The reform of ambulatory care: a financial paradox. The purpose of this paper is to examine the financial factors which have effectively constrained the movement toward major reform in the out-of-hospital medical care area within this country. Analysis of the current economic picture in the health field leads inescapably to the conclusion that the major wave of new out-of-hospital programs predicted in the early 1970s is not likely to occur in the immediate future. The financial constraints are so substantial that the expansion of new forms of delivering ambulatory care services (HMOs, restructured OPDs, neighborhood health centers, etc.) into low- and moderate-income communities will proceed more slowly than was originally anticipated. The facts outlined in this paper clearly indicate that many new ambulatory care projects designed to serve low- and moderate-income people will face serious financial difficulties and will place a heavy burden on the resources of sponsoring institutions. In the future, widespread reform in the out-of-hospital area will await major improvements in the way this country finances its ambulatory care services.


[Chemotactic activity in the fluid of bullous pemphigoid blisters]. By a modified Boyden technique, chemotactic activity was present in bullous pemphigoid blister fluids but was also present in the corresponding sera. Heat inactivation (56 degrees C for 30 minutes) only partially reduced the blister fluid chemotactic activity, but almost completely inhibited the activity present in pemphigoid sera. Control blister fluids exhibited some chemotactic activity, but in contrast to pemphigoid blister fluids, this activity was almost entirely abolished by heat inactivation. The chemotactic activity remaining in heat inactivated pemphigoid blister fluid was inhibited by N-CBZ-alpha-glutamyl-L-tyrosine and by antiserum to C5 but not with antiserum to C3. Our studies suggest that complement-dependent chemotactic activity is present in bullous pemphigoid blister fluids, findings which further implicate complement activation in the pathogenesis of this disease.


Aging in mammalian cell population: a review. Research on in vitro aging and development is reviewed within a framework provided by three aspects of population growth--birth, canalization and death. Although there are periodic changes in the birth rate coupled to periodic changes in the in vitro environment, there do not appear to be any age-related changes in the birth rate of dividing cells. There appear to be distinct subpopulations of dividing and nondividing cells, each with its own characteristic morphological and functional properties; thus, Weiss-Kavanaugh theory may be applicable to the growth, maturation and senescence of mammalian cell populations. Substantial cell losses occur during subcultivation and transfer; correction for these losses requires substantial reinterpretation of existing experimental findings. The various measures of age are poorly correlated with one another; there is wide variation from population to population. A uniform measure of age has been found in the cell generation, the number of ancestors of a given cell. Studies of intrinsic variation in development can provide additional insight into the developmental process. The framework of birth, canalization and death permits reduction in the number of competing hypotheses of aging in mammalian cell populations. Additional experimental evidence is needed to discriminate among the remaining hypotheses.


Natural history of bell's palsy: the salivary flow test and other prognostic indicators. Fifty-one patients with Bell's palsy were evaluated within two days of onset and followed for six months without surgical intervention or effective medical treatment in order to observe the natural history of the disease. Sixty-three percent had a complete return while 37 percent had incomplete return. Age, the presence of pain, and taste alterations had no prognostic value. The progression of the palsy, response to maximal stimulation and salivary flow testing were approximately 80 percent accurate in predicting outcome. The salivary flow test was the most useful prognostic indicator since salivary flow became reduced within two days of onset in the patients likely to develop denervation while the other tests did not become altered until 3 to 14 days after onset. In patients with Bell's palsy, the salivation test seems to be the only method capable of predicting denervation before it begins; therefore, it should be ideal for selecting patients for appropriate treatment.


Prognostic significance of lymph node histology in patients with squamous cell carcinoma of the larynx, pharynx, or oral cavity. In a double-blind retrospective analysis, sections of lymph nodes regional to head and neck squamous cell carcinomas were microscopically examined to assess morphologically the immunologic pattern of response. Patients whose nodes showed evidence of immunologic stimulation had five-year survival rates significantly higher than those whose nodes showed no evidence of immunologic stimulation. None of the patients whose nodes showed the lymphocyte depletion pattern survived five years. The stage or histologic grade of the tumors did not influence these correlations. Metastases occurred much more frequently in patients whose nodes showed immunologic activity than in those whose did not. The data support the concept that immunologic capacities are important host defense mechanisms against malignancy. Histologic assessment of immunologic activity in regional nodes seems to be an important parameter for predicting survival.


Nonunion of the mandible.

Nonunion of the mandible. Nonunion of the mandible was evaluated over a five-year period (1968-1973). Fourteen cases were noted out of 577 mandibular fractures for an incidence of 2.4 percent. Causes of the complications were determined by a careful review of the poorly healing and successfully treated cases of mandibular fracture. The most important feature in nonunion cases was the large proportion of edentulous patients. In these cases immobilization appeared difficult, especially when only one form of fixation was used to stabilize the fracture. Other suspected causes of nonunion were postoperative trauma and osteomyelitis. These factors were most prevalent in the lower socio-economic groups. Factors which did not appear important were sex, age and cause of the fracture. Analysis of the site of injury, combinations of sites, timing of treatment, periosteal stripping and general health of the patient failed to demonstrate any predisposition to the complication. Treatment of nonunion was confined to standard techniques of debridement, antibiotic therapy and further immobilization. Although most patients responded to this therapy, six patients required closure of the deficit by bone grafting. On the basis of accumulated data, it was possible to clarify the factors in the development of nonunion. It was also possible to recommend methods of prevention of the complication and to substantiate the success of several forms of therapy.


DMSO in otology.

DMSO in otology. The most controversial therapeutic agent in the past decade has been dimethylsulphoxide (DMSO), an industrial solvent to which great healing powers have been attributed. After initial laboratory testing, DMSO was rapidly introduced into veterinarian medicine and clinical medicine as an experimental agent with the ability to relieve pain, reduce swelling and edema in trauma, to show anesthetic, antibacterial and anti-inflammatory properties when applied topically to the skin. Ninety percent DMSO was used alone and in conjunction with alkaloids and antibiotics to test the clinical properties attributed to this drug. Although DMSO was found not to be ototoxic, laboratory and clinical testing which included double blind studies on patients with otological infections demonstrated that DMSO had no antibacterial, anesthetic or anti-inflammatory properties when applied within the external auditory canal. There was no indication that 90% DMSO, when combined with these various preparations, potentiated or acted synergistically to enhance their penetration through the dermal barrier.


Effects of droperidol in management of vestibular disorders. The chemo-therapy of vestibular disease has involved a wide spectrum of pharmacological agents insofar as their mode of action is concerned. In our experience, however, droperidol is one pharmaceutical agent which is remarkably effective in depressing vestibular disturbance regardless of etiology. This medication (also called Inapsine) belongs to a relatively new class of compounds known as butyrophenones and its pharmacological action can best be described as a dopa blocking agent. The activity of droperidol on the nervous system first became evident when it was used in combination with the potent analgesic fentanyl citrate in order to produce an anesthetic condition that has been termed neuroleptanalgesia. This mixture (also called Innovar) is rapid in action and results in complete suppression of vestibular activity of both normal subjects and those with Ménière's disease as described by Dowdy, et al., in a preliminary report. These impressive results have prompted us to evaluate the effectiveness of this medication in the treatment of different disorders of the labyrinth. The patients chosen for evaluation were referred for vestibular examination at the Toronto General and St. Michael's Hospitals. Electronystagmography was used to record objectively the effects of the drugs being tested while subjective symptoms including side effects were also noted. These studies involved 20 patients receiving Innovar while 12 patients were tested with Inapsine. Innovar administered in a single dose (droperidol 5 mg, fentanyl 0.1 mg) to patients undergoing acute episodes of vestibular disease (vestibular neuronitis and Ménière's disease) was found effective in the following symptoms and/or signs: nausea, vertigo, nystagmus, the positive past-pointing test and the Romberg test. Innovar appeared to be effective in the amelioration of vomiting although the population was too small to demonstrate statistical significance in this regard. The drug mixture appeared to have no effect on improving auditory acuity and had no significant effects on tinnitus. Adverse reactions to the drug combination were unusual, and, occurring in three patients, were mild as manifested by drowsiness. Since the above findings confirmed the marked effectiveness of the fentanyl-droperidol mixture in the management of vestibular disease, it was decided to determine the relative effectiveness of the droperidol component alone and this was determined by comparing the effectiveness of the drug with placebo in a double-blind study. Review of our findings involving this double-blind study indicates significant responses to Inapsine. This therapy clearly provided the statistically significant response (p less than 0.1, Fisher's Exact Test). This was particularly apparent at the 60-minute evaluation point. While some of the patients receiving Inapsine had recovered earlier, by 60 minutes none of the placebo patients but all of the Inapsine patients had recovered from the vestibular symptoms of Ménière's disease...


[Unusual clinical course of malignant lymphoma(author's transl)]. Primary malignant lymphoma of the gastrointestinal tract and intestinal involvement in diffuse lymphoproliferative diseases are far more common than generally believed. A typical clinical course of these disorders may rose considerable diagnostic problems. Scirrhous growth patterns, diffuse gastrointestinal polyposis and multiple colonic ulcers are presented as rare variants of malignant lymphoma of the digestive tract.


[Isolated malignant lymphoma of the rectum(author's transl)]. A case of primary and isolated, diffuse reticulosarcoma of the rectum is reported. There has been a history of blood diarrhea for 12 years in a 60 years old man, with no change in his general condition. Treatment with cyclophosphamide was started and maintained for two and a half years with complete local regression, and very good clinical results.


[Induced filament formation in Salmonella enteritidis by means of sodium chloride]. Induced morfological variations of bacteria by means of different agents has been known for many years. In this study the influence of sodium chloride on filament formation of S. enteritidis is studied, and the concentrations between 5-7% has been found effective in filament formation.


