Observations concerning fractures of the lateral humeral condyle in children. From an anatomical study and clinical review of fractures of the lateral humeral condyle in children, the following conclusions are drawn. The mechanism of injury is a violent varus force with the elbow in extension, the condyle being avulsed by the lateral ligament and the extensor muscles. If the fracture is incomplete, with an intact hinge of pre-osseous cartilage medially, the fragment will not be displaced. If the fracture is complete the fragment may be displaced, and open reduction with internal fixation is mandatory. The results of open reduction more than three weeks after the fracture are no better than those of no treatment at all, and may kill the lateral condylar fragment by damaging its blood supply. The major problem of a neglected fracture is tardy ulnar nerve palsy; to avoid this, immediate anterior transposition of the nerve is recommended, operation for the fracture itself being of no benefit.


The anatomy of the metacarpo-phalangeal joints, with observations of the aetiology of ulnar drift. One hundred normal fingers were dissected and arthrographs obtained by injection of chromopaque-gelatin mixture, allowing comparison between the radiographic and macroscopic configuration of the synovial capsule. Synovial recesses protruding from each side of every metacarpo-phalangeal joint were found in relation to the collateral ligaments and corresponding exactly with the site of radiological erosions. A group of bursae lying on the superficial aspect of collateral ligaments were also demonstrated. A rudimentary intra-articular meniscus was found. The results of examination of the insertions of the interossei showed differences from traditional descriptions. The cause of rheumatoid deformity was suggested to be the rheumatoid process arising in the lateral recesses and lateral bursae, weakening the collateral ligaments, which give way in the directions of the deforming forces. These are derived from the long flexor tendons, which were shown to exert an ulnar and volar strain on the metacarpo-phalangeal joint of every finger during grip.


The neurovascular island flap for defective sensibility of the thumb. In six patients with defective sensibility of the thumb the transfer of a neurovascular island flap was performed according to Littler's technique. This review one to eleven years later was mainly to determine if reorientation of the cortical representation of stimuli had developed and if tactile gnosis had persisted. The pick-up test was carried through by the three patients with a lesion of the dominant hand. All six patients referred pin-prick in the flap to the donor finger; all had absent two-point discrimination corresponding to the flap, although it had been present within normal limits a few months after operation; and all had better touch, pain and temperature sensibility in the flap than in the surrounding recipient area. All six reported functional improvement. For the best results an intelligent patient is required who has a lesion of the dominant hand and is prepared to use or exercise it regularly.


Congenital fistulae of the coronary arteries. Clinical considerations and surgical management in 23 patients. Experience gained during the past 18 years at the Texas Heart Institute in the surgical treatment of 23 patients with coronary artery fistulae is reported. Patients ranged in age from three to 63 years; 18 were women. The right coronary artery was most frequently involved (14 patients) and in 18 patients the fistulous communication was terminal. Cardiac catheterization and angiography were aids in determining the exact diagnosis in all but two patients. During the last three years cardiopulmonary bypass was used in five of eight patients, and it is believed that extracorporeal circulation should be employed routinely. Terminal fistulae were ligated with sutures distally, close to the cardiac chamber. Lateral fistulae, when single, can be closed if feasible by tangential arteriorrhaphy. However, in most of these patients multiple communications and aneurysmal dilatation are encountered which would be treated more successfully by proximal and distal ligation of the fistula and distal coronary bypass revascularization. There were no operative deaths in our series. It is believed that with the help of today's advanced methods in anesthesia, extracorporeal circulation and coronary artery bypass surgery, all patients with coronary artery fistulae, once diagnosis has been made, should undergo surgical treatment.


Fractures of the clavicle and injuries of the sub-clavian artery. Report of 10 cases. During four years, the authors have observed ten lesions of the sub-clavian artery associated with a fracture of the clavicle. The clinical picture in one case out of two was that of an acute ischemia of the upper limb. The surgical repair has been performed in 8 cases. The thoracic approach was necessary three times. The clavicle was resected in most cases. The prognosis of these lesions depends on the rapidity of their recognition, and of their treatment, and on the fact whether the brachial plexus is involved or not


Physicochemical properties of kinetoplast DNA from Crithidia acanthocephali. Crithidia luciliae, and Trypanosoma lewisi. The protozoa Crithidia and Trypanosoma contain within a mitochondrion a mass of DNA known as kinetoplast DNA (kDNA) which consists mainly of an association of thousands of small circular molecules of similar size held together by topological interlocking. Using kDNA from Crithidia acanthocephali, Crithidia luciliae, and Trypanosoma lewisi, physicochemical studies have been carried out with intact associations and with fractions of covalently closed single circular molecules, and of open single circular and unit length linear molecules obtained from kDNA associations by sonication, sucrose sedimentation, and cesium chloride-ethidium bromide equilibrium centrifugation. Buoyant density analyses failed to provide evidence for base composition heterogeneity among kDNA molecules within a species. The complementary nucleotide strands of kDNA molecules of all three species had distinct buoyant densities in both alkaline and neutral cesium chloride. For C. acanthocephali kDNA, these buoyant density differences were shown to be a reflection of differences in base composition between the complementary nucleotide strands. The molar ratios of adenine: thymine:guanine:cytosine, obtained from deoxyribonucleotide analyses were 16.8:41.0:28.1:14.1 for the heavy strand and 41.6:16.6:12.8:29.0 for the light strand. Covalently closed single circular molecules of C. acanthocephali (as well as intact kDNA associations of C. acanthocephali and T. lewisi) formed a single band in alkaline cesium chloride gradients, indicating their component nucleotide strands to be alkaline insensitive. Data from buoyant density, base composition, and thermal melting analyses suggested that minor bases are either rare or absent in Crithidia kDNA. The kinetics of renaturation of 32P labeled C. acanthocephali kDNA measured using hydroxyapatite chromatography were consistent with at least 70% of the circular molecules of this DNA having the same nucleotide sequence. Evidence for sequence homologies among the kDNAs of all three species was obtained from buoyant density analyses of DNA in annealed mixtures containing one component kDNA strand from each of two species.


An assessment of value of long posterior flaps in below knee amputation by skin blood pressure. The pretibial and calf skin blood pressure was measured in 34 legs, of which 20 suffered from ilio-femoral arterial stenosis and 14 from popliteal arterial stenosis. The constantly higher calf than pretibial pressure in both groups of patients studied strengthens the place of the long posterior flaps in below knee amputation.


Deoxyribonucleic acid-envelope complexes from Escherichia coli. A complex-specific protein and its possible function for the stability of the complex. The different Escherichia coli envelope fractions (cell wall, cytoplasmic membrane, and DNA-envelope complex fragments) were isolated by free-flow electrophoresis and analyzed by sodium dodecylsulfate-acrylamide gel electrophoresis. The DNA-envelope complex fragments possess a specific protein (mol wt 80,000-90,000). Upon treatment with trypsin, this protein disappears and the complex breaks down, thus releasing DNA, cell wall, and cytoplasmic membrane. Disaggregation of the complex can also be achieved by high salt concentrations. Lysozyme treatment dissolves the murein layer within the complex but does not disaggregate the complex. From these and other results on the stability of the DNA-envelope complex, conclusions can be drawn about the possible linkage within the described envelope particles.


A high-yield technique for preparing cells fixed in suspension for scanning electron microscopy. Human leukocytes fixed in suspension were allowed to settle onto poly-L-lysine-coated glass coverslips and prepared for observation with the scanning electron microscope (SEM). The coverslips were dehydrated in ethanol, critical point dried with CO2, and coated with gold-palladium. With the aid of a locator grid, several fields were photographed with light microscopy after the cells had settled onto the poly-L-lysine-coated coverslips and again after completion of the processing before SEM observation. Quantitative comparison of the number of cells present after settling with the number retained for final viewing with the SEM revealed a cell yield approaching 100%. This simple, reproducible, high-yield technique for processing cells fixed in suspension for SEM prevents changes in surface architecture induced by collecting live cells onto various substrates before fixation and also avoids potentially selective cell losses. Such a technique should allow quantitative correlations between SEM and other morphological and functional parameters.


A screening method to detect clonal secretion of DNP-specific antibody. Spontaneous variants of the IgA immunoglobulin secreting mouse myeloma, S194-2, were isolated by cloning the line on soft agar and screening for the loss of secreted S194 immunoglobulin. Because S194 IgA possesses DNP binding activity, the screening method was designed to test for clonal secretion of antibody which specifically precipitated DNP-ferritin conjugates. Precipitates formed over IgA secreting S194 clones, whereas none were evident over nonsecreting XCl clones nor IgG secreting MOPC 21 clones (MOPC 21 IgG does not bind DNP). In addition the method was sensitive to the amount of immunoglobulin secreted. By continual selection of exceptionally reactive clones with this assay, a S194 culture was obtained which secreted five to six times as much IgA as the original mass culture. Spontaneous variants were isolated from six independent subclones of this parent line with an overall frequency estimated at 2.7 X 10(-5) per cell per generation. Biochemical analysis of these variants showed that all of them secreted reduced or undetectable amounts of IgA. No variants were obtained which secreted IgA molecules altered at the DNP binding site, or which secreted immunoglobulin subunits alone. Variants of the latter class have, however, been obtained in high frequency in other myeloma strains by other investigators.


The formation of annulated lamellae induced by the disintegration of microtubules. Investigations with different 'antitubulins' have shown that different cell types in culture response to prolonged treatment with the formation of annulated lamellae. These annulated lamellae are possibly derived from previously accumulated smooth endoplasmic profiles. A hypothetical explanation would be that annulated lamellae (and the nuclear membrane) are sites of tubulin synthesis or microtubular polymerization. Their appearance after induced microtubule disintegration could then be viewed upon as a reactive hyperproduction of such sites.


The perturbation of the human erythrocyte membrane by phospholipase C. A study has been made of freeze-fractured preparations of erythrocyte ghosts modified by phospholipase C (Clostridium welchii). Such membranes show a decrease in surface area of up to about 47% and lipid droplets appear on their external surface but there is no loss of protein. Freeze-fracture of maximally hydrolysed membranes exposes only very small areas of A faces and these appear particle-free. Most of the membranes are simply cross-fractured. At lower levels of hydrolysis there is more extensive exposure of A fracture faces but the particle density is less than in control preparations. If such exposed faces were representative of the whole membrane then the particle density would have been expected to increase. It is suggested either that areas of membrane with increased particle density do not fracture or that the particles revealed by freeze-fracture involve phospholipid as well as protein and are not revealed in the absence of phospholipid.


