years in Japan. The number of pancreatic cancer deaths in 1990 was 13,318, accounting for 6.1% of all cancer deaths in Japan. The increasing trend of pancreatic cancer mortality is observed more markedly in the elderly population over 60 years of age, and especially in persons over 80. Possible reasons for the increase of pancreatic cancer were discussed. The geographic distributions of pancreatic cancer mortality in Japan and around the world indicate that the mortality is higher in northern Japan and even higher as the latitude increases. Some possible reasons for the inverse relationship between the pancreatic cancer mortality and the latitude were discussed. From epidemiological studies several risk factors for pancreatic cancer were reported; smoking, drinking, excess intake of meat and cholesterol, coffee, radiation, cholecystectomy, etc. However, more epidemiological studies are needed to identify and confirm risk factors for pancreatic cancer and to promote primary prevention of pancreatic cancer.


[Treatment and present status of pancreatic cancer].

The Pancreatic Cancer Registry of the Japan Pancreas Society registered 11,317 patients of pancreatic cancer during these ten years. Among these patients, resectional procedures were performed on only 3,743 cases (33.1%). The actual 5-year survival rate of the patients who underwent resection was 16.6%. As for small cancer which was less than 2cm, the 5-year survival rate was 41.0%. In pancreatic cancer local recurrence was more frequent than other cancers of pancreatic head lesions. Extended operation which means lymphangiectomy more than R2 has not improved survival rate generally But some patients who underwent extended operation have survived long period. Multi-disciplinary treatment of pancreatic cancer has been tried.


[Selection of methods for diagnosis and treatment of pancreatic cancer].

The prognosis for ductal cancer of the pancreas is extremely poor. Diagnosis of pancreatic cancer in the earlier stages has become possible by taking note of early symptoms, mild abdominal pain, back pain, anorexia, diabetes and obstructive jaundice. Presently, measurements of amylase in serum and urine, serum elastase-1, serum CA 19-9 and US are usually used for screening patients with the symptoms. Furthermore, for correct diagnosis, intensive study by US, dynamic CT, ERCP, MRI, cytological examination and CEA of pancreatic juice, endoscopic pancreatoscopy and endoscopic ultrasonography are used. The results of surgical treatment for resectable pancreatic cancer are not generally favorable. Extended pancreatic resection (pancreatoduodenectomy, total pancreatectomy or distal pancreatectomy) with en bloc dissection of the lymph nodes has been performed for patients with invasive cancer. However, local recurrence and distant metastasis usually occurred after surgery. It seems difficult to cure pancreatic cancer by surgery alone. To improve the prognosis of resectable pancreatic cancer, multimodality treatment with intraoperative radiation therapy and chemotherapy is performed and a better outcome is achieved.


[Involvement of lymph nodes and neural plexus in carcinoma of the pancreas].

We studied 428 lymph nodes attached to the head of the pancreas (13,14,17) in 18 patients with ductal carcinoma of the pancreatic head. These were classified into the small size of the lymph nodes less than 5mm (group S), the moderate size of the lymph nodes (group M) and the large size of the lymph nodes more than 10 mm (group L). The metastases were seen in 76 nodes, which consisted of 49 with group S, 14 with group M and 13 with group L. The lymph node involvement in group (14) S was found in 7 of 18 patients (38.9%), that in group (14) M was in 4 (22.2%) and that in group (14) L was in 2 (11.1%). In these involved cases, the primary tumors tended to be locate in the portion near the superior mesenteric artery, such as in the uncinate process. Invasion of extrapancreatic neural plexus was noted in 9 of 18 patients (50%). There was no significant correlation between nerve plexus invasion and lymphatic invasion by Spearman's rank correlation. In addition, any close relationship between plexus invasion and primary tumor location could not be indicated. These results suggested that neural invasion in pancreatic carcinoma is independent of lymphatic invasion, and the routes of cancer spread via the neural plexus are different from those via the lymphatic vessels. Those without liver metastases survived longer than those with liver metastases, which were characteristically multiple.