[The production and standardization of streptolysin-O]. The production of streptolysin-O by using the S84 strain of beta hemolytic streptococcus is explained. The Rantz-Randall and Hartley media with the Gooder method have been used because better results could be obtained in a shorter time and it was more economical. In obtaining a potent streptolysin-O not only the method but the strains and media must be taken into consideration. The hemolytic potency of the obtained streptolysin-O is within the necessary limits and there is no need to concentrate it. The pH of the media was adjusted 5-6 hours after the culture began because the formed acid during the growth of streptococci decreased the growth of the organism and its toxin yield. The toxin was stored in the deepfreeze for daily use. In ASO tests it was subjected to a reduction process with sistein-L for 10-30 minutes.


Hepatorenal syndrome: a disease mediated by the intrarenal action of renin. The functional renal failure accompanying advanced liver disease is characterized by azotemia, a urine of very low sodium concentration and systemic hypotension with decreased renal perfusion and high renal vascular resistance. Patients with this disorder have a markedly reduced ability to excrete free water and develop hyponatremia, ascites and edema. It is postulated that this renal dysfunction is due to hepatic failure to make renin substrate. Renin released from the kidney is thus unable to exert its pressor effect. The resultant hypotension and renal hypoperfusion continue to stimulate excessive synthesis and release of renin. It is postulated that the overdriven renal renin system increases renovascular resistance at the level of the glomerular arterioles. This causes decreased renal blood flow and decreased glomerular filtration rate leading to salt and water retention and azotemia. Since no renin substrate is available for human infusion, this hypothesis could be tested either by infusion of angiotensin II to restore systemic blood pressure and renal perfusion or by beta adrenergic blockade with propranolol to attempt to decrease the intrarenal effects of renin, restore glomerular blood flow and filtration and thus return of renal function.


Coagulation and renal disease.

Coagulation and renal disease. The role of coagulation in relation to the aetiology, pathogenesis and progression of renal diseases is discussed. The intimate interdependence between the coagulation process and platelet function, fibrinolysis, complement activation and kinin release is emphasized; these processes are usually involved in most types of immunological inflammation. Coagulation abnormalities occurring in distinct renal diseases are reviewed and the benefits derived from therapy aimed at correcting these abnormalities are compared with the known natural histories of these diseases.


Double-blind crossover trial of bromhexine (Bisolvon) in the treatment of chronic bronchitis. The results of a double-blind crossover trial of bromhexine (Bisolvon) in the treatment of chronic bronchitis are reported. Benefit was shown by statistically significant changes in the peak expiratory flow rate, ascultatory findings and sputum volume. Benefit was also demonstrated by changes in dyspnoea, sputum, consistency and ease of expectoration, but these were without statistical significance. A review of the literature together with the results of this trial suggest that, when adequate consideration is given to a number of therapeutic variables, Bisolvon will be effective medication for most patients with chronic bronchitis associated with thick, tenacious sputum.


Endoscopically controlled trial of alginate and antacid in reflux oesophagitis. A double-blind crossover trial of Gaviscon (alginate/alginic acid plus antacid) versus standard antacid is reported in 20 patients with symptomatic hiatus hernia. Gaviscon was well tolerated but clinical improvement was equally good with antacid in this short-term (six-week study). At the beginning, endoscopic evidence of erosions or "oesophagitis" was common (in 12 of the 20 subjects). Oesophagoscopic evidence of improvement was seen in 50% of patients with both types of medication over a three-week period, compared with subjective improvement in 84%. Long-term studies are necessary to establish the natural history of peptic lesions of the oesophagus and their treatment, whether conservative or surgical.


[Enchondroma of the hand (author's transl)]. The problems of the enchondroma of the hand, its diagnostics and treatment if discussed in this paper. 12 cases of handskeletonenchondroma, 9 with pathological fracture, 3 without fracture, are the occasion of this report. The treatment is in our opinion the scraping of infested tissue (excochleation) and filling the defect with bonemeal and immobilise the hand in plaster-bandage for 4 to 5 weeks. 8 to 12 weeks after operation the defect and fracture were consolidated.


[Effect of intramuscular dihydroergotamine on blood circulation in the early postoperative phase. A clinical study]. The effects of Dihydergot (1,0 mg i.m.) and a placebo on orthostatic regulation disturbances were examined during the mobilisation in the first post-operative phase. According to a modified Schellong-test, 100 fresh-operated patients with hyper- rsp. hypodiastolic regulation disturbances were checked on the first post-operative day. In comparison with the placebo, Dihydergot showed a stabilisation of the systolic blood pressure and a decrease of the pulse rate during orthostatic conditions. Neither Dihydergot nor placebo influenced the diastolic blood pressure. Orthostatically caused side effects were observed less frequent within Dihydergot - therapy than under placebo.


Special Escherichia coli serotypes among enterotoxigenic strains from diarrhoea in adults and children. 106 enterotoxigenic Escherichia coli strains from children and adults from many parts of the world were serotyped for O and H antigens. Some O:H types, i.e. O6:H16, 08:H9, O15:H11, O25:H42, O78:H11 and O78:H12, were found repeatedly from different geographical locations. Some of these O:H serotypes were only found rarely among more than 20000 E. coli strains collected over many years from different locations and sources. It is suggested that these special O:H serotypes represent clones which have been selected to the special conditions in the small intestine and selected to carry the plasmids necessary to provoke diarrhoea.


Management of acute leukemia in adults.

Management of acute leukemia in adults. The treatment of acute leukemia in adults, while not yet as successful as that in children with regard to either remission rate or prolongation of life, can now regularly result in at least 50% responses in acute myelocytic leukemia and 70-80% in acute lymphocytic leukemia. Intensive specific chemotherapy and supportive therapy throughout the resultant period of myelo and immuno-suppression are necessary to achieve these remission rates. Further investigations aimed at both prolonging the remissions so obtained and at improving the response rate further are essential.


Infections in children with acute leukemia. Twenty children with ALL that died in 1959-1960 and 59 children with ALL that died in 1969-1970 were analyzed according to the infections at both their terminal illness and their initial presentations. Despite the availability of more effective agents for pseudomonas and staphylococcus, the pattern of infecting organisms at the terminal illness did not change appreciably in this decade. E. coli, pseudomonas, staphylococcus, and candida were the principal organisms involved as a cause of death. Thirty-five of these 79 patients were febrile when they initially presented, prior to the institution of chemotherapy. Seven of the 35 patients (20%) had proved infections. It appears that the fever in the majority of patients at their initial presentations was noninfectious in origin. In 1969-1970, 13 pulmonary aspirates were performed to aid in the etiological diagnosis of diffuse interstitial pneumonia. Only a single case (8%) of pneumonia due to pneumocystis carinii was detected, and it is our suspicion that the majority of these interstitial pneumonias were viral in origin.


Therapy of infections in neutropenic patients: results with gentamicin in combination with cephalothin or chloramphenicol. Gentamicin in combination with cephalothin (Gent-Ceph) or with chloramphenicol (Gent-Chloro) was utilized in the treatment of 55 infections occurring in 49 cancer patients. Responses were obtained in 78% of the infections treated with Gent-Ceph and in 64% of those treated with Gent-Chloro. Pneumonia and septicemia were the most common infections in this study. Among the cases of penumonia, 64% responded to Gent-Ceph and 67% to Gent-Chloro. Among the cases of septicemia, 88% responded to Gent-Ceph and 50% to Gent-Chloro. All of the identified organisms producing infection were gram-negative bacilli. Of these, E. coli was the most common. All organisms were resistant to cephalothin in vitro, and only 41% of them were resistant to chloramphenicol. However, resistant organisms responded significantly better to the Gent-Ceph combination (p less than 0.025). Also, response to therapy among patients with severe neutropenia (less than 100 neutrophils/mm3) was better for those patients treated with Gent-Ceph (p = 0.07). The combination of gentamicin with cephalothin or with chloramphenicol did not increase the frequency of side effects expected from gentamicin alone. No significant hematological toxicity was seen among those patients treated with chloramphenicol. Gentamicin in combination with cephalothin or chloramphenicol is an effective and safe antibiotic combination against gram-negative bacilli infections occurring in cancer patients. The efficacy of Gent-Ceph in patients with severe neutropenia is particularly advantageous.


Methods for measurement of cerebral blood flow in man. A survey of the currently available methods for the measurement of cerebral blood flow in man is given. Many of the clinically important brain diseases such as tumors, stroke, brain trauma or epilepsy entail focal or regional flow alterations. Therefore a special emphasis is placed on methods allowing measurements of regional cerebral flow, rCBF. The intra-arterial 133Xenon injection method is now widely used as a standard method for rCBF measurement. It affords a good two-dimensional resolution when using a suitable dynamic gamma camera which allows a high counting rate to be recorded. But, due to the superposition of tissues the three-dimensional resolution is limited. This, in particular, means that smaller areas of ischemia (low flow) tend to be overlooked  whereas local hyperemia is readily discerned. The 133Xenon inhalation method is less accurate, contaminated by extra-cerebral uptake, and insensitive both for detecting regional ischemia and regional hyperemia. The spatial resolution is also much more limited. For these reasons great caution must be exercised in  interpreting the results. Methods yielding three-dimensional rCBF data will be needed in order to gain more precise information both on spatial localization and, especially, on ischemic areas. The most promising is computer-assisted axial tomography with freely diffusible radioactive isotopes or with x-rays using an intra-arterial injection of contrast. But, the available techniques are still too slow: in order to measure blood flow one "exposure" must be taken every second. Only a few methods give quantitative information of the blood flow in the human brain. This is mainly due to the inaccessibility of the brain within the skull and to the complexity of the cerebral arterial and venous systems. Before reviewing the various methods used in man, it should be mentioned, that much of the fundamental knowledge has been gained by methods only applicable to animals. Measurements of the diameter of the small arteries on the surface of the brain antedates even the classical studies of Roy and Sherrington (1890). This technique continues to be useful, modern technical improvements consisting of the use of micropipettes and a stereo microscope in combination with an image splitter and a television camera which allows the accurate assessment of diameter variations of a few percent [22]. Autoradiography of brain slices using diffusible indicators is the best quantitative method for measuring local blood flow in a great many parts of the brain [7, 45]. Microspheres are also being used, but it is still not quite clear that this technique gives reliable quantitative data in small masses of tissue [34, 41, 50].


