High dose (bolus) intravenous methylprednisolone at the time of kidney homotransplantation. A completely randomized double-blind study of bolus methylprednisolone versus dextrose in water, administered at the time of human kidney transplantation, has failed to demonstrate any beneficial effect of the steroid therapy. No differences were observed in the number of complete, irreversible graft rejections, the number of acute rejection episodes, or the number of postoperative steroid boluses administered in the treated or the control groups. Similarly, there were no differences in the mean serum creatinines at 30, 60, 90 days post-transplantation. There was a slight increase in mortality and incidence of complications in the group of patients receiving an intravenous bolus of methylprednisolone at the time of transplantation as compared to controls. The failure to demonstrate any beneficial effect and the slight increased mortality and morbidity associated with the bolus methylprednisolone dosage makes this therapy unjustifiable.


Trachea-innominate artery fistula: successful management of 3 consecutive patients. Trachea-innominate artery fistula is an uncommon but frequently fatal complication of tracheostomy. Three successive patients who developed this complication while receiving ventilatory assistance through a tracheostomy tube were successfully managed, with long-term survival. Bleeding was controlled by direct digital pressure on the innominate artery or by hyperinflation of the balloon cuff of the tracheostomy tube. In 2 patients, replacement of the tracheostomy tube with an orotracheal tube improved direct access to the innominate artery for digital compression. Late follow-up examination of the right carotid circulation revealed complete reversal of flow in the right internal and common carotid arteries in the 2 patients studied.


Calcium-antagonists and islet function X. Effect of suloctidie. Suloctidil (0.5 to 5.0 micrometer) inhibits insulin release evoked by glucose or alpha-ketoisocaproate in pancreatic islets. The drug also inhibits basal and glucose-stimulated 45calcium net uptake by the islets. In an artificial system, suloctidil inhibits A23187-mediated calcium translocation. It is proposed that the inhibitory action of suloctidil upon islet function may be due to interference with B-cell native ionophoretic system(s).


Diet and probucol in lowering cholesterol concentrations. Additive effects on plasma cholesterol concentrations in patients with familial type ii hyperlipoproteinemia. Probucol [4,4-(isopropylidendithio bis)(2,6-di-t-butylphenol)], as as an adjunct to diet, was evaluated for its effect on lowering the plasma cholesterol level in patients with familial hypercholesterolemia (type II). The trial had a double-blind, placebo-controlled, crossover design. About half of the 30 patients responded to a low-cholesterol modified-fat diet with a decrease in the plasma cholesterol level of approximately 13%. When probucol was added to the diet of the responders, their plasma cholesterol level was lowered a further 13%. Patients who did not respond to the diet did show reduced plasma cholesterol concentrations when receiving probucol plus the diet. Analysis of the cholesterol content of the various lipoprotein fractions showed that the low-density lipoproteins accounted for most of the total plasma cholesterol level decrease. There was, as expected, no effect on plasma triglyceride concentrations. Neither the 7-dehydrocholesterol nor the desmosterol level was increased in the plasma of patients treated with probucol for three months. Probucol is useful as an adjunct to diet in lowering plasma cholesterol levels in patients with familial hypercholesterolemia. The drug was well tolerated by all patients.


Cholera-like diarrhea in Canada. Report of a case associated with enterotoxigenic Escherichia coli and a toxin-producing Aeromonas hydrophila. A 67-year-old Indian patient was admitted with an acute cholera-like illness. Toxigenic Escherichia coli producing both heat-stable and heat-labile enterotoxins grew from cultures of feces. In addition, an Aeromonas hydrophila producing a cytotoxic toxin was also isolated from this patient's feces. The unusual severity of this patient's illness may have resulted from coinfection with these two toxigenic organisms, although any role of the toxin produced by a hydrophila is speculative.


[The Corynebacterium pyogenes infection in cattle. 1. Incidence of the pathogen]. Reported are the incidence of Corynebacterium pyogenes together with different pathological changes as well as the existence of latent Corynebacterium pyogenes infections and their widespread occurrence. Corynebacterium pyogenes was established from 609 in 2,130 samples of pathological processes, accounting for 28.6%. The pathogen was cultivated from various processes, including enlarged tail lymph nodes (61.1%), tail phlegmons (56.3%), abscesses (49.1%), epiphysiolyses (45.2%), liver abscesses (31.8%), panaritia at beginning of fattening (20.5%), aborted foetuses (14.9%), foetal membranes in cases of incarcerated placenta (12.0%), and panaritia on end of fattening (3.4%). The same pathogenic microorganism was recorded from nine per cent of apparently intact heifer udders, before pasturing. Corynebacterium pyogenes was cultivated also from nasal mucous membrane (8.4%) and retropharyngeal lymph nodes (37.2%). The highest detection rate was 71.6%, obtained from the tonsils.


[The Corynebacterium pyogenes infection of cattle. 2. Tenacity of Corynebacterium pyogenes]. Some common agents were tested for their effectiveness against Corynebacterium pyogenes. The pathogen proved most susceptable to Wofasteril. All germs were killed within ten minutes by a 0.005% solution. Equally good action was recorded from all the other tested agents as well (lactic acid, Lugol's solution, formalin, cupric sulphate, alcohol, and aethacridine. Other studies were conducted with the view to testing the survival capacity of Corynebacterium pyogenes in different media and storage conditions. The pathogen survived three months in routine media and mastitis secretion at room temperature. Regrowth of 38 in 50 strains took place after nine months of refrigerator storage in slanting blood agar tubes with paraffin plugs. Germs sampled from mastitis secretion and stored in a refrigerator were cultivable even after one year had elapsed. The detectability rate of Corynebacterium pyogenes did not change over months by storage of wound infection material at 12 degrees C below zero. The pathogen remained detectable five days from artificial contamination of cattle skin.


The treatment of depression with L-5-hydroxytryptophan versus imipramine. Results of two open and one double-blind study. In the last few years several open studies supported the hypothesis that L-5-HTP may be an effective antidepressant. Because of the lack of a controlled double-blind trial we started our own investigations to confirm this hypothesis in L-5-HTP. In 1972 we performed two open dose finding trials with L-5-HTP in combination with Benzerazide. These open studies were followed by a double-blind trial comparing L-5-HTP in combination with Benzerazide to Imipramine in 30 patients. Assessments were carried out on day 0, 5, 10, 15 and 20. For data collection we used the Hamilton Rating Scale for Depression, the AMP-system, a Global Rating Scale of Severity of Depression and a Brief Rating Scale for the Behaviour on the ward. In this article we report only a part of the results, mainly on the findings with the AMP-system and the Hamilton Rating Scale for Depression. During our double-blind trial we could not find any significant difference in efficacy of L-5-HTP and Imipramine. The same was found in an open trial. Furthermore the L-5-HTP results showed no difference compared with the results of an Imipramine treatment in 40 patients in earlier double-blind studies. L-5-HTP and Imipramine caused different patterns of side effects. L-5-HTP caused mainly gastrointestinal side effects and Imipramine caused mainly dryness of the mouth and tremor. The gastrointestinal side effects caused by L-5-HTP seemed to be dose dependent.


Management of early postoperative complications of arterial repairs. Of 1,703 patients undergoing arterial procedures during a three-year period, 81 (4.7%) required reoperation within 72 hours because of early complications. Thrombosis (58 patients) and hemorrhage (19 patients) were the most frequent complications encountered. Reoperation was successful in salvaging a successful outcome in the majority of patients after both hemorrhagic and thrombotic complications. The results seem to justify a continued aggressive approach to the management of early complications following vascular reconstructive procedures.


Vascular access in a University transplant and dialysis program. Results, costs, and manpower implications. Vascular access has become the most common operation performed at North Carolina Memorial Hospital, Chapel Hill. Three hundred vascular access procedures performed between 1971 and 1975 were reviewed as to results, costs, and manpower commitment. Subcutaneous radial arterial venous fistula was the procedure of choice, with a 67% two-year patency and the lowest incidence of complications. An average of 1.7 operations per patient was necessary to maintain access. Patients used an average of 19 hospital days per year of dialysis for vascular access and an average of 35 hospital days per year of dialysis for all medical problems. Cost of hospitalization averaged $6,818 per patient per year of dialysis, and for vascular access alone averaged $3,452 per patient per year of dialysis. To create and maintain vascular access, 1,000 hours of operating room time were required, at an expense of $200,000. Vascular access in support of patients undergoing chronic hemodialysis requires a massive commitment of dollars, time, and personnel.


Innominate artery endarterectomy. A 16-year experience. Transsternal endarterectomy was performed in 34 of 37 patients with symptomatic atherosclerosis of the innominate artery, with a mortality of 6%. Thirty of the 32 survivors are asymptomatic at an average of 6.1 years postoperatively. Six of these patients who had ulcerated, nonstenotic atherosclerotic lesions have had complete cessation of preoperative transient ischemic attacks. Normal arterial patency has been maintained for follow-up periods varying from seven months to 16 years.


The rapid concentration and purification of influenza virus from allantoic fluid. Influenza virus was quantitatively recovered from infectious allantoic fluid by precipitation with 8 percent (wt/vol) polyethylene glycol 6000 (PEG-6000). Virus concentrated by PEG-6000 treatment was rapidly purified by gel permeation chromatography through controlled pore glass beads. The purity of virus preparations achieved by this method, when judged by three independent criteria, was comparable to virus preparations purified by conventional density gradient procedures.


[In vivo and in vitro studies of a cytoplasmic polyhedrosis virus isolated from Euxoa scandens, Riley (Noctuidae, Agrotinae)(author's transl)]. A virus isolated from the larvaes of Euxoa scandens (Noctuidae, Agrotinae) was studied by histological and histochemical techniques, and by electron microscopic observation of virus suspensions and ultrathin sections of infected tissues. Our studies demonstrated that the virus in icosahedral in shape, measures 70 nm and belongs to the cytoplasmic polyhedrosis virus group. Only the midgut cells of the larvae were found to be infected and the virus particles were localized in inclusion bodies most of which had a paraspherical, polyhedral shape. It was possible to infect Lymantria dispar L. cells in vitro with free virus or with extracts obtained from the diseased larvae. The virogenic stroma and the first small inclusion bodies in this stroma were detected in the cytoplasm at 18 and 36 hours post infection, respectively. These polyhedra had a cubical shape, reached their maximum size after 48 hours and were located in the cytoplasm of over 90 percent of the cells.


