A simple multiple chamber apparatus for measuring chemotaxis of polymorphonuclear leukocytes utilizing centrifugation of the chambers before incubation. A simple apparatus for measuring chemotaxis is described which contains thirty chambers per unit. Only very few cells and small volumes of chemotactic factor solution are required per chamber. For satisfactory results the apparatus must be centrifuged briefly prior to incubation. Under these conditions results can be obtained that are equivalent to or, with short incubation times, superior to other commonly used modified Boyden chambers.


A combined autoradiography--immunofluorescence technique for the study of lymphocyte traffic in relation to antigen localisation. A combined autoradiography-immunofluorescence method is described for the simultaneous detection of antigens and lymphoid cells on cryostat tissue sections. The method is discussed here with reference to studies on cell traffic and antigen localisation in the chicken spleen.


A rapid, semi-automated counting procedure for enumeration of antibody-forming cells in gel and nucleated cells in suspension. A commercially available bacterial colony counter has been modified to permit rapid, highly accurate, semi-automated enumeration of antibody-producing plaque forming cells in semi-solid support medium as well as enumeration of nucleated cells in suspension on a standard hemacytometer chamber. This apparatus should therefore serve as an enormous time-conserving accessory to most modern laboratories involved in immunological research.


Micro mixed hemadsorption assay--a sensitive method for detecting antibodies against tumor-associated antigens. Antibodies against methylcholanthrene (MCA)-induced sarcomas in Fischer (F344) rats were detected by a modified micro mixed hemadsorption (MHA)-assay. The assays detected anti-tumor antibodies as titers up to 1 : 320 in sera from hyperimmunized rats and at titers up to 1 : 160 in sera from rats bearing a 5-8 cm3 progressively growing tumor. MHA-titers decreased when sera were absorbed with sarcoma cells prior to MHA-assays. IgG antibodies in sera from tumor bearing rats showed titers of 1:20 and 1:5. These anti-tumor sera formed rosettes on the corresponding sarcoma cells as well as other sarcomes induced by MCA in F344 and Lewis strain rats tested. The assay was modified for a micro technique using a microtest plate (No. 3034, Falcon, CA). This modification yielded as assay requiring only 10 microliter of test sera. The test is quantitative and highly sensitive and results are reproducible. Several critical factors which influence test results in this assay were examined.


A direct hemolytic plaque assay on polylysine-coated coverslips for scanning electron microscopy of antibody forming cells. A direct immunoplaque assay was utilized without agar or other semi-solid matrix for examining antibody secreting cells by scanning electron microscopy. For this purpose a polylysine procedure was used whereby 'charged' coverslips absorbed onto their surface an even monolayer of target sheep erythrocytes. Hemolysin secreting splenocytes derived either from mice immunized in vivo with SRBC or from normal or primed splenocytes immunized in vitro with the same antigen formed large numbers of hemolytic plaques on the RBC-coated polylysine treated coverslips. SEM examination of such plaque-forming cells revealed the presence of cells with the typical surface morphology of lymphocytes present in whole spleen cell suspensions. Many of the lymphocytes were covered with numerous microvilli while a small percentage were relatively free of such villi and exhibited a much smoother surface. Examination of lymphocytes secreting hemolytic antibody on polylysine coated coverslips sensitized with target erythrocytes thus permits the direct examination and analysis of surface morphologic features and also permits a direct comparison with other features revealed by light and fluorescent microscopy.


Immunofluorescence using dichlorotriazinylaminofluorescein (DTAF). II. Preparation, purity and stability of the compound. Dichlorotriazinylaminofluorescein (DTAF) is quickly and easily prepared under anhydrous conditions in high yield and purity. DTAF stored desiccated at 4 degrees C for over a year undergoes about 1% hydrolysis but with no loss of its protein-labelling efficiency.


Cell wall antigens in soluble cytoplasmic extracts of candida albicans as demonstrated by crossed immuno-affinoelectrophoresis with concanavalin A. Crossed immuno-affinoelectrophoresis with Concanavalin A precipitated four antigens from soluble extracts of the yeast and mycelial phases of Candida albicans. Two of these antigens were also present in spheroplast preparations. One of the Concanavalin A precipitated antigens was destroyed by periodate and none were digested by pronase. Sequential treatment with pronase and periodate destroyed two of the remaining three antigens. The Concanavalin A precipitated antigens appear to be glycoproteins, two of which are associated with the cell wall of C. albicans.


A controlled double-blind comparison of reactogenicity, immunogenicity, and protective efficacy of whole-virus and split-product influenza vaccines in children. A double-blind randomized study with bivalent influenza virus vaccines was conducted to compare the local and systemic reactions and immunogenicity of a whole-virus vaccine and a split-product vaccine in children. Fevers of greater than 100 F were more frequent after vaccination with whole-virus than split-product vaccine especially in children one to four years old (69% vs 22%; P less than 0.01). Fevers of greater than or equal to 103 F did not occur in children who previously had been given influenza virus vaccine, even in the absence of preexisting homologous serum antibody. The immune response to the A/Port Chalmers/1/73 antigen in the vaccine was similar after administration of either whole-virus or split-product vaccine. However, split-product vaccine induced significantly less hemagglutination-inhibiting antibody to B/Hong Kong/5/72 virus in children younger than 10 years who had not been previously immunized; only 43% developed detectable antibody vs. 100% of those vaccinated with whole virus vaccine (P less than 0.01). These studies indicate that (1) in young children whole-virus vaccine causes fever more frequently than split-product vaccine; (2) young children previously vaccinated with influenza virus vaccine are unlikely to experience fever subsequent to immunization with a related antigen; and (3) split-product vaccine induces less antibody to B/Hong Kong/5/72 virus than whole-virus vaccine in immunologically unprimed young children.


Immunization against retrograde pyelonephritis. III. Vaccination against chronic pyelonephritis due to Escherichia coli. Vaccination with formalin-treated cells of Escherichia coli serotype O6 protected against unilateral retrograde pyelonephritis due to E. coli O6 in rats with partial ureteral obstruction. This protection was manifested not only by less parenchymal destruction and shrinkage of the pyelonephritic left kidney, but also by less secondary pyelonephritis and compensatory hypertrophy in the opposite right kidney. Vaccinated rats eliminated E. coli from the kidney more rapidly, but even when infection persisted in the kidney, the chronic pyelonephritis was less severe in vaccinated rats. High levels of antibody to E. coli lipopolysaccharide were found in vaccinated animals and may have contributed to protection. These results raise the question of whether vaccination ought to be considered for patients predisposed to chronic bacterial pyelonephritis.


A rabbit model of diarrhea due to invasive Escherichia coli. A nonpiliated strain of invasive Escherichia coli of human origin (HInvEC) was given to rabbits (weight, 0.7-1.1 kg) in doses ranging from 1.5 X 10(8) to 2.5 X 10(10) bacteria. E. coli strain HInvEC colonized the ileum, cecum, and colon in large numbers for one to three days and produced diarrhea in 91 ((58%) of the 156 rabbits. A dose of 2.5 X 10(10) bacteria reliably and repeatedly elicited diarrheal disease in 80% of the animals. The acute pathohistology as determined by light microscopy, transmission electron microscopy, and immune fluorescent microscopy was manifest in the distal ileum, cecum, and colon. Prominent findings included mucosal ulcers, bacterial invasion of the lamina propria, and a polymorphonuclear infiltrate in the lamina propria. Diarrhea due to strain HInvEC was followed by a rise in the titer of serum antibody to O antigen of E. coli.


Bismuth subsalicylate inhibits activity of crude toxins of Escherichia coli and Vibrio cholerae. The inhibition of the activity of enterotoxins by bismuth salts was assessed in laboratory models. In the Y-1 adrenal cell tissue culture system, a commercial preparation containing bismuth subsalicylate reduced the activity of crude toxin from Vibrio cholerae by 10(4)-fold as compared with the activity of controls. Similar results were obtained with use of the adult rabbit ligated intestinal loop model. The preparation failed to affect crude Escherichia coli or cholera toxin activity once these toxins had become bound to intestinal mucosa. Pretreatment of ligated loops with the preparation reduced the fluid accumulation mediated by crude E. coli and cholera toxins by 78% and 91%, respectively. Bismuth subsalicylate and the complex vehicle of the preparation also inactivated toxin; however, bismuth subsalicylate was more effective when combined with the vehicle. Bismuth subcarbonate failed to inhibit fluid accumulation in ligated loops. Preparations containing bismuth subsalicylate may be effective in the prevention of diarrhea mediated by toxigenic E. coli.


The medical treatment of secretory otitis media. A clinical trial of three commonly used regimes. A clinical trial was undertaken to evaluate three medical treatments commonly used for chronic secretory otitis media. The treatments compared were Ephedrine nose drops, an oral antihistamine and decongestant (Dimotapp) and autoinflation of the middle ear. Changes in middle ear compliance and pressure were used as objective criteria of the efficacy of treatment in addition to changes in pure-tone threshold and to clinical assessment. Symptoms and abnormal signs tended to remit during the trial but there was no evidence from pure-tone audiometry and tympanometry that any of the treatments was beneficial. The period of observation enabled 28% of the children to avoid surgical treatment. Good and bad prognostic features are described which should help in deciding whether to manage a case conservatively or whether to proceed directly to surgery.


Evaluation of skin tests and desensitization in allergic rhinitis. A study of thirty-seven cases of allergic rhinitis is presented. The effect of the treatment on patients' symptoms and on the state of their skin sensitivity has been assessed. From this study it is concluded that the skin tests do not form a reliable method of assessing nasal allergy, nor is there a useful correlation following desensitization by vaccine therapy between the state of the skin sensitivity and the symptomatic effectiveness of treatment.


A global display of the heart vector (spherocardiogram). Applicability of vector-and polarcardiographic infarct criteria. The spatial loop of the heart vector can be projected on the Aitoff projection of the globe. The complete information that is contained in the orthogonal leads in displayed on a single graph when the vector magnitudes are indicated by the diameter of circles drawn around the vector projection in short time intervals (spherocardiogram). Diagnostic vector- and polarcardiographic criteria were applied to the spherocardiograms of 68 survivors of inferior myocardial infarction and 30 healthy men. Sensitivity increased from 65% (standard 12-lead ECG) to 87% (VCG criteria) (P less than 0.001) to 94% (VCG and PCG criteria combined), with no false-positive diagnoses. The spherocardiogram can be obtained by use of an "intelligent plotter." In contrast to the vectorcardiogram (VCG) and the polarcardiogram (PCG), it permits the direct visual study of the spatial direction and the spatial magnitude of the heart vector and of their sequential changes during the heart cycle.