A new method for the electromagnetic optimization of stereotaxically implanted electrodes in the brain: preliminary results. A method of optimizing the geometrical and electrical parameters of multielectrodes implanted in the brain is presented. The method should be valuable for the standardization of the implantation procedure. It bases on numerical solutions of the partial differential equations governing the electric potential. A description of the computer program developed is given, results pertaining to special cases are included, as well as other possible applications.


A method for the deletion of restriction sites in bacterial plasmid deoxyribonucleic acid. A general method has been developed for the deletion of restriction endonuclease sites in bacterial plasmid DNA. The procedure involves partial digestion of the covalently closed circular plasmid DNA with an appropriate restriction endonuclease under conditions which allow accumulation of unit-length linear DNA molecules, a controlled digestion of the exposed 5' ends with the lambda 5'-exonuclease, and in vivo recircularization of the resulting linear DNA in a bacterial host cell. The method has been used for the deletion of one of the two EcoRI sites in the plasmid pML2 (colE1-Km). Two of the resulting plasmids, pCR1 and pCR11, have a single EcoRI cleavage site, but retain genetic determinants specifying resistance to colicin E1 and kanamycin, and thus may be useful as vectors for the cloning and amplification of DNA in bacteria.


Pattern of somatic segregation of the cytoplasmic drug-resistance factors in yeast. The pattern of somatic segregation of the cytoplasmic factors confering resistances to chloramphenicol, erythromycin and oligomyin in S. cerevisiae was studied. The fractions of the zygotes heterozygous for the chloramphenicol-resistance factor and for the erythromycin-resistance factor decreased exponentially with generation number of zygotes. The rate of the segregation was highest for the chloramphenicol-resistance factor and lowest for the oligomycin-resistance factor. The segregation rate as well as the transmission polarity of the chloramphenicol-resistance factor varied with different carbon sources with which the parental haploids were grown prior to mating.


Biogenesis of mitochondria. XLII. Genetic analysis of the control of cellular mitochondrial DNA levels in Saccharomyces cerevisiae. The proportion of total cell DNA which is mitochondrial DNA was measured in haploid, diploid and tetraploid strains of S. cerevisiae grown under a standard set of conditions. For all strains tested the mitochondrial DNA level was in the range 16%-25% of total cell DNA. Repeated measurements of the cellular level of mitochondrial DNA in two haploid strains showed that these strains have measurably different cellular mitochondrial DNA levels (17% and 24% of total DNA, respectively) under our conditions. These two grande strains were used to investigate the role of the mitochondrial and nuclear genomes in the regulation of the mitochondrial DNA level. We have shown by genetic analysis that the difference between these two strains is determined by at least two nuclear genes. The mitochondrial genome is not involved in the regulation of cellular mitochondrial DNA levels. A number of purified petite clones derived from independent spontaneous petite isolates of the grande strain which contained 24% mitochondrial DNA were also studied. The mitochondrial DNA levels in all but one of these petites fell in the range 20-25% of total cell DNA. From these results we conclude that, in general, the mitochondrial DNA level in petite strains is controlled by the same mechanism as operates in grande strains. We propose a general model for the control of the cellular mitochondrial DNA level, in which the amount of mitochondrial DNA per cell is determined by regulation of the number of mitochondrial DNA molecules per cell. This regulation is mediated through the availability of a set of nuclear coded components, possibly a mitochondrial membrane site, which are required for the replication of mitochondrial DNA.


Replication of E. coli duplex DNA in vitro. The separation of the DNA containing fractions of a lysate from the soluble enzymes and their complementation properties. An E. coli lysate after being gently washed to remove soluble components, supports replicative DNA synthesis, if soluble proteins and the deoxyribonucleotide triphosphates are added. This DNA synthesis is dependent on ATP and on the presence of the gene products of the dnaB, dnaG, and polC (DNA polymerase III) genes. It continues at the replication forks preformed in vivo and "Okazaki fragments" are intermediate products of the reaction. Two different methods were used to prepare the washed DNA containing fraction. The one method involves washing of a cell lysate situated on a dialysis membrane. The other method involves DNAase treatment of a lysate and sedimentation of the degraded DNA through a glycerol gradient. Both washed preparation contain not only the DNA and the replication forks but also functional amounts of DNA polymerase III and of the dnaB gene product. Other factors, that are essential for replicative DNA synthesis, including the dnaG gene product, are washed out of the DNA containing preparations and the system is reconstituted by readdition of the soluble proteins.


Rapid test for assay of ozone sensitivity in Escherichia coli. A rapid test devised for assay of ozone sensitivity in Escherichia coli is described. The detection of new mutants, either more resistant or more sensitive than wild type strain to ozone, and the genetic analysis of ozone recombinants are now possible. Results confirm that ozone resistance is probably involved with DNA repair mechanism; and show that ozone and ultraviolet light inhibit the cell division capacity of lon mutant in a similar way.


lamB mutations in E. coli K12: growth of lambda host range mutants and effect of nonsense suppressors. Over sixty EMS induced mutations affecting gene lamB, presumably the structural gene for the lambda receptor in Escherichia coli K12, were examined for growth of lambda host range mutants and effect of nonsense suppressors. By the first criterion the mutations could be grouped in three classes. Bacteria with class I mutations allow growth of lambda mutants with extended host range (noted lambdah) of the type already described (Appleyard, MacGregor and Baird, 1956). Bacteria with class II mutations allow growth of lambdah mutants with still more extended host range (noted lambdahh). No host range mutants of lambda could be found which would grow on bacteria with class III mutations. Using nonsense suppressors it was found that class I and II consist of missense mutations, while class III consists of nonsense mutations. Exceptions are likely to exist (especially in class III) but were not found among the mutations tested. These observations are briefly discussed in terms of outer membrane protein integration and of phage receptor interaction.


Mutation of lambda during prophage induction by nitrosamides. Approximately 6% of Escherichia coli K12 (lambda wild-type) cells whose prophage was induced by treatment with N-methyl-N-nitrosourea initiated plaques on E. coli K12S which contained wholly or mostly clear plaque-forming mutants (lambdac). "Fuzzy" plaque-forming mutants (lambdaf) were also recognised, at lesser frequencies. Less marked mutation occurred during prophage induction by N-ethyl-N-nitrosourea, and no apparent mutation occurred during induction by methyl and iso-propyl methanesulphonates, or by a non-inducing treatment of the lysogen with ethyl methanesulphonate. Mutagenic effects of treatment of susceptible host cells or of phage alone, prior to infection, seem not to account for the phenomenon described.


Evidence against autorepression of the betabeta' operon in Escherichia coli. By using rifampicin to increase the rate of beta and beta' synthesis in a heterodiploid strain of E. coli carrying the mutation rifpr (Km7), which codes for a rifampicin sensitive RNA polymerase to which the drug binds weakly, and the dominant mutation rifRD, which codes for a rifampicin resistant RNA polymerase, the concentration of these subunits in the cell was increased 1.6 fold. Measurements made after removal of rifampicin from the cells showed that the excess beta and beta' subunits did not reduce the rate of their own synthesis below normal.


[A study of the reaction between antibodies and DNA by the method of immune complex formation on the membranes of nitrocellulose filters]. The conditions were developed to measure antibodies to denatured and native DNA. It was shown that membrane filters treated with alkali adsorbed denatured DNA complexed with antibodies. Utilizing this method it was shown that antibodies to denatured DNA react with pyrimidines (probably thymine). This assay provides proof of the wide existence antibodies to native DNA in the sera of patients with systemic lupus erythematosus. DNA-binding of sera was significantly depended on reaction condition.


[Affinity modification of phenylalanyl-tRNA-synthetase in the presence of ligands]. The kinetics of the affinity modification of phenylalanyl-tRNA synthetase from E. coli MRE-600 with chb-tRNA was used for investigation of copling between the binding sites of tRNA and other ligands. It was shown that ATP, phenylalanine and their mixture do not change the efficiency of complex formation but decrease specifically the rate of enzyme alkylation. L-Tyrosine and L-valine do not influence the enzyme alkylation. ATP is more effective protector than L-phenylalanine. In the presence of both ATP and phenylalanine the enzyme alkylation is excluded. The possibilities of this method for studying the coupling between binding sites are discussed.


[Oxytetracycline binding to E. coli ribosomes]. Binding of oxytetracycline to E. coli ribosomes was studied by equilibrium dialysis. The results are consistent with the existence of two classes of binding sites for the antibiotic on ribosomes having different reactivities. There is one strong binding site as well as about 500 weak ones. The association constant for strong complexes is about 10(3) times greater than the value for weak ones. Oxytetracycline and tetracycline bind to ribosomes as magnesium chelates. Increase of the concentration of Mg2+ leads to the formation of two types of magnesium chelates of the antibiotic: chelate 1 which is formed at a relatively low concentration of Mg2+ and has a stiochiometry 1:1, and chelate 2 which probably corresponds to the attachment of second ion to the antibiotic molecule. The strong binding of oxytetracycline to ribosomes prevents the template dependent association of aminoacyl-tRNA with ribosomes. However, no changes in the extent of the antibiotic binding were found upon addition of aminoacyl-tRNA, poly(U) and chloramphenicol to oxytetracycline-ribosome complexes. It has been suggested that inhibiting effect of oxytetracycline on the protein synthesis involves an allosteric mechanism.


[Paraneoplastic symptoms of neuroblastoma (author's transl)]. Frequently the first clinical sign of neuroblastoma is not caused by local or metastatic tumor growth but is a paraneoplastic symptom (PNS). Such PNS are fever, diarrhea, hypertension, weakness of muscles, Horner's syndrome and myoclonic encephalopathy. Certain PNS disappear with tumor removal, other do not. The clinical importance of PNS is the prognostic and especially diagnostic value. The pathogenetic relations between tumor and PNS as discussed in the literature are interesting but mostly speculative. Effects of Catecholamines and/or immunologic reactions are thought to be the most probable cause of PNS.--The article is based on current literature; in addition, two short case histories are presented.