Chromatographic resolution of enantiomers selective review. Recent research has produced a notable increase in knowledge useful for chromatographic enantiomer resolution. Some major advances have emerged in the understanding of asymmetric solute-solvent interactions, and many successful separations by gas and by liquid chromatography have been reported. This review presents a selective discussion of the major advances, with primary emphasis on the use of chiral stationary phases. The latter offer advantages (over indirect techniques) such as generally easier sample preparation, decreased analysis time, and simultaneous chemical as well as optical purity analysis.


Purification of Escherichia coli B-specific p-aminobenzoate "pick-up" protein to homogeneity by affinity chromatography. Of the satellite fractions of Escherichia coli B dihydrofolate synthetases, a non-enzymic protein that is specifically able to bind p-aminobenzoate and sulphonamides has been purified 6000-fold by p-aminobenzoylcellulose affinity chromatography. The protein was named p-aminobenzoate "pick-up" protein according to its function, i.e., to bring p-aminobenzoate into reaction with L-glutamate and pteridine during dihydrofolate biosynthesis. About 4 mg of pure protein (0.532% recovery, calculated from the total p-aminobenzoate binding capacity of the unfractionated supernatant separated from the crude bacterium plasma) can be obtained from 500 g of harvested cells. The product is homogeneous in polyacrylamide gel electrophoresis both in the absence and presence of sodium dodecyl sulphate, and has a molecular weight of 15,000 daltons +/- 5% as measured by sodium dodecyl sulphate gel electrophoresis and Sephadex G-75 gel column chromatography. p-Aminobenzoate and sulphonamide ligand binding studies showed a single binding site per p-aminobenzoate pick-up protein molecule. KD values for p-aminobenzoate and some sulphonamides as well as for L-glutamate, L-gamma-glutamyl oligopeptides, some pteridines and folate antagonists are also presented in order to illustrate the specificity of the receptor protein.


Attenuated influenza A vaccine (Alice) in an adult population: vaccine-related illness, serum and nasal antibody production, and intrafamily transmission. Ninety-five healthy adults, ages 18 to 56 years, received two intranasal doses, 2 weeks apart, of a live, attenuated, influenza type A (H3N2) vaccine (an inhibitor-resistant recombinant strain of A/England/42/72 named "Alice"). Ninety-two persons were given placebos similarly. Ninety-three percent of 68 subjects with initial serum hemagglutination-inhibition (HI) titers of greater than or equal to 1:40 to influenza A (H3N2) had a fourfold or greater antibody increase in postvaccination sera. Forty-four percent of 27 subjects with an initial HI titer of greater than or equal to 1:80 had similar increases. Overall, 77% of vaccinees had fourfold or greater antibody titer increases. Vaccinees had geometric mean serum HI titers (GMT) of 1:26, 1:123, and 1:166 at 0, 14, and 30 days, respectively. The GMTs for placebos were 1:21, 1:22, and 1:21. Thirty-five vaccinees were examined for both serum and nasal antibody; 89% had significant increases in one or both. Nasal antibody response was directly related to the level of initial serum HI titer in that 83% of 12 persons with prevaccination HI titers of 1:80 greater than or equal to 1:80 showed significant nasal antibody rises, whereas only 61% of the remaining 23 subjects with prevaccination HI titers of less than or equal to 1:40 did so. The number and severity of clinical signs and symptoms reported by vaccinees and placebos did not differ significantly. The greatest differences noted between groups were for nasal congestion on days 0 to 6 (8.3%) and rhinitis on days 14 to 20 (5.9%). Four vaccinees shed Alice after primary vaccination, but viral titers were low (10 to 100 tissue culture-infective doses/ml). One member in each of 15 cohabiting male-female couples received Alice while the other received a placebo; one of the placebo members had significant increases in serum and nasal antibody, indicating a possible transmission.


Anaerobic specimen transport device.

Anaerobic specimen transport device. A device is described and evaluated for the anaerobic transport of clinical specimens. The device limits the amount of oxygen entering with the sample to a maximum of 2%, which is rapidly removed by reacting with hydrogen in the presence of a palladium catalyst. The viability on swabs of 12 species of anaerobes, four strains of facultative anaerobes and a strain of Pseudomonas aeruginosa, was maintained during the length of the tests (24 or 48 h). The results demonstrated that this device protected even the more oxygen-sensitive clinical anaerobes from death due to oxygen exposure. This device can be used for swabs as well as for anaerobic collection and liquid and solid specimens.


[Acute postoperative necrotizing enteritis. Apropos of one case after total hysterectomy with bilateral annexectomy]. The authors report a case of acute necrotising enteritis occurring on the 7th day after total hysterectomy with bilateral removal of the adnexa for fibroids in a 45 year-old woman. This is the first case in the literature to occur after hysterectomy. The clinical picture included the onset of intestinal obstruction with severe general toxic manifestations. The diagnosis was made at operation and, in spite of intestinal resection, the patient died on the 6th day, with liver and renal failure, anuria and irreversible collapse. The blood and stool cultures were negative, but the histological appearance of the lesions, without any apparent suppuration, were in favour of a vascular etiology. Necrosis of the mucosa and inflammatory oedema of the sub-mucosa, were accompanied by vascular changes suggesting thrombosis and congestion.


Selective medium for growth of Proteus.

Selective medium for growth of Proteus. A medium containing heart infusion agar supplemented with bile salts, lithium chloride, sodium thiosulfate, and sodium citrate was developed for the selective growth of Proteus.


Modified fluorescent antibody technique to detect immunoglobulin M antibodies to Toxoplasma gondii in congenital infection. Using a modified fluorescent antibody technique immunoglobulin M antibodies to Toxoplasma gondii were studied in infants' sera. The modified technique involved prolonged incubation of patients' sera with antigen at 4 C.


Is aromatization of testosterone to estradiol required for inhibition of luteinizing hormone secretion in men? A variety of studies in man and animals demonstrate that testosterone (T) is aromatized to estradiol (E) in the hypothalamus and limbic system. These observations suggested the possibility that conversion to E is an absolute requirement for the biologic activity of T on the hypothalamic-pituitary axis. Since this hypothesis implies a common mechanism of action of these two steroids, the demonstration of divergent effects of T and E on luteinizing hormone (LH) secretion would exclude this possibility. To test this hypothesis, the actions of T and E on three separate aspects of LH release (mean LH, pulsatile LH secretion, and responsiveness to LH-releasing hormone [LH-RH]) were contrasted. T and E, infused at two times their respective production rates into normal men, reduced mean LH levels similarly during 6 h of steroid infusion and for 6 h thereafter. However, these steroids exerted different effects on pulsatile secretion. E reduced the amplitude of spontaneous LH pulse from pre- and postinfusion control levels of 75+/-14 and 68+/-5.6% (SEM) to 39+/-5.7%. In contrast, T increased pulse amplited to 96+/-14% and decreased pulse frequency from basal levels of 3.4+/-0.31 to 1.8+/-0.31 pulses/6h. The site of suppressive action was determined by administering 25 microgms of LH-RH to the same men during T and E infusions and during three additional control periods without steroid administration. LH-RH produced similar 170-190% increments in serum LH during the three control periods and during T infusion. In contrast, E markedly blunted (76+/-31%, p less than 0.005) the LH response to LH-RH. Under the conditions of acute steroid infusion at doses (utilized in these experiments) producing similar inhibition of mean LH, E but not T acted directly on the pituitary to diminish LH-RH responsiveness. As further support that androgens can act without conversion to estrogens, the effects of a nonaromatizable androgen, dihydrotestosterone (DHT), on mean LH levels were studied. DHT, infused at the same rate as T, suppressed mean LH to a similar but somewhat greater extent than T. Since T and E produced divergent effects on LH secretion and a nonaromatizable androgen, DHT, suppressed mean LH, aromatization is not a necessary prerequisite for the action of androgens on the hypothalamic-pituitary axis.


Mechanisms of endotoxin tolerance. The role of the spleen. Splenectomy markedly impaired the production of circulating anti-endotoxin antibodies during the initial 10 days after .v. administration of a Boivin preparation of Escherichia coli endotoxin (ET) in both rabbit and man. Increase in antibodies with secondary (flocculating and bactericidal) activities were virtually abolished, whereas increases in antibodies with primary (binding) activity were significantly reduced. On the basis of these findings, splenectomized rabbit and man were employed to test the hypothesis that the early phase (less than 72 h) of pyrogenic tolerance to endotoxin is independent of anti-endotoxin antibody but that such antibody contributes significantly to the later phase (less than or equal to 72 h) of tolerance. In the splenectomized rabbit, the initial pyrogenic reponses to ET and the subsequent tolerant responses at 24 and 48 h were comparable to sham-operated controls...


A state-trait analysis of alpha density and personality variables in a normal population. In Study I eyes-open and eyes-closed percentage time resting alpha in normal young male adults was correlated positively with psychological test scores that reflected greater energy, feelings of confidence and control, and lesser social inhibition. Study II was consistent with Study I in that alpha density was related inversely to a projective measure of maladustment as well as measures of state and trait anxiety. The effects of visual stimulation on the size of the relationship between alpha and psychological trait measures suggested that this is a highly unstable relationship likely to appear only when experimental arrangements maximize the congruency betweey psychological states and traits. Finally, it was suggested that the application of a state-trait rationale to alpha phenomenon might be useful to organize the relationship between physiological and psychological variables and could serve as a starting point for conceptualizing the potential effects of biofeed-back applications.


Automated MMPI interpretation based on a modification of Gilberstadt's codebook. Several limitations to commercially available automated MMPI reports prompted the psychology staff at Topeka VA Hospital to develop its own automated interpretive system. The computer programs of the system require further modification, and local validity studies of the automated interpretations are needed. However, it is hoped that this project will encourage others to consider the development of a local automated interpretive system as an alternative to commercial interpretive services.


