Modulation of the susceptibility of inbred and outbred rats to arthritis induced by cell walls of group A streptococci. Inbred Buffalo rats were resistant to the induction of experimental arthritis induced by systemic injection of cell wall fragments in a crude whole-cell sonic extract of group A streptococci. This was in contrast to the susceptibility of outbred Sprague-Dawley and certain other inbred strains. Preliminary breeding studies indicated that genetic control of resistance of susceptibility is multigenic. When Buffalo rats were infected with a saline suspension of isolated cell wall fragments, chronic remittent arthritis developed. Suspension of isolated cell wall fragments, chronic remittent arthritis developed. Suspension of the isolated cell walls in the supernatant fraction of group A streptococci solubilized by sonication eliminated the arthropathogenicity in Buffalo rats. Thus, a component separable from the cell wall fraction can modulate the arthropathogenicity of cell walls in rats, but the effect depends upon the genetic background of the rat. The antibody response of Buffalo rats to the polysaccharide antigen of cell walls was also affected by the supernatant fraction of sonicated group A streptococci.


Relationship of hemagglutination to other biological properties of serologically classified isolates of Escherichia coli. The ability of 170 serologically classified strains of Escherichia coli to agglutinate human erythrocytes was examined. Erythrocytes of blood group A were more sensitive indicators of this property than were those of groups B or O. The predominant receptor was shown to be mannose containing; however, an additional receptor was found in two of nine strains studied. Natural mannose-like inhibitors were not found in unconcentrated urine obtained from 12 humans. Isolates from the urine or blood of patients with infections agglutinated erythrocytes significantly more frequently than did isolates from feces. Urine isolates of 10 common serogroups and isolates of less common serogroups did not differ in their ability to agglutinate erythrocytes. Among isolates from the urine of patients with infections, the ability to agglutinate erythrocytes did not correlate with either the serogroup of the strain or the clinical syndrome of the patient. Of the several other biological properties that were examined, only the production of colicins showed a significant association with the ability to agglutinate human erythrocytes.


Effect of estrogen and testosterone on the gastric secretion of rats and conscious rabbits. Shay rats and conscious rabbits were used to study the effect of sex hormones on gastric secretion. Daily injections of estradiol-di propionate and testosterone-propionate were given separately to each set of animals, while the control animals received solvent alone for the same duration of time. Estrogen inhibited gastric acid output but augmented the mucus secretion as evidenced by increased hexosamine and fucose contents; and testosterone had the reverse effects. The effect of estrogen was more potent that of testosterone. An inverse relationship between gastric acid and mucus secretion has been noted. Peptic activity varied independently of the acid output. These hormones seemed to vary the acid output by modifying the composition of mucus secretion.


Experimental gram-negative bacterial sepsis: prevention of mortality not preventable by antibiotics alone. Outbred Swiss mice were inoculated intraperitoneally or intravenously with one 90 to 100% lethal dose of Escherichia coli O:18, Proteus mirabilis, or Klebsiella pneumoniae. After carefully timed intervals, aminoglycoside antibiotics were begun at dosages nnd intervals predetermined to constitute optimal therapy. With progressive increases in delay of antibiotic therapy, mortality rates increased progressively from 0% to 90 to 100%. Standardized models of infection were developed by selecting delay periods before initiating antibiotic therapy such that 50 to 70% mortalities resulted. Utilizing these models, agents with reputed anti-endotoxin activity were administered concomitantly with the delayed antibiotic therapy to determine if any could prevent gram-negative septic mortality no longer preventable by the antibiotics alone. The following were observed: (i) adrenal corticosteroids prevented mortality that was no longer preventable by optimal aminoglycoside antibiotics alone. The following were preventable by optimal aminoglycoside antibiotic therapy alone; (ii) specific antisera also did so, provided anaphylaxis was circumvented; (iii) in one model (P. mirabilis), such protection by adrenal corticosteroids and specific antiserum could be additive; (iv) adrenal corticosteroids and specific antiserum acted synergistically with the aminoglycoside antibiotics--no protection was achieved by delayed administration of the steroids or antiserum alone; (v) timing was crucial--the synergistic protective activity of adrenal corticosteroids and of specific antiserum with aminoglycosides declined rapidly as infection progressed; (vi) cyclophosphamide pretreatment markedly impaired the synergistic protective activity of specific antiserum and of adrenal corticosteroids with aminoglycosides; (vii) no reputed anti-endotoxin agents other than adrenal corticosteroids and specific antiserum proved capable of preventing mortality not preventable by aminoglycoside antibiotics alone. These included antisera to rough mutant Enterobacteriaceae of Rc, Rd, and Re chemotypes, anticoagulants (heparin), ascorbic acid, antiproteolytic agents (aprotinin), alpha adrenergic blockers (phenoxybenzamine), prostaglandin synthetase inhibitors (acetylsalicylic acid, sodium salicylate, indomethacin), nicotinamide, glucose, and insulin-glucose-potassium mixtures.


Bactericidal activity of fractionated granule contents from human polymorphonuclear leukocytes: antagonism of granule cationic proteins by lipopolysaccharide. Granule extracts from human polymorphonuclear leukocytes (PMN) were prepared with 0.2 M (pH 4.0) acetate. A fraction (valley AB) with distinctive bactericidal activity against cell wall mutants of Salmonella typhimurium LT-2 was obtained after fractionation of the granule extracts by Sephadex G-100 column chromatography. The smooth parent LT-2 strain was less sensitive to the bactericidal action. Susceptibility of the rough mutants to bactericidal action increased as sugar residues decreased in the lipopolysaccharide (LPS) (Re greater than Rd2 greater than Rd1 greater than Rc greater than Ra). Cationic protein(s) responsible for bactericidal activity could be selectively removed from the fraction by absorption with whole LT-2 cells or purified LPS. Loss of cationic protein species was confirmed by cationic polyacrylamide gel electrophoresis. Purified LPS from LT-2 or the deep rough mutant TA2168 inhibited the antimicrobial activity of the killing fraction in in vitro assays. A minor protein species (vAB1) from the valley AB fraction had an apparent molecular weight of 36,000 to 37,000 and represented a major bactericidal activity of the fraction. Small amounts of the isolated vAB1 protein were bactericidal for the smooth parent LT-2 strain.


Role of Escherichia coli K capsular antigens during complement activation, C3 fixation, and opsonization. Escherichia coli strains with K capsular polysaccharides are relatively resistant to phagocytosis by polymorphonuclear leukocytes, in contrast to E. coli strains without K antigens. This inhibition of phagocytosis is related to an impaired recognition of the K+ strains by the phagocytes due to ineffective opsonization. All five strains without K antigens were readily phagocytized after opsonization in 5% normal serum, compared with no uptake of the K+ strains. Evidence is presented that the decreased opsonization of the K+ strains in normal serum is caused by a low rate of complement activation of the strains, with subsequent absence of C3b fixation or C3d fixation or both to the cell wall of the bacteria. After removal of the K+ antigens by heating of a K+ E. coli strain, the strain was able to activate complement, to bind C3b or C3d or both, and to become opsonized. Complement was then activated via the classical and alternative pathways, which was comparable to the complement consumption by K- E. coli.


Microbial ecological basis of infant botulism as studied with germfree mice. The possible role of the indigenous intestinal microflora in the toxicoinfection of human infant botulism was studied with adult germfree mice. Intraintestinal botulinum monoassociation was consistently produced when mice were fed 10 C. botulinum type A  spores. Control germfree mice became enterically infected when placed in the same isolator with, but separated from, animals that had been fed spores. When transferred into a room holding a colony of normal mice, the highly susceptible gnotobiotes became resistant to challenge of 10(5) spores after about 3 days of the conventionalizing exposure. The findings are interpreted as evidence that enteric botulinum infection occurs in human infants whose intestinal tract has not yet been colonized by bacteria which are indigenous to adults and prevent growth of C. botulinum. Intestinal monoassociation could not be developed in germfree infant mice younger than 7 days.


Systemic and gastrointestinal candidiasis of infant mice after intragastric challenge. Systemic and gastrointestinal infection can be established in infant mice after intragastric challenge with Candida albicans. Differences in virulence of the six strains tested were noted. As early as 3 h after infection, some but not all livers, spleens, and kidneys contained C. albicans, but the peak number of colony-forming units in these organs was seen at 6 h. The early colonization of the organs could not be attributed to aspiration of the inoculum since about 90% of lungs and livers tested yielded no colony-forming units at 10 to 15 min postinfection. In animals with systemic infections, lungs, livers, kidneys, and spleens showed similar numbers of colony-forming units within the organs during the first 6 h postinfection- and then the number declined progressively up to 72 h. The gastrointestinal tract was colonized throughout a 20-day period of study. Counts made at intervals beyond day 1 yielded between 10(5) and 10(6) colony-forming units in the stomach, ileum, and cecum. Preparatory techniques for scanning electron microscopy preserved the yeast, intestinal mucus layer, and epithelial surface and made it possible to visualize the association between the pathogen and host tissues within the digestive tract.


Serum immunoglobulin levels in mice. Determination of the low IgA level in AKR mice by an irradiation-resistant factor. A comparison was made between the serum immunoglobulin (Ig) levels in H-2 compatible AKR and C3H mice. The IgG1 and especially the IgA level in preleukemic AKR mice was much lower than in age-matched C3H mice, while the IgM concentration was hardly different for AKR and C3H. Lethally irradiated AKR and C3H mice reconstituted with syngeneic bone marrow (BM) cells showed a return to serum Ig levels which are normal for these strains. In AKR mice reconstituted with C3H BM cells low IgA levels were observed. On the other hand, in C3H mice reconstituted with AKR BM cells high quantities of IgA appeared, showing the AKR allotype. It is concluded that the low serum IgA concentration in AKR mice is not a reflection of a genetically determined inability of the B cell line to produce IgA, but rather a manifestation of a genetically determined capability to prevent IgA synthesis.


Persistent clonotypes associated with group A streptococcal polysaccharide antibody response in man. Elevated anti-streptococcal group A polysaccharide antibodies are present in the sera of acute rheumatic fever patients. Analytical isoelectric focusing of sera taken in the acute phase of the disease and sequentially for up to 2 years later reveals a stable clonotype pattern of anti-group A polysaccharide antibodies. In addition, with reinfection and recurrence of the rheumatic fever, the same clonotype pattern of antibodies is present. This finding indicates that naturally acquired immunity is associated with persistence of clonotype expression.