A computer program for ECG classification according to the Minnesota code. A program for the automated generation of Minnesota-codes from the standard 12-lead electrocardiogram (ECG) recorded at rest has been developed. The program has been written as a part of the Modular TNO ECG/VCG Processing System. Results of the program on two sets of ECG'S (279 predominantly normal recordings and 286 consecutive recordings from a Cardiological Department) are presented. These electrocardiograms were also coded by hand by different ECG technicians. An agreement of 83% between hand and computer coding was obtained. One-third of the disagreements (6% of the cases) is caused by small differences (less than 5%) in the measurements between technicians and computer.


The influence of lead strength on the S-T changes with exercise electrocardiography (correlative study with coronary arteriography). The contribution of relative lead strength to S-T segment depression amplitude during exercise was evaluated in 98 patients who had both a treadmill stress test and a coronary arteriogram. This was accomplished by constructing an exercise S-T depression to R wave ratio (S-T/R) and then relating these ratios to the extent of coronary disease found with arteriography. The additional criterion of 1 mm S-T depression for the bipolar V5 and 0.5 mm for the late unipolar V5 was also reviewed. These criteria were then compared to the sensitivity and specificity of the usual 1 mm S-T depression criterion. The S-T/R ratio of 0.04 improved the detection of significant coronary disease over the usual criteria. The ratio of 0.1 was effective in avoiding false positive tests but lacked sensitivity. This would suggest that strong lead systems may give false positive S-T changes with exercise. The use of 0.5 mm depression as abnormal for the post-exercise unipolar V5 improved sensitivity without loss of specificity over the usual criteria of 1 mm S-T depression criteria. This may be a reflection of the voltage differences between the bipolar lead and the unipolar lead in these two lead systems. It is concluded that lead strength must be considered when evaluating the S-T response to exercise.


Simple techniques to relieve anxiety.

Simple techniques to relieve anxiety. Many patients can obtain rapid, short-term relief of anxiety through the use of simple, meditative techniques. Anxiety, tension, mild depressive feelings, and psychophysiologic symptoms frequently respond to such techniques. Five techniques are described, including physical self-support, attending to unpleasant feelings, listening to thoughts, listening to sounds, and paying attention to one's breathing. The techniques are easy to learn, innocuous, and well accepted by most patients. Patients who experience relief with simple psychological techniques are often more hopeful and more accessible to treatment.


Growth characteristics and polyene sensitivity of a fatty acid auxotroph of Candida albicans. A fatty acid auxotroph of Candida albicans 6406, designated A' 44 and originally isolated as an oleic acid requiring strain, has been shown to be a delta9 desaturase mutant. Although lacking this step in fatty acid biosynthesis, it appears to retain the ability to desaturate monounsaturated fatty acids. The polyene sensitivity of the organism grown on different fatty acid supplements varied between 0-08 +/- 0-02 and 1-20 +/- 0-30 microgram amphotericin B methyl ester ml-1 for exponentially growing cells. In spite of this variation, the sterol composition remained fairly constant, the major differences lying in fatty acid composition. Stationary-phase cells were more resistant to amphotericin B methyl ester, although again this change was not associated with changes in sterol content. The organism was most resistant when grown in the presence of oleic or linoleic acid. Protoplasts derived from resistant organisms grown on these two fatty acids were also resistant, indicating that the structure of the cell wall was less important than that of the plasma membrane in determining polyene sensitivity under these conditions.


The DNA contained by nuclear polyhedrosis viruses isolated from four Spodoptera spp. (Lepidoptera, Noctuidae); genome size and configuration assessed by electron microscopy. The mol. wt. of the DNA from four nuclear polyhedrosis viruses isolated from Spodoptera littoralis, S. exempta, S. exigua and S. frugiperda were determined to be 84, 80, 68 and 74 X 10(6), respectively, by electron microscopy. The molecules were demonstrated to exist as double-stranded relaxed circular or supercoiled DNA, though linear forms of DNA were also observed.


A new method to detect lymphocytic choriomeningitis virus-specific antibody in human sera. A plaque reduction method for measuring lymphocytic choriomeningitis virus-sensitizing antibody in human serum is described. One volume of virus and one volume of serially diluted human serum were mixed and incubated for 2 h at 37 degrees C. One volume of suitably diluted anti-human immune globulin antiserum was added and incubation continued for 0-5 h. Residual infectivity was then determined by means of a plaque assay employing L cell monolayer cultures and a methyl cellulose containing overlay medium. Of 75 sera from as many persons, 20 were positive with titres ranging from 640 to 10240. All positive sera were from verified cases or from persons who had had occupational contact with the virus. Close correlation of results was found between this method and a neutralization test employing mice, the one exception indicating that the in vitro assay for sensitizing antibody is more sensitive than the mouse assay for neutralizing antibody.


[The morphotype of Marfan's syndrome].

[The morphotype of Marfan's syndrome]. The aim of this paper was to determine the morphotype of Marfan's syndrome based on the examination of three patients affected with this disease. After having described the clinical picture of our patients, we carried out anthropometric measurements with calculation of indexes. This study revealed that patients No. 1 and 2 showed nearly identical morphotypes, while the third case presented an abortive form of Marfan's syndrome with slight signs of hypoandria. The morphotype of Marfan's syndrome can be briefly outlined as follows: excessive height; macroskelia, hypermacroskelia; brachycormia; long upper limbs; arm span exceeding the height; narrow shoulders; narrow and often deformed chest; arachnodactyly of hands and feet; kyphoscoliosis or scoliosis; mesocephaly or brachycephaly; large forehead; leptoprosopic or hyperleptoprosopic face; high arched palate.


Fluvoxamine-a new serotonin re-uptake inhibitor: first clinical and psychometric experiences in depressed patients. The clinical efficacy of fluvoxamine (DU 23000)--the first selective serotonin re-uptake inhibitor of the new class of 2-aminoethyloximethers of aralkylketones was investigated in endormorphous depressed patients during 5 weeks treatment with mean daily dosages of approximately 150 mg DU 23000. A marked and statistically significant improvement of the overall and detailed psychopathology was noted by means of the Global Clinical Impression and Hamilton Rating Scale as early as in the first week of drug administration. Bipolar patients tended to improve more than unipolar ones, retarded depressions more than agitated ones. An additional anxiolytic medication was occasionally required. The drug was well tolerated. Psychometric and laboratory findings did not show any significant changes. The findings are discussed in the light of the indolamine hypothesis of depression.


Dl-phenylalanine in depressed patients: an open study. In an open study dl-phenylalanine in doses from 75-200 mg/day was administered to 20 depressed patients for 20 days. Patients were classified according to the International Classification of Diseases (ICD). The AMP system, the Hamilton depression scale and the von Zerssen self rating questionnaire were used for documentation of psychopathological, neurologic and somatic changes. In addition a global clinical impression was agreed upon by experienced psychiatrists. At the end of the trial 12 patients (8 with complete, 4 with good response) could be discharged without any further treatment. 4 patients with partially untypical depressions experienced mild to moderate responses, whereas 4 patients did not respond at all to the phenylalanine administration. Depressive "core symptoms" as depressed mood, retardation and/or agitation were preferentially, anxiety and sleep disturbances moderately and hypochondriasis and compulsiveness were not influenced. It is concluded that dl-phenylalanine might have substantial antidepressant properties and that further more controlled investigations are warranted.


Formation of cobalt-free corrinoids in Rhodopseudomonas spheroides. Co-free corrinoids (CFCs) were found in the cells of Rhodopseudomonas spheroides grown without cobalt salt. A predominant fraction of three CFCs on paper-electrophoregram was further purified, and investigated physico-chemically as well as microbiologically in comparison with that isolated by Toohey from Chromatium. The electrophoretic as well as spectrophotometric patterns of CFC from Rh. spheroides were partly different from those of Chromatium CFC. The former CFC was a competitive inhibitor of cyanocobalamin in Ochromonas malhamensis. The findings obtained indicate that the CFC from Rh. spheroides resembles that from Chromatium in chemical structure with some difference, and that the compound has an anti-vitamin B12 activity in O. malhamensis.


Induction of chick embryonic intestinal disaccharidases by hydrocortisone and sucrose in the organ culture system. The effect of hydrocortisone and sucrose on the development of chick intestinal disaccharidases was studied using the organ culture system. When intestines of 15- and 17-day-old embryos were cultured in the presence of hydrocortisone, there was significant enhancement of disaccharidases activity compared with the control. However, there was no effect in the 20-day embryonic intestines. On the other hand, the disaccharidase activity of cultured intestines from 20-day-old chick embryos were significantly stimulated by the addition of sucrose. The observed increase in disaccharidase activity induced by the administration of hydrocortisone in 17-day-old embryos in vitro was sensitive to actinomycin D and cycloheximide. The activity induced by the administration of sucrose in 20-day-old embryos in vitro was sensitive to cycloheximide but insensitive to actinomycin D.


An objective method for measuring the surface morphology of cavities and restorations in vivo. A method was developed for quantifying morphological characteristics of cavities and restored teeth, in a quest for more knowledge of factors which determine the long clinical success or failure of restorations, and which may therefore be used in making objective assessments of their quality. The method involved obtaining sequential silicone rubber replicas of teeth in vivo, sectioning them in planned planes, and making objective linear and angular measurements directly from X 10 photographs of the resulting profiles and from positive models. It would seem that the method could be applied in a variety of clinical investigations.


Removal time: a factor in the accuracy of irreversible hydrocolloid impressions. Controversy exists regarding the correct time of removal of an alginate impression from the mouth. To investigate the effect of time of removal on accuracy, a series of alginate impressions were made of the lower left quadrant of a subject having a cast gold crown with four reference marks on tooth no. 19. The impressions were removed from the mouth at 1-5, 2, 3, 4-5 and 7 min after the insertion of the tray. Accuracy of the impressions was assessed by comparing the distances between the reference marks in stone casts with standard measurements taken from the gold crown prior to cementation. Impressions removed at 1-5 and 7 min produced the greatest distortions buccolingually. For the mesio-distal lengths all time intervals produced casts which were larger than the standard. The reasons for these findings are discussed and possible explanations are presented.