A comparison of classification rates of the original and revised Marks and Seeman rules. The Marks and Seeman rules for profile classification were compared with revised rules. The rate of classification on a large sample of psychiatric profiles was 16.88% for the original rules and 49.72% with the revised rules. The revised rules will make the codebook applicable to more cases.


Evaluation of a content-analysis system for therapeutic interviews. The Zimmer and Cowles system for content analysis was tried out on psychotherapeutic sessions and on interviews with disturbed patients. It was found that the system indeed did seem to pick up improvement in psychotherapy, and to a lesser degree, differences in speech behavior between patients with radically differing pathologies. It also was concluded that the computer program for the content analysis system is not easily portable, but a SNOBOL equivalent is made available.


Clinical and sign prediction: the draw-a-person and female homosexuality. The validity of predicting female homosexuality from empirical signs from the Draw-A-Person (DAP) was compared to the validity of psychologists' "blind" predictions from the same DAP protocols. Four specific DAP signs significantly predicted homosexual drawings from those of heterosexual controls; patterns derived from these signs were even better predictors. Two of four clinicians predicted sexual orientation greater than chance; one predicted as well as the optimal sign pattern. In view of the expected shrinkage involved in cross-validating the empirical signs and patterns, clinical prediction probably would equal or surpass the accuracy of statistical prediction. Individual differences in clinical prediction and the process of clinical prediction were discussed.


Formation of cockroach interganglionic connectives: an in vitro analysis. Individual ganglia of the cockroach embryo (Periplaneta americana) were explanted on clean glass coverslips immersed in a chemically defined liquid medium and incubated for periods up to eight weeks. Substantial, straight interganglionic connections were formed between: (1) rows of ganglia arranged in the normal in vivo configuration; (2) rows of ganglia placed in abnormal orders; (3) rows of ganglia which never form connections in vivo because they occur singly in the embryo; and (4) rows of ganglia in natural sequences but which have had their rostro-caudal axes rotated 90 degrees in relation to the line of the row. Therefore fascicles and interganglionic connectives were formed without regard to normal in vivo relationships. Daily observations with a Nomarski microscope indicated that several processes are involved in connective formation. (1) Initial outgrowth is in a random, radial pattern. (2) Intersecting fibers from adjacent ganglia are deflected toward each others' perikarya. (3) Initially bowed fiber connectives are straightened, perhaps by increases in fiber tension or by fiber shortening which may be brought about by neuronal or extraneuronal (glial) processes. (4) Outgrowing fibers follow already established fiber pathways. The present results indicate that fiber-fiber and fiber-target interactions play a significant role in the formation of interganglionic connectives. In this system, the spatial relationships between ganglia determine the patterns and varieties of permissible neuronal connections. Thus, major, straight nerve trunks may be formed between adjacent ganglia which are growing out fibers on a glass surface submerged in a liquid medium which offers minimal orientation cues and provides a growth substrate vastly different and simpler than that encountered by outgrowing fibers in vivo.


Pharmacological response data for comparative bioavailability studies of chlorpromazine oral dosage forms in humans: I. Pupilometry. Owing to the insensitivity of even the presently best chemical or radiological assay procedures, it is not feasible to perform comparative bioavailability studies of chlorpromazine oral drug products using blood or urine sampling; this is particularly the case for oral doses below 100-150 mg/70 kg. In contrast, the use of temporal miotic response data, which correlates with blood levels of unchanged drug, permits dose-response vs time profiles to be recorded with oral dose levels as low as 5-10 mg/70 kg. The monitoring of pupilometric data in up to 16 human volunteers demonstrated a sensitivity to both extents and rates of chlorpromazine bioavailability and revealed differences to exist between liquid and solid oral dosage forms of chlorpromazine.


Guanethidine in antihypertensive therapy: experience with an oral loading regimen. Guanethidine sulfate, a potent antihypertensive agent with a prolonged duration of action, was given in large oral doses to eight hypertensive patients in a loading technique. Blood pressure control resulted within one to three days without side effects, with total loading doses varying from 125 to 650 mg. Based on the drug's pharmacokinetic properties, a maintenance dose required to sustain the desired antihypertensive effects was calculated from the loading dose for each individual. Blood pressure was satisfactorily controlled in the seven patients followed for at least 12 months, and no modification of the calculated guanethidine dose was required. Side effects were minimal and well tolerated. The ease of initial blood pressure regulation with this regimen and the precision with which a maintenance dose can be determined suggest that guanethidine deserves a more prominent role in the therapy of established hypertension.


Comparative efficacy of halcinonide and fluocinonide creams in psoriasis and eszematous dermatoses. The clinical efficacy of halcinonide and fluocinonide creams was compared in the treatment of 392 patients with corticosteroid-responsive dermatoses, including psoriasis, and various eczematous dermatoses such as atopic dermatitis, eczematous dermatitis, and neurodermatitis. The severity of the condition treated was moderate or severe in most of the patients. Usually, the creams were applied three times daily for two to three weeks. In psoriasis, halcinonide was superior to fluocinonide (P less than 0.05). There was no significant difference between halcinonide and fluocinonide in the treatment of the eczematous dermatoses. Both creams were well tolerated, each being associated with local side effects (such as burning sensation, dryness, erythema, and pruritus) in 4.9 per cent of patients.


An evaluation of bruxism control: massed negative practice and automated relaxation training. Behavior modification techniques of massed negative practice and relaxation training were applied to separate groups of individuals who had been diagnosed as "bruxers" by multiple criteria. When assessed by an objective index of grinding, neither technique was found to have reduced bruxism significantly. Grinding and state of anxiety scores of bruxers were significantly higher than those of nonbruxing controls. Bruxers did not differ from nonbruxers on trait anxiety measures.


Localization of rate-limiting barrier to penetration of endotoxin through nonkeratinized oral mucosa in vitro. The penetration of tritiated bacterial endotoxin through nonkeratinized oral mucosal epithelium was studied using an in vitro model system and radioautographic tracer techniques. The basement membrane region of the epithelium was the rate-limiting barrier to penetration, and this barrier effect was independent of the direction and duration of penetration as well as any clearance effects of the vasculature.


SEM investigation of the variability of enamel surfaces after simulated clinical acid etching for pit and fissure sealants. Etching preferentially occurs on cuspal inclines and on premolars vs molars. After longer times, etching occurs near the pits and fissures. Enamel rods etch at cores and prism borders simultaneously in the same area. Longer etching times produce more enamel surface relief, permitting better sealant adaption to the enamel.


Effect of prior acid etch on rate of Sn3F3PO4 formation subsequent to topical application of SnF2. The effect of prior acid etch on the rate of Sn3F3PO4 formation subsequent to in vitro SnF2 interaction with human dental mineral has been investigated using light microscopy, surface replicas, and internal reflection spectroscopy. Results showed that Sn3F3PO4 forms more rapidly on etched surfaces as compared with nonetched controls. The observed accelerated rate was attributed to increased reaction surface provided by prior acid etch plus a rougher surface conducive to crystal nidus formation.


Eikenella corrodens: a clinical problem. E corrodens occurs as a significant clinical infection more frequently than suspected or cultured at the present time. It is essential that the dentist or physician work closely with the laboratory clinician in order to use proper techniques for its isolation. Inconsistencies between in vitro disk sensitivity and clinical drug response are noted. Because of clinical response, the clinician must carefully follow the patient's daily progress to recognize antibiotic treatment failure so that combination therapy or appropriate incision and drainage procedures may be initiated.


Nutrition research and education in the Age of Franklin. A Bicentennial study. Two hundred years ago, the United States was just emerging as a new nation. Chemistry and biology, on which the science of nutrition is based, were also just beginning or in their infancy. Dietetics and nutrition education, being applied sciences, were concerned then--as they are now--with the solution of practical problems of everyday living. Dietetics was an important part of medical practice in colonial days. Much of the teaching then about the value of diet in health and disease was provided by pithy statements, based on empiricism backed by authority, by which the science of medicine was taught to students, and by which health instruction was offered to the public. The experimental method of studying "Nature," promulgated by Francis Bacon, was just beginning to be employed in studies of nutrition. Delay in accepting experimental results, such as Lind's demonstration of the value of citrus fruits in the treatment of scurvy, may be attributed in part to a lack of understanding of the experimental method. In part, it may have been due to the absence of animal experimental methods that are capable of providing clear-cut and convincing evidence. Three of the greatest experimental scientists of the eighteenth century--Lavoisier, Count Rumford, and Benjamin Franklin--busied themselves with matters of concern to dietitians and home economists. Their work and that of others provided a firm foundation for the advances in scientific knowledge during the last two hundred years.


Effect of age on intravenous glucose tolerance and insulin secretion. Twenty-seven normal volunteers whose ages ranged from 22 to 67 (mean, 37 years) were given intravenous glucose tolerance tests (IVGTT). Age was not correlated with the glucose disposal rate constant (KG), incremental insulin secretion (deltaI), or the "insulinogenic index (deltaI/DELATG). The volunteers were divided into three age groups: 1) mean age 25 years, 2) mean age 42 years, and 3) mean age 62 years. Groups 2 and 3 did not differ from Group 1 with respect to the mean level of fasting plasma glucose, KG, or deltaI/AG. Group 2 (but not Group 3) had a greater mean deltaI than Group 1, and Group 3 (but not Group 2) had a higher mean fasting insulin concentration than Group 1. No significant deterioration was detected in the intravenous glucose tolerance of healthy volunteers up to age 67. This may be attributable to the previously described feed-back system that calibrates the pancreatic beta-cell response according to the insulin sensitivity of the peripheral tissues.


The immunopathology of the aging rat kidney. Immunofluorescence studies of rat kidneys from 3-24 mo. of age demonstrated deposition of immunoglobulins, predominately IgM, within the glomerular mesangium by age 3 mo. Immunoglobulins eluted in acid buffer, did not fix complement, were not associated with inflammatory changes, and increased markedly with the onset of proteinuria at about 12 mo. Rats 24 mo. old also had mesangial deposits of IgG and fibrin. No basement membrane deposits were seen, and autoantibodies to antigens in normal kidney, liver, spleen, and skeletal muscle were not demonstrable in serum or eluates of kidneys from aged animals. The focal and segmental glomerular sclerosis which develops in aged rats does not appear to be mediated by glomerular deposition of auto-antibody or immune complexes. Mesangial accumulation of macro-molecular material, perhaps as a consequency of the age-associated increase in glomerular permeability, may contribute to the development of the glomerular sclerosis of aging in the rat by impairing mesangial phagocytic or clearing mechanisms rather than through immunologically mediated tissue injury.