California encephalitis virus transmission by arctic and domestic mosquitoes. A zero passage arctic mosquito isolate of California encephalitis (CE) virus (showshoe hare subtype) was transmitted by wild-caught Aedes communis mosquitoes after 13 days incubation at 13 degrees and 23 degrees C, AFTER 20 days incubation at 13 degrees C, when mosquitoes imbibed 1 mouse LD50 in a blood meal. Transmission occurred after 20 days incubation at 13 degrees and 23 degrees C when mosquitoes were injected intrathoracially with 1 or 0.1 mouse LD50. Virus was also transmitted by A. aegypti 13 days after infection with 100 mouse LD50 by feeding or intrathoracic injection, and incubation at 13 degrees C. Virus antigen was detected in salivary glands of 42 percent virus-positive A communis mosquitoes by direct immunofluorescence, and in 50 percent or less of A aegypti mosquitoes by immunoperoxidase and immunofluorescence, with somewhat greater regularity by the indirect than the direct technique.


[Histopathology of lymphogranulomatosis]. The current histological classification of lymphogranulomatosis is presented. The possibility of the occurrence of the cellular phase of nodular sclerosis is discussed. In contrast to the current opinion on the origin of Berezovsky-Sternberg giant cells from reticular cells, the evidence in favour of their lymphocytic genesis is presented. Some problems of therapeutic pathomorphosis and thanatogenesis of patients with lymphogranulomatosis when current methods of treatment (radiation and polychemotherapy) are used are considered.


Clinical comparison of 10 percent and 25 percent intravenous sodium fluorescein solutions. Sodium fluorescein solutions, 3 ml of 25% solution and 5 ml of 10% solution, were compared with a double-blind crossover method in a group of 41 normal volunteers and in a group of 42 patients who had diverse ophthalmic disorders. Following injection of the solutions into the antecubital vein, visualization, serial fluorescein angiograms, and five-minute phase angiograms were studied and compared. The untoward reactions reported in both studies were of types usually associated with sodium fluorescein, the most common of which was a mild, transient nausea. On the basis of our results, there is no significant difference in the incidence and severity of adverse reactions between the 10% and 25% solutions. In the volunteer study, the 25% solution was significantly superior in visualization and paired comparison (P less than .001) in the patient study, the 25% solution was significantly superior in angiogram quality (P less than .01), five-minute phase angiogram (P less than .05), and paired comparison (P less than .005). The overall superiority of the 25% concentration in a 3-ml volume was demonstrated both subjectively and objectively in the volunteer study and in the patient study.


Karl Wittmaack: his life, temporal bone collection, and publications. On the 100th anniversary of his birth. Karl Wittmaack (1876-1972) was professor for Oto-Rhino-Laryngology at the universities of Jena (1908-1925) and Hamburg (1926-1946). He contributed a lot of pioneer work to experimental pathology of the ear. He left a unique collection of serial sections of temporal bones from animals (55,000 slides) and man (102, 000 slides). This paper gives some data on Wittmaack's life, his temporal bone collection and the unpublished list of his publications.


[To Wittmaack's theory of "hearing without the organ of Corti" (author's transl)]. 1911 Wittmaack had shown by experiments in cats that the organ of Corti is independent from the cochlear nerve but dependent from a normal internal auditory artery. Similar findings he could observe in his temporal bone collection in cases of acoustic nerve tumors. On the other hand many human cases with the compression phenomenon of the organ of Corti had intact cochlear nerve fibers and neurons, and nearly normal hearing. Thus Wittmaack concluded that some parameters of hearing are transmitted by the nerve endings in the organ of Corti without the haircells. This hypothesis is discussed by means of examples of Wittmaack's temporal bone collection in the light of our present knowledge.


Serological responses in experimental bovine tuberculosis. Five two-year-old heifers were each inoculated intravenously with 0.02 mg M. bovis strain AN5. Clinical, haematological and microbiological observations were made during the course of the experiment and antibody levels were measured before and after infection by means of the indirect immunofluorescent antibody (IFA) and bentonite flocculation tests. All cattle developed M. bovis infection varying in severity from peracute tuberculous pneumonia resulting in death within 33 days to chronic progressive generalised tuberculosis. Only cattle developing peracute or acute forms of tuberculosis showed marked haematological changes characterised by leucopenia with lymphopenia. Bacteraemia was detected in the two cattle with peracute tuberculosis 22 days after infection. Anti-mycobacterial antibody was detected after infection in all cattle but fluctuated markedly during the course of the disease. Of a total of 61 serum samples examined from all cattle after inoculation with M. bovis, only 38 were positive to the IFA test and 30 to the bentonite flocculation test. Only 18 were positive to both tests at any one time. IgM was the predominant type of anti-mycobacterial antibody detected by the IFA test and this was found to cross-react with M. avium in almost every sample.


Depression: a multivariate study of Sir Aubrey Lewis's data on melancholia. Principal component analyses were carried out on 51 items abstracted from Lewis's 1934 and 1936 papers. The first component was bipolar, differentiating between endogenous items and those that were mainly neurotic. The distributions of the first component scores by cluster indicated that there were two separate clusters of patients, one mainly endogenous, the other neurotic. It was concluded that Lewis's data indicate that there are at least two qualitatively different depressive illnesses. Further component analyses were carried out using the 25 endogenous items. The first component was a general one of endogenous depression. The distributions of its scores were bimodal, indicating that there were two groups of patients, those who suffered from endogenous depression and those who did not. These analyses indicated that endogenous depression is a categorical illness.


Effect of renal transplantation on uremic deafness: a long-term study. In order to investigate the influence of a functioning transplant on uremic hearing loss, audiometrical controls were performed on 13 patients before and after renal transplantation. During renal dialysis treatment there was a marked hearing loss for the higher frequencies between 2 000 and 8 000 Hz. Hearing capacity improved to normal after transplantation, the best audiometric results being obtained 21.4 (8-42) months after surgery. There was a significant improvement in hearing especially for middle- and high-tone frequencies. It is assumed that uremic toxins, possibly responsible for sensorineural hearing loss in patients with chronic renal failure may be sufficiently removed by a functioning transplant.


Joint Committee on Aviation Pathology: IX. Laboratory examination of unidentified suspected tissue fragments found at aircraft sites. The identification of victims of an aircraft accident may be very difficult because of the degree of fragmentation associated with the accident. Periodically, the Divisions of Aerospace Pathology and Toxicology have been asked to identify tissue, bone, or bloodstains of undetermined origin. Usually this request has been precipitated by situations in which a) it is questionable whether an aircraft has sustained a bird strike, b) unidentified pieces of tissue are found floating at sea, or c) fragments of bone, tissue, or blood-stained flight apparel are found near a crash site. Preliminary studies have shown that gross examination and the methods and procedures used in forensic serology may also be applied in aircraft investigation with very good results. These methods are used as an aid to confirm the identity of the victims involved.


Spontaneous pituitary adenomas in aging rats. A light microscopic, immunocytological and fine structural study. The structural features of 26 spontaneous pituitary tumors in aging female Long-Evans rats have been investigated by different morphologic techniques including immunoperoxidase staining and electron microscopy. By light microscopy, the tumors corresponded to chromophobic-sparsely granulated acidophilic adenomas, containing numerous pigment granules and showing congestion as well as focal hemorrhages. Positive cytoplasmic staining was obtained with Herlant's erythrosin as well as with Brookes' carmoisine methods, used to detect secretory granules of prolactin cells. Immunoperoxidase technique revealed the presence of immunoreactive prolactin in the cytoplasm of many adenoma cells. Growth hormone and TSH immuno-stainings were negative. By electron microscopy, the tumors were found to consist of prolactin cells exhibiting marked variability in subcellular morphology and differing considerably from non-tumorous resting prolactin cells. A decrease in size and number of secretory granules, proliferation of rough-surfaced endoplasmic reticulum, formation of "Nebenkerne", accumulation of free ribosomes, prominence of Golgi complex and the presence of misplaced exocytosis were characteristic features of the adenoma cells and were interpreted as indicating enhanced secretory activity. Crinophagy and transformation of secretory granules into pigment deposits were striking findings in many adenomas. Since all the adenomas seemed to derive from prolactin cells and belong to the same tumor class, it is assumed that prolactin cells in female Long-Evans rats are more susceptible to oncogenic stimuli than other hypophysial cell types.


Mutants of yeast specifically resistant to petite induction by fluorinated pyrimidines. Induction of the cytoplasmic petite mutation in yeast by 5-fluorouracil (5FU) and 5-fluorocytosine (5FC) is known to depend on the incorporation of 5FU into some species of RNA; 5FC is active only following deamination to 5FU. Several mutants ahve now been isolated which are resistant to petite mutagenesis by 5FU but remain sensitive to growth inhibition by this analogue. They fall into two classes: those in class I are also resistant to mutagenesis by 5FC, while class II mutants retain partial sensitivity to the latter agent. The growth of both classes is sensitive to 5FC. The behavior of class II mutants requires that exogenous 5FU is specifically excluded from the site of synthesis of the target RNA involved in petite mutagenesis, while 5FC has access to it. The most likely explanation is that the RNA concerned is synthesized in the mitochondria, and that the mitochondrial membranes of class II mutants are impermeable to 5FU but not 5FC. This is supported by the finding that the membrane-active agent dimethylsulfoxide restored 5FU sensitivity to this class of mutants. No such effect was observed with class I mutants, and these are thought to have altered mitochondrial RNA-synthesizing systems which are unable to recognize fluorinated nucleotides.


Kinetics of nitrogenase of Klebsiella pneumoniae. Heterotropic interactions between magnesium-adenosine 5'-diphosphate and magnesium-adenosine 5'-triphosphate. The effects of MgADP and MgATP on the kinetics of a pre-steady-state electron-transfer reaction and on the steady-state kinetics of H2 evulution for nitrogenase proteins of K. pneumoniae were studied. MgADP was a competitive inhibitor of MgATP in the MgATP-induced electron transfer from the Fe-protein to the Mo-Fe-protein. A dissociation constant K'i = 20 micron was determined for MgADP. The release of MgADP or a coupled conformation change in the Fe-protein of K.pneumoniae occurred with a rate comparable with that of electron transfer, k approximately 2 X 10(2)S-1. Neither homotropic nor heterotropic interactions involving MgATP and MgADP were observed for this reaction. Steady-state kinetic data for H2 evolution exhibited heterotropic effects between MgADP and MgATP. The data have been fitted to symmetry and sequential-type models involving conformation changes in two identical subunits. The data suggest that the enzyme can bind up to molecules of either MgATP or MgADP, but is unable to bind both nucleotides simultaneously. The control of H2 evolution by the MgATP/MgADP ratio is not at the level of electron transfer between the Fe- and Mo-Fe-proteins.