Effects of on-line symptom-processing on history-taking and diagnosis--a simulation study. Techniques for computer-assisted diagnosis have been largely confined to off-line use, and there has been little examination of their potential role directly in the clinical setting. It is argued that the potential benefits of on-line diagnostic aids are considerable. A major barrier to such developments is uncertainty that the practical use of an on-line system would lead to the improvements in diagnostic effectiveness that more conventional off-line systems have already demonstrated. A series of studies in which clinicians took the histories of computer-simulated 'patients' presenting with dyspepsia, and formed diagnoses on the basis of these histories with and without computer assistance, suggested that diagnostic effectiveness may be greatly improved with on-line computer assistance. Some reasons for this improvement are discussed and it is concluded that the clinician and the on-line computer bring different but complementary types of knowledge to the diagnostic task. Though many practical questions remain to be answered the findings establish the principle of on-line symptom processing.


Algebraic framework of an optimization problem in diagnosis. A formal analysis of an optimization problem in medical diagnosis is presented. The mathematical model of the diagnostic process corresponds in this work to an abstract machine definition which is based on the following sets and functions: Set of possible pathological states (diseases) of a patient, set of diagnostic tests (examination methods), set of all possible results of the tests (symptoms and signs), function which chooses successive tests, function performing a test (i.e., assigning to a given test its result), function assigning to each symptom a certain subset of the set of diseases. For a given abstract machine a class of pairs of graphs is formed; their analysis leads to the identification of a class of pairs of subgraphs which corresponds to an optimized diagnostic procedure. The optimization consists of a comparison of the distances between the initial and terminal vertices of the graphs and of a choice of a shortest route to a final diagnosis. For the considered class of pairs of subgraphs a mathematical model of the optimized diagnostic process is reconstructed.


Computer-aided medical diagnosis: literature review. The difficulty of the medical diagnostic task and the advantages of the computer as an aid in this task are discussed. The general strategy and structure of any computer-aided system is presented, and the relationship of diagnostic accuracy to key variables involved in the development, test and use of a computer-aided diagnostic system is examined. These variables include: the computer algorithm, the source of the information used to develop the data base, the number and type of diseases under investigation, the number and type of indicants used, the source of the test sample, and the source of the validated diagnosis. A table of 58 empirically tested computer-aided medical diagnostic systems is presented; each system is summarised in relation to the variables mentioned above and diagnostic accuracy.


Analysis of clinical laboratory data by biplot methods using a three-dimensional display: discrimination of renal stone-patients with idiopathic hypercalciuria and primary hyperparathyroidism. The biplot technique is a very useful graphical method to display the relationships between row and column characteristics in two-way tables. This method is applicable as long as the rank-2 approximation explains a large part (e.g. 95%) of the whole variability. However, since in large tables only a rank-3 approximation will yield such a high degree of explanation, a three-dimensional biplot technique has been introduced, using a 3d-screen as a matter of presentation of clinical laboratory data. The value of such a procedure is illustrated using as a clinical example a patient population with recurrent renal stone formation due either to primary hyperparathyroidism or to idiopathic hypercalciuria.


Cell surface sialylation of glycoproteins and glycosphingolipids in cultured metastatic variant RNA-virus transformed non-producer BALB/c 3T3 cell lines. The sialic acid composition and the display of cell surface sialyl components of several metastatic variant RNA-virus-transformed non-producer BALB/c 3T3 have been studied in culture. The following observations have been made concerning the sialyl components in these lines: (1) the compositions of whole-cell total, protein-bound and lipid-bound sialic acid were not appreciably different; (2) the surface sialic acid studied using the neuraminidase-galactose oxidase method and metabolic labelling followed by neuraminidase hydrolysis showed a positive correlation with the metastatic properties of these lines; (3) the degree of surface sialylation determined by galactose oxidase--sodium borotritide labelling of neuraminidase-treated and untreated cells revealed that 44--89% of exposed galactose and/or N-acetyl galactosamine residues of total cell-surface saccharides were sialylated in highly and intermediately metastatic lines as compared with 11-30% in the poorly and non-metastatic lines; (4) the cell surface glycoproteins and glycosphingolipids contributed equally well in their degree of sialylation and there was a positive correlation with the metastatic properties of the cells in vivo; (5) the cell surface proteins labelled by the lactoperoxidase-catalyzed iodination technique, followed by gel electrophoresis, showed some minor differences between metastatic variant lines. However, glycoproteins detected by the galactose oxidase labelling of neuraminidase-treated and untreated cells showed major differences in composition between the metastatic variant lines. The study of four highly metastatic lines has shown that the cells of these lines were enriched in several sialyl-glycoproteins, whereas three non tumorigenic lines and two poorly metastatic or non-metastatic lines contained unsialylated glycoproteins. The results indicate an enhancement of the degree of sialylation of surface glycoconjugates accompanying the metastatic process in RNA-virus-transformed mouse lines.


Rapid release of fibronectin from human lung fibroblasts by biologically active phorbol esters. A sensitive radioimmunoassay technique has been used to study the effects of several phorbol esters on their ability to release fibronectin from cultured human lung fibroblasts into medium. The biologically active phorbol esters studied rapidly released fibronectin from cells into medium, with concomitant changes in the cellular morphology within 2 h. The quantity of fibronectin released was dose-, time- and promoter-dependent. The earliest release of fibronectin was seen within 30 min of onset of the incubation. Alterations in membrane topology elicited by phorbol esters appear to be responsible for the rapid release of fibronectin molecules from cells into the medium.


The value of a sensitive assay of carcino-placental alkaline phosphatase (CPAP) in the follow-up of gynecological cancers. Using a sensitive enzyme immunoassay, carcinoplacental alkaline phosphatase (CPAP) was determined in sera of 1266 patients with gyneocological cancers. All these patients were referred after initial surgical treatment elsewhere. There were 95 patients with evidence of disease at the time of the study and 1171 without evidence of disease. Of the 95 patients with active disease, 47 were treated for ovarian carcinoma, 36 for carcinoma of the cervix and 12 for endometrial carcinoma. Raised levels of CPAP were seen in 40% of patients with ovarian carcinoma, in 22% with carcinoma of the cervix and in 41% in the small group with endometrial carcinoma. In patients without evidence of disease, raised levels of CPAP were seen in 12% of patients with carcinoma of the cervix, in 6% of endometrial carcinoma and only in 2% of patients with carcinoma of the ovary. Therefore it was considered that in the latter group CPAP studies would prove of some value. In the group of patients with carcinoma of the ovary and evidence of disease, raised levels of CPAP were seen almost exclusively in patients with epithelial tumors. It is considered that CPAP may be of value as a tumor marker in this group of patients. When compared with CEA, CPAP tends to give fewer false positives and correlates better with the presence of disease.


C. parvum treatment of transplanted rat tumours of spontaneous origin. C. parvum (Wellcome CN6134) has been examined for suppression of a range of transplanted rat tumours of spontaneous origin. With five tumours (three mammary carcinomas and two fibrosarcomas) growth of comparatively high cell inocula (with respect to the minimum for growth in control rats) was suppressed by admixture with the vaccine. Equivalent dry weights of Glaxo, Pasteur or Connaught BCGs were relatively ineffective. Intralesional injection of C. parvum into three three established tumours (two mammary carcinomas and one fibrosarcoma) retarded development of only one, the mmamary carcinoma Sp4. With three mammary carcinomas and one fibrosarcoma, active specific immune stimulation with vaccines of viable or irradiated cells admixed with C. parvum was again consistently effective only with carcinoma Sp4, and this tumour was also susceptible to intradermal but not intravenous treatment with C. parvum alone.


The transfer of care: U.S. mental health policy since World War II. Recent criticism of mental health policy has raised many questions about the so-called "mental health revolution." Following World War II, the federal government and the growing mental health lobby planned the first nationally oriented system of psychiatric treatment, rehabilitation, and prevention. The rapidly expanding National Institute of Mental Health coordinated that policy, particularly through its Community Mental Health Centers program. Custodial state hospitals were depopulated and their patients "dumped" in nursing and boarding homes, which now constitute the largest arena for and most expensive form of psychaitric care. While there has been some progress in decreasing the hospital population and in improving conditions, as well as in providing services to certain people who otherwise would never receive them, failures have been more dominant. Admission and readmission rates have climbed precipitously. Unplanned hospital discharge has led to hundreds of thousands of ex-patients living in dangerous, nontherapeutic nursing homes were the main concern is profit. They, and many others, are maintained on psychiatric drugs, another source of profit as well as a dangerous technology. Community mental health programs have maintained psychiatry's traditional class, race, and sex biases, and have incurred widespread intrusion into communities. This article shows that such problems are part of an interconnected system in which the driving forces are fiscal crisis, ideological justifications for dumping patients, attempts to pass responsibility from state governments to federal and local bodies, restrictions on government and insurance reimbursements, the free enterprise economics of the nursing home and drug industries, and the professionalist practices of the mental health field.


Partial inhibition of the growth of Mycobacterium lepraemurium in C3H mice immunized with cell wall skeletons. C3H mice stimulated with M. lepraemurium cell wall skeletons (LM-CWS) were challenged with viable M. lepraemurium, and delayed-type hypersensitivity (DTH) to picryl chloride was measured. In one type of experiment the mice were challenged at the time when stimulation of cell-mediated resistance by means of LM-CWS was undertaken. The major purpose was to investigate principles pertaining to immunotherapy. In contrast to the loss of a detectable DTH response to picryl chloride, development of murine leprosy was partially suppressed. In the second type of experiment the mice were stimulated with oil-attached LM-CWS seven weeks before challenge with M. lepraemurium. Findings were: a) that nonspecific DTH as measured by sensitization and challenge with picryl chloride was activated before the infection with M. lepraemurium and b) that the DTH which developed was associated with partial protection against the growth of lepromata. The murine leprosy which developed in C3H mice stimulated with LM-CWS was progressive after some delay.