Pediatric kidney transplantation for cystinosis. In an experience of more than 700 kidney transplants, three recipients are known to have had congenital cystinosis. A cadaver kidney transplant in a 10 yr old child with nephropathic cystinosis functioned well for  7 1/2 yr before it was rejected and the graft was free of recurrent cystinosis after that interval. This prolongation of life was associated with marked accumulation of cystine in the patient's thyroid gland, presenting as a mass in the neck. If additional longevity is achieved in this patient, abnormal intracellular cystine accumulation may be expected in other host tissues. Retransplantation was carried out with the father as donor, accepting the possibility of increased cystine levels in the retransplant. This patient's age of 18 yr identifies him as one of the longest known survivors of infantile nephropathic cystinosis.


The effect of povidone iodine on plaque and salivary bacteria. A double-blind crossover trial. A double blind crossover trial was carried out to assess the effect of povidone iodine on plaque accumulation in vivo and to measure the total salivary aerobes and anaerobes throughout the study. When compared to the placebo preparation, povidone iodine was without effect on plaque accumulation in all the subjects and there was a progressive increase in plaque throughout the 10-day periods. A 30 to 40 % overall reduction in aerobes and anaerobes occurred with the active preparation which was significant. There appears to be no indication for the use of povidone iodine as an adjunct to oral hygiene or in the treatment of chronic gingivitis.


Bunolol metabolism by dogs: identification of basic metabolites and their conjugates. Female beagles dosed once with encapsulated 14C-bunolol (10 mg/kg) excreted 61% of the isotope in urine in 24 hr. The pooled urine contained a minimum of 18 labeled compounds. Two previously unknown metabolites were purified and were identified by UV and mass spectral data; they were hydroxybunolol (10.1% of urinary radioactivity) and hydroxydihydrobunolol (9.8%). The urine also contained bunolol (0.7% of urinary carbon-14), dihydrobunolol (0.5%), conjugated dihydrobunolol (2.8%), beta-(5-oxytetralonyl)lactic acid (16.3%), and (5-oxytetralonyl) acetic acid (7.1%).


The secretion of pepsin.

The secretion of pepsin. 1. Ligation and division of the vessels supplying the stomach, except those from the spleen, result in greatly increased pepsin secretion in response to pentagastrin, pilocarpine or 2-deoxy-D-glucose. 2. This effect was still present 6 months after initial ligation. 3. Analysis of dose-response curves shows that for pepsin secretion the Vmax values were raised by this procedure. 4. Right-sided vessel ligation and division does not alter acid secretion in response to the stimuli used. 5. It is suspected that the procedure of right-sided vessel ligation removes a non-competitive inhibitor mechanism to gastric pepsin secretion.


Stimulus-secretion coupling in pancreatic acinar cells: influences of external sodium and calcium on responses to cholecystokinin-pancreozymin and ionophore A23187. 1. The roles of Na and Ca ions in stimulus-secretion coupling were analysed in the isolated and perfused rat pancreas.2. Partial replacement of NaCl with LiCl produced a diminution in both amylase output and pancreatic juice flow which were induced by 5 m-u. CCK-PZ/ml., and almost normal responses were usually regained immediately after the reintroduction of a standard concentration of NaCl. Nearly total replacement of NaCl with LiCl caused an almost complete inhibition of the responses, although 25 mM-NaHCO(3) and 1 mM-NaH(2)PO(4) were still present, and only partial recovery was obtained after the re-introduction of a standard concentration of NaCl.3. A quantitative relationship was found between the amount of amylase released by CCK-PZ and the [Na(+)](o) over the range 26-157 mM in the presence of 2.5 mM-Ca. A similar relationship was also observed when [Ca(2+)](o) was decreased to 1.0 mM, but the responses were reduced to about one half of those observed with 2.5 mM-Ca.4. The most satisfactory theory which explains the cellular mechanism of CCK-PZ-induced amylase output, and which fits the experimental data, requires the dominant activity of a complex composed of a carrier molecule bearing one Ca and four Na molecules, if there is no interaction between Na(+) and Li(+).5. A quantitative relationship was also found between the amount of pancreatic juice flow stimulated by CCK-PZ and [Na(+)](o), over the range 26-157 mM, in the presence of 1.0 or 2.5 mM-Ca.6. A similar quantitative relationship was found between the amount of amylase released by Ca-ionophore A23187 and [Na(+)](o) in the presence of 2.5 or 5.0 mM-Ca. The most satisfactory theory which fits this experimental data also requires the dominant activity of a complex composed of a carrier molecule bearing one Ca and four Na molecules, if there is no interaction between Na(+) and Li(+).


An in vitro system for studying insulin release: effects of glucose and glucose-6-phosphate. 1. Investigation of the ionic requirements of the in vitro insulin release system, which consists of cod islet plasma membrane and rabbit islet granules incubated at pH 6.5, showed that the presence of Ca(2+) was obligatory for the system to operate.2. Glucose-initiated insulin release was as effective in the presence of beta-gamma-methylene ATP, as it was in the presence of ATP. This analogue of ATP is a substrate neither for adenylate cyclase nor for any known animal membrane proteases. The effect of ATP on glucose mediated release is allosteric.3. Glucose (16 mM)-initiated insulin release was slower than that induced by glucose-6-phosphate (4 mM); 150 and 120 sec, respectively.4. The lag found with glucose-mediated insulin release was dependent upon glucose concentration. The lower the glucose concentration, the longer the lag. With 1 mM glucose the lag extended to 30 min.5. Once insulin release was initiated, the rate and amount of insulin release was independent of the glucose concentration.6. Pre-incubation of membranes with Ca(2+), glucose and ATP prior to the addition of granules, abolished the extended lag that had been obtained with 1 mM glucose. Events in the plasma membrane are the major contributor to the generation of the extended lag.7. The glucose analogue 5'thio-D-glucose, although not able to release insulin, was shown to compete with glucose for the glucoreceptor. By increasing the ratio of analogue to glucose the lag time increased. Thus, the lag time is dependent upon the ;effective' external glucose concentration.8. The max. amount of insulin released by 4 ng of membrane in the presence of glucose (16 mM) was 300 ng. The fact that membranes became refractory to glucose after this max. amount of insulin was released showed that recycling of release sites was not taking place in vitro and that granule: granule interactions were not occurring.9. The 120 sec lag before glucose-6-phosphate-initiated release was independent of glucose-6-phosphate concentration. The rate of insulin release with glucose-6-phosphate was concentration dependent.10. Glucose-6-phosphate did not cause further insulin release from a membrane that had released the max. amount of insulin it was capable of in the presence of glucose. The addition of tolbutamide (10 mM) to such a membrane did cause insulin release. This suggests that glucose and glucose-6-phosphate share a final common pathway.11. Adrenaline and somatostatin did not inhibit glucose-mediated insulin release.


An investigation of the effectiveness of indirect retainers. A mandibular bilateral distal-extension base removable partial denture was lifted from a model under standardized conditions. The amount of denture base displacement under various loads and the forces of removal were measured electronically. The framework was constructed to allow repeated changes in the type of clasp, location of indirect retainer, and position of the rest seat on the terminal abutment tooth. The usefulness of an indirect retainer in preventing occlusal displacement of the denture base appears to be limited. The type of clasp had the greatest influence on the amount of denture base movement. Proximal surface guiding planes were also found to be important in preventing lifting of the denture base. Use of mesial instead of distal rests on the terminal abutment teeth did not decrease indirect retention.


Factors influencing the retention of dowels. A technique for assessing the axial retention of dowels has been developed. This method uses whalebone instead of extracted teeth. Threaded dowels appear to have better resistance to axial displacement than other types. Resistance of threaded dowels to torsional forces can be significantly improved by a rotation lock technique.


An indirect-direct method of crown fabrication for existing removable partial denture clasps. A technique that uses a combined indirect-direct method for the fabrication of a crown under an existing removable partial denture clasp has been presented. Advantages of this method are as follows: (1) The coping is placed directly on the preparation so the rest and retentive surfaces are more accurately developed than with other methods. (2) Fewer adjustments are required because of the accuracy of this method as compared with waxing the crown in one step.


Surface charge of trypanosoma cruzi. Binding of cationized ferritin and measurement of cellular electrophoretic mobility. The surface charge of epimastigote and trypomastigote forms of Trypanosoma cruzi was evaluated by means of binding of cationized ferritin to the cell surface as visualized by electron microscopy, and by direct measurements of the cellular microelectrophoretic mobility (EPM). Epimastigote forms had a mean EPM of -0.52 micrometer-s-1-V-1-cm and were lightly labeled with cationized ferritin. In contrast, bloodstream trypomastigotes had a much higher EPM (-1.14), and the surface was heavily labeled with cationized ferritin. When trypomastigotes from staionary phase cultures were isolated on DEAE cellulose columns, the mean EPM was found to be significantly lower (-0.63), and labeling with cationized ferritin decreased. With a mixed population containing epimastigote, trypomastigote, and intermediate forms, EPM values ranging between -0.70 to -1.14 were found. From these observations we conclude that there is a definite increase in negative surface charge during development from epi- to trypomastigote forms of T. cruzi.


Regulation of the hypothalamic--pituitary--ovarian axis in women. To account for the regulation of cyclic gonadotrophin release, the separate and interactive effects of the hormonal variable at the levels of CNS-hypothalamus, the pituitary and the ovary have been reviewed. The pituitary gonadotrophs, as target cells exhibited a remarkable cyclic change in their capacity which was correlated with the oestradiol levels. The ultimate release is determined by the relative size of the two pools' releasable gonadotrophins which are themselves regulated by the relative inputs of LH-RH and oestradiol, respectively. LH-RH appears to serve as a primary influence on the gonadotroph, stimulating gonadotrophin synthesis, storage and release. Oestradiol, for the most part, amplifies the action of LH-RH and induces the development of a self-priming effect of LH-RH, except that it impedes LH-RH-mediated gonadotrophin release. The pituitary capacity increases several-fold from the early to late follicular phase, and this is considered to be the prerequisite for the development of a mid-cycle surge. CNS-hypothalamic dopamine, norepinephrine, prostaglandins as well as LH-RH systems are involved in the negative and positive feedback effect of oestradiol. The possible steps and interactive elements in the triggering of LH-RH release for the initiation of the mid-cycle LH/FSH surge are considered.