[Hyperpyrexia and shock (author's transl)]. In childhood hyperpyrexia is the most important factor causing the irreversibility of shock. The combination of high fever and circulatory impairment is more frequent during the first years of life. This behaviour is due to the high resistance of the arterial system in infancy. Marked general vasoconstriction increases the risk of a reduction in circulation and of heat loss, and causes hypoxia and rise of fever. The further course of shock is largely determined by microcirculatory failures. Under hyperpyrexia the disturbance of homeostasis can be intensified by shivering, blocking of perspiratio sensibilis, hyperosmolarity, brain edema, and DIC. In most cases of meningococcal sepsis shock and DIC begin with vasoconstrictive centralisation of circulation. The high-output-shock is extremely rare in children with high fever. The control of all important functions of a febril child in shock is the best baseline for the treatment. It is necessary in all shock patients in hyperpyrexia to reduce the fever and to repair the peripheral circulation. The therapy consists of antipyretic drugs, physical cooling, infusions of buffer-bases, dopamine, antibiotics and so on. In DIC heparin or streptokinase are indicated. In severe circulatory impairment combined with high fever prednisone is useful, in brain edema dexamethasone. The fatality rate of our cases has been diminished by a systematic therapy of hyperpyrexia and shock from 10 to 3 percent.


Effects of cytochrome p-448 and p-450 inducers on microsomal dimethylnitrosamine demethylase activity and the capacity of isolated microsomes to activate dimethylnitrosamine to a mutagen. The relationship between microsomal dimethylnitrosamine (DMN) demethylase activity and the capacity of isolated hepatic microsomes to activate DMN to a mutagen was examined using microsomes from C57 and DBA/2 mice which had been exposed to three different types of microsomal enzyme inducers: phenobarbital, which induces cytochrome P-450, 3-methylcholanthrene, which induces cytochrome P-448, and the polychlorinated biphenyl, Aroclor 1254 which appears to induce both types of cytochromes. DNM induced mutagenesis was assayed by a Salmonella auxotroph reversion test. With the C57 mice all three inducers increased both the activity of microsomal DMN demethylase and the capacity of the microsomes to activate DMN mutagenicity. In each case, however, the increase in mutagenicity was disproportionately greater than the increase in DMN demethylase activity. This was particularly evident with microsomes prepared from Aroclor induced mice. Microsomes from 3-methylcholanthrene treated DBA/2 mice were not induced for DMN demethylase or the activation of DMN mutagenicity. In addition the capacity of Aroclor to function as an inducer was relatively poor in this strain. Both DMN demethylation and mutagenesis were inhibited by the addition of either SKF 525-A or benzo (a)pyrene to the reaction mixtures. Thus microsomal activation of DMN to a mutagen and DMN demethylase appear to involve both cytochromes P-450 and P-448.


Indirect selection for auxotrophic mutants of Saccharomyces cerevisiae using the antibiotic netropsin. The small basic oligopeptide antibiotic, netropsin, can be successfully employed as an effective counterselecting agent in Saccharomyces cerevisiae. The use of the drug results in approximately a 35-fold enrichment of auxotrophic mutants in a mutagenized culture of yeast. The experimental procedure is quite simple and less time consuming than other presently used methods for indirect mutant selection in yeast.


The absence of caffeine inhibition of post-replication repair in excision deficient strains of Escherichia coli B and K12. The effect of caffeine on postreplication repair, as seen in alkaline sucrose gradients, conjugation, and ultraviolet light (UV) survival, was studied in excision deficient strains of Escherichia coli K12 and B. A caffeine concentration of 2 mg/ml was chosen for the study which did not inhibit colony formation. Both E. coli K12 AB2500 and E. coli B WWP2 were more sensitive to UV when plated on caffeine plates. Conjugation was not inhibited in the E. coli K12 strain; however, the same procedure confirmed caffeine inhibition in the E. coli B strain [17]. Caffeine did not inhibit postreplication repair in either strain, as determined by sedimentation profile studies of DNA on alkaline sucrose gradients. No strand breakage or degradation was observed in parental or post-UV replicated DNA for as long as 50 min incubation in caffeine. Thus caffeine concentrations that inhibited two recA gene product related phenomena did not cause immediate changes in size of DNA or inhibit the rate of a DNA gap generating postreplication type of DNA repair.


Genetic activity of the antimicrobial food additives AF-2 and H-193 in Saccharomyces cerevisiae. The genetic activity of the antimicrobial food additives AF-2 and H-193 has been investigated in Saccharomyces cerevisiae. The strains chosen for the present studies were D5 for the induction of mitotic recombinational events and XV185-14C for the induction of reversion of the mutants lys1-1, his1-7 and homs3-7. When three concentrations (25, 50 and 100 mug/ml) of AF-2 were used in the reversion system of strain XV185-14C, there was an increase in the frequency of hom+ and his+ revertants as a function of incubation time, while the lysine mutant exhibited a very low frequency of induced reversion. When AF-2 and H-193 were compared at the same concentration and exposure time, AF-2 exhibited a higher genetic activity in both systems than H-193. However, H-193 was genetically more active in inducing revertants than AF-2, when the comparison was made at the same survival level. Cells of both haploid and diploid strains were found to be more sensitive to inactivation by AF-2 than by H-193 It should be pointed out that the solubility of H-193 was lower (about 4 mug/ml saturation) than the solubility of AF-2 (120 mug/ml saturation). The haploid strain was more sensitive to both compounds than the diploid strain.


Induction of point mutations by different chemical mechanisms in the liver microsomal assay. A selection of chemical agents with different mechanisms of chemical mutability was tested with the liver microsomal assay by using different bacterial tester strains, namely: Salmonella typhimurium TA 1535, TA 1536, TA 1537, TA 1538 and G46. The tested agents had been selected according to the following criteria. They are all well-known mutagens and can be divided into alkylating agents, anti-metabolites, acridines and those that form radicals in the cell. The mutagens were: dimethylnitrosamine (DMN), diethylnitrosamine (DEN), methyl-nitro-nitrosoguanidine (MNNG), cyclophosphamide, Captan, amethopterine, azathioprine, 6-mecaptopurine, trypaflavine, isoniazide and hydrazine. All except amethopterine gave positive results, showing that this system is very sensitive. In a comparison of the different strains and mutagens we found a correlation between the diameter of the molecule and the permeability of the bacterial cell membrane.


Evaluation of the genetic effects induced by vinyl chloride monomer (VCM) under mammalian metabolic activation: studies in vitro and in vivo. As part of a programme of investigations on the biological effects of the industrial compound vinyl chloride monomer (VCM), the raw material for the production of polyvinyl chloride (PVC), analyses on the genetic effects by this compound have been done by experiments (in vitro) which have taken mammalian metabolism into account. Vinyl chloride in the presence of purified microsomes (sedimented at 105,000 g) obtained from mouse liver was converted into an active metabolite(s) which produced gene mutations in the yeast Schizosaccharomyces pombe (forward mutation) and gene conversions in two loci of a diploid Saccharomyces cerevisiae. Moreover, the compound was active in the host-mediated assay, when mice were treated with an oral dose of 700 mg/kg. The role is discussed of mutagenicity tests for the prediction of both genetic and carcinogenic risks of chemical compounds in industrial use.


The resistance factor to Plasmodium vivax in blacks. The Duffy-blood-group genotype, FyFy. Duffy-blood-group-negative human erythrocytes, FyFy, are resistant to invasion in vitro by Plasmodium knowlesi. The FyFy genotype is found predominantly in African and American blacks, who are the only groups completely resistant to infection by P. vivax. To determine if the FyFy genotype is the vivax resistance factor, we performed blood typing on 11 black and six white volunteers who had been exposed to the bites of P. vivax-infected mosquitoes. Only the five FyFy blacks were resistant to erythrocytic infection; the remaining six blacks and all whites had the Duffy-positive determinants (Fya or Fyb or both) and had contracted malaria. We conclude that Duffy determinants (Fya or Fyb or both) on the erythrocyte surface are required for invasion of erythrocytes by vivax merozoites.


Anti-B lymphocytotoxins in renal-allograft rejection. To determine the possible role of the B lymphocyte alloantigen system in renal-transplant rejection, we examined serum specimens from 81 allograft recipients for cytotoxic activity against a panel of normal B lymphocytes. Specimens from 22 of 25 recipients undergoing allograft rejection demonstrated strong B-lymphocyte cytotoxicity whereas only 13 of 56 recipients with normal allograft function showed similar B lymphocyte cytotoxocitiy (P less than 0.0001). In the serum samples of recipients with graft rejection who were followed sequentially, B-lymphocyte cytotoxicity preceded or was concurrent with the onset of functional impairment. The results show that anti-B-lymphocyte antibodies are associated with rejection, but it is quite possible that they are the products of rejection rather than the cause.


On the fungitoxicity of some new thiocyanatopyrazole derivatives: electron microscopical study in Trichophyton mentagrophytes. Four thiocyanatopyrazole derivatives were synthesized and their fungistatic activity was demonstrated in vitro against a number of dermatophytic fungi. In Trichophyton mentagrophytes, the most active compound induced as unusual increase of the plasma membrane with production of intra and extracytoplasmic complexes, a deterioration of nuclear and mitochondrial membranes and a formation of autophagic-like vacuoles. Plasmolysis, accompanied by an almost complete disorganization of cytoplasmic structures, seemed to be the final event. A possible mechanism of action of the compounds were discussed.


Reflections on 200 years of science in the United States. In spite of its obvious importance today, the history of the sciences in the USA is usually neither the subject for research nor part of courses taught by non-American historians. Nor is this history known and understood, particularly in Europe. This is in marked contrast to an avid interest in current US science policies and developments, which cannot be wholly explicable without an understanding of their historic origins. Broadly speaking, these origins are US variants of certain western European traditions resulting, as it were, in cults of knowledge, nation, and people. Science and scientists have flourished, but uneasily, in the resulting environment.