The aminoacylation of transfer ribonucleic acid. Recognition of methionine by Escherichia coli methionyl-transfer ribonucleic acid synthetase. The mechanism of the recognition of methionine by Escherichia coli methionyl-tRNA synthetase was examined by a kinetic study of the recognition of methionine analogues in the ATP-PPi exchange reaction and the tRNA-aminoacylation reaction. The results show that the recognition mechanism consists of three parts: (1) the recognition of the size, shape and chemical nature of the amino acid side chain at the methionine-binding stage of the reaction; (2) the recognition of the length of the side chain at the stage of aminoacyl-adenylate complex-formation; (3) the recognition of the sulphur atom in the side chain at the stage of methionyl-tRNA formation. It is proposed that the sulphur atom interacts with the enzyme to induce a conformational change. A model of the active site incorporating the mechanism of methionine recognition is presented.


The apparent molecular weights of human intestinal aminopeptidase, enterokinase and maltase in native duodenal fluid. The apparent molecular weights of human intestinal aminopeptidase, enterokinase and maltase in native duodenal fluid were estimated by gel chromatography on Sephadex G-200 under different conditions of operational buffer and temperature. No evidence for environmentally induced changes in molecular form was found.


[Possible combinations of antidotal therapy in rats following intoxication with phosphoric acid esters (author's transl)]. In order to improve or supplement the currently used therapy of poisoning with phosphoric acid esters, a protein free extract from calf blood containing low-molecular subtances (Actihaemyl, Solcseryl) has been tested in female Wistar rats. After poisoning with paraoxon, DFP and soman, a combination of Solcoseryl, Toxogonin and atropine sulfate prolonged the time until exitus, improved the overall rate of survival and considerably shortened the phase of regeneration of the experimental animals even when they had been intoxicated with high doses of poison.


[The bronchodilatory effect of fenoterol-HBr in comparison to the new beta2-bronchodilator (NAB 365, clenbuterol-HCl) (author's transl)]. The effect of 4-amino-alpha-[(tert.-butylamino)methyl]-3,5-dichlorobenzyl alcohol hydrochloride (clenbuterol-HCl NAB 365, Spiropent) in comparison to fenoterol HBr was tested in a doubleblind trial in 30 patients with asthma bronchiale. 3 times daily for 7 days 15 patients inhaled 24 microgram NAB 365 or 5 mg fenoterol HBr respectively. The bronchospasmolytical effect proved optimal as one day after inhalation both test groups showed a significant decrease of resistance in the respiratory system. A quantitative difference of efficacy between the tested bronchodilators did not materialize.


Treatment of rheumatoid arthritis with levamisole. A controlled trial. Levamisole, an anthelminthic agent with immunostimulatory properties, was used in a double-blind, controlled therapeutic trial in rheumatoid arthritis. Patients received either levamisole 100 mg 4 days a week, or placebo, for a period of 4 months. Significant improvement in the treated group, as compared with the control group, was found in the number of tender and swollen joints, grip strength, range of joint motion, sedimentation rate, and C-reactive protein. On double-blind global evaluation by the examining physicians, 9 of 14 patients on levamisole and none of 13 on placebo were considered to have improved. Adverse effects did not differ in frequency between the two groups except for mild alteration in taste, which was more common with levamisole.


[Experience with a locally applicable antirheumatic (author's transl)]. Clinical trials with 2-(2-hydroxyethoxy)-ethyl-N-(a,a,a-trifluoro-m-tolyl)-anthranilate (etofenamate, active principle of Rheumon Gel) were carried out on a total of 69 patients suffering from extra-articular rheumatic complaints and painful spinal syndromes as well as from post-operative and post-accident complaints. Criteria for assessment included spontaneous pain, pressure pain and pain on movement and also limitation in joint mobility. The new gel formulation proved to have a good analgesic efficacy both in a double blind trial against placebo gel and the open study. Those patients treated with Rheumon Gel showed improvement in the symptoms spontaneous pain and pain on movement, in a large number of which patients showing improvement, in a large number of which patients showing improvement the spontaneous pain was completely eliminated. The differences in therapeutic effect compared to the placebo group as well as those of the final clinical assessment were statistically significant. Particularly good therapeutic results were observed in extra-articular rheumatic complaints and in activated arthroses. The skin tolerance of Rheumon Gel was found to be excellent. The gel form permits good and rapid penetration through the skin. The nursing staff also willingly administered the product because of its pleasant protective properties for skin and clothing.


Septic arthritis of the glenohumeral joint. Unique clinical and radiographic features and a favorable outcome. Seven patients (eight shoulders) with sepsis of the glenohumeral joint were studied clinically and radiographically. Despite the advanced age of the patients, the presence of gram-negative organisms, and multiple risk factors in each patient (including serious chronic underlying diseases), needle drainage and parenteral antibiotics were all that were required for successful management, provided early diagnosis with prompt institution of antibiotics and drainage occurred. Contrast arthrography safely guided therapy and revealed rotator cuff tears in four of six shoulders as well as frequent extra-articular extensions of the disease. A nonleukemic patient with Aeromonas hydrophilia sepsis and arthritis is reported who survived with eradication of infection and preservation of joint function. A poor prognosis for shoulder sepsis is not substantiated.


The study and control of environmental radioactivity and its relevance to the control of other environmental contaminants. The history of radioactivity as an environmental contaminant is briefly traced. The basic principles concerning radiological protection and their application to the natural environment are reviewed. The relevance of these aspects of radiological protection philosophy and methodology to the control of other environmental contaminants is examined, especially the development and application of basic standards to waste disposal situations. It is concluded that many of the control procedures developed for radioactivity could be applied with advantage to other potential pollutants.


[Experience with stereotaxic brain surgery for spasmodic torticollis]. For diagnostic and therapeutic purposes, a differentiation of torticollis spasmodicus into horizontal, rotatory, and horizontal-rotatory forms is advisable. They are supplemented by an additional retrocollis component, by further signs of torsion dystonia, and by a pure form of retrocollis. The 24 patients treated by the authors stereotactically are classified accordingly. The stereotactic exclusion of target points in the thalamus (ventro-oral nuclei, mainly V.o.i., H1, nucleus interstitialis Cajal) brought about a removal in 20.8 per cent, considerable improvement in another 20.8 per cent, a satisfactory improvement in 16.8 per cent, and a positive effect on the wryneck symptoms in 25 per cent. In 16.6 per cent of the cases no change could be achieved. Side-effects were not observed. The recommended therapeutic order ranges from peripheral interventions (injections, separating of the muscle branch of the N. accessorius) to the stereotactic operations and finally cervical rhizotomy (in rare cases).


[Utilization of magneto-biological effects in neurosurgery]. After referring to the application of magnetoes used until now for fixation of ferromagnetic substancies in aneurysms, the new results obtained with externally exployed magnetic fields are discussed. Target site is calculated according to stereotactic principles. In the magnetic field the circulating blood is influenced in such a manner, that in the anode region clotting will occure, wherease in the region of cathode the clotting will be inhibited. After developing the appropiate equipment, these conditions were studied  on the basis of experimentally produced aneurysms in thyroid arteries of animals as well as in 30 ptients. It is assumed, that magnetic fields increase the immunoresistance of the organism and also exert a direct influence on the growth of tumourcells.


A preliminary study of intravenous methanol extraction residue of BCG in treatment of advanced cancer. Twenty-four patients with advanced cancer not reacting to conventional therapy were treated with 97 courses of i.v. MER (methanol extraction residue of BCG). MER was administered by i.v. infusion over a 4-h period, twice a week, in dosages varying from 0.05 mg to 1.25 mg. The skin reactivity to 5 recall antigens was evaluated in the patients. All patients except 4 were anergic. Twelve patients had no side-effects. Anergic patients had less side-effects than ergic patients. The side-effects recorded in the others were fever, chills, vomiting and tachycardia. The reaction subsided within 24 h after treatment and was tolerable for most patients. In 2 patients an objective improvement was observed. No changes in cutaneous reactivity, renal and hepatic functions were found. A significant increase in peripheral leucocyte count was noted in two patients and slight a increase in the remainder.


Pitfalls in the use of the lung colony assay to assess T-cell function in irradiated mice. Mice depleted of T lymphocytes by thymectomy, whole-body irradiation and bone-marrow reconstitution showed a marked increase in susceptibility to the development of lung colonies after i.v. injection of cells of an immunogenic fibrosarcoma. However, a similar increase was observed in unthymectomized, irradiated and reconstituted mice that had recovered their T-cell function, as evidenced by rejection of allogeneic skin grafts. In both thymectomized and unthymectomized mice subjected to whole-body irradiation, the lung-colony-forming efficiency was high 1 day after irradiation, declined to a minimum at 7 days, and thereafter increased again, unless the animals were held in a pathogen-free environment. Reconstitution of T-cell-depleted mice with thymocytes and/or a thymic lobe graft tended to increase further, rather than reduce, lung-colony-forming efficiency. Induction of profound lymphopenia, by irradiation of the whole body except the thorax, did not significantly increase lung colony yields. These studies show that the lung colony assay is not a reliable method of assessing T-cell function in irradiated mice.


Chronic leg ulcers treated by the pinch graft method. Forty-nine patients with chronic leg ulcers were treated by pinch grafting. The initial success of this procedure was high for both gravitational and arterio-sclerotic ulcers. Over half the grafted gravitational ulcers and 70% of grafted arteriosclerotic ulcers were intact after 2 years. Some grafts remained stable for 6 years. Arteritic ulcers did not respond as well; none of the grafted ulcers survived more than 6 months. Pinch grafting is still a simple, cheap and effective therapy offering prolonged graft stability as well as quicker healing to those patients who are not fit for more extensive surgery.


Evolution of the lesion of discoid lupus erythematosus: a comparison with lichen planus. The tissue processes leading to the development of the epidermal changes in the lesion of discoid lupus erythematosus have been studied. Typical lesions in fifteen patients have been examined using cell kinetic and immunofluorescence techniques. The results suggest that a very active repair mechanism is operative within the epidermis with heightened epidermopoiesis and epidermal cell migration. The findings have been contrasted with those of previous similar studies of lichen planus. It is suggested that a major difference between the gross and microscopic appearance in the two diseases may be partially on the basis of differing patterns of immunoprotein deposition.


The endocrine pancreas in small-for-dates infants. In a small series of pregnancies complicated by severe fetal growth retardation we found reduction of fetal endocrine pancreatic tissues and of the insulin producing beta cells.


