A study of the synaptogenesis in the cerebellar cortex through chronic treatment and immunocytochemistry of beta-bungarotoxin. The mechanism of synaptogenesis between dendritic spines of Purkinje cells and parallel fibers in the chicken cerebellum was studied through chronic treatment and immunocytochemistry of beta-Bungarotoxin (beta-BT). Attention was directed to the question of whether the presynaptic specializations (presynaptic vesicular grids composed of presynaptic dense projections and associated vesicles) of the parallel fibers can differentiate in the absence of the Purkinje cells. Normal cerebella from 18-day and 21-day chick embryos, incubated with beta-BT and reacted with HRP-labeled anti beta-BT guinea pig IgG, showed a positive HRP reaction on Purkinje cells but not on external and internal granule cells. Thus, in chicken cerebellum, beta-BT primarily affects Purkinje cells. When beta-BT was applied to chick embryos at 3-day intervals, beginning on the 4th day of incubation, the cerebella were markedly reduced in size and most of the Purkinje cells as well as the nerve fibers in the white matter disappeared between the 18th and the 21st day of incubation. Folia of the 21st day experimental cerebella were irregular in shape and the area of the midsagittal section was one fourth that of the controls. In the 21st day cerebella treated with beta-BT, the majority of Purkinje cells disappear. However, the external granule cells remain intact and showed the usual mitotic activity. The majority of the inner granule cells were normal. Some of the parallel fibers, which display presynaptic vesicular grids, established synaptic contact with stellate cells and the dendritic spines of the few Purkinje cells that survived the treatment. However, vast areas of the molecular layer contained neither dendrites of Purkinje cells, nor parallel fibers displaying presynaptic vesicular grids devoid of their postsynaptic counterpart. In such areas, the molecular layer consisted of parallel fibers of uniform diameter, some of which contained accumulations of vesicles, but displaying no presynaptic dense projections. This suggests that parallel fibers may not be able to completely develop the presynaptic vesicular grids in the absence of their target cells.


Psychological stress reduction during dental procedures. Behavioral methods of patient stress reduction during amalgam restorations were evaluated. Eighty adult patients were randomly assigned to one of four groups of 20 each: a control group, a relaxation group, a perceived control group, and an active distraction group. Both relaxation and distraction were found to be effective in reducing patient discomfort.


Non-pressure adhesion of a new adhesive restorative resin. Non-pressure adhesion of a new adhesive restorative resin was investigated employing a new tensile test. The material was adhesive to both enamel and dentin as well as to carious dentin and showed strong adhesion to all substrates tested. Etching further increased the adhesion even to dentin.


Effects of adhesion promoters on resin-enamel retention. The adhesive effects of three adhesion promoters were compared utilizing three different filled resins on acid-etched human permanent teeth. The results demonstrated a significantly greater resistance to dislodgement of resins by shear forces when an NPG-GMA type of adhesion promoter was utilized. Type of resin did not influence resin retention.


The role of diffusible ionic species in the bonding of polycarboxylate cements to dentine: an in vitro study. Treatment of freshly-cut dentine with fluoride ions or high concentrations of metal ions produced changes ranging from mineralization of tubule contents to precipitation of adherent surface layers. Combinations of these treatments with application of fluoridated and non-fluoridated polycarboxylate cements and glass ionomer cements produced both increases and reductions in bond strength which are explained by ionic diffusion at the interface prior to setting.


The CASE system for cancer education.

The CASE system for cancer education. A Computer-Assisted-Self-Evaluation (CASE) program in oncology is described. The program is based on motivation by immediate, informative feedback, and involves the computer-guided interaction of a student with a series of microfiche cards. The computer leads the student through a series of 16 questions and associated explanations and recommendations based on the answer choices. Since all textual materials are placed on microfiche cards, the computer is only required to print simple, prearranged sentences and comments. As a result four students, using different CASE topics, can time-share the same computer terminal. This time-sharing capability, together with the large but compact, low cost information storage afforded by the use of microfiche, makes the cost of this system comparable to that of conventional study aids. The use of the CASE system as an educational aid and self-tutoring mechanism has been well accepted by faculty and students.


Programmed instruction in general pathology: evaluation of performance in comparison to conventional instruction and scholastic achievement. Previous studies relating the efficacy of various teaching methods to student achievement levels have yielded conflicting results. This study compares programmed instruction in pathology with conventional instruction for students exhibiting different levels of academic achievement, as measured by undergraduate GPA. The results of this study reveal that no significant difference in examination performance exists regardless of the teaching method employed when achievement level is considered.


The histologic grossing and reading of wedge-shaped specimens from malignancies taken from the oral lips. A simple method of grossing, sectioning, and reading operative specimens obtained by wedge resections of carcinomas from lower lips is described.