The effects of aging on communication.

The effects of aging on communication. Age can be estimated fairly accurately by listening to the voice and speech of the individual. The critical processes of communication--respiration, phonation, articulation, language, and hearing--are described in terms of the anticipated biological tissue changes of aging and the effect of these changes on the speaking process. With the exception of the common finding of hearing loss in old age, the processes of communication do not seem to be seriously affected by "normal" aging. Complicating factors and diagnostic and remedial implications are discussed.


Formaldehyde-hydrochloric acid treatment. A fluorescence histochemical method for the demonstration of tryptophan residues in peptides and proteins. Treatment with formaldehyde gas and HCl vapor, simultaneously or in sequence, induces fluorescence with indoles, including tryptophan residues of peptides, as is evident from studies on protein droplet models. Among cells that display intense formaldehyde-HCl-induced fluorescence are pancreatic exocrine cells, gastric chief cells, Paneth cells and enterochromaffin cells. Peptide hormone-producing cells that can be visualized by the formaldehyde-HCl treatment include gastrin cells and glucagon cells. The simultaneous procedure has proved superior to the sequential procedure. Simultaneous formaldehyde-HCl treatment appears to be a useful method for the demonstration of tryptophan residues of peptides and proteins. It seems more sensitive than previously described indole methods.


Tissue distribution of lysozyme in man.

Tissue distribution of lysozyme in man. The distribution of lysozyme (LZM) in normal human tissues was determined with the use of the immunoglobulin-enzyme (peroxidase) bridge method. LZM was detected in the following cells and tissues: secretory cells of the lacrimal gland, ductal epithelial cells of the parotid gland and the serous parts of the mixed sublingual glands, the esophageal submucosal glands, bronchial serous submucosal glands, gastric and pyloric glands, Brunner's glands of the duodenum, the Paneth cells of the small intestine, Kupffer cells of the liver and renal proximal tubular cells. In addition, LZM was also found in the mononuclear or polymorphonuclear cells of the placenta, lung, lamina propria of the small intestine, lymph nodes and spleen. This distribution of LZM is discussed in relation to its possible physiologic role in human tissues and particularly to its known antibacterial properties.


Serologic evidence of the postoperative persistence of hydatid cysts in man. The sensitivity of the haemagglutination, complement-fixation and indirect fluorescent antibody tests in the diagnosis of primary and recurrent hydatid disease is presented. In the first, diagnostic titres were obtained in 90% of 50 patients with hepatic and 64%, 60%, and 68% of 25 patients with pulmonary cysts, respectively. In the postoperative study of 62 patients, elevated titres of HA, CF and IFA antibodies in 30 led to the presumptive diagnosis of recurrent disease, confirmed later by radiological and surgical follow-ups. In the 32 others the proportion of positive reactors was 29%, 6% and 28% in HA, CF and IFA tests. These patients had no detectable cysts. This indicates that in postoperative patients a negative CF test may be of a better prognostic value in indicating absence of cysts than the HA and IFA tests.


In vivo transfer of R factors between Escherichia coli strains inoculated into the rumen of sheep. Substantial transfer of R factors occurred in vivo, under certain conditions, in the rumen of adult sheep in the absence of any antibiotic treatment. A starvation period of 24-48 hr. was required to produce the conditions necessary, when even quite low inocula (ca. 10(3) cells) of donor and recipient E. coli could grow within the rumen and reach a population density sufficient for transfer to take place. The results indicate that under the same conditions R factors may be transferred between organisms in the lower intestinal tract also. Without the starvation period, the inoculation of even massive numbers (10(10) cells) of the same organisms resulted in almost no detectable transfer. Some of the experimental animals on which a starvation period was imposed became carriers of either the inoculated recipient E. coli, or of R factor bearing coliforms, and these formed 1-10% of the total coliform population of the faeces for at least 6 weeks.


Clostridium botulinum in the lakes and waterways of London. Mud samples collected during 1974 from a large proportion of the lakes and waterways of London were examined for Clostridium botulinum. Of 69 such sites, 50 (72.5%) contained at least one type of the organism. Of the 50 positive sites, 31, 12, 1 and 10 contained, respectively, types B, C, D and E. Most of the demonstrations of type B required trypsinization of culture filtrates. An examination of 7 lakes in Edinburgh, made for the purpose of comparison, showed that 4 contained type B and one type C. An analysis of the results gave quantitative information on the value of (1) resampling apparently negative lakes, (2) the use of both heated and unheated culture inocula, and (3) trypsinization of culture filtrates.


A method for simultaneous determination of rosette formation and phagocytosis by cells. A fluorescent agent insoluble in water was readily phagocytosed by 5-20% of human blood mononuclear cells, mainly monocytes. These cells were easily detected even amidst abundant rosetting erythrocytes. When rosette assays for the detection of complement or SRBC receptors on the surface of the cells were performed, only phagocytic cells exhibited the complement receptor with the method used in the study, whereas mainly nonphagocytic cells formed SRBC rosettes. The effect on the calculation of the percentage of T lymphocytes (SRBC receptor lymphocytes) of varying amounts of monocytes present in mononuclear cell population is demonstrated. The method presented here might prove useful particularly in studies on Fc or complement receptors on white blood cells.


Detection of isoelectric focused antibody by autoradiography and hemolysis of antigen-coated erythrocytes. A comparison of methods. Mouse anti-group A streptococcal carbohydrate (GAC) antibodies were detected in analytical isoelectric focusing (IEF) acrylamide gels by the hemolysis of GAC-coated sheep erythrocytes immobilized in agarose. This procedure is rapid and reproducible but, because it requires diffusion of antibody from the acrylamide gel into the agarose layer, results in poorer resolution than other methods of detection where antibodies can be fixed in the acrylamide gel after focusing, such as protein staining of purified antibodies or autoradiography of 125I-GAC bound to focused antibodies.


A serial tap method for removal of peritoneal exudate cells from guinea pigs. Production by sensitised lymphocytes of Migration Inhibition Factor has been found to correlate with delayed hypersensitivity. A time course study using serially tapped guinea pig peritoneal cells is described.


Juvenile dermatitis herpetiformis versus "benign chronic bullous dermatosis of childhood." Are these immunologic diseases? Seven cases of juvenile dermatitis herpetiformis have been investigated. Immunofluorescence and histologic studies were made in all and jejunal biopsies in three. Immunopathologic results were positive in all cases including one that had previously been reported to be negative. Two groups could be distinguished according to clinical and histologic criteria, response to sulfapyridine, and character of the immunoglobulin deposits. The first corresponded to dermatitis herpetiformis (DH) of adults, with characteristic lesions of the jejunal mucosa; the second corresponded either to bullous pemphigoid (BP), although in the majority of the cases without circulating antibasement-membrane antibodies, or to a mixed type with the combined features of DH and BP. Repeated biopsies with serial sections are essential for demonstrating immune deposits. The question arises whether any immunologically negative cases of "benign chronic bullous dermatosis of childhood" actually exist.


Pustular psoriasis elicited by streptococcal antigen and localized to the sweat pore. A woman, aged 39 years, presented with a localized, painful, pustular eruption of the neck, scalp, and finger of five years' duration. A diagnosis of pustular psoriasis was made clinically and histologically. It was possible to reproduce the disease by the intradermal injection of killed Group A streptococcal organisms. The induced pustules, as well as those appearing clinically, were intraepidermal and indistinguishable from the Kogoj spongiform abscess, and on serial sectioning showed a distinctive localization to the acryosyringium. Immunosuppressant as well as antistreptococcal therapy in the form of cyclophosphamide and clindamycin was of help. The process is classified as a nonvasculitic pustular bacterid, and as a prototype for antigen localization of lesions to the occluded epidermal sweat duct unit.


Antimicrobial resistance and R-factor transfer among isolates of Salmonella in the northeastern United States: a comparison of human and animal isolates. The antimicrobial susceptibility of 718 isolates of Salmonella from humans and of 688 isolates from animals was examined. Of the 46 different serotypes among the isolates from humans, Salmonella typhimurium accounted for 34%. Thirty percent of isolates were resistant to one or more antibiotic(s). Resistance to streptomycin was most common; resistance to tetracycline was next most common. Over 50% of isolates of S. typhimurium and Salmonella newport were resistant to four antibiotics. Resistance to tetracycline, kanamycin, and ampicillin has increased steadily during the past decade. Most strains possessed R-factors, and resistance to ampicillin, streptomycin, sulfisoxazole, tetracycline, chloramphenicol, and kanamycin (but not that to cephalothin) was transferable. Among the salmonellae commonly isolated from humans, only Salmonella enteritidis showed limited resistance to antibiotics (5.8%). Antibiotic resistance of isolates of S. typhimurium, Salmonella saint-paul, and Salmonella heidelberg from animals was similar to the resistance of isolates from humans. Resistance to kanamycin increased markedly over the level noted in previous studies. R-factor prevalence was high. Antibiograms of the isolates from animals and humans were similar, although some patterns were seen only in isolates from one source. Ampicillin resistance was more common in human isolates, and resistance to tetracycline, sulfonamide, and streptomycin was more common in animal isolates. Salmonellae of serotypes other than S. typhimurium that came from humans were less resistant to all antibiotics than were isolates from animals.


The immune response to acute otitis media in children. II. Serum and middle ear fluid antibody in otitis media due to Haemophilus influenza. The antibody response in serum and middle ear fluid was studied in 40 children less than two years of age who had otitis media due to Haemophilus influenzae. Specific antibody in serum was determined by either a bacteriocidal test or an indirect fluorescent antibody test, and in the middle ear fluid by the latter test. For both assays the infecting bacterium of the patient was used. Half of the acute sera and three-fourths of the convalescent sera had antibody of at least one of the IgG, IgM, or IgA classes; IgG occurred most often. Fourteen patients had significant increases in specific antibody in the convalescent serum. Middle ear fluids from 22 to 29 patients had specific antibody. IgG and IgA antibodies occurred with equal frequency, but IgA antibody was found more often in middle ear fluids when IgA antibody was absent from serum. Thus it appears that infants with otitis media respond systemically and locally with specific antibody to H. influenzae.