Effect of clomiphene on prolactin secretion and lactation in puerperal women. Clomiphene citrate treatment neither inhibited milk secretion nor had a suppresive effect on serum prolactin levels in 10 puerperal women.


Treatment of the premenstrual syndrome.

Treatment of the premenstrual syndrome. A placebo-controlled, randomized, double-blind, parallel group study in hospital and general practice has shown that a combination of belladonna alkaloids, ergotamine tartrate, and phenobarbitone (Bellergal) was effective in treating troublesome symptoms of the premenstrual syndrome of which fatigue, tender breasts, nervousness, irritability, lethargy and listlessness were improved to a statistically significant degree. The drug was given three times daily and caused no side effects.


Peripheral retinal ablation in the treatment of proliferative diabetic retinopathy: a three-year interim report of a randomised, controlled study using the argon laser. A randomised controlled trial is reported of 94 patients with a symmetrical proliferative diabetic retinopathy involving the optic disc, who were treated by a peripheral retinal ablation technique using the argon laser. A highly significant difference in mean cumulative deterioration of visual acuity and blindness was shown in all but the late stages of the disease process between treated and untreated eyes. The untreated eyes exhibited far worse results. The earlier photocoagulation is initiated in the course of the proliferative process in this disease to control or preferably eliminate optic disc neovascularisation, the better the visual prognosis.


A microbiological study of neonatal conjunctivae and conjunctivitis. To investigate the importance of chlamydiae, ureaplasmas, Mycoplasma hominis, and anaerobic bacteria in the pathogenesis of neonatal conjunctivitis in the Harrow population conjunctival specimens from 104 infants with conjunctivitis and 104 similar healthy neonates were examined. The incidence of neonatal conjunctivitis was 8-2%, and no case of neomycin-resistant disease occurred during the study. Staphylococcus aureus, viridans Streptococci, and Escherichia coli were the only micro-organisms isolated significantly more frequently from affected than from control eyes, which suggests that these bacteria may be a cause of the conjunctivitis. All cultures for chlamydiae, M. hominis, Neisseria gonorrhoeae, and anaerobic bacteria were negative. The mother's race, social status, illness, and obstetric events were found to have no effect on the incidence, time of onset of conjunctivitis, or micro-organisms isolated. The clinical characteristics of conjunctivitis were also not related to the micro-organisms isolated. No potential pathogens were isolated from 63-5% of the eyes showing conjunctivitis. The results suggest that some of these cases may be caused by chemical irritation, and the possibility of an infectious aetiology is also discussed.


A nuclear magnetic resonance study of secondary and tertiary structure in yeast tRNAPhe. We present experimental evidence which confirms recently proposed ring current prediction methods for assigning hydrogen-bond proton nuclear magnetic resonance (NMR) spectra from tRNA (Robillard, G. T., Tarr, C. E., Vosman, F., & Berendsen, H. J. C. (1976) Nature (London) 262, 363-369; Robillard, G. T., Tarr, C. E., Vosman, F., & Sussman, J. L. (1977) Biophys. Chem. 6, 291-298). The evidence is a series of temperature-dependent studies on yeast tRNAPhe monitoring both the high- and low-field NMR spectral regions, which are correlated with independent optical and temperature-jump (temp-jump) studies performed under identical ionic strength conditions. Using assignments derived from the new prediction methods, the melting patterns of the hydrogen-bonded resonances agree with those expected on the basis of optical, temp-jump, and NMR studies on the high-field spectral region. The implication of these results is that previous assignment procedures are at least partially incorrect and, therefore, studies based on those procedures must be reexamined.


Ca2+ transport mediated by a synthetic neutral Ca2+ -ionophore in biological membranes. The effect of a synthetic neutral ligand on the Ca2+ permeability of several biological membranes has been investigated. The ligand had been previously shown to possess Ca2+ -ionophoric activities in artificial phospholipid membranes. The neutral ionophore is able to transport Ca2+ across the membranes of erythrocytes and sarcoplasmic reticulum, when lipophilic anions such as tetraphenylborate and carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) are present, presumably to facilitate the diffusion of the charged Ca2+ -ionophore complex across the hydrophobic core of the membrane. In mitochondria, the neutral ionophore promotes the active transport of Ca2+ in response to the negative membrane potential generated by respiration, in the presence of the specific inhibitor of the natural carrier ruthenium red.


Proline transport activity in Escherichia coli membrane vesicles of different buoyant densities. Cytoplasmic membrane vesicles prepared by lysis of Escherichia coli W 3110 spheroplasts in a French press at 0 degrees C are heterogeneous with respect to density due to membrane protein aggregation as a result of lateral phase separation of membrane phospholipids and to the presence of more or less outer membrane. These different vesicle classes can be separated on isopycnic density gradients. Assays for various membrane-associated functions show that the membranes differ not only with respect to density and structure but also with respect to function. The proline transport system (as detected by uptake experiments with the artificial electron donor ascorbate-phenazine methosulfate) shows maximal activities in membrane fractions that have considerably higher densities than the normal cytoplasmic membrane. This is always the case, whether vesicles are isolated from membranes that exhibit a temperature-induced protein aggregation or not. A correlation between high proline transport activity and the presence of vesicles with double membranes (consisting of outer and inner membrane) has been established. The possibility that the outer membrane protects the transport system in the cytoplasmic membrane during the isolation of vesicles is discussed.


Transport of [14C]Gly-Pro in a proline peptidase mutant of Salmonella typhimurium. The transport of [14C]Gly-Pro was examined using a mutant of Salmonella typhimurium (strain TN87) deficient in an X-Pro dipeptidase and an X-Pro-Y iminopeptidase. The dipeptide was taken up by one saturable transport system having a Km of 5.3-10(-7)M and a V of 1.4 nmol/mg dry wt cell per min. The uptake of Gly-Pro was not inhibited by amino acids or tripeptides and the transport system exhibited a rather broad side chain specificity for dipeptides. Dipeptides containing hydrophobic residues were the most potent inhibitors of this dipeptide transport system exhibiting Ki values between 10(-8) and 10(-7) M. In contrast, dipeptides containing glycine residues were particularly weak inhibitors. Finally, Gly-Pro was found to be in the intact form inside the cell and was concentrated more than 1000-fold.


Structural heterogeneity of the cytoplasmic and outer membranes of Escherichia coli. The cytoplasmic and outer membranes of gram-negative bacteria can be isolated from spheroplasts, and separated on sucrose density gradients. Lysis of spheroplasts causes extensive membrane fragmentation and since the characteristics of the fragments obtained by different lysis procedures need not be identical, the influence of the disruption method on membrane composition has been examined. Spheroplasts of Escherichia coli J5 were lysed by osmotic shock, which did not significantly separate the cytoplasmic and outer membranes, but resulted in mixed membrane vesicles. Lysis in the French press and by sonication caused extensive membrane fragmentation and separation. Sonication, however, also caused some fusion between fragments of the outer and the cytoplasmic membranes; this intermembrane fusion increased with sonication time. When the cytoplasmic and outer membranes were well separated and intermembrane fusion was minimal or absent, the cytoplasmic and outer membrane fragments were heterogeneous with respect to density and ovarll phospholipid, protein and lipopolysaccharide composition. In addition, cytoplasmic, but not outer, membrane fragments were also heterogeneous with respect to protein composition. It is concluded, therefore, that membrane fragments obtained from the cytoplasmic and outer membranes are heterogeneous independently of the lysis procedures used to obtain these fragments. Possible reasons for this heterogeneity are discussed.


Rearrangement of intramembranous particles and fusion promoted in chicken erythrocytes by intracellular Ca2+. Ca2+ was introduced into fresh and ATP-depleted chicken erythrocytes through the aid of the inophore A23187. Intracellular Ca2+ (10-40 mM) induced fusion in ATP-depleted cells after 30-60 min incubation at 37 degrees C, but not in fresh cells. Fresh cells underwent a higher degree of haemolysis than ATP-depleted cells after accumulation of Ca2+. Uptake of Ca2+ was the same in these two systems. Intracellular Ca2+ induced rearrangement of intramembranous particles, as revealed by freeze-etching studies. The intramembranous particles in the protoplasmic face of fractured membranes obtained from fresh cells incubated with 1 mM of Ca2+ were more scattered and their density was lower than in control cells. Incubation with higher concentrations of Ca2+ (10-40 mM) induced transient changes in the intramembranous particles' density with the appearance of protrusions and depressions on the protoplasmic and exoplasmic faces of the fractured membranes, respectively. These effects were reversible upon removal of Ca2+ by washing the cells with ethyleneglycol bis(alpha-aminoethylether)-N,N'-tetraacetic acid; rearrangement of intramembranous particles was less evident after accumulation of Ca2+ in ATP-depleted cells, whose fractured membranes did not contain any protrusions or depressions. Transferring Ca2+-loaded cells to the cold caused the formation of large smooth areas devoid of intramembranous particles in the protoplasmic face of the fractured membranes. Cells containing Ca2+ appeared spherical, and removal of Ca2+ restored the normal oval shape of chicken erythrocytes.


Chemical aminoacylation of transfer ribonucleic acid. The reaction of Escherichia coli tRNA with ethyl N-benzyloxycarbonylorthoglycinate. The alpha-carbethoxypentadecyltrimethylammonium (Septonex) salt of tRNA (Ib) was condensed with ethyl N-benzyloxycarbonylorthoglycinate (II) in dimethylformamide in vacuo and in the presence of H3PO4 as catalyst. Pancreatic RNAase degradation and phenylalanine acceptor activity showed a 55--60% conversion to the 2',3'-cyclic orthoglycinate derivative of tRNA (IIIb). The orthoester grouping of IIIb was quantitatively hydrolyzed in 80% formic acid at 0 degrees C for 15 min to give 2'(3')-O-(N-benzyloxycarbonyl)glycyl tRNA (IVb). The latter was stripped at pH 8.8 to give tRNA whose behavior on DEAE cellulose column and gel electrophoresis was similar to that of starting tRNA. The phenylalanine acceptor activity amounted to almost 80% of the starting tRNA.


Physiological studies on a temperature-sensitive Escherichia coli mutant with an altered RNA polymerase beta'-subunit. Some in vivo properties of an Escherichia coli temperature-sensitive mutant (JE10092) with an altered RNA polymerase beta'-subunit are described. RNA synthesis, unlike many peviously isolated temperature-sensitive mutants, stops immediately after the shift to the nonpermissive temperature (43 degrees C). DNA synthesis, protein synthesis and nucleoside triphosphate formation continue after the shift. RNA synthesis is recovered immediately upon transfer to the permissive temperature (30 degrees C). The function of the beta'-subunit in genetic transcription is discussed.