The acute effects of oestradiol-17beta and synthetic LH-RH on plasma LH levels in freemartin heifers. Injection of oestradiol was followed by a surge of plasma LH within 24 h in only 7 of 12 freemartins. Elevations of plasma LH were less than those reported for normal non-cyclic heifers, but some freemartins showed a delayed, or more prolonged, LH response. Responsiveness to oestradiol was not related to degree of chimaerism or plasma androstenedione level, and most of the animals responded similarly in two trials carried out 4 months apart, during which time plasma androstenedione levels had more than doubled. Freemartins which showed an LH surge after oestradiol treatment released greater amounts of LH after the injection of LH-RH than did non-responders.


The survival and transport to the site of fertilization of diploid rabbit spermatozoa. The possible involvement of diploid spermatozoa in the production of triploid zygotes in the rabbit has been investigated in terms of the success of diploids relative to haploids in reaching the site of fertilization, with special reference to any possible selectivity of sperm transport within the female tract. The observed large significant reduction in the incidence of diploid spermatozoa between the ejaculate and the oviducts would greatly reduce the chances of, but not necessarily prevent, a diploid spermatozoon fertilizing an egg. This reduction appears to be due to a combination of the reduced survival of diploids in the female tract and a selectivity of sperm transport dependent on sperm motility.


Chemoimmunotherapy of cancer.

Chemoimmunotherapy of cancer. The preparation of a series of water-soluble mustard haptens for chemoimmunotherapy of cancer is described. Preliminary screening data are given, indicating some activity against P388 lymphocytic leukemia for those compounds containing the most potent immunogenic functional groups.


Antibacterial halogenoacetyl derivatives of amino acids and simple peptides. The vital role of D-alanine and L-lysine in the peptidoglycan crosslinking process in the bacterial cell wall prompted preparation of various small peptides incorporating these amino acids. N-Iodoacetyl or -bromoacetyl derivatives of the peptides were then prepared in the hope that they would serve as active-site-directed irreversible inhibitors of cell wall transpeptidases. Certain of the halogenoacetyl dipeptide esters, but not the corresponding free acids, showed slight antistaphylococcal activity. Subsequent structural variation showed that inclusion of C-alanine or L-lysine was not necessary, since antibacterial activity was at least as good when the dipeptide unite was replaced by glycylglycine or by an omega-aminoalkanoic acid. It was concluded that the observed antibacterial activity was probably not due to specific inhibition of a cell wall transpeptidase.


The emergence of the family practitioner: an historical analysis of a new specialty. The family practitioner evolved as a specialist to replace the rapidly disappearing general practitioner. The lack of adequate postdoctoral medical education programs for general practitioners, the changing role of the general practitioner in relation to the specialist, and the lower status and different working conditions of the general practitioner compared with the specialist contributed to the decline of general practice. Those who attempted to develop the specialty of family practice actively sought to remedy the deficiencies of general practice by providing intellectually rigorous postgraduate programs, by providing a unique area of expertise, and by providing specialty status.


Treatment of experimental Escherichia coli infection in mice with colicine V. Concentrated non-toxic preparations of colicine V were obtained by filtering centrifugates of soft-agar cultures of a Col V+ K12 strain of E. coli through Millipore filters in which the colicine V was retained. These preparations, given subcutaneously, favourably influenced the course of disease in mice infected intraperitoneally with a pathogenic strain of E. coli that was very sensitive to colicine V in vitro. A beneficial effect was noted even when treatment was delayed until the mice were visibly ill.


Freeze-fracturing of monolayers (capillary layers) of cell, membranes and viruses: some technical considerations. A novel hinged device for freeze-fracturing of cell monolayer in the Balzers freeze-etch unit is described. It is economical on biological material and enables oriented adsorption of sheet-like membrane fragments. For freeze-fracturing 'by hand' a monolayer is formed on a positively charged piecie of mica (with polylysine) and this is covered with another piece of mica, thin brass plate of filter paper. Such a sandwich is frozen in liquid nitrogen and fractured by means of forceps. Several modifications of this technique as well as practical examples are described. Among possible application are: negative staining of intramembranous protein particles; chemical or physical analyses of single membrane leaflets; identification of protein complexes by immunoelectron microscopy, etc.


Visualization of vesicles in semi-thin sections by the heat removal of epoxy resins. A partial removal of the embedding medium from sections of tissue with hollow structures results in the formation of phase object. The removal of epoxy resin by the heat of a gas-burner flame is a simple method which does not lead to shifts and losses of sections from glass slides.


Retrohepatic vena cava balloon shunt introduced via the sapheno-femoral junction. Experimental in-vitro and in-vivo testing of a retrohepatic vena cava shunt has shown effective shunting of inferior vena caval blood by catheters with outside diameters of 28 French. A technique of insertion of such a catheter via the groin is shown to be feasible in humans. Control of vena caval bleeding by a balloon catheter prototype during liver resection in dogs and in a human patient has been demonstrated.


Isolation and characterization of a bacteriophage T5 mutant deficient in deoxynucleoside 5'-monophosphatase activity. A bacteriophage T5 mutant has been isolated that is completely deficient in the induction of deoxynucleoside 5'-monophosphatase activity during infection of Escherichia coli F. The mutant bacteriophage has been shown to be deficient in the excretion of the final products of DNA degradation during infection of E. coli F, and about 30% of the host DNA's thymine residues were reinocorporated into phage DNA. During infection with this mutant, host DNA degradation to trichloroacetic acid-soluble products was normal, host DNA synthesis was shut off normally, and second-step transfer was not delayed. However, induction of early phage enzymes and production of DNA and phage were delayed by 5 to 15 min but eventually reached normal levels. The mutant's phenotype strongly suggests that the enzyme's role is to act at the final stage in the T5-induced system of host DNA degradation by hydrolyzing deoxynucleoside 5'-monophosphates to deoxynucleosides and free phosphate; failure to do this may delay expression of the second-step-transfer DNA.


The transmission of Candida albicans by cadaveric allografts. Two transplant patients suffered Candida infections after receiving homografts from a cadaveric donor whose urine culture yielded Candida albicans greater than 100,000 colonies per ml. In both patients the infections became apparent after large doses of methylprednisolone were administered for acute rejection. Flucytosine proved to be inadequate therapy but modified doses of amphotericin B served to eradicate the infection in each case. Donor urine cultures yielding Candida albicans should be interpreted as representing a transmissible infection.


The application of ileal conduits in pediatric renal transplantation. Our experience with the use of ileal conduits as receptors of renal homografts in 5 of 41 transplant recipients during the preceding 4 years is described. These 5 chronic renal failure patients were between 6 months and 17 years old, and had unsalvageable bladders that required an ileal conduit at an elective time before transplantation. The causes of renal failure in these children included dysplasia and chronic urinary tract infection. In an attempt to retard the rate of renal insufficiency all patients underwent multiple operative procedures on the lower urinary tract. Two cadaveric and 3 kidneys from living relatives were transplanted. One infant (6 months old) died of severe fluid and electrolyte imbalance 5 days post-transplantation. Of the remaining patients 3 are now 2 to 3 1/2 years post-transplantation and exhibit normal homograft function, and 1 died recently of chronic rejection. All conduits functioned well without evidence of ureteroileal obstruction, significant infection or stomal stenosis.


The repair of a congenital H-type urethrorectal fistula using a scrotal flap urethroplasty. A rare case of congenital urethrorectal fistula associated with stenosis of the normally positioned anterior urethra is described. Previously reported embryologic explanations, a detailed approach for surgical management and an alternative treatment are discussed.


Renal trauma.

Renal trauma. The pertinent literature on renal trauma for the last 25 years has been analyzed. An evolutionary pattern is seen in the development of diagnostic methods, while surgical and medical management of renal trauma has become much more precise for specific lesions. Various subareas of interest within the field have emerged, such as pediatric trauma, associated injuries and the subdivisions of blunt and penetrating trauma. Furthermore, therapy has been extended to include those severe vascular lesions that previously were considered untreatable. Various new and experimental concepts are described. Specific recommendations regarding the diagnosis and the therapeutic management are offered in an attempt to bring perspective to these new developments.


Antibody-coated bacteria in the ejaculate: a possible test for prostatitis. An immunofluorescence technique was used to study antibody coating of bacteria in ejaculates from 14 healthy individuals and 51 patients with complaints compatible with the diagnosis of prostatitis. Quantitative bacteriological cultures in the ejaculate were positive in 2 healthy individuals (14%) and in 25 patients with prostatic symptoms (49%). Antibody-coated bacteria could be demonstrated in 25 patients with prostatic symptoms (49%), 8 of whom had negative bacterial cultures, but in none of the healthy individuals. All 5 patients with epididymitis had antibody-caoted bacteria in the ejaculate. The 13 patients with antibody-coated bacteria in the ejaculate were given antibiotic treatment and the bacteria disappeared in 8 cases. The results document the presence of a (presumably local) immune response in bacterial prostatitis. Antibody coating of bacteria in the ejaculate seems to be helpful in the diagnosis of bacterial prostatitis.


Interference of human spermatozoal motility and spermatozoal agglutination by Candida albicans. Human spermatozoa were exposed to concentrations of 10(2) to 10(7) organisms per ml. Candida albicans. A subsequent striking decrease in spermatozoal motility and significant agglutination were observed. The possible role of mycotic genital tract infections in human infertility is considered.


[Urinary infection in urology. A rapid technique for confirmation of the diagnosis and the orientation of medical treatment (author's transl)]. A rapid technique for confirmation of the diagnosis and the orientation of medical treatment of urinary infection. Performance of direct antibiotic sensitivities on urine is a rapid (14 to 18 hours) procedure for determining the presence of organisms in the urine and seeking the antibiotic most active against them. In order to assess the value of the procedure, it was compared with classical bacteriological techniques. The correlation was found to be satisfactory. This procedure of direct sensitivity studies on urine is not in to way in competition with classical bacteriological techniques but is of great value in rapidly confirming the diagnosis of urinary infection and in the orientation of therapy. It eliminates a number of the justifications of blind treatment.