Evaluation of antihemorrhagic activity of V. F. In the prophylaxis of surgical interventions performed in the Dental Clinic for dental avulsions under general anesthesia, the V. F. (peptides deriving from the enzymatic degradation of bovine Factor VIII) has been shown to be particularly active in the reduction of the quantity of blood lost per tooth, corresponding to a reduction in blood loss of an average of 40% to 45%. The "double blind" experiment confirmed a significant hemostatic capacity of the preparation. V. F. in extremely small doses (1 mg/day) divided into two daily, oral administrations, isn't toxic, isn't habit forming and doesn't provoke immunological reactions. On the basis of its positive characteristics (diminution of blood lost without alteration of the parameters of coagulation or platelet aggregation), V. F. seems to be the preparation of choice for the treatment of hemorrhagic diathesis not accompanied by coagulation defect, and also as a preventive measure in minor surgical interventions where small vessels are involved and hemostasis cannot be achieved surgically.


Synthesis of model compounds relevant to the active-site-directed inactivation of L-asparaginase by 5-diazo-4-oxo-L-norvaline. Earlier work has shown that 5-diazo-4-oxo-L-norvaline (DONV) irreversibly inactivates the L-asparaginase from E. coli by formation of a covalent bond in the region of the active site. Model compounds have been prepared to study this acid-labile covalent bond tentatively assigned to a serine or possibly a threonine residue in a decapeptide isolated from 14C-DONV-inactivated enzyme. Appropriately blocked DONV was found to alkylate methanol, and the hydroxyl function of blocked serine or threonine in the presence of boron trifluoride. The labile beta-ketoethers thus formed were reduced to the more stable beta-hydroxyethers. Facile lactonization of these 5-substituted-4-hydroxy-L-norvalines was observed. The diastereoisomers of both the lactonized and open forms of 5-methoxy-4-hydroxy-L-norvaline and related 4-hydroxy-L-2-amino acids of similar length were distinguishable on the amino acid analyzer. The beta-hydroxyethers derived from serine and threonine were hydrolyzed with acid and yielded the expected cleavage products. When the beta-ketoether was reduced by sodium borohydride prior to deblocking, in addition to the beta-hydroxyether, N-blocked amino alcohols were also formed, yielding a complex mixture of products.


Dextranomer in dermatologic conditions.

Dextranomer in dermatologic conditions. Dextranomer, a high molecular weight dextran derivative, was evaluated in 43 patients, and found to be the treatment of choice for decubitus ulcers. It is useful in most leg ulcers and cutaneous wounds, and can aid in the nursing care of terminal patients with gangrene or uclerating carcinoma. Dextranomer hastens the postoperative course in dermabrasion patients. Although patients with bacterial infection show no change with dextranomer, it is useful in hastening the resolution of herpes simplex and herpes zoster lesions.


Real-time digital K-edge subtraction fluoroscopy. We report in vitro and in vivo trials of K-edge fluoroscopy, by which iodine contrast concentration is displayed live, with tissue and bone images suppressed, free of patient-motion artifacts. Iodine and cerium, 125 and 225 mg/cm2 respectively, filter alternate TV fields of cine-pulsed 50 KVP x-rays. Weighted subtraction of successive TV fields isolates the iodine image and simultaneously minimizes artifacts. Digital techniques are used in real time. At our present x-ray tube limit, 500 mA instantaneous current, the patient exposure is 180 mR/sec and quantum mottle limits the image quality. Integrating four successive difference images provides a compromise between mottle and smoothly moving displays. Cardiovascular images of a 17-kg dog, using 1 ml/kg Renografin-60 injected into a foreleg vein, show that a 15-cm chest thickness is our present practical maximum. This method may be useful in diagnosing cardiovascular anomalies in infants without catheterization or suspension of breathing.


Computerized fluoroscopy techniques for intravenous study of cardiac chamber dynamics. A computerized fluoroscopy system which was recently developed in our laboratories permits image contrast increases of 8-16 relative to conventional image intensifer fluoroscopy and permits study of canine and human ventricular wall motion using peripheral intravenous injections. Two time-dependent image subtraction algorithms are illustrated in connection with observation of artificially infarcted dog hearts. The first algorithm produces a display analogous to direct ventriculography using catheterization. The second displays regions of dyskinetic motion as anomalous image grey shades.


A stereotactic head frame for use with CT body scanners. A prototype stereotactic head frame has been constructed for use in conjunction with a computed tomographic (CT) body scanner. Interactive software has been developed to allow target delineation using a standard CT scanner computer and image display console. The mathematic equations fundamental to this software are described. In preliminary experiments, it has been demonstrated that this frame can accurately direct a probe to an appropriately delineated target in a series of CT scans. A theoretic method for determining accuracy is presented; results suggest that this system represents a significant improvement over classic methods of neurosurgical stereotactic localization.


A selective radioenzymatic assay for the determination of octopamine and phenylethanolamine in plasma and cerebrospinal fluid. Preliminary results in human and experimental hepatic encephalopathy. A sensitive radioenzymatic assay for the simultaneous determination of phenylethanolamine and octopamine in biological fluids is described. It is derived from the radioenzymatic assay originally described by Molinoff et al. (1969) and subsequently modified by Saavedra (1974). The enzymatic reaction is based upon the methylation of phenylethanolamine and octopamine by phenylethanolamine-N-methyl transferase using 14C-S-adenosylmethionine as the methyl donor. The N-methyl derivatives of the two amines are separately extracted and estimated. Selectivity is increased by optimization of extraction and evaporation and by subsequent extraction of the two compounds. Phenylethanolamine and octopamine levels were determined in plasma of human subjects and in plasma and CSF of dogs. The levels were found significantly elevated both in human and experimental hepatic encephalopathy.


[Conservative surgery of spontaneous rupture of renal grafts]. 17 cases of spontaneous rupture of renal allografts were noted after 285 renal transplantations performed during the years 1967-1978. All ruptures occurred within the first two weeks after transplantation. Acute rejection, combined with hypertension, dialysis and/or anticoagulation seem to be the main etiological factors of graft rupture. Due to severe hemorrhage surgical exploration had to be performed in 15 patients. While removal of the graft was necessary in 4 patients the kidney could be preserved by tamponade and suture in 11 patients. 5 patients later lost their graft, due to chronic rejection, while 8 patients (6 of the 15 patients who needed surgical exploration) currently have satisfactory graft function.


[Long-term observations on different methods of nephropexy]. In 29 patients with nephroptosis two different methods of nephropexy were compared; nephropexy using sutures passing through the parenchyma (n = 16) and nephropexy using tissue adhesives (n = 13). The first group was mobilized 3.5 days after operation, whereas the second group was mobilized one day after operation. On later follow-up 79% of the patients had no or minor complaints. Those patients who had the same disturbances as preoperatively had all been treated by nephropexy using sutures passing through the parenchyma. In 56% of this group radiological recurrence was seen, whereas in the group using tissue adhesives there was only 8% radiological recurrence. We think therefore that the nephroxepy using tissue adhesive is the simplest and least traumatic method.


Browplasty as an adjunct to rhinoplasty. Brow modifications are discussed with respect to their role as aids in achieving certain aesthetic effects when rhinoplasty is being performed. If a deep nasofrontal angle should not be brought forward, reduction of the brow may be indicated. If the nasofrontal angle should not be retrodisplaced to deepen a shallow angle, brow augmentation may prove helpful in separating the nose from the forehead or in making the nose appear shorter in the vertical dimension. Augmentation and reduction browplastic techniques are discussed, and selected methods are illustrated. Some involve additional resection of frontal bone or procerus muscle at the time of nasal-hump removal. Others employ grafts of bone and/or cartilage removed from the nose at the time of septorhinoplasty. The versatile aesthetic surgeon should be capable of changing all structures adjacent to the nose. Certain difficult cosmetic problems are best treated by directing appropriate attention to these structures and to the nose rather than by concentrating on the nose alone. That the brow is one of these important abutting landmarks is demonstrated.


[Treatment of ureteral obstruction and urinary fistulas after kidney transplantation]. In 285 renal transplantations, performed during the years 1967-1978, 6 ureteral obstructions (2,1%) and 15 urinary fistulas (5,3%) were observed. Ureteral obstructions occurred in the late phase after transplantation and were caused by strictures at the uretero-vesical anastomosis (two patients), compression of the ureter by enlarged kidney during rejection (one patient) resp. lymphocele (one patient) and strictures at the pyelo-ureteral junction (two patients). Satisfactory results were achieved by surgical treatment in all patients. Urinary fistulas occurred in the early postoperative phase. Two vesical, 12 vesico-ureteral and one calyceal fistula were observed. 7 fistulas (1 vesical, 6 vesico-ureteral) closed spontaneously after temporary drainage of the bladder. 8 fistulas were repaired surgically. While satisfactory results were obtained in 13 patients, two patients died due to infection and sepsis after reoccurrence of fistulas.


[Experiences with clindamycin in orthopedic surgery and traumatology]. 60 cases of orthopedic surgery and traumatology were treated 64 times altogether with an average dose of clindamycin of 3 X 300 mg/day. 40 patients were given clindamycin as preventive treatment. 12 patients were treated for acute infections of the locomotor system and other 8 patients 12 times for chronic osteitis. In the group having received preventive trqatment, infection occurred bu 1 out of 40 patients. As to the 12 cases of acute infections, 10 recovered, 1 improved and 1 patient got worse. Concerning the 12 treatments of 8 patients with chronic osteitis, in 1 case the inactivation of the infection was obtained. 9 cases showed significant improvement whereas in 2 cases an aggravation was noticed. In 5 patients the following side effects occurred: 2 cases of allergic exanthema, 2 cases of mild diarrhoe and 1 case of pyrosis. This study shows that clindamycin is an antibiotic with a broad field of application in orthopedic surgery.


Cytochemical localization of lectin labeled vesicles in GERL region of hepatoma ascites cells. The fate of lectin labeled internalized plasma membrane in the ascites tumor form of the Chang rat hepatoma growing under in vivo and in vitro conditions was investigated cytochemically. Ascites cells were incubated in Convanavalin A (Con A) and horseradish peroxidase (PO), either with or without prior glutaraldehyde fixation and subsequently treated with 3',3-diaminobenzidine. In cells fixed before Con-A-PO labeling the reaction product was localized as a continuous and even layer upon the external surface of the plasma membrane. If unfixed cells were treated with Con A, coupled with PO at 4 degrees C and reincubated in phosphate buffered saline at 37 degrees C for varying periods of time, the Con-A-PO layer was of irregular thickness. In as little as 15 min of reincubation endocytotic vesicles containing PO positive material were closely associated with GERL components of the Golgi Apparatus. Localization of acid phosphatase (ACPase) within GERL vesicles, similar in size and location to those containing Con-A-PO reaction product, indicates that the Con-A-PO labeled vesicles may be a component of the Golgi apparatus in hepatoma cells.