Synthesis of inducible enzymes in irradiated yeast cells. Ultraviolet effects on transcription and the influence of recovery processes. The induced synthesis of arginase was measured in several yeast strains after ultraviolet light irradiation. There was an exponential dose-related reduction which was the same in all cell lines tested. This sensitivity is compatible with the size of the arginase structural gene if it is assumed that one pyrimidine dimer suffices for blocking transcription. The ultraviolet-induced synthesis inhibition is susceptible to photoreactivation and liquid holding recovery. The latter process is absent in a rad2 mutant and reduced in a rad9 mutant.


The mode of condensation of aspartic acid and dihydroxyacetone phosphate in quinolinate synthesis in Escherichia coli. Dihydroxy [3-14C]acetone phosphate was prepared enzymatically from [1-14C]glucose and use as a substrate in a partially purified quinolinate synthetase system prepared from Escherichia coli mutants. Carbon-by-carbon degradation of the resulting [14C]quinolinate showed that 96% of the 14C was located in carbon-4, indicating that carbon-3 of dihydroxyacetone phosphate condenses with carbon-3 of aspartate in quinolinate synthesis in E. coli.


[Sequential Edman degredation].

[Sequential Edman degredation]. Since Edman's first publication in 1950, the stepwise degradation of proteins and peptides is universally performed by protein chemists. We extensively reviewed the different manual degradations. We take two examples of manual degradation: a semi-micromethod and a micromethod in order to illustrate the evolution of manual degradation. The "dansyl-Edman" procedure proposed by Hartley in 1963 completes the manual N-terminal determination of peptides. We describe the different procedures of identification of PTH-amino acids: paper chromatography, thin layer chromatography, gas chromatography and liquid chromatography under high pressure and various modified Edman degradation procedures. Possibilities and limits of the liquid phase Sequenator of Edman reported in 1967 and the solid phase Sequencer of Laursen reported in 1971 are also considered in detail.


[Phospholipid composition of E. coli cells and membranes under repression and derepression of alkaline phosphatase biosynthesis]. Lipid composition of E. coli membranes and cells in conditions of repression, derepression and constitutive synthesis of alkaline phosphatase is studied. The identity of qualitative composition of phospholipids and neutral lipids in these conditions is demonstrated. Derepressed and constitutive enzyme syntheses are correlating, a certain increase of phosphatidylglycerol in the total phospholipid pool being more pronounced in cells, than in membranes. The enzyme synthesis correlates also with the increase of 14C-label incorporation into lipids.


Decrease of lysosomal enzymes in macrophages incubated with supernatants of mixed culture of allograft donor and recipient lymphocytes. Incubation of mouse peritoneal macrophages (thioglycollate-induced) for 72 hours with the supernatant of a mixed lymphocyte culture (MLC) between skin allograft donor and recipient results in a decrease of macrophage acid phosphatase (EC 3.1.3.2.) and beta glucuronidase (EC 3.2.1.31). The alteration of these lysosomal enzymes is not explained by a loss of cell viability.


Positive cross-match for B-lymphocyte antigens (IA like) and kidney allograft behaviour. We describe six cases of kidney graft performed against a positive anti-B lymphocyte cross-match. These antibodies were found after retrospective and systematic screening of the effect of the recipient sera upon donor frozen B lymphocytes. As opposed to the consequences of anti-HLA "SD" preimmunisation, none of the transplantation rapported here failed by acute rejection. The benefic role of anti-B lymphocyte antibodies "Ia like" present at the time of grafting is then suggested.


Clinical and polygraphic effects of d.1 5 HTP on narcolepsy-cataplexy. d.1 5 hydroxy-trytophan (600 mg a day) or a placebo were administered during 4 weeks following a double blind cross over design to 11 narcoleptic-cataplectic patients. Daily number of cataplectic and narcoleptic attacks did not vary. The 36 hours polygraphic recordings performed at the end of each treatment exhibit: a trend toward a decrease of the duration of the day time sleep and a significant increase of the duration of the night sleep.


Toxic effects of fatty acids on yeast cells: dependence of inhibitory effects on fatty acid concentration. The yeasts Saccharomyces cerevisiae, Candida utilis, and Candida lipolytica were used to investigate the action of different concentrations of fatty acids (from acetic to myristic acid) on cell growth, division, uptake of inorganic phosphate, and substrate oxidation. The former two yeasts were found to undergo an inhibition of growth, cell division, and phosphate uptake at lower acid concentrations and to experience the inhibition of substrate oxidation at higher acid concentrations. The concentration dependence of the action of fatty acids can be classified into four categories: 1) subthreshold concentrations which do not inhibit growth and have either no effect on, or stimulate, oxygen consumption; 2) threshold concentrations which lower the rate of growth, cell division, and phosphate uptake but do not inhibit the oxidation of carbon substrate; 3) above-threshold concentrations which inhibit partially even substrate oxidation, and 4) microbicide concentrations. Candida lipolytica displays the same sensitivity toward the action of fatty acids as the above yeast species; however, the threshold concentrations are higher and can be quickly lowered owing to oxidation by the yeast. The concentrations of fatty acids found in the medium after cultivations of yeast with n-alkanes are of the same order as limiting concentrations; the formation of acids with twelve and less carbons in the molecule can thus be assumed to be one of the basic reasons for lowering of biomass yields during cultivations on these hydrocarbons.


Comparison of daily versus intermittent chlorambucil and prednisone therapy in the treatment of patients with chronic lymphocytic leukemia. Ninety-six patients with stage III and stage IV chronic lymphocytic leukemia (CLL) were randomized into one of three treatment schedules. Prednisone was common to all three schedules and was given daily in an initial dosage of 0.8 mg/kg for the first 14 days, with successive halving of the daily dose on days 15 and 29 for a total 6-wk course. Prednisone was then given once a month at 0.8 mg/kg once a day for each of 7 consecutive days. Schedule I was prednisone plus chlorambucil (CLB) given as a once-a-month dose of 0.4-0.8 mg/kg; schedule II was both drugs, but the CLB was given as a daily dose of 0.08 mg/kg; schedule III was prednisone alone. Complete and partial remission (CR + PR) was 47% for schedule I, 38% for schedule II, and 11% for schedule III. Patients who responded (CR + PR) in each of the treatment schedules survived longer than the nonresponders. Complete remission was obtained in both CLB treatment schedules, but not with the prednisone alone regimen. Although overall survival was best in the intermittent CLB arm, there was no significant difference in survival time between the three treatment schedules. Toxicity was minimal in all three regimens. Augmentation of the intermittent monthly CLB, even to 1.5 and 2.0 mg/kg, was tolerated without undue marrow toxicity. About 22% of these patients either had diabetes mellitus at the time of entry on the study or manifested hyperglycemia during the course of treatment and observation.


Progenitor cells in canine cyclic hematopoiesis. Granulocytic (colony-forming units in culture, or CFU-c) and erythrocytic (erythropoietin-responsive cells, or ERC) progenitor cells in canine cyclic hematopoiesis (CH) have been shown to fluctuate over the cycle and in the same phases as one another. The ERC cycle is preceded by 3 or 4 days by a rise in serum erythroid-stimulating activity and is followed by a reticulocytosis. During the cycle CFU-c show a differential sensitivity to two sera, one normal and one containing elevated amounts of colony-stimulating activity. The proliferation rate of CFU-c also fluctuates from well above normal to considerably less than normal over the cycle. These results are discussed in the light of present knowledge of the pathogenesis of canine CH. We suggest that these results support the contention that CH is a disorder of hemopoietic stem cells and that the cycling of humoral factors and peripheral blood cells may follow as a consequence.


Experimental design and statistical analysis of an in-use test of germicidal detergents. Present methodology for the in-use testing of germicidal detergents is too time-consuming for routine use by a hospital environmentalist. A simplified experimental design and statistical analysis, amenable to routine use, is presented for the in-use testing of germicidal detergents against water alone. As an illustration of our methodology we evaluated two germicidal detergents versus water alone. Under our conditions of use, it was found that water alone was equally and significantly as effective (p less than 0.001) as the two germicidal detergents in reducing microbial contamination of floors.


Effect of intrahypothalamic phentolamine on hypothermia produced by peripheral noradrenaline in the pigeon. 1 The effect of intrahypothalamic phentolamine (1 and 1 microliter of a 10 microgram/microliter solution) on hypothermia induced by intramuscular injection of noradrenaline (NA, 2 mg/kg) at different times (2, 10, 20 min) after phentolamine was investigated in pigeons. 2 Administration of phentolamine shortly before NA was shown to attenuate hypothermic responses to NA. 3 It is suggested that the attenuation is due to blockade of central hypothermic effects of intramuscular NA. 4 The mapping of injection sites in the brains was carried out.


Modification, by aspirin and indomethacin, of the haemodynamic and prostaglandin releasing effects of E. coli endotoxin in the dog. 1 Dogs treated with aspirin (10 mg/kg) or indomethacin (1.5 mg/kg) 45 min before, and 3 h after, an LD50 dose (1 mg/kg) of E. coli endotoxin were alive 72 h later. 2 Although all dogs in both treated groups survived, only those treated with indomethacin were protected against the fall in blood pressure 1-2 min following endotoxin. 3 Endotoxin increased the level of prostaglandin F2alpha in both the mixed venous and arterial blood. No increase was observed in the aspirin and indomethacin-treated groups. 4 Aspirin and indomethacin treatment did not modify thrombocytopaenia or blood coagulation parameters following endotoxin.


Delusional depressions: natural history and response to treatment. A review of the abundant literature concerning the distinction between delusional and non-delusional depressions, especially of the work of Aubrey Lewis, reveals that before the introduction of specific therapies most in-patients with major depressive illness eventually recovered; the small percentage who did not almost all came from the delusional group. The dichotomy lost its clinical significance after the introduction of ECT, as both groups were equally responsive. However, accumulating evidence indicates that unipolar delusional depressives are significantly less responsive to tricyclic anti-depressant therapy than non-delusional depressives. The presence or absence of delusional thinking should be considered as a significant criterion in the classification of depressive disorders, and the presence or absence of delusional thinking should influence the choice of treatment for severely depressed patients.