Furosemide in acute oliguric renal failure. A controlled trial. A randomized study was conducted on 66 patients with acute established oliguric renal failure. Intravenous doses of furosemide ranging from 1.5 to 6.0 mg/kg were given every 4 h to 33 of the patients; the remaining 33 patients served as controls. A persisting diuretic response was observed in 5 treated patients and in 2 controls. Hemodialyses were required in most of them. Furosemide did not significantly modify in cured patients the mean oliguric period, the number of dialyses and the mean period of renal insufficiency.


The role of vesico-ureteric (V-U) reflux in the pathogenesis of kidney scars in the rat. In Wistar rats V-U reflux with distilled water and sterile saline of varying osmolar strength produces scars in the perihilar region of the kidneys in 80% of animals. Using Indian ink as a marker, rupture of the forniceal epithelium regularly followed V-U reflux. Intrapelvic pressure rose to 120 mm Hg during the reflux procedure. A slowing of proximal tubular transit time was observed by the Lissamine Green technique in the nephrons in the perihilar region immediately after the kidney had been subjected to reflux. It is suggested that the kidney scars which develop after reflux of sterile solutions are ischaemic in origin. It was shown that kidneys damaged by reflux have an increased susceptibility to haematogenous infection.


[CT findings in chronic subdural hematomas (author's transl)]. CT findings of 46 patients with operatively confirmed chronic subdural hematomas are reviewed. The analysis of the EMI scans resulted in three different types of CT findings. Type 1  is characterized by decreased attenuation of the hematoma contents compared to brain tissue. The hematoma is visualized as a lens-shaped low density area between the skull and the surface of the brain. Type 2 apart from low density areas contains zones of increased attenuation due to recent bleeding into a watery chronic subdural hematoma. In many cases sedimentation causes a well-defined horizontal borderline between the thin fluid parts in the anterior portion and the blood debris in the posterior portion of the hematoma sac. Type 3 shows the same average absorption values as normal brain tissue, a direct visualization is not possible. However , the presence of a midline displacement in combination with ventricular compression and absence of a circumscript lesion even after contrast enhancement, allows the diagnosis of a unilateral chronic subdural hematoma in these cases too. Bilateral chronic subdural hematomas may cause considerable diagnostic difficulties if only one or none of the hematomas is visualized. A relatively small midline displacement points to a second bleeding on the opposite side. Most frequent were hematomas of type 1 (37%), type 2 and 3 could be observed in 30,5% resp. 32,5% of cases respectively.


Friedrich-Christian Rosenthal-biographical note. A short biographical note about Friedrich-Christian Rosenthal, a German anatomist, disciple of Reil, born in Greifswald on the 3rd of June 1780, died prematurely in the same town on the 5th of December 1829, leaving unfinished an important work on the anatomy of the brain and cranial nerves. His name is still associated with the spiral canal of the inner ear and to the basal cerebral vein.


Studies with bromocriptine. Part 2. Double-blind comparison with levodopa in idiopathic parkinsonism. A double-blind crossover study was performed in 12 patients with idiopathic parkinsonism to compare their response to bromocriptine with their response to previous optimal drug treatment, including levodopa. There was a 26 percent overall improvement with bromocriptine; rigidity, tremor, and facial expression showed the greatest response. Seven of eight patients who were taking levodopa at the beginning of the study was taken off the drug completely. Adverse reactions were transient and dose-dependent. Bromocriptine promises to be an effective new therapeutic agent in the treatment of idiopathic parkinsonism.


Effect of papaverine on cerebral electrogenesis. A double-blind, placebo-controlled study was conducted in 20 elderly patients with dementia associated with diffuse cerebrovascular disease to determine the effects of papaverine on the electrical activity of the brain. Frequency spectrum analysis of electroencephalograms showed the mean electrical content of the delta-theta band (0 to 7.5 Hz) was decreased significantly and content of the alpha band (7.6 to 12.5 Hz) was increased significantly from baseline. The changes in electroencephalographic activity observed in this study suggest that papaverine favorably affects neuronal metabolism, possibly through improved perfusion of the tissue, although the exact mechanism of action remains unknown.


[The possibility of inducing subcutaneous granulomas using plant foreign bodies. Experimental research]. Experimental research designed to provoke subcutaneous granulomas by means of vegetable foreign bodies in animals is reported. The possibility of influencing the ongoing picture by means of anti-inflammatory drugs was also investigated. The findings were similar to those observed in a patient with a similar foreign body responsible for a perineal granuloma. The anti-inflammatory substances employed, however, had no effect on the aspecific granulomatous reaction.


[Synthetic PH-RH as a pituitary function test in anorexia nervosa]. The hypophyseal gonadotrophin LH reserve was studied in 9 adult women, 5 of whom were suffering from nervous anorexia (N.A.) and 4 normal, by means of subcutaneous injection of 50 mcg of synthetic GN-RH. Basal values of plasmatic LH proved to be significantly lower in N.A. than in the controls where the response to GN-RH was prompt. In patients with N.A., on the other hand, response was practically absent and differences were significant at all stages of the test. The parallel study of basal steroiduria and following methopirone confirmed the torpid hypophyseal response in N.A. These findings confirm previous personal reports and indicate that the GN-RH test is a useful technique for diagnostic and prognostic definition of N.A.


[Frontal vertebral cleft in the newborn]. In the newborn and foetus in the last months of gestation it is possible to see in lateral radiography of the spine, a longitudinal radiotransparent band which may divide the bone nucleus of the vertebral body into two portions. This front vertebral separation should be considered an expression of a reversible abnormality rather than a malformation to the extent that it almost always concerns a differentiation delay in the vertebral structures. The literature and personal cases show, in fact, that the finding disappears more or less rapidly.


[Physiopathology and clinical aspects of respiratory tract infections. Review]. A topographical account is given of the (mostly viral) infections that strike the upper airways and the lung parenchyma sites caused by bacteria, Mycoplasma, Rickettsiae and fungi. The different features of the three main syndromes that ensue: obstructive and restrictive ventilatory insufficiency, and alveolo-capillary block, are examined. The need for care in the administration of antibiotics is stressed, since germ resistance must be restricted as far as possible. In the case of chronic forms of lung disease, careful clinical surveillance and active therapeutic management are mandatory to prevent the establishment of irreversible, incapacitating consequences.


[Autologous skin grafts in laparoceles]. The theoretical, practical and experimental premises of autologous skin graft in the treatment of laparocele according to the technique of Zavaleta and Uriburù are discussed. The validity of the technique, already acknowledged by other workers, is confirmed by personal experience of operations on geriatric patients.


[Deep immersion in the light of current scientific knowledge]. Physiological and technical problems related to deep diving are discussed. Starting from a brief summary of fundamental data, the Author deals with breathing mixture, the diver protection, copression rates and other various problems the principal syndromes originated by gases at high pressure in hyperbaric conditions. An analysis of the most important physical factors which can interfere with the tolerability for long period in such artificial athmospheres has been conducted.


Effect of clomiphene citrate on gonadotropin responses to LRH administration in secondary amenorrhea and oligomenorrhea. Clomiphene citrate was administered to 17 patients with either secondary amenorrhea or oligomenorrhea to study its effect on hypothalamic-pituitary response. Measurement of pulsatile gonadotropin output was accomplished utilizing samples collected every 20 minutes for 6 to 8 hours before and after clomiphene administration. Response to 100 mug synthetic luteinizing hormone releasing hormone (LRH) was measured at the end of the sampling period. Patients with polycystic ovarian disease who ovulated showed increased baseline FSH and LH, decreased peak LH, and a decrease in the percentage increase over baseline for both LH and FSH. On patient wil clinical anorexia nervosa responded to clomiphene as an estrogen, with lowered baseline LH and FSH values. Patients with resolving anorexia responded to clomiphene as an antiestrogen, with increased baseline gonadotropins, and decreased gonadotropin peak values. A patient with a surgically treated chromophobe adenoma showed no change in parameters measured before and after clomiphene administration. Baseline and pulsatile LH output appear to reflect the tonic output of gonadotropin as affected by estrogen acting in a negative feedback system, and the peak response to LRH administration, the response to the positive feedback of estrogen. Thus, LRH stimulation in clomipheneresistent patients may be of value in diagnosing the site and degree of the defect and aid in improving therapy.


Group B streptococcal colonization in pregnancy. Group B beta hemolytic streptococcal infection of the newborn, acquired from the maternal genital tract, has emerged as an important cause of morbidity and mortality. In that the risk to the infant for colonization and infection may relate to the degree of streptococcal exposure, a semiquantitative determination of genital tract colonization was made in 210 pregnant women. Twelve women (6%) were colonized with 10(0) to 10(5) colonies of streptococci per sample. Among colonized women, 70% had used oral contraceptives in the year prior to pregnancy, whereas only 35% of uncolonized women gave such a history (P less than .05). There was an inverse relation between colony count and duration of pregnancy. Six of 9 untreated, colonized women had 1 to 3 repeat cultures which were negative for streptococci indicating that treatment for carriers, if available, would not be necessary much of the time.


The predictability of intrauterine infection by analysis of amniotic fluid. Amniotic fluid samples from 95 internally monitored patients were examined to determine whether the appearance of polymorphonuclear leukocytes or bacteria could predict intrauterine infection. All patients delivered vaginally. More than one polymorphonuclear leukocyte per oil field were seen in specimens of 32% of patients; bacteria were seen in specimens of 52% of patients, and organisms were grown in 93% of specimens, yet, the overall maternal infection rate was only 6.3%. Moreover, infection developed in only 10% of patients with polymorphonuclear leukocytes in the fluid and 6% of patients with positive gram stain or cultures. For patients who deliver vaginally, the appearance of polymorphonuclear leukocytes or bacteria does not predict infection.


The effect of L-dopa and clomiphene citrate on peripheral plasma levels of luteinizing hormone-releasing factor. Response of luteinizing hormone-releasing factor (LRF) and gonadotropin levels to orally administered L-dopa and clomiphene citrate were measured in 13 healthy female volunteers. Testing was carried out during the early follicular phase of the menstrual cycle. The results indicated a suggestive but statistically nonsignificant elevation of peripheral plasma LRF following L-dopa administration but no response following clomiphene ingestion. No acute increase in gonadotropin levels was demonstrated in either group. A low but statistically significant positive correlation was found between luteinizing hormone and LRF values determined from the same samples.