Mitochondrial calcium of intact and mechanically damaged bone and cartilage cells studied with K-pyroantimonate. Cellular cation was localized with K-pyroantimonate osmium fixation in whole fetal mouse metatarsal bones and in deliberately mechanically damaged specimens. X-ray microprobe analysis of ultrathin sections showed a positive correlation between the concentration of Ca (and Sb) and the amount of electron-dense precipitate. In non-damaged osteoblasts and growth-plate chondrocytes dense precipitate had accumulated along the plasmalemma and the mitochondrial membranes, whereas damaged cells showed the precipitate on round granules in the mitochondrial matrix but not on membranes. Intermediate stages between these two patterns were also found. In a non-calcifying tissue such as liver no membrane-bound precipitate was found in intact cells. However, damaged liver cells showed precipitate-containing mitochondrial granules similar to those in damaged bone cells, but only after incubation of the damaged tissue for 1 h in a Ca-containing balanced salt solution. Freezing of fresh whole bones in liquid N2 before fixation in K-pyroantimonate osmium did not change the precipitate pattern in the damaged cells, but in intact cells it produced a random distribution of precipitate unrelated to membranes. The results are compared with those obtained in other studies on the subcellular localization of calcium and in biochemical studies on membrane versus matrix loading in calcium-accumulating isolated mitochondria.


The triple procedure; combined penetrating keratoplasty, cataract extraction and lens implantation. Results of combined keratoplasty, extracapsular cataract extraction and lens implantation (triple procedure) are reported for 67 eyes having at least 12 months follow-up. The average age of the patients was 73; the majority were female with a pre-op diagnosis of Fuchs's dystrophy. Post-op visual acuities were 20/40 or better in 72% of the eyes. No implants were removed and only one eye required regrafting. The discission rate was 32%; discissions were usually performed a year post-op. We feel the favorable results are due to uniform use of microsurgical extracapsular catarat extraction at the time of surgery with good capsular fixation of the lens implant.


Psychiatric presentation of Jakob-Creutzfeldt disease. A case of presenile dementia, which on a post-mortem examination proved to be due to Jakob-Creutzfeldt Disease, is described. The most dramatic early clinical feature was that of hysterical aphonia, temporarily removable by hypnotic suggestion. Anxiety symptoms and irritability also occurred early on, followed by a transient hallucinatory psychosis. The hysterical features persisted throughout. In view of the lack of dementing features or neurological signs, a psychogenic diagnosis was repeatedly made by several neurologists. This case illustrates the fact that primary hysterical neurotic features almost never occur for the first time in mid-life.


Sodium valproate in tardive dyskinesia.

Sodium valproate in tardive dyskinesia. Recent findings suggest that tardive dyskinesia may involve GABA-ergic influences in addition to dopaminergic receptor hypersensitivity and relative cholinergic hypofunction. Sodium valproate, which may increase brain GABA, moderately recuded tardive dyskinesia with doses of 900--3000 mg/day, as measured by a tremorgraph and rating scales. There was no correlation between dosage, blood levels, or clinical response. Although the symptoms were not completely controlled, valproate and other GABA-ergic agents may be useful compounds in studying and treating tardive dyskinesia.


Mutations in putative intervening sequences of the mitochondrial cytochrome b gene of yeast produce abnormal cytochrome b polypeptides. The apoprotein of yeast cytochrome b is translated on mitochondrial ribosomes and coded for by a split gene which is located in the COB-BOX region on mitochondrial DNA. With the aid of an antibody against cytochrome b, we identified the cytochrome b-cross-reacting polypeptides of respiration-deficient mutants mapping either in coding or intervening sequences of the cytochrome b gene. Most mutations in the coding regions caused the accumulation of a single apocytochrome b fragment whose apparent molecular weight (12,000 to 26,600) depended on the map position of the mutation. In contrast, mutations in putative intervening sequences often led to multiple new polypeptides immunologically related to apocytochrome b. Some of these abnormal polypeptides were considerably larger than wild type apocytochrome b. This suggests that mutations in intervening sequences can thus generate aberrant polypeptide products.


ilvU, a locus in Escherichia coli affecting the derepression of isoleucyl-tRNA synthetase and the RPC-5 chromatographic profiles of tRNAIle and tRNAVal. A mutation in the ilvU locus of Escherichia coli has led to a complex phenotype that included resistance to thiaisoleucine, a loss of derepressibility of isoleucyl tRNA synthetase, and an alteration of the RPC-5 chromatographic profile of the branched-chain aminoacyl-tRNA's. The alterations were manifest in an increase in the amount of Species 2 of both tRNAIle and tRNAVal at the expense of Species 1. A similar alteration, but independent of (and additive to) that caused by the ilvU mutation, was observed upon limitation of either isoleucine or valine. The shift in profile caused by limitation was also independent of the reduced growth rate or the derepression of the isoleucine and valine biosynthetic enzymes that also result from limitation. During chloramphenicol treatment nearly all tRNAIle and tRNAVal formed appears as species 2. Upon recovery from chloramphenicol, Species 2 of both acceptors are converted to Species 1. It is proposed that the ilvU product not only allows derepression of isoleucyl-tRNA synthetase but also retards the conversion of tRNA2Ile to tRNA1Ile and that of tRNA2Val to tRNA1Val. The mutated ilvU loci abolish the derepression and are more efficient in retarding the conversion.


Thioredoxin catalyzes the reduction of insulin disulfides by dithiothreitol and dihydrolipoamide. Thioredoxin from Escherichia coli was shown to catalyze the reduction of insulin disulfides by dithiothreitol. A quantitative assay was developed which measures the rate of insulin reduction spectrophotometrically at 650 nm as turbidity formation from the precipitation of the free insulin B chain. Thioredoxin, at 5 microM concentration, accelerated the reaction between 0.130 mM insulin and 1.0 mM dithiothreitol at pH 7 around 20-fold. The pH optimum of the reaction was 7.5. Thioredoxins from E. coli and calf liver showed similar specific activities. Stopped flow fluorescence measurements of the rate of reduction of thioredoxin-S2 by dithiothreitol showed a second order rate constant of 1647 M-1 s-1 at pH 7.2. This is between 10(2) to 10(3) times larger than the reaction between insulin or linear model disulfides and dithiothreitol. It is consistent with a ping-pong mechanism of thioredoxin catalysis since reduced thioredoxin is known to react very fast with insulin. Thioredoxin also catalyzed lipoamide-dependent reduction of the insulin disulfides in a coupled system with NADH, lipoamide, and lipoamide dehydrogenase. The fast spontaneous reaction between dihydrolipoamide and thioredoxin-S2 provides a mechanism for NADH or pyruvate-dependent disulfide reduction. The implication of the dithiol-disulfide oxidoreductase activity of thioredoxin for the regulation of enzyme activities by thiol oxidation-reduction control is discussed.


Membrane receptors for aspartate and serine in bacterial chemotaxis. High affinity binding sites for serine and aspartate have been characterized in membranes from Salmonella typhimurium and Escherichia coli. Greater than 80% of these sites have been identified as chemotaxis receptors. Mutants lacking binding sites for these amino acids have been shown to have corresponding defects in taxis. The substrate specificity of each of the receptors in Salmonella is very high; most analogs of serine and aspartate do not bind to these receptor sites and do not affect chemotaxis. The transport of these amino acids is apparently not related to chemotaxis. At least 2500 serine receptors and 1200 aspartate receptors with dissociation constants of about 5 microM are present in the membrane fraction of logarithmically growing cells.


Identification of the amino acid residues of proteins S5 and S8 adjacent to each other in the 30 S ribosomal subunit of Escherichia coli. When Escherichia coli 30 S ribosomal subunits are reacted with protein-protein bifunctional reagents, a number of protein pairs as well as aggregates containing three or more ribosomal proteins are formed. In the present study we have purified one of the protein pairs obtained by reaction of 30 S ribosomal subunits with either radioactive or nonradioactive dimethylsuberimidate. Following molecular weight determination and ammonolysis, the pair was shown to consist of ribosomal proteins S5 and S8. The "native" structure of the complex was surmised from its capacity to be reconstituted into a biologically active 30 S ribosomal subunit. From peptide maps and primary structure determination of various peptides it was demonstrated that the cross-linking bond between ribosomal proteins S5 and S8 involves primarily the residues Lys-93 of protein S8 and the COOH-terminal lysine (Lys-166) of ribosomal protein S5. This result is substantiated by the finding that a mutant carrying an altered S5 lacking the COOH-terminal lysine yields a greatly reduced amount of S5-S8 cross-link. In addition to the points of cross-linking it was found that Lys-30, Lys-68, and Lys-86 of S8 and Lys-5 of S5 react with dimethylsuberimidate, indicating that these residues are available for reaction and suggesting their topographical localization on the ribosomal surface.


The primary structure of a glyceraldehyde-3-phosphate dehydrogenase gene from Saccharomyces cerevisiae. The complete nucleotide sequence of the coding, as well as the flanking noncoding regions, of a yeast glyceraldehyde-3-phosphate dehydrogenase gene was determined. Both the 5' and 3' noncoding sequences are extremely AT-rich and regions of partial dyad symmetry are present immediately adjacent to the 5' and 3' ends of the translated portion of the gene. The sequence AAUAAA is present in the 3' noncoding region of this gene and is a part of an extensive region of dyad symmetry which is structurally related to the 3'-terminal portion of both procaryotic mRNAs, as well as some eukaryotic mRNAs. The coding region of this gene does not contain intervening sequences. Establishment of the primary structure of this glyceraldehyde-3-phosphate dehydrogenase gene provides a basis for further studies involving in vitro mutation of the gene and subsequent analysis of gene expression in vivo.