[Extensive radical surgery for carcinomas of the head of the pancreas].

Since 1973, we have applied extensive radical surgery for the head of the pancreas in order to improve not only the resection rate but also the surgical therapeutic results. The main points of our surgical procedure are as follows: (1) complete resection of surrounding connective tissues in retroperitoneum including extrapancreatic neural plexus. (2) extensive lymph node dissection, and (3) combined resection of the portal vein. As a result, our 3-year survival rate has increased to 31.4% and the 5-year survival rate to 27.9% in patients who underwent the macroscopically complete resection. These surgical therapeutic results are not satisfactory, but we have had 10 patients who survived more than 3 years. It is also true, however, that this procedure is extremely invasive and requires careful, long-term nutritional management after surgery. Therefore, the cooperation of not only the patients themselves but also their families is indispensable for the success of the treatment.


[Chemotherapy for advanced pancreatic carcinoma].

In advanced pancreatic cancer, chemotherapy has no curative potential, and the goal is to palliate symptoms or delay their onset so as to improve the quality of life of patients. There is no standard chemotherapeutic regimen with a clear advantage in survival prolongation or response rate, over any other regimen. Moreover, difficulties in determining the chemotherapeutic response have made accurate determination of the response rate virtually impossible for each trial. 5-FU and MMC are two main drugs so far in single-agent chemotherapy, but streptozotocin, doxorubicin, ifosfamide, epirubicin and CDDP are also investigated. FAM and SMF are the representative regimen of combination chemotherapy, but recently FP or biochemical modulation have been under close scruting. For greater improvement of chemotherapy, a new drug or combined modality approach is awaited.


[Radiation therapy of pancreatic cancer].

We have been using external beam radiotherapy (EBRT) and intraoperative radiotherapy (IORT) for both resectable and unresectable pancreatic cancer patients. EBRT (50-60 Gy) was combined with IORT (25-33 Gy) whenever possible, but otherwise EBRT or IORT was given alone. In patients with unresectable tumor but no distant metastasis, the median survival time (MST) was 7.5 months (M) for the EBRT group and 9 M for the EBRT+IORT group. These MST's were significantly longer than the MST of 3 M of patients who had been treated without radiation (historical control). In non-Stage IV patients undergoing non-curative resection, the MST was 12.5 M for the EBRT group, 15.5 M for the EBRT+IORT group, and 7 M for the historical control. In patients undergoing macroscopic curative resection, the MST was 14 M for the EBRT group, 10 M for the EBRT+IORT group, and 10.5 M for the historical control. In Stage IV patients (with distant metastasis), the MST was 4.5 M for the EBRT group, 4 M for the EBRT+IORT group, 2 M for the IORT group, and 2.5 M for the historical control. Thus, radiotherapy appeared useful especially in non-Stage IV patients undergoing non-curative or no resection. A decrease or relief of pain was obtained in 90% of patients with unresectable lesions. Radiotherapy seems to play an important role in the treatment of pancreatic cancer but more aggressive combined treatment seems to be necessary to further improve the dismal prognosis of pancreatic cancer patients.


[Sensitivity test for anti-tumor agents-3. MTT assay and its clinical effect].

MTT assay, a sensitivity test of anti-tumor agents was performed, and its clinical usefulness, was discussed. In 15 surgical specimens, the cell suspensions were prepared aseptically, and divided into three processing; namely, Papanicolaou (Pap) smears to confirm the malignant cells, MTT assay, and cell cultures in chamber slides. MTT assay was evaluated only when tumor cells in the chamber slide were observed 50% or more by Pap staining. Drugs judged to be effective were applied for patients, resulting in 64.2% of predictive accuracy in the sensitivity. Conclusions; 1) MTT assay was developed for sensitivity test of anti-tumor agents, 2) Strict assessment was carried out by the confirmation of cancer cells using chamber slides, 3) On clinical usefulness, predictability for the sensitivity was 64.2%, that for resistance was 100%, and over all predictability was 66.7% 4) MTT assay was useful for the determination of effective and for elimination of ineffective drugs.