The bronchodilator effects of aerosolized terbutaline. A controlled, double-blind study. The bronchodilator effects of aerosols of a high-dose of terbutaline sulfate (1.5 mg), a low-dose of terbutaline sulfate (0.75 mg), isoproterenol (0.3 mg), and placebo were compared using forced expiratory spirometry, flow-volume curves, and body plethysmography in a double-blind, six-hour, controlled study in 25 patients with reversible airflow obstruction. After isoproterenol therapy, the values peaked at 15 minutes, and none were significantly different (P less than .05) from placebo after the 30-minute observation point. The values for high-dose terbutaline peaked at one hour at a level that exceeded responses to isoproterenol. All values except the forced vital capacity at five and six hours and functional residual capacity at six hours were significantly greater than placebo (P less than .05) at all observation points. The low-dose terbutaline values peaked earlier and at a lower value than the high-dose terbutaline values, and several indexes were significantly greater (P less than .05) than after isoproterenol therapy beyond the two-hour point.


Treatment of Parkinson's disease with lergotrile mesylate. Lergotrile mesylate, an ergot alkaloid derivative and putative dopamine agonist, was effective in the majority of patients with Parkinson's disease who were showing signs of disease progression despite treatment with levodopa combined with a peripheral decarboxylase inhibitor (carbidopa). Among 20 patients completing a six-month trial, there was a significant (P less than .01) reduction in rigidity, tremor, bradykinesia, gait disturbance, and total score when lergotrile was added to levodopa plus carbidopa. Mean daily dose of lergotrile mesylate was 52 mg, and the mean daily dose of levodopa was reduced by 15%. Abnormal involuntary movements were decreased on addition of lergotrile and reduction in levodopa while mental changes and orthostatic hypotension were increased. Elevations in serum transaminase levels were noted in three patients. The ergot alkaloids promise to be an important new class of antiparkinsonian drugs.


Nocardia asteroides sinusitis. Presentation as a trimethoprim-sulfamethoxazole responsive fever of unknown origin. A patient with a yearlong fever of unknown origin responded to trimethoprim-sulfamethoxazole and was discovered to have culture-proved Nocardia asteroides sinusitis, with absence of detectable disease in other organs. An inhalational route is postulated as the mode of entry of the organism, with localization in the maxillary sinus.


Bowel perforation with candidiasis.

Bowel perforation with candidiasis. Spontaneous multiple jejunal perforations developed in a relatively normal patient. Candida albicans was cultured from a biopsy specimen of an area of perforation and from peritoneal fluid. Yeasts and pseudohyphae were seen deep within the necrotic mucosa. Serial determinations of precipitating and agglutinating antibodies support the diagnosis of invasive candidiasis causing this unusual presentation.


A case of renal transplant recipient complicated with cryptococcosis and amphotericin B induced acute tubular necrosis. An adult renal transplant recipient was complicated with cryptococcal lung granuloma and meningitis. Treatment with the antifungal agents, 5-fluorocytocin and clotrimazole had to be discontinued due to side effects. Whereas, the intrathecal administration of amphotericin B proved effective for meningitis but intravenously it induced acute tubular necrosis to the transplanted kidney. In order to cure the persistant fungal lung granulomas in renal transplant patients early surgical excision seems to be essential.


Unilateral Shwartzman reaction: cortical necrosis in one kidney following in vivo perfusion with endotoxin. Unilateral renal cortical necrosis was selectively induced by in situ perfusion of the rabbit kidney with a perfusate containing 50 microgram of endotoxin followed by the i.v. administration of 250 microgram of endotoxin 24 hr later. The results strongly support the idea that the initial event in the genesis of renal cortical necrosis during the Shwartzman reaction is a specific local effect of endotoxin on the vascular endothelium.


[Keratoplasty in complicated cases (author's transl)]. Prognosis of corneal surgery has improved considerably owing to certain modern advances such as improved anesthesia, antibiotics, steroids, immunosuppressive drugs, better instruments, etc. Therefore it is now possible with the help of new techniques and medications to obtain very satisfactory results, even in cases which, in the past, were considered hopeless cases. Some examples from the author's personal experience are presented.


[On the technical preconditions of using preserved graft for keratoplasty (author's transl)]. By the aid of the preserving solution that was mentioned by McCarey and Kaufman, the so-called MK-medium, it is possible to preserve human corneas up to six days. Now we inform about a method for gaining graft that permits the use of the rotor trephine with its already known advantages, such as low cutting pressure, low deformation of the tissue margines and the possibility of watching the cutting process.


[Diphtheria: its history and epidemiology (author's transl)]. A survey of the historical and epidemiologic development of diphtheria is presented. The last four centuries are described particular attention is devoted to the most important centers of the epidemic during this time. Special consideration is given to the last one hundred years in Germany.


Measles antigen distribution in brains of chronically infected hamsters. An immunoperoxidase study of experimental subacute sclerosing panencephalitis. Weanling (21-day old) hamsters were inoculated intracerebrally with hamster-adapted, HBS strain of subacute sclerosing panencephalitis virus and studied between days 6 and 51 of infection with light microscopic immunofluorescent and ultrastructural immunoperoxidase methods. Characteristic measles fuzzy nucleocapsids developed and persisted in brain cell cytoplasm while smooth nucleocapsids developed in both nucleus and cytoplasm. Measles virus antigens appeared not only in relation to nucleocapsid but also in cytoplasm and along the inner aspect of cytoplasmic membranes of brain cells including neuronal dendrites. No budding virions were seen. Focal concentrations of bound hamster IgG occurred within foci of infected cells during the chronic infection. These studies show that in hamsters, persistent central nervous system measles infection is due to morphologically identifiable virus structures even when the host serologic response is active. The finding of viral antigens within the cytoplasmic membrane along with focal collections of hamster IgG in the same areas suggests that a "blocking factor," possibly antibody, protects infected cells from immune surveillance and destruction.


The reticuloendothelium as the target in a virus infection. Pichinde virus pathogenesis in two strains of hamsters. The course of Pichinde virus infection in two strains of hamsters, LVG and MHA, was studied by sequential frozen-section immunofluorescence and light and electron microscopy. The major destructive effects of the infection were in the spleen and liver. In the spleen, primary target cells were macrophages in the marginal zone of the white pulp with subsequent spread into elements of the red pulp. In the liver, there was Kupffer cell and hepatocellular infection. The extent of involvement correlated with the outcome of infection; more extensive and progressive necrosis occurred in the fatally infected MHA than in the LVG strain in which infection was self-limiting. In neither strain of animal was there demonstrable infection of lymphoid cells. Similarly, lesion sites did not have mononuclear inflammatory infiltrations which are characteristic of most viral infections. These findings suggested that, in contrast to the situation in other rodent arenavirus infections, the lesions in these hamsters were probably not consequences of immunopathologic host response but rather were a result of direct viral effects in concert with a genetically determined host susceptibility.


Delirium tremens in the Royal Navy and British Army in the 19th century. Nineteenth-century health records of the Royal Navy and British Army reveal remarkable differences in the prevalence and mortality of delirium tremens between commands and services.


Effects of alcoholics' expectation of a drink. The expectation of receiving alcohol influenced the drinking behavior of alcoholics and social drinkers resulting in increases in the amount of placebo consumed and higher estimates by both alcoholics and social drinkers of the percentage of alcohol in the placebo.


Prognostic indices for survival during postcardiotomy intra-aortic balloon pumping. Methods of scoring and classification, with implications for left ventricular assist device utilization. To define more clearly a salvageable patient for possible utilization of a left ventricular assist device prior to multiple organ failure and irretrievability during postcardiotomy intra-aortic balloon pumping (IABP), we made prospective and retrospective analyses to determine prognostic indices for survival. Serial left ventricular function curves (IABP on-off), scoring methods, hemodynamic and renal function tracking trajectories, survival versus nonsurvival data envelopes, and classification methods were developed and used. All patients requiring postcardiotomy IABP support who were in Class A survived; 80 percent of the patients in Class B survived. All patients who remained in Class C for 12 hours or more following operation with IABP support died. These preliminary analyses suggest that the postcardiotomy IABP-supported patient with a score of less than 6 who remains in Class C for 12 hours or more is at the highest possible risk and is a probably candidate for more effective support with a left ventricular assist device.


Reconstruction of bony canal with autogenous bone graft. The advantages of preservation of the bony posterior wall of the external auditory canal during surgery for chronic infection have been stressed by many authors. The superior canal wall is often partially destroyed by cholesteatoma, or must necessarily be removed, to insure adequate removal of attic pathology. Numerous techniques and grafting material will be reviewed. Our technique of using autogenous bone, cut with a thin chisel which curls to the shape of the ear canal, will be presented and illustrated.


Mandibular replacement after resection for tumor. The ideal natural or prosthetic mandibular replacement should be adjustable at the time of surgery, completely stable, free from tissue reaction or rejection, rapidly incorporated into surrounding tissue, and unlimited in lifespan. A brief review of clinically utilized mandibular replacements is discussed in relation to the ideals. At this time the replacement most adequately satisfying these principles is autogenous cancellous bone and marrow supported by a titanium mesh trough. This article describes the details of external mandibular fixation and the reconstructive procedure including preoperative preparation and common postoperative complications. Modifications of the prosthesis and surgical technique are suggested in order to decrease the chances of postoperative exposure, a complication in any type of mandibular reconstruction.


A comparative trial of co-trimoxazole and amoxycillin in the treatment of acute exacerbations of chronic bronchitis. A single-blind comparative trial of the effectiveness of co-trimoxazole and amoxycillin in the treatment of acute exacerbations of chronic bronchitis was carried out on 60 hospital patients. Both forms of treatment were equally effective in producing clinical improvement and reduction of sputum purulence and volume. There was no significant difference, either in the speed of recovery, or in the relapse rate, after treatment with co-trimoxazole and amoxycillin.


A comparative study of co-trimoxazole and amoxycillin in the treatment of acute bronchitis in general practice: a multicentre study. One hundred and five patients with acute bronchitis were treated with co-trimoxazole, and amoxycillin, in a single-blind trial. The present study confirms that co-trimoxazole and amoxycillin are effective, and well tolerated agents, both suitable for the management of acute bronchitis.


Cardiovascular monitoring in the coronary care unit. The present status of cardiovascular monitoring in the coronary care unit is reviewed. Major emphasis is placed on electrocardiographic monitoring, the only form of monitoring used on most patients who have suffered recent myocardial infarction. The capabilities and limitations of computer systems to perform electrocardiographic monitoring are reviewed, as are present techniques for hemodynamic monitoring and computerized integration of electrocardiographic, hemodynamic, and other patient data.