Does the peritoneum need to be closed at laparotomy? Closure of vertical laparotomy wounds was randomized between a two-layer technique of continuous catgut to peritoneum and continuous nylon to sheath and a one-layer technique in which the peritoneal suture line was omitted. In 162 two-layer closures there were 4 burst abdomens and 7 wound hernias (6.8 per cent wound failures); in 164 one-layer closures there were 5 burst abdomens and 7 hernias (7.3 per cent failures). Of 21 patients in this series with jaundice, the abdominal wounds dehisced in 3, and 4 patients developed incisional hernias (33.3 per cent failures) compared with a 5.2 per cent failure rate in the 305 non-jaundiced patients (P less than 0.01). Closure of the peritoneum as a separate layer, as widely advised and practised, appears to play no significant role in the healing of the laparotomy wound.


Cryoprecipitated plasma perfusion preservation and cold storage preservation of duct-ligated pancreatic allografts. It has been shown previously that, at least in dogs, a vascularized pancreatic allograft with ligation of the pancreatic duct can maintain normal beta-cell function for at least 5 years. In this study common organ preservation techniques, as used in human cadaveric kidney transplantation, were applied to canine pancreatic allografts to determine the influence of 24-hour preservation on beta-cell function, graft survival and histological appearances. Three groups of dogs were compared: group A consisted of 9 dogs with fresh grafts; group B consisted of 5 dogs who received grafts preserved for 24 hours by pulsatile hypothermic cryoprecipitated plasma perfusion; and group C was composed of 5 animals who received grafts that had been flushed with Collins' solution followed by hypothermic storage for 24 hours. It appeared that both preservation methods were equally effective and that preservation did not alter either the graft's function or its histological appearance. No significant differences after transplantation were observed in the endocrine function tests of the three groups when compared with the preoperative values; neither was there a significant difference in the mean graft survival time between the groups.


Treatment of borderline diabetes: controlled trial using carbohydrate restriction and phenformin. A five-year therapeutic trial of carbohydrate restriction with or without phenformin (50 mg/day) was performed in men with borderline diabetes. The aim of treatment was to diminish the enhanced risk of cardiovascular disease and deterioration of glucose tolerance. Cardiovascular morbidity and mortality were not significantly affected by any form of treatment, alone or in combination. The predominant risk factor for cardiovascular morbidity and mortality and for overall mortality was the initial blood pressure level. The baseline plasma cholesterol concentration significantly predicted the onset of intermittent claudication. One implication of the results is that hypotensive treatment, supplemented when necessary with hypolipidaemic treatment, may be more effective in preventing the progression of arterial disease in people with mild to moderate glucose intolerance than conventional antidiabetic therapy.


Bacteriology of abscesses of the central nervous system: a multicentre prospective study. Pus from 46 patients with abscesses of the central nervous system (CNS) was examined for bacteria; bacteria were found in all patients. Streptococci were isolated from 36 patients and most isolates were Streptococcus milleri, Lancefield Group F, Ottens and Winkler type O III. Staphylococci were isolated from nine patients, organisms of the bacteroides group from 11, Proteus spp from seven, Klebsiella aerogenes from one, and Haemophilus aphrophilus from one. Pure cultures predominated over mixed cultures. Streptococci were isolated from abscesses of all types, and at all sites, but members of the Enterobacteriaceae and of the bacteroides group were isolated, in mixed cultures, principally from abscesses of the temporal lobe secondary to infection of the middle ear. Staphylococci predominated in abscesses that followed accidental or surgical trauma. Compared with fully sensitive control organisms, microbes infecting half the patients were resistant to penicillin. The prognosis of abscess of the CNS is grave, and the microbiological findings have important consequences for treatment. Prompt inoculation of specimens to culture plates and prompt incubation are mandatory if bacteria are to be cultured. Inhibitors of antimicrobial agents should be added to culture media if antibiotics have been administered. Provided that the site of the abscess and the antecedent history are ascertainable, the neurosurgeon should be able to start appropriate treatment while awaiting the results of culture.


Comparison of RPR 'teardrop' card test, VDRL and FTA-ABS tests results on sera from persons with suspected yaws in Columbia. A small study comparing results of the rapid plasma reagin (RPR) teardrop card test performed in the field, with results of Venereal Disease Research Laboratory (VDRL) and fluorescent treponemal antibody absorption (FTA-ABS) tests performed in the laboratory on venous blood specimens from the same suspected yaws patients was undertaken in Columbia in July 1975. The results suggest that the RPR teardrop card test may be used to screen for infectious, or potentially infectious, yaws patients under field conditions, but that it will not reliably detect patients with VDRL titres of 1:2 or less, or all patients in whom sera are reactive in the FTA-ABS test.


Neurosyphilis.

Neurosyphilis. In patients with abnormal neuropsychiatric symptoms and a reactive fluorescent treponemal antibody absoption (FTA-ABS) test in the cerebrospinal fluid (CSF) or serum, a normal CSF cell count and total protein concentration does not exlude late syphilis involving the central nervous system. In these patients, the presence of plasma cells in the CSF cytogram, increased concentration of CSF immunoglobulin G (IgG), immunoelectrophoretic abnormalities in the precipitates of the IgG and of the Fab fragments of IgG in the CSF immunoelectropherogram, and an increased serum level of immunoglobulin M (IgM) suggest an active, potentially treatable neurosyphilis.


The Viennese contribution to venereology. A history of venereology in Vienna from the first manifestations of the French disease in 1498 until the first half of the twentieth century is described. Notable events were the founding of the old Vienna School by van Swieten in the years after 1745, followed by the revival one hundred years later by von Hebra of the scientific basis for dermatovenereology. An account is given of teachers and discoverers of venereological importance after von Hebra and Sigmund to Arzt. The importance of Landsteiner's and Wagner von Jauregg's contributions finalise the historical account.


Receptive fields of cutaneous mechanoceptive neurons in the frog, Discoglossus pictus, following skin transplantation at larval stages. The receptive fields of individual spinal ganglion cells were mapped in frogs in which a large patch of belly skin had been transplanted to the back prior to metamorphosis. Wiping reflexes aimed at the belly could be elicited both from regenerated normal and transplanted belly skin. We concluded that the sensory neurons mediating misdirected responses could not be the same ones as those mediating normal wipes, since unit receptive fields were either on normal or on grafted belly skin, but never both. A proposed mechanism for explaining the origin of cutaneous reflex connections on the basis of selective innervation of peripheral tissues could hereby be discarded.


Simple "planilabe" for rapid establishment of the stereotaxic horizontal zero plane in rabbits. A device for rapid determination of the stereotaxic horizontal zero plane in the rabbit is described. The instrument is designed to provide reference points needed to establish the appropriate relative position of the commonly used calvarial landmarks, bregma and lambda, in a single operation.


Safety evaluation of Aspergillus fumigatus grown on cassava for use as an animal feed. A safety evaluation of Aspergillus fumigatus I21, grown in a cassava carbohydrate and salts medium, was undertaken. Male weanling rats were fed the fungus at 20, 30 and 40% of the diet for 90 days. A control group was given soybean oil meal as the sole source of protein. Weekly determinations of the body weights and feed consumptions were made. A few days prior to termination of the feeding study, a kidney function test was undertaken on the rats. At the end of the feeding period hematology, blood biochemistry, urine analyses and histopathology studies of various tissues were carried out, and organs were weighed. Rats fed A. fumigatus I21 gained less weight than the controls, but kidney weights were increased. Increases in serum alkaline phosphatase and glutamic-oxaloacetic transaminase were not related to dose level. The blood urea nitrogen was increased for the rats fed 40% of the fungus. Rats fed 30 and 40% of the fungus I21 showed a significant drop in albumin. Deficiency in methionine or other essential amino acids through a limited feed consumption may have caused a decrease in albumin synthesis. Rats fed the highest level of the fungus showed increases in neutrophils and monocytes concomitant with decreases in lymphocytes and eosinophils which may be a response to stress. The urine analyses did not reveal any significant differences. The test rats were capable of concentrating urine adequately when deprived of water for 24 hours. No significant differences between the control and experimental groups were found by histopathological examinations.


An experimental model of candida endophthalmitis. With the more widespread use of hyperalimentation, systemic steroids and broad spectrum antibiotics, particularly in immunologically suppressed patients, Candida endophthalmitis is becoming more common. The drugs that are used to treat it are very toxic; treatment should be stopped as soon as possible. We wished to know if the clinical appearance of a lesion could be related to the number of organisms in it. We injected 16 rabbits intravenously with a suspension of Candida Albicans and produced typical ocular lesions in all of them. The fundi were observed by indirect ophthamoscopy and periodically groups of rabbits were killed and quantitative cultures of their eyes were made. Our results show that this experimental model gives reproducible results. We found that when the lesions are beginning to regress, culture shows either no or very little growth. If, in the human, the ophthalmoscopic appearance of a lesion is similarly related, it could be a guide in deciding the need to continue treatment.


A rapid method for the determination of cellular protein in the presence of elemental sulfur. Cellular protein in the presence of elemental sulfur is determined by the Folin reagent after treatment with benzene. Using this procedure a generation time of 46.2 +/- 4.2 h was observed for Thiobacillus acidophilus grown on elemental sulfur.


Complex medium toxicity to some DNA repair-deficient strains of Salmonella typhimurium. The recovery of several strains of Salmonella typhimurium LT-2 which had first been grown in minimal medium varies when the organisms are grown on minimal medium agar and complex medium agar. The strains tested included mutants with deficiencies in DNA-repair systems (uvrB-and rec-), a deep rough (rfa-) mutant, and a double mutant carrying both the uvrB- and the rfa-mutation. The uvrB- and rec-mutations imparted sensitivity to complex medium agar. The rfa-mutation suppressed the sensitivity of the uvrB-mutant to complex medium agar. Differences in colony-forming ability were not observed when the bacteria were first grown in the complex medium broth.


Pregnancy in renal transplant recipients: report of two successful pregnancies in a patient with impaired renal function. Pregnancy in renal transplant recipients is common and, in spite of several potential problems, overall maternal and fetal outcome has been good in patients with transplants that are functioning well. The presence of renal impairment or hypertension, or both, usually leads to complications, especially in the mother. A patient is described who had a baseline creatinine clearance of about 35 mL/min-1.73 m2 and two successful pregnancies. Renal function deteriorated in the 3rd trimester of the first pregnancy but was reversible; permanent loss of function occurred in the 3rd trimester of the second pregnancy. The potential fetal and maternal risks and details of management of pregnant transplant recipients are reviewed.