Leukocyte migration in vivo: a new method of study. Quantitative in vivo migration of leukocytes into tissue has been analyzed by a new technique. This new method differs from previous methods by utilizing tape stripping of skin rather than skin abrasion, thereby preserving dermal vascular endothelium and the basal lamina of the epidermis. By preserving these two physiologic membranes, this technique simulates physiologic leukotaxis. Results in sixteen control patients revealed a mean of 1.12 X 10(6) leukocytes per chamber per 24 hours. In four patients with immunodeficiency this value was of 9.26 X 10(3) leukocytes per chamber per 24 hours clearly distinguishing this group from control groups (p less than 0.01). Reproducibility of duplicate chambers, simplicity, and comfort of the plastic chambers enhance its use by the clinical investigator as a secreening test for abnormalities in leukocyte movement.


Determination of urinary carbamylaspartate and dihydro-orotate in normal subjects and in patients with hereditary orotic aciduria. An isotope dilution assay for urinary dihydro-orotic acid and carbamylaspartic acid (CAA) has been developed which has been shown to yield accurate measurements for these pyrimidine precurosrs. Dihydro-orotic acid could not be detected in 24-hour urine specimens from 10 normal adults and 7 normal children, or in specimens from 2 children with hereditary orotic aciduria Type I. Small amounts (approximately 10 mumole per 24 hours) of carbamylaspartic acid are excreted in normal urine, and there was a modest elevation in CAA excretion in the 2 patients with hereditary orotic aciduria.


A comparison of methods of extra temporal facial nerve repair. The development during the past 100 years of methods of repair of the divided facial nerve is discussed, from the early attempts to bring the nerve ends together inside a tube of vein. The success of the repair is enhanced by the care of the blood supply to the nerve and by measures to avoid scar developing between the ends of the nerve. Rest of the suture line is aided by the support of some form of tube, but unless this latter is kept below I cm. in length interference with the radial blood vessels to the nerve occurs. Intubation also encourages parallel growth of the nerve fibres and discourages fibroblast proliferation. Animal experimentation shows that the results when a soft silicone tube of special shape is used are superior to those obtained if the nerve is left free in the tissues, buried in muscle, or placed inside a vein.


BCG in cancer and leukemia treatment and prophylaxis-A review. Five international oncology meetings crystallized the concept that the immune system plays a dominant role in the prevention and inhibition of neoplasia; that the cancer antigens are relatively weak, therefore eliminating weak or uneffective cellular immunity which is paramount in tumor rejection; that humoral antibodies against neoplastic antigens may block the cytotoxic action of T cells against the tumor cells. A number of agents have been found capable of stimulating the immune system (T-cell activation) but from a clinical standpoint BCG had had the widest application in a variety of tumors and leukemia. Thus the emphasis in this review will be on BCG.


A technique for intensifying BCG sensitivity. Sensitization to BCG (Bacille Calmette-Guérin) appears to be more effective when it is carried out at the site of a delayed hypersensitivity challenge reaction to DNCB (1-chloro, 2,4-dinitrobenzene) than when it is carried out at unchallenged sites in non-sensitized animals. The effectiveness of BCG sensitization was determined by measurement of the intensity of the PPD (Purified Protein Derivative of tuberculin) 24-hour skin test. Possible mechanisms for this phenomenon and its implications for cancer immunotherapy are considered.


Potential roles of androgens and the anabolic steroids in the treatment of cancer - a review. Androgenic hormones are utilized in clinical practice as a bone marrow stimulant as well as replacement therapy in certain endocrinologic disorders. In the oncologic realm breast cancer has shown some responsiveness to pharmacologic doses of androgens. However, recent work reveals that androgens are capable of stimulating the fibrinolytic mechanism and more importantly enhance the immune response. These latter properties represent a significant new role for the androgens and anabolic agents. Hence, adjunctive utilization of androgens with cancer chemotherapeutic agents may result in an effective synergistic combination in the therapy of malignant disease.


Effects of hypophysectomy and short-term growth hormone replacement on insulin release from and glucose metabolism in isolated rat islets of Langerhans. The effects of hypophysectomy and short-term GH replacement on insulin release and on some aspects of glucose metabolism in isolated rat islets of Langerhans were investigated. The effects on body, pancreas and adrenal gland weights, and on the levels of blood plasma constituents were also measured. Three to four weeks after hypophysectomy the early and late phases of insulin release from islets incubated with high concentrations of glucose, but not with low concentrations of glucose or with xylitol, leucine, arginine, tolbutamide, citrate or butyrate, were significantly lowered. Short-term GH replacement partially reversed the depression in glucose-stimulated insulin release. This reversal effect was not dependent on the increase in body weight of rats after GH replacement when the fall in adrenal gland but not in pancreas weight was also reversed. Nine out of the 12 plasma constituents measured, including glucose, were maintained in the control range of levels, but albumin, inorganic phosphate and urea nitrogen levels were altered after hypophysectomy or GH replacement. Three to four weeks after hypophysectomy, total glucose oxidation and glucose utilization by the islets were slightly depressed. Hypophysectomy appeared to slow down glucose 6-phosphate utilization in the islets. However, the functional capacity of the glucose phosphorylating, glucose-6-phosphate and 6-phosphogluconate dehydrogenase activities were not changed. Short-term GH replacement caused improvements in these islet functions.


Changes in insulin content of, and insulin and RNA synthesis in, isolated rat islets of Langerhans after hypophysectomy and short-term growth hormone replacement. Three to four weeks after hypophysectomy, the insulin content and glucose-stimulated insulin or total RNA synthesis in the pancreatic islets were estimated. The ratio of the glucose-stimulated insulin release to the islet insulin content was lowered. After short-term GH replacement, insulin release and insulin content were slightly increased such that the ratio of release to content remained virtually unaltered. Glucose-stimulated insulin synthesis was also depressed but improved slightly after GH replacement. However, there was no significant change in the incorporation of [5-3H]uridine into islet total RNA after hypophysectomy or subsequent GH replacement.


Identification and characterization of the monoblast in mononuclear phagocyte colonies grown in vitro. A liquid culture technique for growing mononuclear phagocyte colonies on a glass surface is described. This useful and reliable technique made it possible to study immature mononuclear phagocytes. In the mononuclear phagocyte colonies the cells grow separate from each other in a single layer. Three types of cells are recognized in these colonies, namely nondividing macrophages, and proliferating promonocytes and monoblasts. The macrophage and the promonocyte exhibit the typical characteristics previously demonstrated by the other methods, whereas the monoblast could only be fully characterized by the present liquid culture method. This proliferating cell (labeling index with [3H]thymidine, 92-96%) is almost round (diameters, 10 X 10 mum), has only a small rim of strongly basophilic cytoplasm, almost devoid of granules, and shows a certain degree of ruffling of the cell surface. The monoblast is positive for esterase with alpha-naphthyl butyrate as substrate (91%), for peroxidase (78% in the peroxidase-positive colonies), and lysozyme (43%). The monoblast is able to pinocytize dextran sulphate (15-20%) and to phagocytize opsonized bacteria (20-30%), latex particles (47%), and IgG-coated red cells (96%). IgG receptors (94%) and complement receptors (16%) are present at the cell surface. In these respects the monoblast has the typical characteristics of the mononuclear phagocytes, but its properties show it to be a more immature cell type than the promonocyte. On the basis of these criteria and the sequence of appearance of the different cell types during incubation and during the development of the individual mononuclear phagocyte colony, monoblasts being present before promonocytes appear in the colony, it is concluded that the monoblast is the precursor of the promonocyte. In these cultures granulocyte colonies are also formed, consisting of myeloblasts, (pro)myelocytes, stabs, and polymorphonuclear neutrophils. Besides the typically tight structure of this kind of colony, the granulocytic cells themselves are quite distinct from the mononuclear phagocytes by their morphology, cytochemical characteristics (e.g. all negative for esterase with alpha-naphthyl butyrate, but 96% positive with N-acetyl DL-alanyl 1-naphthylester), functional characteristics (pinocytic index 13-21%; phagocytic index; for opsonized bacteria 15-36%, for latex particles 10%, and for IgG-coated red cells 0%), and their very small number of IgG receptors and lack of complement receptors. On the basis of these criteria, these granulocytic cells are easily distinguished from the immature cells of the mononuclear phagocyte colonies. The present study confirms the conclusion that the mononuclear phagocytes are a separate cell line, quite distinct from the granulocytic series, since even the most immature cells so far identified--the monoblast and the myeloblast--have quite different characteristics.


T and B cell in hapten-specific carrier-determined tolerance. BDF1 mice were made tolerant by a single i.v. injection of 1 mg of DNAP-gamma1 or by weekly i.v. injections of 0.2 mg of DNP-gamma1 given for a month. In both instances, spleen cells of tolerant animals were fractionated to obtain pure populations of T cells (nonimmunoglobulin-bearing cells), referred to as tolerant T cells, and B cells (immunoglobulin-bearing cells) referred to as tolerant B cells (immunoglobulin-bearing cells) referred to as tolerant B cells. The control cells were similarly fractionated to obtain normal T and B cells. Mixtures of tolerant T cells and normal B cells, or conversely, normal T cells and tolerant B cells were used to repopulate lethally irradiated recipients. These recipients were then immunized with dinitrophenyl-keyhole limpet haemocyanin and in certain instances with other antigen horse red blood cells. The immune response to both antigens was measured using the direct hemolytic plaque assay. It was found that both T and B cells were tolerant and that tolerance was hapten specific at both T- and B-cell levels. While B-cell tolerance was demonstrated at a 1/1 T/B ratio, a 4/1 T/B ratio was necessary to show T-cell tolerance. Thus, the hapten-specific carrier-determined tolerance involves not only B cells but also T cells. The implication of this finding for the cellular mechanism of tolerance in an experimental model closely related to self tolerance is discussed.