[Antihypertensive therapy with a new beta-blocking agent Timolol. Double blind study and comparison with Alprenolol and Pindolol (author's transl)]. In a double blind study including 24 patients with essential hypertension the beta-blocking agent Timolol showed a mild antihypertensive effect. These patients had been pretreated with hydrochlorothiazid to which they responded already with a significant lowering of their blood pressure before Timolol was added. The effect of Timolol equals the effects of Pindolol and Alprenolol. We also found a suppression of the plasma-renin-activity under Timolol. This effect did not correlate with the degree of blood pressure reduction. There were no side effects noted except for a lowering of the pulse rate about which some of the patients complained and which is typical for beta blocking agents without intrinsic symphaticomimetic activity. According to our results this new beta blocking agent for antihypertensive therapy has very much the same properties as the other beta-blocking drugs already in use.


Platelet activating factor (PAF). A possible direct mediator of anaphylaxis in the rabbit and a trigger for the vascular deposition of circulating immune complexes. Evidence is presented that IgE-induced, basophil-derived, platelet-activating factor (PAF) causes sequestration of rabbit platelets during sublethal IgE-induced anaphylaxis, and produces a state of specific desensitization in the platelets upon their subsequent return to the circulation. Moreover, depletion of platelets from rabbits undergoing lethal anaphylaxis abrogated the mortality and markedly reduced other parameters of the anaphylaxis. It was suggested that PAF may represent a major mediator of this reaction. A number of lines of evidence have suggested in addition that PAF may play a role in acute experimental immune complex disen that PAF may play a role in acute experimental immune complex disease in rabbits by causing release of vasoactive amines from platelets, lase in rabbits by causing release of vasoactive amines from platelets, leading to increased vascular permeability and deposition of circulating immune complexes along filtering vascular membranes. This data, providing evidence for the action of PAF in vivo and implicating this action in two allergic reactions, supports the contention that PAF is an important mediator of acute allergic reactions.


Late cutaneous reactions due to IgE antibodies. IgE antibodies can produce a late inflammatory response 6--12 h after allergen challenge which is characterized by diffuse edema, erythema, pruritus, tenderness and heat. That IgE is involved in inducing the late reaction was shown by the abolition of both immediate and late responses by passive transfer tests: (1) by heating atopic serum at 56 degrees C for 4 h; (2) by removing IgE from the atopic serum by a solid phase anti-IgE immunoabsorbent, and (3) by competitively inhibiting the binding of IgE antibodies to cells by an IgE myeloma protein. Also, both responses were induced by affinity chromatography-purified IgE antibody followed by antigenic challenge. Very similar lesions could be induced by intradermal injection of Compound 48/80. The late phase is characterized by edema and a mixed cellular infiltration, predominantly lymphocytic but also containing eosinophils, neutrophils and basophils. Direct immunofluorescent staining did not show deposition of immunoglobulins or complement components, except IgM in two of 15 and C3 in one of 15 patients, respectively.


Spontaneous, ultraviolet and ionizing radiation mutagenesis in two auxotrophic strains of Salmonella typhimurium carrying an R plasmid. Ultraviolet-induced, gamma-induced and spontaneous mutation yields were studied in two different auxotrophic strains of Salmonella typhimurium in the presence and absence of the UV-protecting drug resistance transfer factor R-Utrecht. One strain, carrying the hisC527 (amber) mutation, showed significantly increased spontaneous, UV- and gamma-induced mutability in the presence of the R-Utrecht plasmid. The other strain, carrying the trpD1 mutation (thought to be a missense mutation), also showed significantly increased UV mutability in the presence of the R-Utrecht plasmid. The other strain, carrying the trpD1 mutation (thought to be a missense mutation), also showed significantly increased UV mutability in the presence of the R factor, but appeared to show no significant increase in spontaneous mutability and only a very slight increase in gamma-mutability when carrying the R factor. These results demonstrate that the R-Utrecht plasmid, known to enhance UV-induced mutation yields in S. typhimurium, can also significantly enhance both spontaneous and gamma-induced mutation yields in this species. The latter effects are not so discernible with all markers, however, as shown by the results with strains carrying the trpD1 mutation. Enhancement of spontaneous mutability thus appears to be correlated with enhancement of gamma-mutability rather than UV mutability.


Repair of pyrimidine dimers in radiation-sensitive mutants rad3, rad4, rad6 and rad9 of Saccharomyces cerevisiae. The ability to remove ultraviolet (UV)-induced pyrimidine dimers was examined in four radiation-sensitive mutants of Saccharomyces cerevisiae. The susceptibility of DNA from irradiated cells to nicking by either the T4 UV-endonuclease or an endonuclease activity found in crude extracts of Micrococcus luteus was used to measure the presence of dimers in DNA. The rad3 and rad4 mutants are shown to be defective in dimer excision whereas the rad6 and rad9 mutants are proficient in dimer excision.


Evidence for inactivation of DNA repair in frozen and thawed mammalian cells. A variety of cell strains and lines were frozen and thawed by conventional techniques for cell storage. Following thawing, extracts of cells were prepared and incubated with UV-irradiated E. coli DNA. Thymine dimer excision activity present in extracts of unfrozen cells was lost in extracts of recently thawed cells. The ability to exercise dimers was restored after about 40 h post-thawing, but the recovery was inhibited if cells were cultured in the presence of puromycin. Correlating with the loss of dimer excising activity there was a reduced cell viability as measured by trypan blue dye exclusion.


The induction of mutations to 2-thioxanthine resistance in inhibitor depleted conidia of Aspergillus nidulans by gamma-radiation in the presence of oxygen or nitrogen. A strain of Aspergillus nidulans has been used to study the inactivating and mutagenic effect of 60Cogamma-rays in the presence of oxygen or nitrogen. Mutation was studied by the 2-thioxanthine system which selectively detects forward mutation at a number of gene loci (at least 16). Mutants resistant to conidial pigmentation effects of 2-thioxanthine can be divided into four main classes (2TxR, hx, uaY and cnx) and three of these classes (hx, uaY and cnx) can be further characterized at the gene level. The results demonstrate the existence of a marked differential forward mutational response of gene loci in Aspergillus conidia which is dependent upon whether gamma-irradiation in aqueous suspension was carried out in the presence of oxygen or of nitrogen: this effect is independent of the dose of radiation exposure. The specificity for mutation is altered by the presence of the self-inhibitor of germination for the anoxic treatment but not the oxic irradiation. The implication of different oer's (oxygen enhancement ratios) for mutation induction in different classes or genes for the mechanism and type of damage induced by the two radiation conditions are discussed.


Comparison of the genetic activity of aflatoxins B1 and G1 in Escherichia coli and Saccharomyces cerevisiae. The ability of aflatoxins B1 and G1 to induce back mutations to arg+ in Escherichia coli K-12/343/113 was compared with the induction of mitotic gene conversion to ade+ in the diploid yeast strain Saccharomyces cerevisiae D4, ade-2. In analogy to previous results with other microorganisms, the compounds were not genetically active per se, indicating that under the experimental conditions employed none of the tester strains were able to activate the compounds to mutagenic products. In experiments using liver homogenates (S-9 fraction) of male Golden Syrian hamsters previously treated with phenobarbital, aflatoxin B1 exhibited strong genetic activity both in E. coli and in S. cerevisiae, whereas the mutagenic activity of aflatoxin G1 was markedly lower and could be detected only in the E. coli tester strain. These results correlate the findings that aflatoxin G1 is a less potent carcinogen and mutagen than aflatoxin B1.


Legionnaires' disease: description of an epidemic of pneumonia. An explosive, common-source outbreak of pneumonia caused by a previously unrecognized bacterium affected primarily persons attending an American Legion convention in Philadelphia in July, 1976. Twenty-nine of 182 cases were fatal. Spread of the bacterium appeared to be air borne. The source of the bacterium was not found, but epidemiologic analysis suggested that exposure may have occurred in the lobby of the headquarters hotel or in the area immediately surrounding the hotel. Person-to-person spread seemed not to have occurred. Many hotel employees appeared to be immune, suggesting that the agent may have been present in the vicinity, perhaps intermittently, for two or more years.


Legionnaires' disease: isolation of a bacterium and demonstration of its role in other respiratory disease. To identify the etiologic agent of Legionnaire's disease, we examined patients' serum and tissue specimens in a search for toxins, bacteria, fungi, chlamydiae, rickettsiae and viruses. From the lungs of four of six patients we isolated a gram-negative, non-acid-fast bacillus in guinea pigs. The bacillus could be transferred to yolk sacs of embryonated eggs. Classification of this organism is incomplete. We used yolk-sac cultures of the bacillus as antigen to survey suspected serum specimens, employing antihuman-globulin fluorescent antibody. When compared to controls, specimens from 101 to 111 patients meeting clinical criteria of Legionnaires' disease showed diagnostic increases in antibody titers. Diagnostic increases were also found in 54 recent sporadic cases of severe pneumonia and, retrospectively, in stored serum from most patients in two other previously unsolved outbreaks of respiratory disease. We conclude that Legionnaires' disease is caused by a gram-negative bacterium that may be responsible for widespread infection.


Antibodies to oligodendroglia in patients with multiple sclerosis. We demonstrated antibodies to isolated oligodendrocytes and to oligodendroglia in brain sections by indirect immunofluorescence technic in serums of 19 of 21 patients with multiple sclerosis. We also found such antibodies in three of five patients with subacute sclerosing panencephalitis and one of four patients with acute disseminated encephalomyelitis, but not in patients with other neurologic diseases or normal persons. The antibodies were absorbed by preincubation of serum with isolated oligodendrocytes or whole white matter, but not with purified myelin or liver tissue. Immunofluorescent staining was blocked by either rabbit anti-oligodendrocyte serum or non-fluoresceinated goat anti-human immunoglobulin. These findings suggest that antibodies to oligodendroglia are distinct from antibodies to myelin and that demyelination in multiple sclerosis could be a consequence of an immunopathologic reaction directed against oligodendroglial cells.


Aspirin prophylaxis of venous thromboembolism after total hip replacement. We assessed aspirin prophylaxis against venous thromboembolism in a prospective, controlled, double-blind study of patients over 40 years of age, who had undergone total hip replacement. Radiographic phlebography was the diagnostic end point. Thromboembolism developed in 11 of 44 patients receiving aspirin, as compared to 23 of 51 receiving the placebo (P less than 0.03). Unexpectedly, this protection was limited to men. In four of 23 men on aspirin thrombi developed, as compared to 14 of 25 receiving placebo (P less than 0.01). Corresponding figures for women were seven of 21 versus nine of 26. Review of a similar group of patients receiving aspirin revealed significantly greater protection (P less than 0.03) in men (three of 15) than in women (15 of 27). These data establish statistically significant prophylaxis in men over the age of 40 by 600 mg of aspirin given twice daily. The absence of a protective effect in women remains unexplained.