Biosynthesis of yeast glycoproteins. Processing of the oligosaccharides transferred from dolichol derivatives. The oligosaccharides previously bound to dolichol diphosphate were isolated from Saccharomyces cerevisiae cells incubated with [U-14C]glucose. Five compounds were obtained that migrated with RGlucose of 0.100, 0.120, 0.145, 0.180, and 0.215 on paper chromatography. All of them contained mannose and 2 N-acetylhexosamine residues. The substances that migrated with the three lower RGlucose values had, in addition, glucose units. The structure of the oligosacchardies was very similar if not identical with that of the oligosaccharides isolated from the dolichol diphosphate derivatives synthesized "in vitro" by yeast or rat liver particulate preparations or "in vivo" by dog thyroid or rat liver slices as judged by their migration on paper chromatography, monosaccharide composition, and degradation compounds produced by alpha-mannosidase treatment or acetolysis. The oligosaccharides previously bound to asparagine residues in proteins were isolated from yeast cells which had been pulsed with [U-14C]glucose and chased with medium containing the unlabeled monosaccharide. The samples taken after very short pulses contained four oligosaccharides that migrated with RGlucose of 0.100, 0.120, 0.145, and 0.180 on paper chromatography. The first three compounds contained glucose, mannose, and 2 N-acetylhexosamine residues whereas the one that migrated with a RGlucose of 0.180 was devoid of the former monosaccharide. Samples taken after short chase periods revealed that the compounds that migrated with the lower RGlucose values gradually disappeared and were converted to the oligosaccharide with the higher RGlucose value was they lost their glucose residues. Similar analysis as those mentioned above showed that the structures of these compounds were similar to those of the dolichol diphosphate-bound oligosaccharides. Samples taken after longer chase periods revealed that the oligosaccharide that migrated with a RGlucose of 0.180 was subsequently either enlarged by the addition of more mannose residues or trimmed to smaller sizes.


High resolution thermal denaturation analyses of small sequenced DNA restriction fragments containing Escherichia coli lactose genetic control loci. Differential melting curves are reported for four DNA restriction fragments (789, 301, 203, and 95 base pairs in length) spanning the lactose control region. All but the smallest melt with two or more subtransitions. Maps are proposed which identify the positions of regions of different thermal stability in the sequences. The sizes of regions comprising subtransitions range from 60 to 200 base pairs. An analysis is made of the cooperativity exhibited between regions in the sequence. The effect on the shape of the differential melting curves of Na+ between 10 mM and 0.5 M as well as that of Mg2+ and glycerol has been determined. An 81-bp-long sequence of unusual thermal stability occurs at the lactose promoter. Its TM change, resulting from the above change in salt concentration, is out of step by 1.5 degree C with the neighboring DNA sequence. The potential biological significance of this behavior is discussed.


Structural studies of the membrane-derived oligosaccharides of Escherichia coli. Membrane-derived oligosaccharides are a novel class of glucose-containing oligosaccharides found in the cell envelope of Escherichia coli and other Gram-negative organisms (Schulman, H., AND Kennedy, E.P. (1979) J. Bacteriol. 137, 686-688). Previous work has shown that these oligosaccharides contain sn-1-glycero-P and smaller amounts of phosphoethanolamine, derived from membrane phospholipids, attached to position 6 of certain of the glucose residues. The structure of the parent oligosaccharides (obtained by reduction with borohydride followed by alkaline hydrolysis) has now been studied. The oligosaccharide was permethylated, followed by hydrolysis and conversion of the products to methylated glucitol acetates, which were then analyzed and identified by gas-liquid chromatography and mass spectrometry. The membrane oligosaccharides contain 10 to 12 D-glucopyranoside residues/mol, linked solely by 1 yields 2 and 1 yields 6 bonds. They are highly branched structures, with four nonreducing termini per mol. Glucose units at the branch points are doubly substituted at positions 2 and 6. The low specific rotation of the oligosaccharide (+8.3 degrees) indicates that the glycosidic bonds are predominantly or entirely beta.


The hydrodynamic shape, conformation, and molecular model of Escherichia coli ribosomal 5 S RNA. The structure of ribosomal 5 S RNA has been examined using several physical biochemical techniques. Hydrodynamic measurements yield a s020,omega and [eta] of 5.5 x 10(-13) x and 6.9 ml/g, respectively. Other parameters calculated from these values indicate the shape of 5 S RNA is consistent with that of a prolate ellipsoid 160 A in length and 32 A wide. Sedimentation equilibrium results show that 5 S RNA exists as a monomer in the reconstitution buffer with an apparent molecular weight of 44,000. Ultraviolet absorption difference spectra show that approximately 75% of the bases in 5 S RNA are involved in base pairing, and of these base pairs 70% are G-C and 30% are A-U. These results on the overall shape and secondary structure of 5 S RNA have been incorporated with the results of other investigators as to the possible location of single-stranded and double-stranded helical regions, and a molecular model for 5 S RNA is proposed. The molecular model consists of three double helices in the shape of a prolate ellipsoid, with two of the double helical regions at one end of the molecule. The structure is consistent with the available data on the structure and function of 5 S RNA and bears similarity to the molecular model proposed by Osterberg et al. ((1976) Eur. J. Biochem. 68, 481-487) based on small angle x-ray scattering results and the secondary structure proposed by Madison ((1968) Annu. Rev. Biochem. 37, 131-148).


The 6-phosphogluconate dehydrogenase reaction in Escherichia coli. This study is an attempt to relate in vivo use of the 6-phosphogluconate dehydrogenase reaction in Escherichia coli with the characteristics of the enzyme determined in vitro. 1) The enzyme was obtained pure by affinity chromatography and kinetically characterized; as already known, ATP and fructose-1,6-P2 were inhibitors. 2) A series of isogenic strains were made in which in vivo use of thereaction might differ, e.g. a wild type strain versus a mutant lacking 6-phosphogluconate dehydrase, as grown on gluconate; a phosphoglucose isomerase mutant grown on glucose or glycerol. 3) The in vivo rate of use of the 6-phosphogluconate dehydrogenase reaction was determined from measurements of growth rate and yield and from the specific activity of alanine after growth in 1-14C-labeled substrates. 4) The intracellular concentrations of 6-phosphogluconate, NADP+, fructose-1,6-P2, and ATP were measured for the strains in growth on several carbon sources. 5) The metabolite concentrations were used for assay of the enzyme in vitro. The results allow one to calculate how fast the reaction would function in vivo if ATP and fructose-1,6-P2 were its important effectors and if the in vitro assay conditions apply in vivo. The predicted in vivo rates ranged down to as low as one-tenth of the actual rates, and, accordingly, one cannot yet draw firm conclusions about how the reaction is actually controlled in vivo.


In vivo methylation of prokaryotic elongation factor Tu. In Salmonella typhimurium and Escherichia coli, elongation factor Tu (EF-Tu) is methylated as shown by its incorporation of labeled methyl residues from [methyl-3H]methionine. Analysis of the nature of the methyl-containing residues by protein hydrolysis, followed by paper chromatography and high voltage electrophoresis showed that both mono- and dimethyllysine are present. Eighty per cent of the EF-Tu molecules are methylated if methylation occurs at a unique lysine residue. The EF-Tu fraction which is not methylated is still able to accept methyl groups, as shown by methylation of approximately 10% of the EF-Tu after addition of chloramphenicol (D-(-)-threo-2,2-dichloro-N-[beta-hydroxy-alpha-(hydroxymethyl)-o-nitrophenethyl] acetamide) to inhibit further protein synthesis. There is no evidence of turnover of the methyl residues. We attempted to separate the methylated from the nonmethylated form of EF-Tu by isoelectric focusing on polyacrylamide gel, but were unable to do so.


Precursor maltose-binding protein is active in binding substrate. Precursor maltose-binding protein synthesized in vitro was shown to be active in binding maltose by affinity chromatography.


Application of the principles of enzyme kinetics to clonal growth rate assays: an approach for delineating interactions among growth promoting agents. The interaction of mitogenic factors on a single cell type and the comparative activity of a given factor in diverse cell types have been studied by applying the principles of Michaelis-Menten kinetics to clonal growth data. Such comparisons are facilitated by derivation of two parameters; Km mitogen, the mitogen concentration that gives half-maximal clonal growth and a theoretical maximal growth rate, RMAX T. Both parameters are analogous to the Km and VMAX as applied to enzymatic reactions. Use of these parameters permits meaningful comparisons between cells with different growth rates. Using kinetic analysis of dose-response data, we found that normal human epithelial cells require 200 times more fetal bovine serum protein (FBSP) than a malignant line to multiply at their respective half-maximal rates. Further, the Km FBSP of normal cells was reduced to that of the malignant line by the inclusion of growth factors (EGF or FGF, and hydrocortisone) in the medium. On the other hand, even though greater levels of serum were required when growth factors and hydrocortisone were not present, their inclusion did not alter RMAX T. Interactions between mitogenic factors were shown to be unidirectional. Although EGF reduced the Km FBSP, FBSP did not change the Km EGF. The same type of analysis revealed that hydrocortisone, which potentiated the mitogenic activity of EGF did not change the Km EGF. Kinetic analysis of cell growth should prove useful in studies on the relation between growth and tumor promotion as well as in the evaluation of growth-inhibiting chemotherapeutic agents.


[Original removing technique of the kidneys for transplantation. An experimental study (author's transl)]. The depicted procedure minimizes the hazards of aggressive manipulations, and excludes any possibility of so-called "warm ischaemia". The kidneys are flushed out in situ with cool pulsatile perfusion through an aortic cannula. Kidneys, aorta and inferior vena cava are then removed en-bloc without interrupting the perfusion, and preserved in Collins' solution at 4 degrees C. After a 6 to 19 hour storage time, one of the kidneys is transplanted on another dog, while the second one is submitted to histological examination. Nine transplantations were carried out, followed in 7 cases with a most satisfactory diuresis resuming, and with urinary ionic levels, as well as daily urea output, normalization within 48 hours. Histologic examination showed an unaffected glomerular apparatus, but some mild tubular lesions.


[Removal of human kidneys under "in situ" hypothermia by aortic and caval cannulations. Technique and first clinical results (author's transl)]. After dissection and cannulation of aorta and vena cava, the kidneys are washed out "in situ" with a cooling perfusion, avoiding any possibility of so-called warm ischaemia. The kidneys and their vessels, still attached to aorta and vena cava, are then en bloc removed, which enables a satisfactory preparation of the vessels for subsequent anastomosis to be performed. After an experimental study [6], four kidneys were removed according to this procedure, and transplanted after an average cold-storage time of 23 hours. Diuresis recovery was immediate, and normalization of serum creatinin, and of urinary sodium and potassium levels, was achieved within 6 days.


[180 cases of umbilical hernia repaired in a new way (author's transl)]. We describe a new method for the cutaneous repair of umbilical hernias. The cut of the skin makes two flaps suppressing the navel which is generally salient. After the aponevrotic repair which is made by vertical suture with slowly resorbable material, the repair of the two cutaneous flaps builds a new navel which aspect is very close to the natural one. This method has been used once with complete satisfaction, for the repair of an omphalocel.