An equipment for standardized casting of Co-Cr alloys in dentistry. The temperature and the chemical character of an acetylene-oxygen flame change with change in the gasmixture. When heating a Co-Cr alloy with this flame both temperature and chemical character in the parts of the flame used may influence the temperature increase of the alloy. To study the influence of different acetylene-oxygen flames on the heating process of dental Co-Cr alloy, a gasmeasuring and casting equipment was constructed. This made it possible to cast in a standardized way.


Lymphomas as sequelae of the transplantation of CO2-treated skin autografts in mice. Inbred strains BALB/c and CBA and noninbred Swiss mice were used for transplanting skin autografts exposed before transplantation for approximately 48 h to (a) culturing in room air and (b) culturing in 45--48% CO2 in air. These pre-transplantation manipulations of skin autografts led to malignant lymphomas in the hosts. The lymphoma incidence was highest in the recipients of the CO2 -treated grafts; moreover, it was greater than the spontaneous incidence even in the recipients of grafts exposed to culturing in air alone, in some types of mice. The following abnormalities of the reticuloendothelial system were noted: (1) proliferation of lymph follicles into irregular masses of pleomorphic cells, (2) hyperplasia with concomitant atrophy of the lymphoid tissue (o) replacement of the lymph follicles by malignant lymphoid cells. Renal lesions resembling membranes glomerulitis occurred occasionally. The occurrence varied in different strains.


Transfer factor - hypotheses for its structure and function. Transfer factor (TF) is a dialyzable extract from primed lymphocytes that is able to transfer specific delayed hypersensitivity from one animal to another. On the basis of available data we suggest that TF is a polypeptide with a molecular weight below 15,000 daltons. We hypothesize that TF is the variable light or heavy chain domain of immunoglobulin: such a molecule conforms with the accepted properties of TF and also has the necessary specificity requirements. We also hypothesize that TF is part of a receptor site. beta-2-microglobulin, a molecule that is an integral part of cell surfaces, could be the anchor for TF. beta-2-microglobulin has homologies with the constant  portion of immunoglobulin light or heavy chain and thus would combine with the variable domain (TF) to form a complete receptor site for a specific  antigen. The properties of TF suggest its mode of action, which is discussed in detail in the text. The biologic advantages of TF is its ability to confer immediate (immunologie specific) protection while the 'normal' immune response develops.


Penetrating keratoplasty: a computer analysis. A computer analysis of 87 penetrating kertoplasties done in a uniform manner by a single surgeon revealed the following: 1. On a statistical basis small grafts (7.0 mm) provided better visual acuity than larger grafts (8.0 mm). 2. On a statistical basis small grafts will be clearer postoperatively than larger grafts. 3. On a statistical basis the age of the donor is not related to either graft clarity or visual acuity.


Soft tissue trauma.

Soft tissue trauma. Prior to surgical repair of maxillofacial injuries, a surgeon should formulate an operative plan based upon a careful and complete pre-operative analysis. Obviously this may effect the timing of repair. However, it is more efficacious to delay surgery for up to 24 hours than to close lacerations over a lacerated facial nerve, a severed parotid duct, or other undiagnosed lesions. Repair should include meticulous cleansing and removal of all embedded foreign material if hypertrophy, scars, or tattooing is to be avoided; repair of underlying soft tissue damage, including mucosa, muscle, nerve, cartilage, and subcutaneous tissue; and meticulous closure of the lacerations in accordance with their anatomical location. In wounds involving tissue loss the judicious application of skin grafts, as well as local or regional flaps, is of infinite value. With the careful adherence to the basic principles of plastic reconstructive surgery, the majority of patients with maxillofacial injuries should obtain a good functional and esthetic restoration. In patients in whom this cannot be accomplished because of extensive tissue damage, the primary repair should enhance the feasibility and results of secondary reconstruction.


Operative treatment of pressure sores in paraplegics by rotation flap. Sixty rotation flaps (in 40 paraplegics) to cover pressure sores and unstable scars in the region of the buttocks are reported. There were 12 complications (20 per cent), none jeopardising the result of the operation. Advantages of the rotation flap are its good blood supply if generously outlines and the possibility of using the same flap a second or even third time if necessary.


[Heterotopic autotransplantation of the atrium in the rat. Effect on specific granules (author's transl)]. A technique for the autotransplantation of part of the right atrium in the rat kidney is described. The morphology of these grafts has been studied by light and electron microscopy at intervals varying from 15 to 346 days after transplantation. On light microscopy, the grafts show an organoid organization with a central cavity filled with blood surrounded by an endothelium around which concentric layers of cardiocytes are present. Electron microscopy reveals that the population of specific granules is not affected by transplantation. In the beginning, the cardiocytes show severe abnormalities of myofilaments, mitochondria and sarcoplasmic reticulum. The granular sarcoplasmic reticulum is much more abundant than in control cardiocytes. Most of these changes regress with time so that, after 346 days the transplanted cardiocytes appear almost normal. These experiments indicate that the specific granule population of atrial cardiocytes probably does not contain any appreciable amount of catecholamine and is not dependant on the nervous system or on a local stimulus.


["In vitro" effect of medium size molecules on lymphocyte proliferation (author's transl)]. Eluates from uremic sera were obtained by chromatography on sephadex G 25. They were assayed on lymphocytes cultured in the presence of various stimulants. Lymphocyte proliferation induced by mitogens or allogeneic cells was markedly inhibited in the presence of medium size molecules (MM), or of larger molecules (MW greater than 5000).


[Intermolecular antigenic competition. Influence of the site of antigen injection (author's transl)]. We have studied the intermolecular antigenic competition in mice, after simultaneous injections of two antigens by different ways and in various places. When the two antigens are administered by I.P. route, and when TNP-SHRBC (Test-Ag) and BSA (inhibitory Ag) are used, only an inhibition of the anti-hapten (TNP) response is observed but not of the anti-carrier response (SRBC). When these antigens are replaced by SRBC (Test Ag) and HRBC (inhibitory Ag), there is no antigenic competition. When the inhibitory Ag is the BSA and the test Ag a strong dose of LPS (10 mug) there is no competition but it occurs when a weak dose of LPS is used. When the two antigens are injected by subcutaneous route in the same leg and the PFC enumerated in the corresponding inguinal lymph-node there is no inhibition but an increased response against the test Ag. On the contrary, competition is obtained when the test Ag (TNP-SHRBC or SRBC) is injected in the right leg and the inhibitory-Ag (BSA or HRBC) in the left one. These facts lead to conclude that an inhibitory humoral factor is responsible for this phenomenon, and that this factor is probably thymodependent because this competition disappears when Nude mice are used.


[Effect of low lung volume ventilation on the relative proportions of carbon monoxide partial ductances (author's transl)]. Lacoste has shown the interest of determination of overall ductance of CO and partial expired alveolar ductance and arterio-alveolar partial ductances in the assessment of the efficacy of gaseous exchanges in the lung. DuCO was, by definition, the product : DuACO X DuaCO, the increase in partial ductance may theoretically compensate reduction in the other, the overall ductance then remains normal. This theory was verified studying the effects of low lung volume ventilation. Under these conditions, the dead space series becomes reduced and the DuACO should increase at the same rate, for ventilation occurs at the level of the closing volume. The inspired air is then directed preferentially towards the lung apices. These artificial changes in distribution of ventilation should produce a reduction in DuaCO. The measurements carried out confirmed these theories during low lung volume ventilation ; whereas the differences observed in overall ductance were not significant, those observed on partial ductance were very definitely significant. It appears that isolated measurement of overall ductance is insufficient and may lead to misdiagnosis of a change in the lung exchanges.


[Lipid calcium interactions in experimental and human nutrition (author's transl)]. A balanced intake of alimentary lipids is necessary for calcium and phosphorus absorption, as for growth and calcification of bone. In lipid deprivation or excess, important disorders of phospho-calcic metabolism appear particularly in young growing subjects. The qualitative content of ingested fats has, too, a great influence : lipids containing short and medium-chain fatty acids, essential fatty acids and oleic acid stimulate calcium absorption. An excess of long chain and saturated lipids, or intake of erucic acid depress calcium absorption and retention. These facts are possible pathophysiological mechanisms in human disorders: The so-called humanized milks are close to human milk regarding their capacity of stimulation of phospho-calcic absorption and growth. In these milks, oleic and linoleic triglyceride level must be increased. In adult pathology, lipidic deficiency of steatorrhea is partially responsible for calcium and vitamin D malabsorption. Conversely, lipid-calcium interactions are not one-way, and an elevated dietary calcium depresses saturated lipid absorption, and has a hypolipemic action interesting in prevention of atherosclerosis of aged patients.


[Automatic complement fixation reaction applied to the diagnosis of influenza (author's transl)]. Auto-analysis has been adapted to the study of complement fixation on flu antigen-antibody complexes. The antigen used consists of a complete virus of strain A2/AICHI/68/H3N2 (antigen of envelope V). The advantages of this method reside in the reproducibility of the results and in instrumental reading with graphic recording and conservation of a graphical result. The recording of the percentage of hemolysis given by the auto-analyser permits calculation of the rate of the reaction K37 of complement fixation on the formed immune complex. This value is independent of temperature, time of fixation and the initial quantity of complement used. It is proportional to the quantity of specific antibody. Thus, the value of K37 is proposed as mode of expression of the results replacing the limit serum dilution.


[Investigations on production of spheroplasts in different species of the genus Haemophilus isolated from pathological material of the respiratory tract (author's transl)]. One hundred and fifty three strains belonging to 5 different species of the Genus haemophilus isolated from pathological material of the respiratory tract, have been submitted to the action of inductive agents. Under their influence, all those strains, and consequently all the species examined undergo morphological changes and give rise to spheroplasts. The present work demonstrates that this phenomenon not only belongs to Haemophilus influenzae but probably is a common characteristic of the Genus Haemophilus.