Precautions in medical care of, and in handling materials from, patients with transmissible virus dementia (Creutzfeldt-Jakob disease). We have formulated a series of precautions to be observed in caring for patients with Creutzfeldt-Jakob disease and in handling their tissues. The virus resists inactivation by simple boiling in water. Also ineffective are 10 per cent formalin, 70 per cent alcohol and ionizing and ultraviolet radiation. Autoclaving for one hour at 121 degrees C and 20 psi inactivates the agent completely. Five per cent hypochlorite, 0.03 per cent permanganate, phenolics and iodine solutions are adequate disinfectants inactivating large infective doses of the virus. Special isolation wards for afflicted patients seem unwarranted. Workers exposed to infected saliva, nasopharyngeal secretions, urine or feces need to and should wash thoroughly with ordinary soap. Needles and needle electrodes should be autoclaved or incinerated and discarded. Demented persons should not be used for donations of blood or other tissues. Although precautions are necessary, the epidemiologic evidence does not suggest an unusual risk of Creutzfeldt-Jakob disease for medical workers.


The effect of freezing and the influence of isolation medium on the recovery of pathogenic fungi from sputum. The primary objective of this study was to determine whether freezing sputa in dry ice had any effect on the recovery of pathogenic fungi. Sputa seeded with each of five fungi (Histoplasma capsulatum, Blastomyces dermatitidis, Cryptococus neoformans, Coccidioides immitis, and Aspergillus fumigatus) were frozen and stored for 24, 48, and 72 hours on dry ice. H. capsulatum was killed, and only a few colonies of B. dermatitidis and C. neoformans were isolated from these sputa. However, A. fumigatus and C. immitis withstood the effects of freezing. A second objective was to compare the recovery of all five fungi from seeded sputa stored at room temperature for 24, 48, and 72 hours, on yeast extract-phosphate agar with NH4OH and on Sabhi agar. The yeast extract-phosphate agar with NH4OH was superior to Sabhi agar, for the isolation of all fungi studied, except A. fumigatus.


Sudden fatal pulmonary calcification following renal transplantation. A 42-year-old male was hemodialyzed for 2 years with excellent control of calcium-phosphate metabolism. He received a cadaveric renal transplant but experienced a prolonged episode of acute tubular necrosis during which he could not tolerate phosphate-binding antacids. His calcium X phosphate product became markedly elevated for 20 days. Following a brief period of function, the homograft was removed on the 45th post-transplant day after severe rejection and subsequent infection. Chest X-ray was normal. Six days after graft nephrectomy, he became acutely dyspneic and markedly hypoxemic. Diffuse, flocculent pulmonary infiltrates appeared on the chest film. The patient expired 1 day later. At postmortem examination, there was severe, diffuse pulmonary alveolar calcification demonstrated by chemical and histologic examination. Although unlikely, the prolonged post-transplant period characterized by elevated calcium X phosphate product may have played a pathogenetic role. Calciphylaxis may have occurred, with hyperparathyroidism as the sensitizing agent and any of several drugs acting as challenger.


Acute hyperkalemia risks in recipients of kidney graft cooled with Collins' solution. The authors present the first case of cardiac arrest, occurring at the time of vessel clamps removal, of a kidney transplantation cooled prior to grafting with Collin's solution. Monitoring of cardiac (K) has demonstrated the role of Collin's solution (K = 141 mEq/l) in the genesis of this incident. The mean +/- SD increase of the K concentration in the right atrium within the seconds following the removal of the graft vessels clamps was 2.6 +/- 1.5 mEq. Acute electrocardiographic abnormalities primarily represented by sudden apparition of hyperkalemic T waves and extrasystols occurs in more than 50% of the cases. The effects of progressive blood release in the graft and other preventive manipulations are studied and discussed.


[Experimental comparative study of microsurgical nerve sutures. II. Water-proof sutures and suture by simple approximation of the stumps]. After having demonstrated in a previous paper the advantages of an early surgical repair of injured nerves over a delayed suture, the author, following the same methods--electrophysiological and histological controls--comes to the conclusion that the so-called water-proof suture technique compared with a simple bringing up together of both stumps of the nerve, gives by far higher degrees of regeneration.


[Immunocytochemical localization of gliofibrillary proteins (GDAP) in human cerebral tumors. Histological and in vitro studies]. On the basis of studies utilizing antibody to GFAP (glial fibrillary acidic protein) in the indirect immunofluorescent and immunoperoxydase methods we report the presence of GFAP in 5 astrocytomas, 1 ependymoma and 1 medulloblastoma. The GFAP was evidenced on cryostat sections of frozen material and in short-term tissue culture. Five others tumors including 1 oligodendrocytoma, 1 choroid-plexus papilloma, 1 meningioma and 2 secondary sarcomas were negative. Possible applications of antibodies to GFAP for localization and therapy of brains tumors were considered.


[Cimetidine in the treatment of peptic ulcer]. Cimetidine, a non-thiourea-containing histamine H2-receptor antagonist, has been employed in the treatment of peptic ulcer. We studied 50 patients, partly with double-blind method, and partly in a free trial. Duodenal ulcers were completely healed in 80% of the cases, at the control endoscopy after a 4-week period of treatment with cimetidine (1000 mg/day). Peptic ulcer in general healed in 76% of the cases. Gastric secretion was significantly reduced after cimetidine. An important improvement in subjective symptoms was noted in every patient. No toxic effect was noted.


Feedback regulation of metabolism by dietary constituents: lipids. Cholesterol is distributed in different body pools, Input in these pools takes place through absorption of dietary cholesterol and endogenous synthesis. Absorption is limited in man. Endogenous synthesis is under negative feedback control, but its physiological relevance in man is less well established. Recent studies in familial hypercholesterolemia have shown a slower catabolism of low density lipoproteins (LDL) and an overproduction of apoprotein B. It seems that also the synthesis of the apoprotein B is controlled by a feedback mechanism. Overall concentration of lipids and lipoproteins in plasma is determined by the interaction between  several genetic and dietary feedback mechanisms.


Animal models in drug development: historical aspects. The historical aspects of drug development and evaluation are anecdotically related. Clinical trials have proven the effectiveness of animal tests in the vast majority of cases, and the effort has been well spent. Similar of more noteworthy success may be obtainable with model systems in the study of prostatic cancer.


Effect of dianhydrodulcitol (DAD) on the primary immune response of normal and tumor bearing rats. The effect of dianhydrodulcithol (DAD) administered in a dose of 5 mg/kg on the number of plaque-forming cells (PFC) in spleens and on the titre of hemolytic antibodies in the sera of rats immunised with sheep red blood cells (SRBC) have been examined. The compound elicited a short-lasting suppressive effect when applied after immunisation; the number of PFC decreased two days after treatment while 5 days after drug administration increased as compared to the untreated animals. Treatment prior to immunisation proved to be ineffective. The titre of circulating antibodies showed changes similar although of lesser extent. Five days following treatment marked infiltration of plasmacytes was present in the axillary lymph nodes. Rats bearing transplantable Guérin tumor showed similar changes in immune response as the tumor free animals following DAD treatment.


Tumors in two generations of mice in different environmental conditions. The influence of environmental carcinogens on the developing embryo has been investigated using SWA mice as models and 1-ethyl-1-nitrosourea (ENU) as the carcinogen. The percentage of tumor development among the F1 generations of siblings delivered and nursed by mothers treated with ENU was higher than that of the F1 generations of siblings delivered of treated mothers but nursed by untreated foster mothers. The presence of multople tumors was also more frequent in this group compared to the siblings which were exposed only transplacentally to ENU. The second generations also developed malignant tumors. Two successive generations of siblings which were delivered of untreated mothers but nursed by foster mothers treated with ENU on the 12th day of pregnancy, showed a higher percentage of tumors when compared to the control group. This result is of great significance as the siblings were not exposed to the carcinogen transplacentally, and the foster mothers were treated with only a single dose of ENU long before the lactating period, namely, on the 12th day of pregnancy.


Oral manifestations in the paraneoplastic syndrome. A 52-year-old woman with advanced cancer of the breast also suffered from pemphigoid eruptions on the skin, in the mucous membranes of the oropharynx, and in the conjunctivae. The pemphigoid lesions were suppressed by treatment with steroid hormones and disappeared after surgical removal of the malignant breast tumor. With regard to its clinical course, the disease entity described is justifiably classified as a "paraneoplastic bullosis". The literature on this subject is briefly reviewed.


Benign mucous membrane pemphigoid (cicatricial mucosal pemphigoid): a reconsideration. The name cicatricial mucosal pemphigoid is suggested in an attempt to clarify several synonymous terms and to omit the prefix "benign." The clinical features are reviewed and seven case reports illustrating different aspects are presented. The severe effects of ocular and pharyngeal involvement are highlighted, immunologic findings and treatment are discussed, and the link with neoplasia is emphasized.


Unicameral bone cysts. a current synthesis of reported cases. A review in depth of the recent literature relating to bone cysts and their treatment discloses many important differences in case material, and concern about the frequency of recurrence after surgical treatment by curretage and the insertion of grafts. The newer forms of treatment, subtotal resection, with or without the insertion of autogenous grafts, and even diaphysectomy, should still be considered to be on trial, despite the fact that the first patients who had these operations have now been followed for five to 15 years. Definitive evaluation of each procedure awaits its use in a large enough number of cases, well documented as to criteria for selection, clinical data, complications, and follow-up.


A critical evaluation of the application of amino acid racemization to geochronology and geothermometry. In this review we have critically evaluated the application of the diagenetic racemization of amino acids to geochronology and geothermometry. Although there has been enthusiastic support given to this new method, it is our opinion that recent developments suggest a more cautious approach. We have discussed the pitfalls and inhereent complications, while outlining the advances which have been accomplished. We conclude that this is an innovative approach which will add valuable information to the scientific literature. However, since our fundamental understanding of diagnetic racemization is still limited, many of the age and paleotemperature estimates which have been assigned to fossil specimens may be unreliable.