Low dose pulsatile gonadotropin-releasing hormone in anorexia nervosa: a model of human pubertal development. Patients suffering from anorexia nervosa were studied to determine whether gonadotropin-releasing hormone (GnRH) could induce the hormonal changes which occur during normal puberty. Three amenorrheic patients were studied at low body weight (less than 70% ideal BW). All three patients were prepubertal, as evidenced by immature LH and FSH responses to a standard GnRH test (2.5 micrograms/kg BW) and the absence of spontaneous LH peaks both during the day and during sleep. Low doses of GnRH (0.025--0.05 microgram/kg), aimed at producing peak plasma GnRH values of approximately 200 pg/ml, were given by iv bolus injection every 2 h for 5 days. Plasma responses of FSH, LH, and estradiol were measured by RIA. Preinjected FSH values rose rapidly to plateau (range, 15--30 mIU/ml) on the second to third day before falling despite the continued administration of GnRH. In contrast, plasma LH and estradiol increased gradually throughout the 5 days of injections. Acute FSH responses to GnRH initially exceeded those of LH but subsequently decreased, whereas LH increments increased progressively after the first 36 h of injections. The 5 days of low dose GnRH pulses induced maturation of the hormone responses to the standard GnRH test, so that LH release exceeded that of FSH at the completion of the study. These changes in the patterns of FSH and LH secretion are similar to those seen during normal puberty in girls and during the follicular phase of the menstrual cycle. The results demonstrate a changing pattern of pituitary response to physiological administration of GnRH and indicate that the changes in gonadotropin secretion during normal puberty are consistent with the effects of the single decapeptide GnRH.


Group B beta-hemolytic streptococci causing pharyngitis. Group B beta-hemolytic streptococci were isolated from the throats of 49 of 1,110 patients who had pharyngitis. Compared with patients whose throat cultures were negative for beta-hemolytic streptococci, those harboring group B were more likely to have enlarged tonsils (P less than 0.001), exudate (P less than 0.02), and tender enlarged anterior cervical lymph nodes (P less than 0.01). Group B should not necessarily be dismissed as a nonpathogen when identified in the pharynx of patients with exudative pharyngitis; laboratories which report beta-hemolytic streptococcal isolates from the pharynx only as group A or non-group A should be encouraged to perform definitive group identification of all beta-hemolytic isolates to further evaluate the role of other streptococcal groups as the causative agents for pharyngitis.


Biotyping of Escherichia coli by a simple multiple-inoculation agar plate technique. A nine-test system using multiple-inoculation agar plates for biotyping of Escherichia coli is described. Testing of 959 strains resulted in 78 biotypes. On repeated testing, 96% of 182 strains had identical biotypes or differed by only one test. This system provides satisfactory differentiation among strains and is reproducible. Precise standardization of inoculum size is not required. Multiple inoculation allows time and cost-efficient testing of large numbers of strains.


Use of an immunoperoxidase method for identification of Bacteroides fragilis. An indirect immunoperoxidase (IP) slide test was evaluated for the laboratory identification of Bacteroides fragilis. Antigen-antibody complexes were detected with goat anti-rabbit immunoglobulin G-peroxidase conjugate with 3-amino-9-ethyl-carbazole as the peroxidase substrate. Ninety-one percent of 44 B. fragilis strains tested were IP positive (3+ to 4+ reactions) with greater than or equal to 1:160 dilutions of rabbit antiserum produced against whole cells of B. fragilis ATCC 23745. The antiserum was species specific. No cross-reactions were observed with 35 Bacteroides strains of other species or with a variety of facultative or aerobic gram-negative bacilli. Four B. fragilis strains were IP negative. One of these (VPI 2393) was the deoxyribonucleic acid (DNA) homology group II reference strain. The other three were clinical isolates. IP-negative and representative IP-positive strains were tested for DNA homology with the type strains for DNA homology groups I and II (VPI 2553 and VPI 2393). Two of the three clinical isolates were classified as DNA homology group II, and the remaining strain was classified as a group I. Capsular material known to be unique to B. fragilis was common to both DNA homology groups as indicated by reactions with purified anticapsular antiserum. The IP technique provides a suitable alternative to fluorescent microscopy for the rapid immunological identification of B. fragilis.


Rapid identification of Enterobacteriaceae with the micro-ID system versus API 20E and conventional media. The Micro-ID system for rapid (4 h) identification of Enterobacteriaceae was evaluated by testing 433 enteric bacilli and 9 other gram-negative bacilli. Each isolate was identified with conventional tubed media and was also tested in the Micro-ID and API 20E systems. The overall accuracy of both systems was 97%. Micro-ID tests for the Voges-Proskauer reaction, indole and H2S production, and ornithine and lysine decarboxylase all demonstrated a 97 to 99% correlation with conventional methods. Only 86% of the Micro-ID urease tests agreed with Christenson urea agar. Two inoculum densities were tested in Micro-ID panels, with 157 stock cultures. Over 90% of the tests were unaffected by changes in inoculum density. Tests with four control strains suggested that the Micro-ID system was more reproducible when a light inoculum was used. The Micro-ID system was found to be a very convenient method for rapid, accurate, and precise identification of the Enterobacteriaceae.


Practical technique for quantitating anaerobic bacteria in tissue specimens. Quantitative bacteriology has considerable influence on the care and management of surgical wounds. Heretofore, these techniques have been limited to measurements of aerobic bacteria. A technique is reported herein which permits quantitation of obligately anaerobic bacteria in tissue specimens. This technique is easily reproduced in any clinical laboratory and eliminates the need for expensive anaerobic chambers.


[Lymphatico-venous experimental anastomosis (author's transl)]. Since the pioneer work of Nielubowicz et Olszewski successful anastomoses have been caried out between lymphnodes and veins in experiments and in the clinic as well. The creation of patent anastomoses between lymphatic trunks and veins still present many problems, primarily due to the small size of the lymphatic vessels. The microsurgical technique permits the authors to overcome these difficulties. End-to-side anastomosis between lymphatic trunk and the superficial femoral vein was carried out - using stereo microscopic - on rabbits, with a modification of Cordeiro's and Degni's technique; a longitudinally divided plastic catheter was introduced into the vein and the lymphatic trunk was pulled into the lumen and fixed to the upper venous wall with one suture. End-to-end anastomosis was created between lymphatic trunk and the superficial femoral vein or one of it's branches with a technique using a small piece of plastic catheter, which was introduced into the lymphatic trunk on one side and to the vein on the other side in order to prevent the transfixation of the vessels wall. Interrupted 11/0 atraumatic sutures were used to create the anastomosis. With both of these methods patent anatomosis can be carried out between lymphatic trunks and veins.


Quantitative assay of soluble beta-hemolytic streptococcal antigens via an immunochemical turbidimetric method with a spectrophotometer. Soluble, group A, B, C, and G beta-hemolytic streptococcal antigens were successfully identified in a prototype spectrophotometric system by an immunochemical turbidimetric assay. Any spectrophotometic system which can take a zero reading followed by a second reading 2 or more min later can be used for the assay. Maximum absorbance was obtained near a wavelength of 340 nm. A wide range of linearity between antigen concentration and absorbance was observed at some antibody dilutions, resulting in a simple assay which can be used to quantitate amounts of antigen in solution. Minimal cross-reactions that present no problem in interpretation was observed. Simulated emergency samples were solubilized and assayed for group A and B bacteria within 3 h of colony recognition. Reproducibility of the absorbance resulting from the antibody-antigen reaction was great, with low coefficients of variation over a period of 50 days. The simplicity of the assay solutions, requiring only antisera and a buffer, and the accessibility to high levels of quality control are among the greatest assets of the technique to clinical laboratories.


Reticulate bodies as single antigen in Chlamydia trachomatis serology with microimmunofluorescence. Formalin-fixed, purified reticulate bodies (RB) of Chlamydia trachomatis immunotype C/TW-3/OT were used as a serological test antigen in the microimmunofluorescence test. The sensitivity and specificity of the RB antigen were compared to elementary bodies (EB) used as antigens in the detection of C. trachomatis antibodies in human sera by microimmunofluorescence. RB reacted with all known C. trachomatis immunotypes with the same sensitivity as the homotypic EB. In routine serology with sera and endocervical secretions, the RB antigen had a sensitivity similar to that of the EB in detecting serum antibodies, endocervical secretion antibodies, and antibodies of immunoglobulin M and G classes. No false-positive reactions were detected with control sera. All positive reactions showed type-specific antibodies against an EB immunotype. RB seemed to demonstrate chlamydial group reactivity; sera from 10 psittacosis patients diagnosed clinically and serologically by complement fixation showed five positive, three equivocal, and two negative reactions. By immunofluorescence, RB appeared as distinct rings demonstrating uniform peripheral surface fluorescence at their rims. The EB appeared as pinpoint-sized dots. C/TW-3/OT RB used as a single test anitgen should provide a simple and sensitive serological assay for the detection of C. trachomatis antibody.


Evaluation of the new API 20C strip for yeast identification against a conventional method. The new API 20C yeast identification system together with appropriate microscopic morphology determinations achieved a 97% correlation with a rapid conventional method. Whereas a group composed of Candida, Torulopsis, Saccharomyces, and Rhodotorula was identified with ease (98% overall correlation), a second group, containing Cryptococcus, Trichosporon, and Geotrichum species, appeared to give the system the most difficulty (90% correlation). Within this group particular difficulty was encountered in identifying varieties of Cryptococcus albidus, C. terreus, C. laurentii, Trichosporon beigelli, and Geotrichum spp. as to species. The API 20C system should be incubated the full 72 h prescribed by the manufacturer. However, when used in conjunction with appropriate morphological tests, presumptive identifications of some Candida and Torulopsis species may be made at 24 to 48 h. To facilitate identifications of the more difficult group of yeasts, ancillary tests for determining nitrate reductase, urease, and phenol oxidase activities should be considered as additions to the strip. Incorporating the phenol oxidase test would be especially important for identification of Cryptococcus neoformans, a yeast which should be identified as quickly and as accurately as possible. The API 20C system with computer assistance has proved to be an easy-to-inoculate, versatile, and fairly rapid method of yeast identification, giving results comparable to those obtained by conventional methodologies.