Effects of continuous or discontinuous maintenance therapy on subsequent remission maintenance in childhood leukemia. This study was designed to determine if resistance to a standard drug during the second remission of children with acute leukemia was reduced by discontinuation of therapy during the initial remission. The initial maintenance therapy was either 6-mercaptopurine (6-MP), methotrexate (MTX), or cyclophosphamide (CYC) given continuously to relapse or discontinued (at random) at 2 or 6 months. Following the initial relapse and after induction of a second complete remission, 72 evaluable patients received (continuously to relapse) either 6-MP (53 patients) or CYC (19 patients) for the second remission maintenance. Resistance of 6-MP occurred during the second maintenance, regardless of the drug used during the initial maintenance, in that the length of second remissions was significantly shorter than the length of first remissions. However, this resistance was most pronounced in patients who initially relapsed while on continuous 6-MP maintenance (medium duration of remission [MDR] of 9 weeks). Patients whose initial relapse occurred after the discontinuation of 6-MP had a MDR of 23 weeks and patients whose second remission was maintained with CYC (after relapse from initial continuous remission on 6-MP) had a MDR of 25 weeks.


Chemotherapy of malignant mesothelioma.

Chemotherapy of malignant mesothelioma. Twenty-three patients with malignant mesothelioma are described as to mode of presentation, symptoms, method of diagnosis and histology, Beginning in 1972, 10 patients were treated with drug combination including Adriamycin, Dacarbazine (DTIC), Cytoxan, and vincristine. Median survival of these patients was 9.5 months. Twelve patients who were treated with other modes of therapy had a median survival of about 4.75 months. One patient died after 22 days in the hospital, for whom a diagnosis was made at autopsy. While historical retrospective controls involving 13 patients are of limited value in assessing the usefulness of a new treatment, the authors feel that combination chemotherapy in 10 patients has shown enough activity to warrant further study. In addition, wide local resection, where possible, probably increases survival.


Experience with the use of adriamycin in combination with other anticancer agents using a weekly schedule, with particular reference to lack of cardiac toxicity. Two hundred and seven patients have been treated using a weekly regimen of adriamycin in combination with various other anticancer agents. Thirty-six of these patients have received between 600 and 1000 mg/m2 of Adriamycin and 27 have received more than 1000 mg/m2 of the agents. While electrocardiographic abnormalities were relatively common in this group of patients, no patient developed evidence of a cardiomyopathy. Significant remission rates were seen with patients having malignant lymphomas, carcinoma of the breast, various soft tissue sarcomas, and carcinoma of the ovary. We now have data on 149 patients given Adriamycin weekly who have received over 600 mg/m2 of the drug. Sixty-four of these patients have received over 1000 mg/m2 of Adriamycin. Eight patients were suspected of having an Adriamycin-induced cardiomyopathy and this was believed to be likely in only four of these patients. One patient died of a cardiomyopathy apparently induced by Adriamycin. It is our opinion that Adriamycin can be given with only a slight risk of developing a severe cardiomyopathy, in doses greater than 600 mg/m2, either as a single agent or in combination with methotrexate, Cytoxan, vincristine, or 5-fluorouracil, if the Adriamycin is given weekly.


Adjuvant cancer chemotherapy after resection of carcinoma of the lung. A prospective randomized trial was conducted by the Veterans Administration Surgical Adjuvant Group in an attempt to discern the value of prolonged intermittent courses of adjuvant cancer chemotherapy after a successful curative resection of a carcinoma of the lung in men. Four hundred and seventeen patients were randomized into three groups; 132 patients received cyclophosphamide (Cytoxan), regimen A; 142 patients received cyclophosphamide alternating with methotrexate, regimen b; and 143 patients received no additional therapy, the controls. The patients in the two treatment groups received an average of 7.1 drug courses. No drug mortality was noted, but toxic symptoms of varying severity were seen after 43.6% of the drug courses. Five-year survival in the two treatment groups was 24.9% (regiment A) and 25.7% (regimen B), respectively, and 23.5% in the control group. No treatment benefit was associated with adjuvant chemotherapy in this trial.


Clinical trial of nafoxidine in adrenalectomized patients with advanced breast cancer. Antiestrogen compounds are relatively new in the treatment of breast cancer. A clinical trial of Nafoxidine therapy is being pursued in our institution. In a selected group of patients with metastatic breast cancer who had, in the past, undergone adrenalectomy, Nafoxidine therapy produced objective tumor regression in six out of ten patients. Of the six patients whose tumors contained demonstrable estrogen receptors, four showed regression (67%), one patient had stable disease, and one showed tumor progression. Of the four patients in whom estrogen receptor estimation was not done, two had, in the past, shown regression after endocrine therapy and they also showed regression of tumor with Nafoxidine therapy. In patients with metastatic breast carcinoma, who have undergone adrenalectomy in the past, a therapeutic trial with Nafoxidine may be worthwhile particularly in patients who have demonstrable estrogen receptor in the tumor of those who have in the past shown regression of tumor after endocrine therapy.


Combined therapy for metastatic extradural tumors of the spine. The effectiveness of combined modality therapy was studied in 29 patients with metastatic extradural spinal tumor who had had a previous diagnosis of malignancy. Dexamethasone was begun upon suspicion of the diagnosis in a dose of 40 mg daily. Following emergency myelography, in all patients without rapid progression, dexamethasone in combination with radiotherapy and chemotherapy, when appropriate, was instituted. If deterioration occurred, decompressive laminectomy was performed. Five ambulatory patients had neurological function preserved and the condition of seven nonambulatory patients was improved to ambulation at discharge with a combination of dexamethasone, radiation therapy, and chemotherapy. These were patients with prostatic carcinoma, Hodgkin's disease, or breast carcinoma. In five patients who failed medical therapy decompressive laminectomy was successful. In patients with metastatic bronchogenic carcinoma, nonsurgical therapy failed and all underwent surgical decompression with a favorable outcome in only two of 10 patients.


A Phase II study of autologous irradiated tumor cells plus BCG in patients with metastatic malignant melanoma. Eighteen patients with surgically incurable metastatic malignant melanoma were treated with a mixture of irradiated (15,000 rads) autologous tumors cells (1-2 X 10(8)) and BCG (Glaxo, 2-4.5 X 10(6) organisms), which was injected intradermally (in five divided doses) every 2 weeks (X5). Four of 18 (22%) evaluable patients achieved objective remissions. It is concluded that this treatment regimen does not have general clinical application because the remissions were infrequent, of shor duration (median, 3 months) and occurred only in patients with minimal, nonvisceral tumor burdens.


Familial immunopathies: report of nine families and survey of literature. Nineteen individuals are reported who represent nine familial instances of various immunopathies. Multiple myeloma was diagnosed in 10 members of five families, lanthanic (idiopathic) paraproteinemia in five members of two families and either myeloma or lanthanic paraproteinemia in four members of the remaining two families. The parent-child relationship occurred in three instances, siblings were affected in three, and first cousins in three families. Immunochemical studies revealed IgG paraprotein in nine cases; IgA  in three; IgMl type in three subjects belonging to the same family; Bence-Jones protein in one case and biclonal paraproteinemia, IgGk plus IgAl in one. Three individual cases of lanthanic paraproteinemia, discovered in a prospective study of 76 relatives of subjects with immunopathies, suggest that there may be a higher frequency of immunopathies among family members than observed in the general population of comparable age. The published reports on familial paraproteinemias are reviewed..


Polyhistioma: a malignant tumor of bone and extraskeletal tissues. Polyhistioma, a neoplasm whose basic cells are small and round like those of Ewing's sarcoma, but which differentiate into various mesenchymal structures, most often bone, is described. Those cases that produce cartilage have been called mesenchymal chondrosarcoma; the others therefore are mostly urecognized. The name "polyhistioma" is suggested in the hope that with this terminology more of these tumors will be diagnosed. Polyhistiomas are not excessively rare; they affect bone and soft tissue. Half the patients with polyhistiomas died within 2 years. Treatment has resulted in survival of over 20 years. Thirty-eight of the 144 patients with polyhistioma have survived 5 years or more following first definitive treatment. Thirty-seven cases of the disease are presented.


Histiocytic lymphoma with sclerosis arising from a nodular lymphoma with a special stromal reaction. Histiocytic lymphoma with sclerosis was found together with a small nodular lymphoma in a cervical lymph node biopsy from a 48-year-old man. Since the cellular origin of this entity is unclear and its ultrastructure has not been described before, we processed formalin-fixed samples for electron microscopy, which revealed three cell types: small lymphocytes with cleaved nuclei, large lymphocytes with vesticular noncleaved nuclei, and mesenchymal stromal cells occasionally bearing desmosomes or hemidesmosomes. In addition, there was an increase of the intercellular connective tissue, which consisted of a mixture of normal and fibrous long spacing collagen fibers. The results indicate that histiocytic lymphoma with sclerosis can evolve from a nodular lymphoma, and that diagnostic information can be obtained by electron microscopy of tissue samples previously fixed in formalin.


An ultrastructural study of seven cardiac myxomas. Seven cardiac myxomas (CM) were studied by light and electron microscopy (EM) and their features compared with previously reported CM. Tumor cells were enmeshed within abundant stroma composed of fine electron dense granules. These cells were present either singly or more often in closely apposed small groups. The most distinctive ultrastructural feature in all seven CM was the presence of numerous cytoplasmic filaments. Our findings did not support a distinct separation into multiple cell types that could be clearly classified since the tumor cells had combined features of smooth muscle cells and fibroblasts. There has been no agreement on the principal cell type observed in CM, which has resulted in numerous theories about their histogenesis. Although the cell of origin of CM remains elusive, we fell that CM arise from primitive mesenchymal cells with multipotential capabilities for cell differentiation. Evidence is presented supporting the fact that CM are neoplasms and not thrombi. CM rarely recur but no bona fide metastasis has been reported.


A rapid in vitro method for measuring cell proliferation in human breast cancer. A method has been developed for studying in vitro the cell proliferation kinetics of human breast cancer, Surgical specimens from primary tumors were studied in 56 patients. Viable cell suspensions for assay were obtained by the dissociation of tumor tissue with collagenase. Mean Labeling indices of 2.43 +/- S.D 2.05 and 4.48 +/- S.D. 3.73, respectiviely, were found after incubation with 3HTdR for 2 hours and 24 hours. Mean S-times of 21.9 +/- S.D. 4.3 hours were estimated by 3H and 14C-TdR double-labeling. The kinetic data have been validated by parallel labeling studies in vivo and in vitro in four patients. The processing of autoradiographs using gold latensification provided slides for kinetic analysis within 3 days. The assay offers a method that is useful in the planning and monitoring of drug therapy.