Hypothalamic control of the mammalian sexual maturation. The attainment of sexual maturity is a complex process which requires maturation and interaction not only of gonads and reproductive tract but also of the pituitary and essentially of the neuroendocrine mechanisms which ultimately control gonadotropin secretion. One of the more attractive hypotheses of the sexual maturation presumes the existence of the sensitivity threshold of the regulating system to the negative feedback signal, which differentiates immaturity from maturity. As the subject matures this declines. In an attempt to examine further the maturational alterations of the male hypothalamo-pituitary-gonadal axis, investigations were carried out with regard to simultaneous changes of blood LH, FSH, testosterone and dihydrotestosterone levels during the course of 24 hr; augmentation of pituitary and blood LH and FSH concentrations under the stimulus of LH-RH as a function of time and age; synthesis and release of LH and FSH in the testosterone-blocked animals at various stages of sexual maturation; and in vitro biotransformation of testosterone to its 5 alpha-reduced metabolites by the pituitaries as a function of age. Evidence from the experimental data could be interpreted as a decrement of the feedback set-points during sexual maturatio as reflected by the transition of the responses obtained under various experimental signals. In parallel to these observations, new evidence was presented regarding not only quantitative but qualitative changes in the pituitary gonadotropins as response to the negative and positive feedback signals. This leads to new thinking with regard to the hypothesis of differential sensitivity.


Flexibility of gram-negative bacterial cell wall. Addition of salts (NaCl and MgCl2) to isolated cell wall of E. coli cause appreciable contraction in volume. This contraction in volume of the cell walls is probably due to binding of the ions to wall polymers, including the peptidoglycan layer and the concomitant release of protons. The peptidoglycan layer of the cell wall is thus an elastic rather than a rigid layer.


Infantile cortical hyperostosis Caffey's disease. A 2 1/2-month-old girl with cortical hyperostosis (Caffey's disease) is described with a  brief review of the literature. This is the first case reported from Iran.


Diabetic microangiopathy: renal and retinal aspects. Diabetic microangiopathy is a degenerative process specific to diabetes. Metabolic theory holds that the metabolic defect predisposes to vascular abnormalities, but other theory suggests that microangiopathy and metabolic disorders are of different origin. Metabolic and ultrastructural modifications in kidney and retina are reviewed. Human and animal studies suggest a specific organ response to fortuitous association of several factors leading to microvascular disease.


[Influence of body position on human gas exchanges. Role of age (author's transl)]. We measured blood gases, steady state diffusing lung capacity, global and partial lung ductances in 16 subjects aged from 20 to 63 in supine and seated position. We obtained three types of response. In group I, (n = 6) blood gases and TLCO increased probably chiefly due to an increase of perfusion of lung apices and a more even distribution of regional VA/Q (all these subjects are young and thin). In group II, (n = 4) blood gases and TLCO decreased probably due to a ventilation at closing volume level with a decrease of ventilation in the dependent parts of the lung (2 subjects with abdominal obesity and a third who is the oldest one). In group III (n = 7), PaO2 decreased but DLCO increased. Probably ventilation took a slight place in closing volume. The increase of the exchange surface area is likely to be unable to compensate the arterial hypoxemia induced by the low VA/Q in the dependent parts of the lung. Influence of body position seems to be a function of age which increases closing volume.


Changes in renal inactivation of angiotensin II in rats with hereditary spontaneous hypertension. The inactivation of the pressor effect of angiotensin II by the renal vascular bed is less in spontaneously hypertensive rats than in normal rats. This phenomenon, which is observed only in adult animals but not in young ones, may be due to a slowing in the functional maturation of the kidney tissue.


[Enterobacteria erroneously identified as Salmonella in human faeces (author's transl)]. To differentiate Citrobacter freundii, Enterobacter hafniae, Proteus mirabilis and Alteromonas putrefaciens from Salmonella strains isolated in faeces, the author recommends the use of "Hajna-Kligler" medium, "Nitrate-Motility-Mannitol" medium, "Urease-Indole-Trytophane desaminase" medium and glycerol peptonated water. The lysis of Salmonella and E. hafniae strains by specific phages (Felix and Callow O: 1 Salmonella phage; Guinee and Valkenburg Hafnia phage) is emphasized.


Haemophilus influenzae type b capsular polysaccharide vaccine in children: a double-blind field study of 100,000 vaccinees 3 months to 5 years of age in Finland. A recently developed Haemophilus influenzae type b capsular polysaccharide vaccine was given to 48,977 children 3 months to 5 years of age; an equal number of children receiving group A meningococcal vaccine served as controls. The protection as well as serum antibody response was strongly age-dependent. Among children who had received the H. influenzae type b vaccine when 18 months of age or older, there were no cases of bacteremic disease caused by H. influenzae type b in the first year after vaccination. At the same time 11 such cases were seen in the control group of the same age, a highly significant difference. In the second year after vaccination two cases occurred in the H. influenzae type b-vaccinated group, five in the meningococcal-group A vaccinated group. No protection was seen among children who had been younger than 18 months when vaccinated, even if they received a booster dose of the vaccine. The serum antibody response to the H. influenzae type b polysaccharide, measured by radioimmunoassay, was poor in children below 18 months of age and good in those above it. No effect of the vaccine could be seen on the nasopharyngeal carriage of H. influenzae type b, which was approximately 6% in this age group. Adverse effects of the vaccine were mild.


Studies on the suitability of a cyanine dye (Viher-Test) for indicator dilution technique and its application to the measurement of pulmonary artery and aortic flow. The spectrum of a cyanine compound [Viher-Test (VT)] was recorded in distilled water, 5% glucose, 0.9% NaCl. The absorption maximum of these solutions was at 760 nm; after adding to plasma or blood the maximum was shifted to 785 nm. The time required for this spectral stabilization was less than 1 s at 37 degrees C for VT in H2O or glucose, it was slowed to 7 s at room temperature, and for VT in NaCl it was more than 30 s at 37 degrees C. VT binds to plasma proteins to at least 95%. The absorbance of VT in H2O (1000 mg/l) decreased by 1.0% per hour. Toxicity (LD50) of VT in H2O given i.v. in mice was 115 mg/kg body weight. Dye dilution determination of the flow in an artificial circulation with VT was within +/- 5% of direct measurements. Data indicate that VT is as suitable as Cardiogreen for indicator dilution technique using cuvette densitometer or reflection photometry. Simultaneous determinations of pulmonary artery and aortic flow from one dye bolus showed no significant difference on the average, but pulmonary artery flow diverged by up to +/- 25% from aortic flow due to incomplete mixing of dye and blood, respiratory changes of cardiac output or transient differences in right and left heart output.


[Recent fractures of the dorso-lumbar spine. Reduction by the double shroud technique (author's transl)]. The use of posterior osteosynthesis in traumatic pathology of the dorso-lumbar spine, entails some throught about the time maintenance of the quality of the reduction and the solidity of equipment. The observation of the advantages and inconveniences of different methods has led us to the double shroud technique. The simultaneous use of Harrington's and Roy Camille's materials gives an excellent reduction from all points of view. Moreover the double shroud technique improves the stability of posterior osteosynthesis.


Pluripotential and committed hemopoietic stem cells. A hypothesis. The hypothesis is proposed that regulation of hemopoiesis is largely accomplished by expansion or contraction of the committed stem cell compartments and that pluripotential stem cells are normally not involved or in cycle. The thesis appears supported by the fact that erythropoietin affects the committed red cell precursors, that 98% of marrow mitoses have been shown to occur in cells clearly recognizable as red or white cell precursors (while the pluripotential stem cells by definition are not so recognizable), and that it has been shown (by the spleen nodule assay) that the pluripotential stem cell compartment in the marrow cannot be readily expanded. The major objection to the proposed hypothesis are tritiated thymidine suicide data, which suggest that up to 20% of pluripotential stem cells may be constantly in cycle in some stains of mice. Preliminary experimental evidence supporting the hypothesis has been obtained: normal pluripotential stem cells which transfused into normal isologous mice are not lost as has been assumed but proliferate after irradiation, suggesting that it takes a special stimulus to "turn-on" the normally quiescent pluripotential stem cells.


Metaphyseal chondrodysplasia.

Metaphyseal chondrodysplasia. Any review of the metaphyseal chondrodysplasias is complicated by their variety and mainly unknown pathogenesis. The more familiar types display considerable clinical and radiological diversity: even more so the rarer disorders which still require complete definition, but differences in their mode of inheritance make diagnostic precision mandatory. These dysplasias present in infancy or in childhood, when the patient, usually dwarfed, may be proportionate, so that some forms may be confused with rickets or other lesions. Mental retardation is unusual, but the skin, hair, nails and facies provide valuable diagnostic features. Radiological abnormalities mainly affect the metaphyses of the shortened limb bones, less often the skull, vertebrae, pelvis, ribs and extremities, and sometimes their distribution may indicate the specific type of dysplasia. In a further complex group multiple systems are involved, notably the pancreas, intestine and lympho-reticular, causing malabsorption and haematological or immunological disorders.


A review of the osteopetroses.

A review of the osteopetroses. The osteopetroses are a group of conditions which are characterized by varying combinations of bony sclerosis and modelling defects. Classical osteopetrosis may be inherited as an autosomal dominant or autosomal recessive: the former variety is benign, heterogeneous and comparatively common, while the latter is precocious, potentially lethal and rare. Many other craniotubular dysplasias and hyperostoses are loosely grouped with the osteopetroses. The commonest of these is the autosomal dominant form of craniometaphyseal dysplasia, while the others which are well known include Pyle disease, and van Buchem disease. Sclerosteosis is a progressive condition in which massive cranial thickening is associated with syndactyly and gigantism. Each of these disorders has specific clinical and radiographic features, which permit recognition. Diagnostic accuracy is crucial for treatment, prognostication and effective genetic management.


[Small airway function tests; techniques of measurements. Review of the literature]. It is usually agreed that obstructive lesions in small airways are the first abnormalities in patients with chronic bronchitis. Consequently, there is now a great interest in the early detection of airways obstruction. Three techniques are described: frequency dependence of compliance, flow-volume curve and closing-volume. The results obtained in healthy subjects and in patients with obstructed airways are discussed.


[Scanning electron microscopy study of rat lung tissue]. Parts of rat lung tissue have been examined by means of a scanning electron microscope after either  chemical or physical fixage. Chemical fixage produces retraction on the tissue structures and the alveoles appear of irregular shape. Physical fixage gives the possibility to observe lung morphology without distorsions; details reproduced are in this case very clear and in a shape which appears very close to the original conditions.