Rapid selective urease test for presumptive identification of Cryptococcus neoformans. A rapid simplified screening method that selectively detected the urease activity of 99.6% of 286 isolates of Cryptococcus neoformans within 15 min was developed for use in clinical microbiology laboratories.


Evaluation of anaerobic incubation for recovery of group A streptococci from throat cultures. No statistical differences were found in the recovery of group A streptococci from throat culture specimens after overnight incubation of blood agar plates in 5% CO2 compared with anaerobiosis. Anaerobic incubation required many more subcultures and resulted in considerably greater technical time and expense.


Long-term sotalol therapy in patients with arrhythmias. Sotalol is a pure beta-adrenergic receptor antagonist. The present study was divided into a first and second therapy period. A total of 38 patients with atrial or ventricular arrhythmias were included in the first therapy period. After a drug-free period of approximately two months, 14 of the 38 patients entered the second therapy period and were given oral sotalol. During the two treatment periods, oral sotalol was given in doses ranging from 40 to 480 mg/day for 0.5 to 11 months in the first period and for four to nine months in the second period. Oral sotalol decreased or abolished arrhythmias in 92 per cent of the patients in the first therapy period and in all the patients in the second therapy period. Minor side effects occurred in two patients. Sotalol possesses a unique class III antiarrhythmic action. The electrophysiological profile is different from other beta-adrenergic blocking agents in that sotalol prolongs the duration of the intracellularly recorded action potential. This property may contribute to the antiarrhythmic efficacy demonstrated with sotalol.


Further observations on hippocampal neurons in dispersed cell culture. The growth of the processes of dissociated hippocampal neurons from 18- to 20-day-old rat fetuses has been studied in vitro using a method that permits cells to be maintained at relatively low plating densities for periods up to three weeks (Banker and Cowan, '77). Most of the cells are spherical or ovoid when they first attach to the substratum (either polylysine or collagen) but within 24 to 48 hours they begin to put out processes, and by the end of the first week in culture a significant proportion (approximately 45%) come to resemble normal pyramidal cells with a more-or-less triangular shaped soma, a single dominant dendrite-like process emerging from the apex of the soma, and several "basal dendrites" arising from the opposite pole of the cell. Comparisons of the lengths of these dendrite-like processes with those of hippocampal cells in the brains of animals sacrificed on the fourth post-natal day and impregnated by a variant of the Golgi-Cox method, indicate that in some cases the rate of process formation in vitro approximates that in vivo and that the general form of the neurons is remarkably like that of immature pyramidal cells. After a week in culture a second type of process can be recognized. These tend to be finer than those we have identified as dendrites; they are relatively uniform in diameter, frequently give off branches at right angles, and in the electron microscope can be seen to form synapses upon the larger processes and cell somata. These axon-like processes differ from the axons of normal pyramidal cells in two important respects: (i) most commonly they arise from one of the dendritic processes, including, on occasion, the putative "apical" dendrites, and only rarely from the base of the perikaryon; (ii) there may be two or more such processes from a single cell. The thicker, tapering processes can be shown (after incubation in 3H-uridine) to contain large amounts of RNA; newly-synthesized RNA does not extend into the finer, axon-like processes.


Once-a-day treatment with sotalol and hydrochlorothiazide in patients with essential hypertension. Eighteen patients with mild to moderately severe hypertension were treated, after a run-in period of placebo for three weeks, with a combination of 160 mg sotalol and 25 mg hydrochlorothiazide for three months. Fifteen patients responded well and, after one month of treatment, had a sustained diastolic blood pressure of less than 100 mm Hg. Additional treatment reduced the blood pressure even further during the second month, with a significant fall in blood pressure after the first month of treatment. The degree of severity of the hypertension did not seem to have an effect on blood pressure response to treatment. Serum potassium values decreased significantly during treatment. They remained within the normal range, and no clinical symptoms of hypokalemia were observed. One patient developed hyperuricemia and had to be withdrawn from the study.


In vivo effect of oral environment on etched enamel: a scanning electron microscopic study. After etching the enamel in teeth of young children with 50% buffered phosphoric acid and allowing the teeth to remain in the oral environment for a few months, an irregular enamel surface similar to the morphology of recently etched enamel was noted by means of scanning electron microscopy. In addition, the enamel surfaces were covered with plaque. Accordingly, observations by other authors, that etched human enamel takes on a normal appearance after short exposure in the oral cavity, could not be confirmed. However, when the surface of the etched enamel was pumiced, the enamel reacquired both the shine and appearance of non-etched enamel.


Character of the hard tooth tissue-polymer bond. I. Study of the interaction of calcium phosphate with N-phenylglycine and with N-phenylglycine-glycidyl methacrylate adduct. A model investigation was carried out to establish the chemical character of the bond between hard tooth tissues and polymeric materials. The interaction of NPG and NPG-GMA with Ca3(PO4)2 and 45Ca3(PO4)2 was studied in aqueous, alcoholic and aqueous-alcoholic solutions. It was shown that NPG and NPG-GMA react in solution with Ca ions which are in equilibrium with calcium phosphate. The reaction proceeds more intensively in aqueous-alcoholic medium due to its ionic character. The IR spectra of the reaction products show the presence of NPG-GMA calcium salt.


Character of the hard tooth tissue-polymer bond. II. Study of the interaction of human tooth enamel and dentin with N-phenylglycine-glycidyl methacrylate adduct. The interaction of powdered human tooth enamel and dentin with NPG-GMA was studied in alcoholic and alcoholic-aqueous solutions. The reaction produces ionized carboxylic groups capable of forming ionic bonds between the calcium ions in the tooth enamel or dentin and NPG-GMA.


Bonding of acrylic resins to dentin with 2-cyanoacrylate esters. Strength and durability of the dentin-acrylic resin joint cemented with 2-cyanoacrylate esters were studied. Maximum adhesion is obtained with isobutyl 2-cyanoacrylate after 1% acid pretreatment of the dentin. Hydrolytic stability is somewhat improved by addition of polymer to the adhesive or coating around the joint.


Strain gauge transduction of lip and jaw motion in the midsagittal plane: refinement of a prototype system. This paper describes the design refinements made in an earlier prototype system for transducing lip and jaw movements in the midsagittal plane. Major improvements over the prototype system included: reduced transducer loading, improved two-dimensional separation and resolution, elimination of possible artifacts due to lateral-medial or rotational movement, electrical isolation of the subject from the transducer, increased capability to transduce movements of children as well as adults, and an accessory instrument for orienting the transducers with reference to defined anatomical planes.


Clinical trials of intraoral dental xeroradiography. A new dental xeroradiographic processor was clinically tested. In comparison with conventional radiographs, xeroradiographs often showed more anatomic detail of teeth and bone and required approximately half the exposure time. These characteristics, the speed of operation and the added features for convenience, suggest that xeroradiography may be important to dental radiography in the future.


Indications for orthodontic-prosthodontic collaboration in dental treatment. In dental practice, combined plans of orthodontic and prosthodontic treatment are underused. Indications for a collaborative effort include preservation of integrity of the dental arch, biomechanical factors, limitations in design of prostheses, esthetic appearance, periodontal considerations, prevention of malocclusion, and better retention of position of teeth.


Importance of combined periodontal and acid-etch composite treatment in restoration of anterior teeth and periodontal health. Severely fractured, hypoplastic, and carious mandibular anterior teeth in a 17-year-old patient precluded the ability to use adequate methods of control of plaque. With simple, inexpensive techniques, periodontal health was restored and a functional and esthetic occlusion was provided. This treatment plan was accomplished with minimal risk of injuring the pulps of the teeth.


Review of methods for removing cast gold restorations. Most techniques and devices described for crown removal, in one way or another, destroy the integrity of today's precision cast crowns. There were only three techniques described that do not require drilling a hole, cutting a notch or slot, clamping with claws or jaws, prying with instruments, or grasping with forceps and pliers. These are the copper band filled with cement, the coping of cold-curing acrylic resin, and the Richwil crown remover. The safest and least traumatic of all crown removal devices and techniques is to cut a slot and pry the crown loose. Although the crown is destroyed, damage to the tooth is avoided.


Dentists' incomes, fees, practice costs, and the Economic Stabilization Act: 1952 to 1976. Bureau of Economic and Behavioral Research. Throughout the 20-year period from 1952 to 1972, dentists' net incomes, adjusted for inflation, increased and provided greater monetary rewards to the practice of dentistry. Evidence discloses a close association between the purchasing power of dentists' net incomes and the general level of economic activity (measured by the GNP inconstant dollars). Dentists are not immune to temporary recessions. The period from 1972 to 1974, with the imposed fee guidelines of Nixon's Economic Stabilization Act, was unusual. With effective fee guidelines during the latter two phases coupled with freely fluctuating input prices, dentists were caught in an income squeeze. During 1972 to 1974, the purchasing power of dentists' net incomes fell at a rate of 10.1% per year as the price index of practice costs outpaced dentists' fees. After the Economic Stabilization Act expired in 1974, trends returned to normal. Dentists' net incomes increased at rates consistent with changes in the GNP and dentists' fees increased slightly faster than the "Price Index of Cost of Conducting a Dental Practice."


Voluntary dental laboratory certification program. Council on Prosthetic Services and Dental Laboratory Relations. Laboratory certification does not offer concrete guarantees of consistent high quality of products or services. It does, however, identify, for the dental profession, a competency and acceptability factor on which to base a predication of performance by the laboratory. Also, laboratory certification establishes a framework within which the dental laboratory industry can work to continue upgrading its facilities and personnel, demonstrates the concern of certified laboratories for continuing competence, and indicates to government and third-party payers a willingness to develop standards endorsed by the industry.


Medical views of depression in the elderly: historical notes. Ancient Greek and Roman physicians recognized the high prevalence of depressive illness in old age and began to differentiate the major mental syndromes of the elderly. Greek humoral theory connected black bile, melancholia and old age, and this formulation dominated medical thinking until the seventeenth century. Beginning with the Enlightenment and continuing throughout most of the nineteenth century, physicians spurned the idea that old age and depression were linked, or tended to view depression as evidence of brain decay. Although twentieth century studies have confirmed that depression in the elderly is a common illness, usually self-limiting and rarely coexisting with dementia, these views have been incompletely incorporated into modern medical practice.