Requirement for T cells in the production of migration inhibitory factor. The question whether B lymphocytes are capable of being activated by antigen in the absence of functional T cells was investigated in a model that excludes participation of T cells by virtue of an immune response gene restriction. Strain 2 guinea pigs are capable of responding to immunization with DNP-PLL, whereas strain 13 animals are not. In the present experiments, animals of both strains were immunized with DNP-PLL complexed to ovalbumin (DNP-PLL-Ova) under conditions in which equal titers of antibodies to DNP were produced by both strains. The failure of T cells of strain 13 animals to respond to DNP-PLL was confirmed by the virus plaque assay. While spleen cells from both strains produced MIF after stimulation with DNP-PLL-Ova, in response to DNP-PLL only strain 2 spleens were able to produce MIF. Cells from neither strain could be activated by DNP-guinea pig albumin to produce MIF. We conclude that B lymphocytes are incapable of being stimulated by antigen in the absence of T cells, and that MIF production is a thymus-dependent response. While the results indicate that MIF production is a valid qualitative assay for T-cell competence, since MIF can be produced by B and T cells, the degree of migration inhibition cannot be regarded as a quantitative measure of T-cell function.


Cellular basis of tolerance in neonatally induced mouse chimeras. In mice, thymectomized as young adults, neonatally induced tolerance persists in the putative absence of cell chimerism. The finding provides evidence that a selective deficiency of specific clones of lymphocytes exists in transplantation tolerance when induced under the conditions of these experiments.


The occurrence of the HL-B alloantigens on the cells of unclassified acute lymphoblastic leukemias. Six cases of acute lymphoblastic leukemia were studied by a variety of T- and B-lymphocyte surface markers. Two appeared to represent T-cell leukemias with the lymphoblasts forming sheep erythrocyte rosettes. The other four lacked all the usual membrane markers. However, indirect immunofluorescence with alloantisera detected the presence of the Ia-related HL-B antigens on the cells of the latter four cases; these antigens were absent in the first two cases. The primary association of the HL-B antigens with B cells raises the possibility that the positive group of cases are of B-cell lineage.


Fibrinogen/fibrin on the surface of macrophages: detection, distribution, binding requirements, and possible role in macrophage adherence phenomena. The peritoneal cavity of guinea pigs proved to be a rich source of mononuclear cells (34-52%) with fibrinogen or fibrin (Fib) on their surface. The Fib was readily detected on the surface of viable cells in suspension by fluorescence microscopy using antisera to guinea pig fibrinogen. The fluorescent staining occurred either in a speckled distribution, similar to that of cytophilic IgG, or in a distinctive net-like pattern that probably represented fibrin formation on the cell surface. The binding of Fib to the cell surface required calcium, but not magnesium, in the medium and could occur in vitro during incubation in heparinized plasma that contained fibrinogen concentrations comparable to that in normal peritoneal fluid (0.58 mg/ml). Cell surface Fib was more susceptible to plasmin and trypsin digestion than surface cytophilic IgG. By morphologic and physiologic criteria, cells exhibiting surface Fib were chiefly, if not exclusively, macrophages. Granulocytes, erythrocytes, and lymphocytes from lymph node and thymus had no sppreciable Fib. Cells with surface Fib were rarely observed among mononuclear cells prepared by Ficoll-Hypaque sedimentation of guinea pig and human blood (1.4 and 4.6%, respectively). Pulmonary alveolar macrophages, functionally distinct from peritoneal macrophages, lacked surface Fib (0.8%). Polymerization of Fib on the surface of macrophages might participate in certain cell interactions, such as the adherence of peritoneal macrophages during the antigen-induced macrophage disappearance reactions. The unexpected finding of Fib binding to the surfaces of peritoneal macrophages raises the possibility of a biologically significant interaction between these cells and the clotting system.


Genetic control of specific immune suppression. I. Experimental conditions for the stimulation of suppressor cells by the copolymer L-glutamic acid50-L-tyrosine50 (GT) in nonresponder BALB/c mice. In the present studies we have confirmed that the random copolymer of L-glutamic acid50-L-tyrosine50 (GT) fails to induce an antibody response in a large number of inbred strains of mice. Nevertheless, GT complexed to methylated bovine serum albumin (MBSA) elicits a GT-specific IgG PFC response in vivo. Furthermore, injection of BALB/c mice with 10 to 100 mug of GT specifically decreases their ability to develop anti-GT PFC responses to a subsequent challenge with GT-MBSA. GT-specific tolerance can be transferred to normal, syngeneic recipients by spleen cells or thymocytes of GT-primed animals. These results indicate that the stimulation of suppressor cells can be observed in nonresponder mice with another synthetic polypeptide besides GAT. Various parameters of GT-specific immunosuppression in BALB/c mice are described. The application of these techniques to the study of the genetic factors controlling the stimulation of specific immune suppression is discussed.


Immunologic properties of bacterial lipopolysaccharide (LPS). II. The unresponsiveness of C3H/HeJ Mouse spleen cells to LPS-induced mitogenesis is dependent on the method used to extract LPS. The C3H/HeJ mouse strain, previously shown to be a nonresponder to bacterial lipopolysaccharide (LPS)-induced mitogenesis in vitro, was demonstrated by the present studies to be competent to respond mitogenically to LPS, but only to LPS preparations obtained by selected extraction methods. These preparations appear to be confined to LPS isolated by mild extraction techniques, such as TCA or butanol. In contrast, those obtained by techniques utilizing phenol were only weakly stimulatory or completely nonstimulatory for spleen cells from the C3H/HeJ. All LPS preparations tested, on the other hand, were highly stimulatory for cells from another mouse strain, namely the C3H/St. The critical importance of the method of extraction of LPS on its mitogenic activity for C3H/HeJ cells was stressed by experiments in which LPS was prepared  from Escherichia coli K235 using either of two procedures. In these experiments, phenol-extracted LPS, although mitogenic in the C3H/St, was completely nonstimulatory in the C3H/HeJ; whereas, butanol-extracted LPS was highly stimulatory in both strains of mice. This striking difference was attributed to a destructive effect of phenol on LPS, as demonstrated by the fact that treatment of butanol LPS with phenol resulted in a total loss of its mitogenic activity in the C3H/HeJ, but in only a partial loss in the C3H/St. In general, the mitogenic response observed with selected LPS preparations in the C3H/HeJ was quantitatively lower and more transient than that seen with the C3H/St, although qualitatively these responses appeared to be similar. This was evidenced by the observation that in both mouse strains LPS was a specific mitogen for B cells, a property which was also attributed in both strains to the same distinct structural region of the LPS molecule, that is lipid A. A preparation of LPS that failed to stimulate B cells from the C3H/HeJ nonetheless had the capacity to block activation of these B cells by a stimulatory preparation of LPS. These results strongly suggest that mitogenic stimulation of B cells by LPS is a function of the structural integrity of both the LPS molecule and putative B-cell receptors for LPS.


A mechanism for the induction of immunological tolerance by antigen feeding: antigen-antibody complexes. We have previously reported on the induction, in mice, of a systemic (splenic) immune response with IgA as the dominant antibody, as a result of a short (4 day) intragastric immunization course with foreign erythrocytes. This response was followed by a prolonged period of hyporesponsiveness to similarly administered antigen. Here it is shown that this hyporesponsiveness is also manifested towards antigen given intraperitoneally, and that one is therefore dealing with tolerance, not with failure to absorb antigen from the gut. In contrast, mice primed parenterally and then challenged intragastrically behaved as if never having any previous contact with the antigen, i.e., with a primary-type splenic response of predominant IgA character. This agrees with our former conclusion that splenic responses to enterically absorbed antigen reflect colonization of the spleen by cells sensitized locally in the gut wall, a site not readily primed by the parenteral route. Serum from intragastrically immunized mice contained a very active tolerogen. In vivo, it was capable of conferring tolerance to nonimmune recipient mice. In vitro, it paralyzed the activity of antibody-producing cells. Inhibitory sera has weak antibody activity, restricted to the IgA class, and contained immune complexes reacting with rheumatoid factor but not with C1q. Elimination of these complexes by means by insolubilized rheumatoid factor abolished the tolerogenic effect. In conclusion, the enterically induced tolerogen seems to consist of immune complexes with IgA as the antibody.


Experimental amyloidosis: the inducer is a polyclonal B-cell activator to which susceptibility is under genetic control. Experimental amyloidosis in mice can be induced by repeated injections of casein. It has now been demonstrated that casein induces strong polyclonal antibody synthesis in mouse B spleen lymphocytes. This effect is much more pronounced in spleen cells from anyloid-susceptible mice (CBA/J) than amyloid-resistant mice (A/J). It is suggested that amyloidosis can be due in some instances to a constant exposure for molecules which induce polyclonal B-cell activation.


Mediation systems in bacterial lipopolysaccharide-induced hypotension and disseminated intravascular coagulation. I. The role of complement. We have studied the role of complement in lipopolysaccharide (LPS)-induced hypotension and disseminated intravascular coagulation (DIC) by comparing the effects of injection of three preparations of LPS from E. Coli 0111:B4, S. minnesota Re595, and S. marcescens. Injections of nonlethal doses of these LPS preparations into normal rabbits produced decreases in mean arterial blood pressure during a 5-h period. When rabbits treated with cobra venom factor (CoF) to deplete C3 were injected with the various LPS preparations, mean arterial pressures fell at a rate and extent essentially identical to that observed in normal rabbits. Rabbits genetically deficient in C6 also demonstrated LPS-induced hypotensive changes. Only minimal, or no changes in plasma C3 levels or serum CH50 values were detected in normal rabbits after LPS injection. Hypotensive changes were also induced in rabbits when complement was rapidly activated by intravenous injection of CoF. In contrast to the hypotension induced by LPS, the fall in arterial pressure associated with the consumption of complement was short lived and required the rapid consumption of considerable amounts of C3. The occurrence of DIC noted in normal rabbits injected with each preparation of LPS was not inhibited in either rabbits treated with cobra factor or in C6-deficient rabbits. The DIC was most pronounced after injection of Re595 and S. marcescens LPS. Injection of the various LPS preparations produced a rapid disappearance of circulating neutrophils and mononuclear cells, which occurred with the same kinetics and to the same extent in normal, CoF-treated, and C6-deficient rabbits. Injection of either Re595 LPS or S. marcescens LPS produced a biphasic disappearance of circulating 51Cr-platelets. In contrast, injection of 0111:B4 LPS affected only slightly the rate of disappearance of 51Cr-platelets. Depletion of C3 by cobra factor treatment had no effect on the disappearance of platelets in animals injected with 0111:B4. In marked contrast cobra factor treatment greatly reduced the initial rapid disappearance of platelets in rabbits injected with either Re595 or S. marcescens LPS, but had no effect in the secondary disappearance phase.