Inhibitory effects of selenium on 1,2-dimethylhydrazine and methylazoxymethanol colon carcinogenesis: correlative studies on selenium effects on the mutagenicity and sister chromatid exchange rates of selected carcinogens. Selenium (Se) inhibition of either the activation of test compounds and/or mutagenic events elicited by activated compounds is suggested by experimental rat assays, mutagenesis assays, and assays with human lymphocytes in culture. The colon tumor incidence in 1,2-dimethylhydrazine (DMH)-treated rats was reduced from 87% to 40% by 4 ppm Se supplements in the drinking water. Supplemental Se decreased the total number of colon tumors induced by DMH more than three-fold and by methylazoxymethanol (MAM) almost two-fold. Coexposure of Salmonella typhimurium TA 1538 to an effective molar ratio of Se/2-acetylaminofluorene=10, Se/N-OH-acetylaminofluorene=10 and SE/N-OH-aminofluorene=300 reduced the mutagenicity to 65, 68, and 61% of their respective controls with mutagen alone. With a molar ratio of Se/N-OH-AAF=100, Se reduced the activity to 28% of the mutagenicity of N-OH-AAF alone. Preliminary data indicating MAM is mutagenic in S. typhimurium TA 1535 and His G 46(6837) are presented. In toxicity studies exposure of human lymphocyte cultures to 1.3 X 10(-9) to 1.6 X 10(-5) M Se yielded sister chromatid exchange (SCE) rates equivalent to background levels of 6--7 SCE per cell. The SCE frequencies of lymphocytes cultured with Se and selected carcinogens are discussed.


Chemoimmunotherapy of metastatic large bowel cancer: nonspecific stimulation with BCG and levamisole. The administration of two chemoimmunotherapy programs to 103 consecutive patients with metastatic colorectal cancer resulted in improved survival for patients who achieved either objective tumor regressions or disease stabilization for more than 8 weeks. Objective tumor regression was observed in 47% of patients treated with the Ftorafur-methyl-CCNU-methotrexate-Bacillus Calmette-Guerin (FTOR-MeM-BCG) program and in 34% of patients treated with the 5-fluorouracil-methotrexate-Baker's antifol (FU-M-BAF) +/- Levamisole program. The combinated median duration of survival for patients who achieved objective tumor regression and disease stabilization with FTOR-MeM-BCG was 13 months compared with 6 months for patients who had progression of disease (p = 0.001). The corresponding values for patients treated with FU-M-BAF +/- levamisole were 11 months and seven months, respectively (p = 0.001). While the role of BCG immunotherapy in these results remains speculative, the administration of levamisole immunotherapy did not appear to have influenced results significantly. Patients who presented at diagnosis with Dukes A, B and C lesions, and therefore had longer disease-free intervals, responded more frequently to chemoimmunotherapy and survived longer than patients who presented at diagnosis with Dukes D lesions. Similarly, greater antitumor effect was observed in patients with lower pretreatment plasma CEA levels evaluation of these pretreatment characteristics may have insignificant implications for the design of future clinical trials.


Tumor biology and clinical trials: the Richard and Hinda Rosenthal Foundation Award Lecture. Laboratory research is often described as basic and clinical research, prognostic or empirical. In this address, the point is made that research may be clinical or laboratory. Good clinical research may give important biological answers. Breast cancer clinical trials are decribed in terms of their biological interpretation. A list of significant biological questions that need answering are presented.


Increased expression of actin-like protein in human and ethylnitrosourea-induced tumors of the nervous system. Twenty-one human intracranial tumors comprising 15 astrocytomas and 6 meningiomas and 26 ethylnitrosourea-induced rat neural tumors comprising 7 astrocytomas and 9 schwannomas were examined by indirect immunofluorescence for reactivity with a human anti-actin antibody. In cryostat sections both human and rat astrocytomas showed an increased reaction with the anti-actin antibody compared to normal astrocytes, and the reaction with astrocytomas was greater  than that with meningiomas. Malignant rat schwannomas also showed prominent anti-actin staining contrasting with the negative reaction in normal Schwann cells. These in vivo observations were paralleled by concurrent studies with impression films and in vitro monolayer cultures of tumor tissue. The results, reviewed in the light pfo previous studies of anti-actin antibody reactivity with other nonneural tumors, suggest that an enhanced actin expression in vivo may be a general feature of the neoplastic state and that this increased expression may be more pronounced in malignant than in benign tumors.


Initiation and characterization of cultured tumor lines from spontaneous reticulum cell sarcoma of SJL/J mice. Three reticulum cell sarcoma lines (LA1, LA6, and LA8) have been established from SJL/J spontaneous "Hodgkin's-like" reticulum cell sarcoma. All cultures are lymphoid with blast-like morphology by light and electron microscopy and produce the type B neoplasm (Dunn classification) when injected into young SJL/J mice. Identification of these tumors as lymphocytic and monocytic was investigated by surface markers, histochemical staining, and phagocytic function. LA6 and LA8 bear receptors for the Fc portion of immunoglobulin complement receptors; Thy 1.2 antigens and surface immunoglobulin were not detected on any of the three lines. No lines were able to synthesize immunoglobulin or phagocytose Degalon beads. Histochemical staining was presumptive of lymphocytes or lymphoblasts with slight differences between the lines. Although a T- or B-cell classification cannot definitively be made for these tumors lines because of their lack of specific markers, the results are consistent with an immature B-cell origin for the SJL/J reticulum cell sarcoma.


Responsiveness to humoral factors of mouse marrow colony forming cells after treatment with cyclophosphamide. Humoral factors affecting granulopoiesis have been detected by culturing bone marrow cells in intraperitoneal diffusion chambers. This study investigated the possibility that treatment with drugs alters the ability of cells to respond to these factors. Three days after treatment with 200 mg kg-1 cyclophosphamide, donor marrow cells were more responsive than normal cells to the factors produced in cyclophosphamide pretreated hosts. The optimum timing of host pretreatment for maximum colony stimulation also differed for cells from cyclophosphamide treated and untreated donors and these effects were found to depend on the dose of drug given to the animals.


Cell cycle characteristics of synchronized and asynchronous populations of human cells and effect of cooling of selected mitotic cells. The method of synchronizing cells by means of mitotic selection has been adapted to the human line NHIK 3025. Increase in cell number as a function of time in asynchronous and synchronous populations was studied as well as mitotic index as a function of time after selection of synchronized populations. Phase durations of the cell cycle of synchronous populations were determined by 3H-thymidine incorporation and scintillation counting. The relative phase durations of exponentially growing asynchronous populations were determined by mathematical analysis of DNA-histograms recorded by flow cytofluorimetry. Both the generation time and the various phase durations of the cell cycle were found to be the same in asynchronous and synchronous populations. It was found that NHIK 3025 cells are damaged by cooling to 4 and 0 degrees C so that cooling of selected cells in order to increase the yield would reduce the quality of the synchronized populations.


Planning the suicide experiments.

Planning the suicide experiments. Suicide experiments involve a great degree of uncertainty in the counting of cell colonies. This work studies from a statistical point of view the precision of the estimation as a function of the number of experimental units which are used. Assuming that the colony numbers in recipients follow a Poisson distribution, we give the necessary number of recipients (a) to determine with a given accuracy the percentage of DNA synthesizing cells (S cells), (b) to test whether or not a cell population is quiescent, and (c) to compare the percentages of S cells in two cell populations.


A catecholaminergic neuron connecting the first two optic neuropiles (lamina ganglionaris and medulla externa) of the crayfish pacifastacus leniusculus. The crustacean optic neuropiles, the lamina ganglionaris and especially the medulla externa, show a specific pattern of green fluorescence with the fluorescence histochemical method of Falck-Hillarp. Normally, only the terminals and the cell bodies fluoresce, but in reserpine-treated animals exogenous catecholamines are taken up by the whole adrenergic neuron and are thus visualized as a whole. Incubating crayfish optic neuropiles in dopamine or alpha-methylnoradrenaline after reserpine treatment demonstrated a tangential neuron connecting the lamina and the medulla externa. The morphology of this tangential neuron differs from the two types of tangential neurons, Tan1 and Tan2, previously characterized with Golgi techniques. The catecholaminergic neuron thus constitutes, a third tangential neuron type.


Immunofluorescence study of LH-RH producing cells in the human fetal hypothalamus. The use of antibodies to synthetic LH-RH has enabled the detection by immunofluorescence of hypothalamic LH-RH producing cells in the human fetus. The perikarya of these cells are located in the pericommissural and peroptic regions, in the lamina terminalis and in the premamillary region. Reactive axons occur in the median eminence. The first LH-RH producing cells are seen as early as nine weeks of gestation. The specificity of immunocytological reaction has been controlled.


Proliferation of lamellar whorls in arcuate neurons of the hypothalamus of male rats treated with estradiol benzoate or cyproterone acetate. The arcuate nucleus of the hypothalamus (AH) of male rats which had been treated either with estradiol benzoate (E2B) or cyproterone acetate (CPA) was examined ultrastructurally for the presence of whorls of endoplasmic reticulum. The incidence of whorl containing neurons (WCN) was 2-4 times higher in the AH of animals treated for 2-3 weeks with E2B or for 2 weeks with CPA than in the AH of oil treated controls. CPA is a powerful anti-androgen while E2B acts both peripherally and centrally to limit testosterone production. These findings, together with previous evidence that whorls proliferate in AH of male rats deprived of androgen by morphine treatment or castration, suggest that steroid feedback (androgen alone or both androgen and estrogen) plays an important role in AH whorl preliferation. The possibility that WCN may be LH-RH containing neurons is suggested by the close correspondence between the number and location of WCN within AH as determined in this study and the distribution of LH-RH containing cells reported by others.


Sexual difference in LH-cells of the neonatal rats as revealed by immunocytochemistry. Localization and number of pituitary LH-cells were studied in neonatal male and female rats (from the birth to 12th day) applying anti-HCG serum in immunoenzymological procedures. The cells increased in number with developing age after birth. The cells in males and females were equal in number until 4 days of age, wheres thereafter the increase of the cell number in females exceeded that in males. After birth, the cells are mainly concentrated ventrally, being ventro-lateral in the anterior region but converging into the medial-ventral area in the posterior part of the gland. Some dispersion in a dorsal direction is also noted in the latter region. At birth the cells begin to appear in the dorsal area in the anterior portion, as well as in the posterior portion, particularly in the area close to the intermediate lobe and in the zone adjacent ot the residual lumen. This was particularly evident in females after 4 days of age. Thus it is concluded that in rats the sexual differences in the pituitary become apparent after the 4th day of postnatal life.