Rapid slide technique with dextranomer beads for bacteriologic assessment of wounds in the elderly: comparison with quantitative biopsy method. A rapid slide technique to provide quantitative bacteriologic assessment of wounds in elderly and debilitated patients is described. It involves the use of material from dextranomer-bead (Debrisan) wound dressings to replace tissue biopsy for deciding when a wound is ready for closure or when a specific therapy is no longer efficacious. In 27 patients an 81 percent correlation was demonstrated between the bacterial count as determined by the new method and that determined by the more complicated tissue biopsy.


The nation's children: do federal programs provide adequate eye/vision care? Government involvement in child health programs is traced from the 1910 White House Conference on Children to current federal programs. This paper discussed the provisions, problems and anticipated changes in four of the leading federal programs offering eye/vision care.


Visual development.

Visual development. This paper summarizes the postnatal development of the visual system in a format that separates the various parts and functions into Input Components, Transmitting Components, Integrative Mechanisms, and Visually Induced Cognitive Behaviour. This treatment of a number of studies and philosophies that comprise the field of infants' vision indicates that most components and mechanisms are fully operative by the end of the second year of life.


[Implantation of intraocular lens in keratoplasty with cataract extraction (author's transl)]. A combined operation a) keratoplasty; b) cataract extraction; c) iridocapsular implant must be advised when a corneal opacity and a cataract require both a surgical treatment. Six months after surgery, functional results are good in 4 cases/5.


Effects of estrogen on 3H-leucine uptake by the hypothalamus and pituitary: correlation with hypothalamic and serum LHRH and LH. An injection of estradiol benzoate (EB, 5 microgram/rat) to ovariectomized rats suppressed serum LH levels 2, 4, 8 and 24 h later; serum LHRH levels were unaltered but the LHRH content in the medial basal hypothalamus (MBH) was significantly elevated at 24 h. EB treatment also modified the sensitivity of the pituitary to LHRH administration: a rapid decrease at 4 h followed by an augmentation in LH release at 8 and 24 h. 3H-Leucine incorporation into proteins of the pituitary and neural tissues was unaffected for 4 h following EB treatment at the time when serum LH and the responsiveness of the pituitary to LHRH were clearly depressed. However, a marked increase in 3H-leucine incorporation into the proteins of the pituitary alone occurred at 8, 16 and 24 h after EB treatment, coincident with the enhanced pituitary sensitivity to LHRH. These studies showed that estrogen promoted storage of LHRH in the MBH and alteration in protein metabolism may be an important initial step in the estrogen-induced augmentation of the pituitary responsiveness to LHRH.


Adrenal and gonadal steroids and pituitary response to LHRH in girls. II. Precocious puberty. Three baby girls between 22 and 30 months of age, presenting with isosexual idiopathic precocious puberty apparently not due to any organic cause, were studied. Basal levels of plasma steroids of adrenal and gonadal origin, circadian rhythm of plasma cortisol, and pituitary response to 25 microgram of LHRH were evaluated. All cases were characterized by high levels of plasma gonadotropins and by a marked response to exogenous LHRH. Normal cortisol circadia rhythm was found in all cases, one of which characterized by slightly raised plasma values. The other adrenal steroids were all higher than those expected for the chronological age, corresponding to those of 5-6 years old girls. On the other hand, steroids of both adrenal and ovarian (A, T) or mainly ovarian origin (E2) and DHT were all found to be higher than those normally reported in girls at stage 2 of sexual development. These data indicate a hypersecretion of gonadotropins in idiopathic isosexual precocious puberty, with a marked gonadal steroidogenetic response. The secretion of adrenal androgens does not appear to have an important role in the etiology of this condition.


[Keratoplasty. Urgent treatment of the corneal perforation (author's transl)]. Sixteen keratoplasties (15 perforating, 1 lamellar) were performed on 12 perforated corneas and on 2 eyes threatened by imminent corneal perforation. The causal disease was metaherpetic kératitis (6 cases), chronic and recurrent ulcers (4 cases), acute keratoconus (1 case) and corneal traumas (3 cases). Enucleation has been avoided and the anterior chamber was restored in all the cases, with or without anterior synechiae. One case only developed ocular hypertension which was cured by fistulisation. Architectonic results are satisfying in all the cases. Recuperation of visual functions is possible only in the most favourable cases. It is indicated to perform keratoplasty before the perforation when this one seems unavoidable and to consider this surgical procedrue as an emergency when the cornea is perforated.


[Value of perforating keratoplasty in the treatment of chronic oedemas of the cornea (author's transl)]. A total of 75 cases of chronic diffuse or central oedemas of the cornea were treated, and the modern techniques of perforating keratoplasty used gave 68% of good anatomical results for all the various etiologies taken together. Prognosis varies according to whether there is one or many etiological factors. In "simple" cases with a single etiopathogenic mechanism, 88% of good anatomical results were obtained and the patient has a 50% chance of recuperating visual acuity from 5 to 10/10 Pa2. In "complex" cases, or when surgical treatment of the oedema had been previously attempted, only 30% of good anatomical results were obtained and there is a 60% chance of not helping the patient in any way.


Pituitary response to LHRH during the puerperium in women. Five breast-feeding women received 100 mug synthetic LHRH at between 19 and 58 days post-partum. One subject was treated twice. LH and FSH responses were monitored using radioimmunoassay. In four women treated at 19,21,29 and 51 days post-partum, the FSH response was greater than the LH response which was absent altogether in three of these women. In two women who were treated at 52 and 58 days both LH and FSH levels was elevated with the LH response being greater than the FSH response. This change in the pattern of pituitary response is considered in relation to the post-partum anovulatory condition.


Maximum allowable cost: can the government control drug costs? In 1973 the federal government moved to limit drug reimbursement to providers in federally sponsored or supported programs, to the lowest cost at which the drug is generally and consistently available unless a difference in therapeutic effect can be demonstrated between the brand name and generic drug. This paper examines the political evolution and rationale for this program and explores the issues surrounding the ongoing controversy regarding publicly financed programs offering drug benefits. The authors speculate that the government's first attempt to control prices of pharmaceuticals, prior to enactment of some form of national health insurance, if successful, will call forth pharmaceutical industry strategies which could negate program benefits.


Statistical and other data-analytic techniques for the evaluation researcher: an identification, classification, and description of methods and resources. The goal of any social/health intervention program is to improve the lot of the people it is designed to serve. Of critical importance is the development and implementation of programs able to achieve such a goal is evaluation research (ER)--a process representing an interface between the generic notion of evaluation and the rigor of social research methodology. The evaluation researcher should be familiar with, and be capable of using, any of a number of (statistical and non-statistical) data-analytic techniques. The objectives of this discussion, therefore, are to (1) identify, categorize, and briefly describe statistical and other data-analytic techniques of potential use to the evaluation researchers; and (2) identify currently available resources, i.e., texts, books of readings, monographs, etc., that offer discussions and analyses of these techniques. It is hoped that such an exposition will lead to a wider understanding, acceptance, and use of these procedures, which can only enhance the quality of subsequent program policy- and decisionmaking.


[The importance of Lancefield Group B streptococci (S. agalactiae) in gynaecology and obstetrics (author's transl)]. A bacteriological study of 10,962 vaginal swabs has made it possible to work out the percentage of women who are carriers of Group B streptococci in their vaginas. The count varies between 9.43 and 17.25 per cent according to the different populations that were studied. Serotyping of the strains of 1,030 vaginal specimens was carried out and it was found that serotypes II and III predominated. We have been able to study 27 strains responsible for infection in the early neonatal period such as septicaemia or meningitis at the same time as we were studying the vaginal flora. The distribution of the serotypes illustrates a predominance of types 1c and III in 70 per cent of cases. Contamination between the mother and the child is obvious but in 95 per cent of cases the strain isolated in the infected child was of the same serotype as that which was isolated in the mother. Group B streptococci are still very sensitive to antibiotics and particularly to the penicillins. It does seem to us to be unrealistic to treat with antibiotics prophylactically in pregnancy. On the other hand careful attention to the newborn and careful bacteriological study of multiple specimens taken from the skin and the orifices gives easy screening for the germ and the possibility of treating infants that are grossly contaminated.


[Cancer of the endometrium. The evaluation of high risk cases (author's transl)]. The epidemiology of cancer of the endometrium has been reviewed by going through the literature in order to find a high risk category. A particular type seems to be discernable: obestiy, endometrial hyperplasia, and the contribution of endogenous or exogenous oestrogens and lack of progesterone are the most marked elements. These factors for cancer of the endometrium are similar to those for cancer of the breast. It has been astonishing to find that these two hormone dependent cancers have a very similar background.


[Vesico-uterine fistulae after Caesarean operation (author's transl)]. The vesico-uterine fistulae represent 4 per cent of all urogenital fistulae. They are rare and are found almost always after Caesarean operation. We have been able to find in the literature 110 vesico-uterine fistulae after Caesarean operation. They very rarely fail to be diagnosed if careful post-operative examination is made and the majority of them are discovered in the year following delivery. Urinary incontinence is the most common reason for consultation. More uncommon is amenorrhoea with menstruation through the bladder. Incontinent women are under constant threat of ascending urinary tract infection. Finally these women, whether they are incontinent or amenorrhoeic, are sterile. Their fertility remains diminished even after surgical cure of the fistula. The only treatment for those who complain of the condition is surgery. It should be undertaken after a careful gynaecological and urological assessment.


Comparison of the protective efficacies of the live vaccine RIT 4025 and an inactivated vaccine against a natural heterologous A/Victoria/3/75 infection. A clinical trial was initiated in South Africa before the winter season of 1976. The study involved 253 volunteers divided into three groups of vaccinees and one control group. Two groups of vaccinees were inoculated with either one or two doses at 2 weeks' interval (10(7.2) EID 50/dose) of the RIT 4025 live recombinant strain [A/Scotland/840/74 (H3N2) serotype] and one group received one injection of an inactivated vaccine [A/Port Chalmers/1/73 (H3N2), 360 i.u., A/Scotland/840/74 (H3N2), 300 i.u. and B/Hong Kong/8/73, 300 i.u./dose]. The serum antihaemagglutinin antibody responses against the heterologous A/Victoria/3/75 strain as measured by the single radial haemolysis test were satisfactory and not statistically different in all groups of vaccinees. On the other hand, the antineuraminidase antibody response was better in the group receiving the killed vaccine. At the end of the influenza season, A/Victoria/3/75 infections were confirmed serologically. Only 12% of the infections were symptomatic. The infection rate was significantly reduced in the live vaccine groups, whereas in the killed vaccine group the percentage of infection was lower but not significantly different from that in the placebo group.