Are we learning what actually goes on when the brain recognizes and controls? Drawing upon recent advances in neuroscience for examples, the thesis is defended that, in contrast to a Kuhnian view of proress by overturning whole sciences, progress amounting to revolution in our understanding of nervous systems is happening by the accumulation of many discrete discoveries, and that this process may be expected to continue for a long time. Twelve propositions are put forward illustrative of ideas developed during and influenced by C. L. Prosser's career, all in the segment of neuroscience concerned with subsystem organization. They range from the generally accepted to the frankly polemical and the merely heuristic. (1) Ongoing background activity has different forms. (2) Codes, both spike and graded, are several. (3) Integrative variables in neuron function are several. (4) Identifiable cells may be widespread. (5) Neuronal circuits for behavior are known. (6) Redundancy is usually overlap. (7) Reliability can be high. (8) Recognition neurons may be common and complex. (9) Command neurons may be common and complex. (10) Pattern is often central in origin. (11) Hierarchies and switches may be common. (12) Subsystem function is an intellectual challenge. Each of these is briefly elaborated and its logical relation to the others suggested. The role of discrete discovery is thus illustrated--in the generation of new conceptual frameworks that gradually become interrelated and cumulatively change profoundly our picture of what's going on in the brain.


Extensive and intensive factors determining the performance of striated muscle. Striated muscle is obviously a versatile tissue, one which has been malleable to selective pressure and has become modified for many specific tasks. The variations which adapt striated muscle to particular functions involve both changes in its structural organization and changes in the chemical nature of its components. Although a number of factors have been identified which contribute to the diversity of muscle performance, it is not yet possible to account adequately for the wide range in muscle performance throughout the animal kingdom. While not a new direction in comparative physiology, developing quantitative explanations for the diversity of muscle performance is still an obvious, remaining task.


Temperature as a selective factor in protein evolution: the adaptational strategy of "compromise". Most of the important functional and structural properties of enzymes are affected by temperature. In order to maintain critical enzymic properties such as regulatory sensitivity, catalytic potential and structural stability, significant changes have been made in enzymes during evolution in different thermal regimes. Regulatory function, as typified by substrate binding ability, has been especially conservative. For a given enzyme, substrate binding ability is maintained at a relatively stable level over the entire temperature range experienced by the organism (enzyme), in spite of wide variation in substrate affinity at temperatures outside the biological range. Similarities in substrate affinity among homologues and analogues of enzymes from bacteria, invertebrates, fishes and mammals, at respective physiological temperatures for the enzymes, demonstrate the crucial importance of regulatory abilities in enzymes. Two facts, (a) that enzymes function at sub-maximal rates, and (b) that low temperature compensation is not effected by wholesale reductions in apparent Km values, argue that regulation outweighs sheer catalytic potential in enzymic function. The efficiency of an enzyme to catalyze a reaction at a rapid rate appears highest in low cell-temperature forms. The finding that catalytic efficiency is inversely correlated with enzymic heat stability suggests that enzymes with relatively great abilities to undergo conformational changes during catalysis are capable of supplying the most energy for activation events, this energy arising in part from the exergonic formation of weak bonds during the activation step in catalysis. Energy changes due to conformational changes may also be used to reduce the net enthalpy change which occurs during ligand binding, a mechanism we refer to as "coupled-compensating enthalpy changes." Comparisons of amino acid compositions of enzyme homologues and analogues from differently thermally adapted species do not reveal major differences, for example, in the overall hydrophobicity of enzymes. We propose that observed differences in enzyme thermal stability derive more from quantitative differences, i.e., differences in total numbers of secondary interactions, than from quilitative differences, i.e., differences in the relative importance of different classes of weak bonds.


Water states and water gates in osmotic processes, and the inoperative concept of molfraction of water. An historical account is given of concepts regarding the mechanism of osmosis and imbibition, starting with Lord Kelvin's gravitational column, where he pointed out that a capillary standing in a dish of water within an isothermal enclosure must have a lowered vapor pressure at its elevated meniscus so as to match that emanating from the surface in the dish, otherwise distillation would violate the Second law. A brilliant sequence to this simple idea followed through Poynting, Arrhenius, Noyes and culminated with Hulett, who in 1901 formulated the "solvent tension theory" of osmosis, stating in essence that the thermal motion of the solute molecules by impact with the free solvent surface put the solvent under tension. This lowers the vapor pressure and thereby also its freezing point. Perrin, in famous experiments on Brownian motion, demonstrated solute-solvent independence within a solution and further support came through Herzfeld, Mysels and Duclaux. We measured negative pressures in salt-free sap of mangroves and other plants matching the osmotic pressure in the leaf cells. A series of measurements on magnetic and gravitational effects on osmotic pressure likewise bore out the tension theory. The fashionable "water concentration theory" is left experimentally contradicted and in violation of the Second law.


Models for coupling of salt and water transport; Proximal tubular reabsorption in Necturus kidney. Models for coupling of salt and water transport are developed with two important assumptions appropriate for leaky epithelia. (a) The tight junction is permeable to both sale and water. (b) Active Na transport into the lateral speces is assumed to occur uniformly along the length of the channel. The proposed models deal specifically with the intraepithelial mechanism of proximal tubular resbsorption in the Necturus kidney although they have implications for epithelial transport in the gallbladder and small intestine as well. The first model (continuous version) is similar to the standing gradient model devised by Diamond and Bossert but used different boundary conditions. In contrast to Diamond and Bossert's model, the predicted concentration profiles are relatively flat with no sizable gradients along the interspace. The second model (compartment version) expands Curran's model of epithelial salt and water transport by including additional compartments and considering both electrical and chemical driving forces for individual Na and Cl ions as well as hydraulic and osmotic driving forces for water. In both models, ion and water fluxes are investigated as a function of the transport parameters. The behavior of the models is consistent with previously suggested mechanisms for the control of net transport, particularly during saline diuresis. Under all conditions the predicted ratio of net solute to solvent flux, or emergent concentration, deviates from exact isotonicity (except when the basement membrane has an appreciable salt reflection coefficient). However, the degree of hypertonicity may be small enough to be experimentally indistinguishable from isotonic transport.


Membrane resistance change of the frog taste cells in response to water and Nacl. The electrical properties of the frog taste cells during gustatory stimulations with distilled water and varying concentrations of NaCl were studied with intracellular microelectrodes. Under the Ringer adaptation of the tongue, two types of taste cells were distinguished by the gustatory stimuli. One type, termed NaCl-sensitive (NS) cells, responded to water with hyperpolarizations and responded to concentrated NaCl with depolarizations. In contrast, the other type of cells, termed water-sensitive (WS) cells, responded to water depolarizations and responded to concentrated NaCl with hyperpolarizations. The membrane resistance of both taste cell types increased during the hyperpolarizing receptor potentials and decreased during the depolarizing receptor potentials, Reversal potentials for the depolarizing and hyperpolarizing responses in each cell type were a few millivolts positive above the zero membrane potential. When the tongue was adapted with Na-free Ringer solution for 30 min, the amplitude of the depolarizing responses in the NS cells reduced to 50% of the control value under normal Ringer adaptation. On the basis of the present results, it is concluded (a) that the depolarizing responses of the NS and WS cells under the Ringer adaptation are produced by the permeability increase in some ions, mainly Na+ ions across the taste cell membranes, and (b) that the hyperpolarizing responses of both types of taste cells are produced by a decrease in the cell membrane permeability to some ions, probably Na+ ions, which is slightly enhanced during the Ringer adaptation.


Mutations affecting aromatic amino acid transport in Escherichia coli and Salmonella typhimurium. A genetic locus, aroT, located between chr and the trp operon in Salmonella typhimurium, and similar genes, aroR and aroS, near the trp locus of Escherichia coli, were found to be involved in the transport of aromatic amino acids. Genetic lesions at these loci cause  a variable diminution in uptake and accumulation of aromatic amino acids, alanine and glycine compared with the wild type. The F'trp episome carries the aro R locus. Curing an E. coli strain of the F'trp episome which covers a chromosomal deletion from cysB through the trp operon and tonB regions, results in a 60 to 80% decrease in tryptophan uptake. The introduction of F'trp into a trp operon-deleted S. typhimurium of low transport ability restores transportability, suggesting that aroT in this organism may be homologous with aroR in E. coli. In E. coli, tryptophan accumulation is normally increased by prior growth in L-tryptophan, while in S. typhimurium it is repressed. In both genera, the trpR gene appears to have no effect on the tryptophan transport capabilities in response to changes in the concentration of L-tryptophan in the medium. Tryptophan transport in the S. typhimurium F'trp hybrid was subject to repression, while in the E. coli strain which carries F'trp covering the equivalent chromosomal delection, an increase in tryptophan accumulation was shown after growth in L-tryptophan supplemented medium.


R factor tetracycline and chloramphenicol resistance in Escherichia coli K12 cmlB mutants. The isolation of Escherichia coli chromosomal mutants that increased the level of resistance of a partially tetracycline-sensitive mutant of RI00-I is described. Plasmid-less derivatives of these moderately resistant mutants were phenotypically similar to the cmlB mutants described by Reeve (1966, 1968), and also mapped in the same region. The level of intrinsic resistance to both chloramphenicol and tetracycline was increased about twofold. Also, the levels of R factor-determined resistance to these drugs were increased by this host mutation and tetracycline resistance was expressed constitutively. A cmlB accumulated tetracycline at a threefold lower rate than the wild-type strain, and it is proposed that the mutants have an altered permeability to the drugs and that this acts synergistically with the products of the R factor chloramphenicol and tetracycline resistance genes.