[Survival and humoral response of mice infected with Treponema pallidum (author's transl)]. To judge the pathogenicity of Treponema palllidum in mice, we inoculated two groups of animals. 1) One with a normal immune system : adult Swiss mice. 2) The other with an immune system presenting a defect in T cells : athymic Nude mice.  No lesions appeared at the points of inoculation and the survival of these animals was not modified compared with control animals. We have also carried out a study of antitreponema antibodies in adult and new-born Swiss mice, using, for the adults, various concentrations of treponema pallidum and various routes of inoculation. In adult mice, the search for antibodies by fluorescence, showed, firstly, that the intradermal route permits a more rapid humoral response than the intraperitoneal route, with higher antibody titers. Furthermore, an inoculum of 8,6 X 10(6) per mice, gives earlier results and higher titers than those obtained with an inoculum twice lower. The earliness of the positive Nelson test is independent of the route of inoculation but related to the injected dose. On the other hand, the Kline reaction remained negative for all groups of mice throughout the whole period of our study. In new-born mice, 76% only became positive on fluorescence and Nelson test.


[Study of oral contraceptives action on blood folate levels (author's transl)]. In 95 women taking reduced-level-oral contraceptives and in 24 same-aged women controls, the measure of erythrocyte and serum folate led to the following conclusions: 1) Folate levels in women consuming the pill were generally found to be of the same range as those of controls. 2) No significant difference could be shown between results for different kinds of contraceptives.


[Antibacterial activity of minocycline alone and associated with other antibiotics (author's transl)]. The authors study in vitro effects of minocycline and compare its activity with tetracycline. 909 strains of cocci and bacilli selected among strains isolated from Clermont-Ferrand Hospital Center during the third trimester 1974 were used. Study involves 3 parts : comparison between bacteriostatic activity of both antibiotics ; evaluation of R-factor resistance ; evaluation of bactericidal activity of antibiotic associations including minocycline. M.I.C. study included all strains. A better bacteriostatic activity was noted with minocycline against multi-resistant strains of staphylococcus, streptococcus, E. coli, Serratia and Moraxella. R-factor resistance has been studied upon 27 strains of Gram-negative bacilli selected for their high M.I.C. to tetracycline (M.I.C. greater than or equal to 64 mcg/ml) and to minocycline (M.I.C. greater than or equal to 32 mcg/ml). Both types of transferable tetracycline resistance characters Ta and Tb have been found. More than 250 bactericidal associations were studied upon 38 strains.


[Use of computers in real time. Clinical supervision of hypertension. Application to research (author's transl)]. High blood pressure has been selected as the subject of a first attempt at constituting an automated online medical records system at the Centre Médico-Chirurgical FOCH. This system is to be used routinely by physicians and nurses for daily care of patients and in statistical analysis of registered data for research purposes. Its operational phase is now beginning : registration of patients, edition of collected data, plannings of activity and abstracts are made routinely. Use of the system for clinical research purposes of an epidemiologic nature and its adaptation to more sophisticated tasks is planned in the near and more distant future.


[Oral vitamin A tolerance tests in hypertriglyceridemia (author's transl)]. HVA tolerance tests were performed to study the post-absorptive lipemia of 32 patients with hypertriglyceridemia. Among them 10 had a normal test and 22 a pathological test. This difference shows the existence of an exogenous factor in the second group of hypertriglyceridemias, which is poorly related to the typing of the WHO classification, but much more to the value of the cholesterol/triglycerides ratio of each patient. The separation of these two groups is of great interest for their therapeutical management, the hypertriglyceridemias with exogenous factor being more sensitive to diet than the others.


[Unusual distribution of fluorescent marking during Schistosoma mansoni schistosomiasis (author's transl)]. The sera of some patients suffering from intestinal bilharziasis determine, on frozen sections of adult S. mansoni, a labelling of the digestive tract disclosed by the fluorescent sera anti-IgG and IgM. This labelling appears early after the primary infestation and may remain isolated. It is found again later, among West Indian patients of all ages infested by S. mansoni. Its development is followed in the hamster and the mouse, experimentally infested. This labelling is also present in the animal infested with S. haematobium, but it appears exceptional among adults urinary bilharzians. No cross reaction of non-specific origin has been observed. The interest, for the screening, of its research with the help of conjugates anti-IgM, has been proved. Its meaning is discussed.


[Formation of "Rosettes" induced by polyethylene glycol]. Human blood cells were washed and treated by PEG 6 000 (40% solution in BME) at 37 degrees for 15 min. A strong agglutination was observed. After dilution with 3 vol. of BME and shaking, microscopic examination at low magnification revealed small aggregates disseminated in dispersed population of erythrocytes. These aggregates were shown to be formed by a polymorphonuclear cell closely surrounded by erythrocytes. The possible explanation of the formation of such "Rosettes" was briefly discussed.


[Normal and pathological elastic tissue under the electron microscope on thin and ultrathin sections (author's transl)]. Three simple methods (adapted from optical techniques) for normal and pathological elastic tissue caracterisation in electron microscopy on thin and ultrathin sections are proposed. Two of these methods (orcein and fuchsin resorcin) seem to have a specificity for arterial and breast cancer elastic tissue. Weigert's method gives the best contrast.


[Tumor immunology (author's transl)].

[Tumor immunology (author's transl)]. Prerequisites for immunobiological interactions between host and tumor are the existence of tumor-specific surface antigens on cancer cells on the one hand, and the ability of the host to recognize and to adequately respond to these signals on the other. It seems that in certain selected animal models these conditions are matched. The relations of the spontaneously arising human tumors to these prerequisites, however, are still largely obscure. It is known that immunological measures can both accelerate or inhibit tumor growth. Thus, immunoprophylaxis and immunotherapy in man is still premature and too risky.


Neonatal pancreatic beta-cell hyperplasia: report of a case with failure of diazoxide and benefit of early subtotal pancreatectomy. A newborn infant with pancreatic beta-cell hyperplasia had persistent hypoglycemia due to hyperinsulinism. After medical management, including the use of diazoxide and constant glucose infusions had proved ineffective, a subtotal pancreatectomy was curative. Cumulative experience seems to indicate that there should be little delay in performing a subtotal pancreatectomy when aggressive medical management cannot maintain normoglycemia in a neonate.


Use of Limulus lysate for detecting gram-negative neonatal meningitis. The Limulus lysate test was evaluated as a method for rapid detection of neonatal gram-negative bacterial meningitis. A total of 208 CSF samples were collected from 145 newborn infants suspected of having meningitis. Initial samples from all six babies with culture-proven gram-negative bacterial meningitis had positive Limulus tests within 30 minutes of incubation. Samples from 14 infants with gram-negative organisms isolated only in blood and/or urine as well as from four neonates with gram-positive organisms in CSF cultures and from 13 with gram-positive organisms in blood cultures all yielded negative Limulus tests. Thus, of 37 newborn infants with bacteria demonstrated in systemic cultures, only those six with gram-negative organisms in CSF had positive CSF Limulus tests. The CSF Limulus test was shown to be a rapid, reliable, and specific test for the detection on neonatal gram-negative bacterial meningitis.


Physical therapy as a determinant of change in the cerebral palsied infant. Twenty-four children under 18 months of age with an initial diagnosis of cerebral palsy were observed for minimum of six months on either experimental or control physical therapy programs using a double-blind study design. Medical and therapy evaluations indicated definite changes in motor, social, and management areas for those subjected to the experimental procedure and particularly among children expected to show higher intelligence. Change is found to be somewhat correlated with age at entry to the study and is more often associated with less actual treatment time. Findings suggest the need for additional treatment modalities for the youngest children who are most likely to have the greatest global involvement.


[Biological changes in 88 cases of Basedow's disease treated by radioactive iodine]. Biological abnormalities, in particular increased T3 and sometimes TSH, are frequently found in thyrotoxic patients treated with radioactive iodine and subsequently enthyroid. A high T3, associated with an increase in FT4 and a low TSH precedes a relapse. An increase in TSH may indicate progression towards hypothyroidism; even if FT4 and T3 levels are within normal limits. Caution must be exercised before affirming that an increased TSH with a high T3 and normal FT4 is indicative of thyroid equilibrium. At all events, the risk of hypothyroidism despite the use of small doses of radioactive iodine is such that the classical limit for the treatment of patients with thyrotoxicosis should be increased beyond the age of 40. In patients with a high TSH despite being clinically euthyroid, the use of thyroid extract in low dosage (50 mg/day) would appear to be desirable in avoiding the subsequent development of hypothyroidism.


[Microbiological study of surfaces in the hospital environment]. A quantitative bacteriological study was made, in several hospital services, of the number of organisms present on the floors and various surfaces. Two sampling techniques were used in parallel, direct imprint and brushing. The first of these techniques, new and easy to use, is suggested in this study for the regular surveillance of the microbiological cleanliness of floors, as well as for the selection, under the particular individual circumstances, of the best composition of disinfectant.


[Trial treatment of glioblastomas in adults and cerebral metastais by adriamycin, VM 26 and CCNU combination. Result of a type II trial]. Forty-three patients with inoperable and/or recurring malignant gliomas, and 30 patients with multiple recurring brain metastases were treated with a combination of adriamycine (45 mg/m2) and 4-dimethyl-epipodophyllotoxin D-thenylidene (VM 26) (60 mg/m2 for 2 days) with 1-(2-chloroethyl) -3-cyclohexyl-1-nitroso-urea (CCNU) (60 mg/m2 for two days). These cycles of treatment were repeated as soon as the hematological restoration was complete. The treatment was well tolerated and the clinical condition of 31 out of 43 glioblastoma patients improved during the two months after the beginning of the treatment. Six out of eight patients with breast cancer metastases, one out of 13 with bronchial cancer metastases and three out of nine with other types of cancer metastases also benefitted from the treatment. Examination of the results obtained reveals the following characteristics: -A low degree of efficiency of the combination in the treatment of brain metastases, except for breast cancer metastases. -Absence of complete correlation between the clinical results observed and the cinegammagraphic developments. -Similarity of the results independent of the initial localization. -Establishment of a six-months median survival period, with ten patients at present in a state of apparently complete remission, 180 to 506 days after beginning of the treatment.


Effect of Prepodyne as a perineal cleansing agent for clean catch specimens. In a study to determine a safe cleansing agent for collection of midstream urine specimens, 35 pregnant women (25 experimental subjects who cleansed the periurethal area three times with Prepodyne and 10 control subjects who did not cleanse the area), Prepodyne was found to be satisfactory. Although iodine was detected in the urine of women who used Prepodyne, the amount was not in sufficient quantity to alter bacterial colony counts or to inhibit growth.


Further study on pharmacology of meclophenoxate and it components in mice. The effects of three-day treatment with meclophenoxate (Centrophenoxin) and its components, p-chlorophenoxyacetic acid and dimethylaminoethanol, on the aggressiveness and pain threshold in mice were investigated. p-Chlorophenoxyacetic acid increased the aggressiveness and pain sensitivity. Dimethylaminoethanol, on the contrary, tended to decrease these items of behaviour. The effects of meclophenoxate reflected this reciprocal activity of components, the activity of p-chlorophenoxyacetic acid prevailing. The results are taken as the evidence of some slowly developing mechanism in the activity of p-chlorophenoxyacetic acid, responsible for some of the effects of meclophenoxate. A possible mode of action of p-chlorophenoxyacetic acid is suggested.


Recognizing the fetus at risk.

Recognizing the fetus at risk. Impairment of either fetal growth potential or placental growth support may cause fetal growth retardation. Impaired growth potential is associated with a number of congenital abnormalities. Awareness of the increased possibility of fetal anomaly comes from the obstetric patient's reproductive history or family history more than from anything else. In general, if the likelihood of fetal anomaly seems increased, investigation in the form of amniocentesis, ultrasonic monitoring of fetal growth, radiologic study, or all three may be required. More common than poor growth potential is poor placental growth support. Here, historical evidence of maternal hypertension or toxemic disorders, among other abnormal clinical findings, is an indication for fetal monitoring.


Exogenous estrogens and endometrial cancer. Reports in the lay press that exogenous estrogens cause endometrial cancer are unjustified with the present evidence. The epidemiologic method used to identify retrospectively an increased association of estrogens with endometrial cancer cannot prove causality. Mortality from endometrial carcinoma has not increased in this country and may actually be starting to decline.


A semi-quantitative test for water supply. A recently marketed reagent strip designed for clinical urinalysis, Microstix, has been found to be useful in rapid and simple examination of water sources for baby chicks.


The cholesterol problem, the egg and lipid metabolism in the laying hen. There is little doubt that high blood serum lipid levels are related to a higher incidence of atherosclerotic disease in humans. Experimental evidence to date suggests that dietary intervention can reduce blood lipid levels in most cases and that some small reduction in occurrence of cardiovascular disease will probably result. On the other hand no reduction in total mortality has been demonstrated in the well constructed dietary studies. It appears that there is considerable variation in the human population with regard to their patterns of lipid metabolism. Some apparently regulate body production of cholesterol in response to dietary changes, others do not. Some seem to excrete excess sterols efficiently, while some do not. It seems likely, therefore, that dietary manipulation would be useful for those disposed by heredity and other conditions to accumulation of excessive sterols in the body. On the other hand drug control of cholesterol biosynthesis and/or sterol excretion may be more effective solutions to the problem of sterol accumulation. Irrespective of whether diet or drugs prove to be the best answer to control of sterol balance, these should be applied only to that segment of the population known to require such treatment. The egg is an important dietary source of cholesterol and as a result is used sparingly in low cholesterol diets. On the other hand normal egg consumption of two eggs per day does not appear to overload cholesterol balance in the healthy human adult since depression in cholesterol biosynthesis and increased sterol excretion will result. Investigation of the lipid metabolism of the laying hen has shown that most of the cholesterol found in the egg is synthesized in the liver where it is under both dietary and drug control. Most of the cholesterol deposited in egg yolk may be essential for embryonic development. Drugs that severely limit cholesterol biosynthesis probably also limit synthesis of adrenal and sex hormones and hence limit reproduction. Moderate depressions in lipogenesis achieved without feeding of large amounts of dietary fat may offer a means for moderating cholesterol deposition in eggs. On the other hand, it also seems clear that genetic selection could be used to moderate egg cholesterol concentration. In any event, a great deal more evidence from well constructed human diet studies will be needed before low cholesterol diets can be recommended to the general population as an aid to control of cholesterol balance and heart disease.


Effects of feeding ethyl mercury chloride to chickens. Four groups, 0, 5, 10 and 20%, of Single Comb White Leghorn chickens (30 males plus 30 females each) were fed a diet  which contained either 0, 5, 10 or 20% ethyl mercury chloride dressed wheat for a period of 88 days. The wheat was dressed with the organic mercury compound at the rate of 500 gm. ethyl mercury chloride per metric ton of wheat. Therfore, the diets contained respectively 0, 25, 50 and 100 mg. organic mercury compound/kg. With average daily feed consumption of 101, 102, 101 and 98 gm. by the individual birds of the respective groups, the birds did not show any symptoms of disease during the course of the study. Egg production, egg quality and mortality of the treatment groups were comparable with those of the control group. The amount of residual mercury in egg white and yolk was determined at intervals. The residual mercury of egg white of the treatment groups was about three times as much as that of egg yolk, and made its significant appearance in the 20% group on the third day of the trial. The concentration was increasing with time in both white and yolk and was parallel to the concentration of the organic mercury in the diet. The liver followed by the kidney of both sexes accumulated the highest amounts of mercury. Tissues of female birds accumulated less mercury than tissues of male birds did probably due to the passage of some of the ingested mercury with the egg white and yolk. The results were discussed on the basis that the kind of mercury compound, daily intake and duration of treatment play major roles in the determination of induced effects.


Polymorphonuclear leucocyte function in chronic renal failure and after renal transplantation. Neutrophil chemotaxis, phagocytosis and bactericidal ability were assessed in patients with chronic renal failure on conservative therapy, in others on regular peritoneal and haemodialysis, and in a group of patients who had received renal allografts. Chemotaxis was abnormal in all groups. The groups on peritoneal and haemodialysis had mildly impaired phagocytosis, while killing ability was normal in all but the group on conservative therapy who showed a mild defect. Serum from groups when activated with endotoxin was poorly chemotactic to normal neutrophils, but functioned normally as opsonins for phagocytosis.


Transplant monitoring: patterns of the immune response. Immune responses, specific to the stored donor tissue, were measured in 26 recipients over 4,000 days. CML positive crossmatches were associated with accelerated rejections (three cases). LDA positive crossmatches resulted in primary non-functioning kidneys (three cases). Post-transplantation. CML (16 hour inculation) was associated with rejection (p equals 0.001), highly predictive of rejection (p equals 0.001), and when positive after rejection treatment, was associated with a failure to respond (p equals 0.005 - 0.01). 51Cr-CDA was also associated with rejection (p equals 0.002). Recovery of these immunologic participants from the explanted kidney substantiated that they were important effector mechanisms in vivo.


Induction of secific immunological tolerance to histocompatible renal and skin allografts after donor strain spleen implantation. Spleens from Lewis X BN F1 hybrid rats were directly anastamosed to the circulation of parental strain Lewis rats by a microvascular technique; no immunosuppressive drugs were given. Donor spleens enlarged massively during the first month after implantation, then grew gradually smaller over succeeding months without compromising their blood supply. Renal allografts were placed into bilaterally nephrectomised recipients that had already borne a splenic allograft for three months. The grafts functioned perfectly and showed no signs of rejection five months later. Donor LBN skin allografts transplanted to these animals showed markedly prolonged survival while third-party BUF rat skin allografts were rejected in first-set fashion. High titres of anti-LBN haemagglutinating antibody could be detected in the circulation of spleen-grafted animals during the first month; the titres fell to zero by the fourth month. Cellular reactivity of recipient cells against LBN antigens measured by the popliteal node GVH assay fell to minimal levels by the third month. These data indicate that the immune response to allografted tissues may be specifically and markedly suppressed in adult animals by continued presence of a donor-strain spleen.


Corticosteroids and proliferation of smooth muscle cells in arteries of renal transplants. In the arteries of 17 rejected renal grafts 'activated' smooth muscle cells (ASMC) were discerned from a 'resting' type. Proliferation and fibre production by ASMC resulted in a marked thickening of intima. Each of four normal Wistar rats received 20 mg prednisolone i.v./day for one week and the development of hypertension was therapeutically prevented. Changes similar to those in the graft arteries were found in the rat aortas. We assume that SMC were stimulated by several mechanisms in rejection but also by extremely high dosed corticoids.


Cyclophosphamide (CP) substituting azathioprine after renal transplantation. Eighteen patients received CP substituting AZ after renal transplantation following evidence of hepatitis. We have compared graft evolution before and after treatment with CP. Twelve patients showed no modification in graft evolution. In four patients the renal function decreased but it did not seem attributable to the change of the drug. Two patients showed intolerance attributable to the change of the drug. In one patient who received CP instead of AZ since the data of the transplant onwards, with no evidence of hepatic lesion, renal function decreased but this did not seem attributable to the use of the drug. The dose of CP in renal transplantation is discussed. We conclude that CP is a good substitute for AZ in renal transplanted patients. Adequate doses seemed to range between 0.7 and 1 mg/kg/day.


Quantitative assessment of renal transplant function on renogram performed with computer assisted gammacamera. A standardisation of renography performed with gammacamera and computer on-line is described. A semi-quantitative measurement of the first and the second phase of the renogram is obtained; our so-called accumulation ratio (AR). The AR is a valuable expression of renal function, which does not depend on diuresis. The changes of AR, in oliguric status, are also discussed. The information from sequential images obtained during renography is presented. With this method functional changes of the graft as well as pathology of the urinary tract can be detected.