A new M-type of group A streptococcus of clinical importance in pyoderma and pharyngitis. A new M-type of group A streptococcus, provisionally designated type 65, is described. The vaccine and other initially isolated strains of this type attracted attention because of the T-agglutination reactions 2/25, not previously encountered among pyoderma streptococci. The investigations characterizing the strains as members of a new type were done with streptococci isolated from patients with pyoderma. However, type 65 was subsequently found to cause both pyoderma and acute pharyngitis.  The T-2 agglutination reactions encountered with original members of this type, plus the cross-reactions later seen with type 65 antiserum and M-type 2 streptococci, prompted a comparison of this new type with M-type 2 streptococci, including those with the T-2 agglutination and others with the 8-25-Imp. 19 complex. The two M-antigens were clearly distinguished from one another in reciprocal bactericidal and precipitin tests with absorbed antisera. They were further distinguished in that all type 65 strains were opacity-factor (OF) negative, whereas type 2 streptococci were uniformly OF-positive. Most M-type 65 strains subsequently found in surveillance studies were shown to be members of the 8-25-Imp,19 T-complex. Type 65 is thus a newly described type which shares with M-types 55 and 57 a commom T-agglutination pattern and, like members of these types, fails to produce opacity factor. In our colleciton of strains, from both pyoderma and pharyngitis, shown to be members of the 8-25-Imp. 19 complex, and OF-negative, only type 65 has been identified to date. In contrast to types 55 and 57, the new type 65 does not appear to be of major importance in causing acute glomerulonephritis.


An enrichment technique for auxotrophs of Agrobacterium tumefaciens using a combination of carbenicillin and lysozyme. A procedure to enrich for auxotrophic and fermentation mutants of Agrobacterium tumefaciens is described. The method is based on the amplification of the killing power of carbenicillin by the addition of lysozyme. Isolation frequencies of some types of mutants are presented, with and without the application of the proposed procedure. The yield of mutants is usually enhanced a hundredfold per enrichment treatment.


Amide utilization in Aspergillus nidulans: evidence for a third amidase enzyme. A mutation in a gene designated gmdA has been found to lead to loss of ability of Aspergillus nidulans to use benzamide, phenylacetamide and several other amides as sole nitrogen sources for growth. The gmdA1 lesion results in low levels of an enzyme, called the general amidase, which has acitivity for a wide range of amide substrates. This enzyme is reressed by certain nitrogen-containing metabolites, including ammonium, but is probably not regulated by induction or by carbon catabolite repression. Evidence is presented for the general amidase being distinct from the previously characterized acetamidase and formamidase enzymes. The data also indicate that there is a fourth amidase capable of the hydrolysis of valeramide and hexanamide.


Hysteria, hypnosis, psychopathology. History and perspectives. A historical outline is given of the search for an explanation of the still elusive nature of hysteria and hypnosis, their mutual relationship, and that which they bear to psychopathology. Charcot regarded hypnosis as an artificially induced hysterical neurosis, and it was he who first introduced Freud to these two states. Freud was the first to see in hypnosis an experimental instrument for understanding psychopathological mechanisms. His subsequent conceptualization of psychoanalysis derived from these two phenomena at this decisive period. In 1895 Freud attempted to achieve a psychophysiological synthesis of the mental apparatus in his "Project for a Scientific Psychology," but then decided not to publish it. Whether or not recent advance in neurophysiology are sufficiently important bo bring about this synthesis remains an open question. In recent years some psychoanalysts have become interested in hypnosis, which one of them described as a focus for psychophysiological and psychoanalytic investigations. Any theory of the psychical apparatus which does not account for such an obvious psychical phenomenon must necessarily be incomplete. Since Charcot, hysteria presents hardly any new openings for experimental work. It is suggested that the solution of psyche-soma interaction might be sought in the study of hypnosis. It is postulated that hypnosis is a "fourth organismic state," not as yet objectifiable (in contradistinction to the waking state, sleep, and dreaming): a kind of natural or inborn mechanism which acts as one of the regulators of man's relationships with  the environment. The author discusses briefly the aims and methodology of future interdisciplinary research on hypnosis, and the study of the transition from one state of consciousness to another, and their potential application to a wide range of subjects, namely, wherever man's relations with the environment are involved.


A review of the effects of diazepam on cognitive and psychomotor performance. Studies evaluating the effects of diazepam (Valium) on psychomotor and cognitive functions are reviewed an integrated. The importance of the full and clear documentation of such drug effects lies in the wide usage of diazepam today for a variety of medical, psychiatric, and dental purposes. The various tasks used to assess drug effects were classified into six major groups based on apparent similarity of functions tapped. These groupings are: reflex speed; critical flicker fusion threshold; attention and vigilance; decision making; learning and memory; psychomotor performance. In all functions except simple reflexive responding; some indications of impaired performances were reported, the results being most definitive for the critical flicker fusion where even small doses lowered the threshold and for a slower performance on letter cancellation tasks. There appeared to be some interaction between diazepam and alcohol although the nature of this interaction is still unclear. Because of the extensive use of both of these drugs and the possibility of a synergistic or a potentiation effect, it is important that this area receive further study. It was suggested that future studies either control for or analyze the data to assess the possible interactive effects of diazepam with subject variables such as sex, personality type, and for population characteristics. These variables have been shown to affect responses in other studies and hence could also interact with cognitive and psychomotor performance. It was noted that most of the studies reviewed used normal, healthy, male volunteer subjects and may not be comparable to the clinical populations for whom the drug is typically prescribed.


Hypothalamic and pancreatic lesions with diabetes mellitus. A case is reported of a neoplasm of mixed mesenchymal and neuroepithelial origin consisting of plasmacytoma, lymphoma, ganglioneuroma, and astrocytoma in the same mass. The tumour arose in the hypothalamus of a 43 year old diabetic woman who also had alpha cell hyperplasia and beta cell hypoplasia of the islets of Langerhans. It is suggested that both hypothalamic and pancreatic lesions produced diabetes mellitus in this patient.


Immunohistochemical demonstration of tubulin associated with microtubules and synaptic junctions in mammalian brain. The distribution of tubulin in brain tissue has been investigated by light and electron microscopic immunohistochemistry using an antiserum raised against electrophoretically purified microtubule derived tubulin. The specificity of the staining is indicated by the lack of staining when non-immune serum is substituted for anti-tubulin serum and the quite different staining obtained with antisera against antigens other than tubulin. The anti-tubulin immunohistochemistry reveals tubulin antigen in microtubules and in the postsynaptic junctional lattice of most synapses. No antigen has been detected in either the synaptic cleft or in the axon terminal. This distribution confirms previous biochemical identification of tubulin as a major postsynaptic junctional component, but suggests that it is not common to all synaptic junctions.


Management of diabetes insipidus in neurosurgical patients. The authors present a brief review of the problem of diabetes insipidus in neurosurgical patients, with particular emphasis on the differential diagnosis of postoperative and posttraumatic polyuria and the management of diabetes insipidus in these periods. A listing of drugs currently used in its treatment is given.


Compound elevated fractures of the skull. The author presents two cases of compound elevated fractures of the skull and discusses the mechanics of their production. These lesions, seldom recognized in modern clinical practice, are first described in the oldest scientific and surgical treatise known, the Edwin Smith Surgical Papyrus, over 5000 years ago.


Retained intracranial metallic foreign bodies. Report of two cases. The authors discuss two examples of extensive migration of retained metallic foreign bodies. The potential for further neurological injury from migration, formation of neurotoxic breakdown products, and the danger of infection are factors to be assessed when considering the removal of retained intracranial metallic foreign bodies.


Comprehensive evaluation of renal function in the transplanted kidney. By means of a comprehensive renal function test based on the analysis of orthoidohippurate kinetics carried out 223 times in 86 renal transplatn patients, we have been able to separate clearly five clinical entities: normally functioning transplanted kidneys, acute tubular necrosis, cell-mediated rejection, humoral (chromin) rejection, and postrenal obstruction. Accurate prediction of the fate of the rejecting kidney can be made while still subclinical as much as a week before manifestations by other techniques are evident. Data on 22 donors studied 44 times are also presented. The comprehensive test consists of measurements of effective renal plasma flow (ERPF), sequential scintigraphy, calculations of excretory index (EI) (percent dose actually found in bladder and voided urine as a fraction of the percent dose expected at a given time after injection at the patient's specific ERPF), and residual urine volume. Formulas and regression equations for the calculation of ERPF, EI, residual urine, etc., are presented.


Total mandibular alveolar osteotomy in the management of skeletal (infantile) apertognathia. When intraoral access is adequate and other physical characteristics are satisfactory, total mandibular alveolar osteotomy can be used effectively to correct skeletal (infantile) apertognathia. The procedure, not frequently used, resulted in significant improvement of a massive open bite in a 15-year-old girl.


Vestibuloplasty with skin grafting.

Vestibuloplasty with skin grafting. A review of 68 vestibuloplasties during a seven-year period indicated that there is no need for the routine use of either antibiotics or corticosteroids after vestibuloplasty for correction of an atrophic mandibular ridge. Vigorous massage after healing was beneficial. Improved tolerance and function of dentures were obtained in all instances. Paresthesia of the lower lip occurred in a significant number of patients.


Anatomic considerations in infections of the face and neck: review of the literature. An attempt was made to summarize the literature concerning the potential spaces between fascial layers in the face and neck and to correlate the variations in terminology used by different authors. It soon became evident in a search of the literature that far too many names are given to the same anatomical space and that there is a wealth of written material for study. As a result, the descriptions given here deal with the terminology that was most frequently encountered (Table). As anatomical relations form the basis of diagnosis and therapy, a thorough knowledge of the nature of infective processes in the facial and cervical regions is essential. The various fascial spaces are described and some general aspects of diagnosis are considered.


Mandibular retrognathia: a review of the literature and selected cases. Many techniques have been developed since the first osteotomy for correction of retrognathism was performed in 1905. These techniques have been in two groups--those that are performed in the mandibular body and those that are performed in the mandibular ramus. Ramus procedures are more favored because there is less morbidity in comparison to body procedures. Regardless of the procedure used, an adequate preoperative evaluation based on oral and radiographic examinations, study models, cephalometric analysis, and photographs is mandatory to achieve satisfactory results. A more satisfactory result can almost always be attained if a cooperative effort is made by the oral surgeon and orthodontist in the treatment of retrognathism.