Bioethics and informed consent in American health care delivery. Bioethics is a multi-dimensional discipline. The traditional aspect being medical ethics, a branch of Western philosophy which, since the time of Hippocrates, has sought to formulate rules of proper conduct for physicians. Ethics and informed consent are interrelated issues. Consent is the central issue on which hangs most of the ethical problems in human experimentation. The informed consent of the human patient is the ultimate protection from the hazards of research and therapy in medicine, the basic premise of this being that every human being has the right to determine what shall be done to his own body. The patient must have full prognosis, complications, sequelae, discomforts, costs, inconveniences, risks and expectations. Medically and ethically what should the patient be told? There appears to be no obvious format, but the patient should be told enough to allow him to make a rational decision. This paper contains an analysis of the reactions of just a few American nurses to this dilemma. The nurse who attempts to use only her scientific training to determine ethical conduct is in a quandary because seldon is there empirical evidence available to support her decision, no matter what it is.


The problems and the values of objective nursing observations in psychiatric nursing care. This paper describes a drug trial which illustrates the problems involved in objective nursing recordings to assess response to a specific treatment. It also highlights some difficulties in recording results. The paper briefly describes the history and diagnosis of a patient and the choice of treatment. The method of formulation of a checklist and the difficulties in completing a study are discussed. The results of the study and their value in planning future work are outlined. Conclusions are drawn about the feasibility of carrying out a controlled drug trial with a patient on a ward but the most important aspects are the ability of nurses to perform objective assessments and the value of this approach when assessing a patient and his response to treatment.


Clinical success and potential failure after single application of a pit and fissure sealant: a four-year report. A single application of a filled chemically initiated BIS-GMA sealant to permanent first molars of children ranging in age from 5 to 8 years covered the original sites in 52.4% of the 185 teeth examined after four years. Retention of sealant is greater in mandibular (64.7%) than in maxillary (42.0%) molars. The rate of loss of sealant was greatest during the first year (20%), then less than 10% per year at the second, third, and fourth recalls. In comparison with two similar studies, the retention of sealant was 20% to 30% greater. Using the parameters of percent effectiveness, net gain, and DMF scores per 100 test and control teeth, the data from the current study indicate a continued positive effect substantially greater than that in other similar studies. Complete loss of sealant does not appear to predispose that surface to caries any more than its contralateral paired surface. However, a partial loss of sealant because of abrasive wear that results in the exposure of the terminal ends of a fissure is a potential failure in that it creates an environment conducive to caries. Thus, even the well-applied sealant does not necessarily constitute permanent obturation of pits and fissures. Periodic clinical observation is necessary to determine the success or potential failure of the sealant treatment.


Soft tissue emphysema.

Soft tissue emphysema. Many cases of soft tissue emphysema have been reported; it is recognized as a common surgical and dental complication. This report adds to the number of recorded cases and emphasizes the potential for emphysema with the use of high pressure dental instruments. It also shows that the point of entry of air may be overlooked and will therefore delay diagnosis. Proper diagnosis and recognition of the potential for widespread secondary infection dictate the management of emphysema. If any doubt should exist, consultation should be obtained without hesitation.


Electroencephalographic and clinical changes as correlated in geriatric patients treated three months with an ergot alkaloid preparation. The results of a 3-month trial with an ergot alkaloid preparation (Hydergine) in 16 geriatric patients showed that, in accordance with a previously proposed working hypothesis, the improvement induced by the drug in electroencephalographic age-related changes was accompanied by clinical improvement in patients with similarly age-related mental deterioration.


Efficacy of nylidrin hydrochloride in the treatment of cognitive impairment in the elderly. A double-blind study was conducted on the effects of nylidrin hydrochloride versus placebo in 60 patients with mild to moderate symptoms of chronic brain syndrome. Their ages ranged from 65 to 99 years. Preliminary results indicated that nylidrin HCl (a vasodilator) is a relatively safe therapeutic agent and more effective than placebo in ameliorating the symptoms of cognitive impairment associated with aging, on both a short term (3-month) and a long-term (9-month) basis. In a dosage of 24 mg daily, it reached its peak effectiveness after 3 months of use.


Neuron-thymic lymphocyte binding by serum IgG of 90- and 500-day-old female Wistar albino rats. In vivo and in vitro IgG binding to neurons was determined by the direct and indirect immunofluorescence and immunoperoxidase techniques in 90- and 500-day-old female Wistar rats. The sera were also tested against other organs of 90- and 300-day-old rats, and an absorption technique was carried out with minced thymus. Only 1 90-day-old rat showed positive in vivo neuron binding. One serum of a young (6.7%) and 17 sera of old (42.5%) rats were positive by the in vitro procedures. The 1 young and 4 of the old positive sera cross-reacted with thymocytes, and when 3 of these were subjected to absorption, neuron igG binding capacity was removed. Significant cross-reactivity with other organs could not be demonstrated. These observations indicate that in these rats there are at least two kinds of serum neuron binding IgG which significantly increase with age; one of these cross-reacts with thymus and the other does not.


Age-related changes in aortic intima of rats. The aortic intima of young and old Wistar rats was studied by light and electron microscopy. The endothelial cells of young rats are flat and regular and lie adjacent to the internal elastic lamina (IEL). Endothelial cells of old rats have irregular shapes and sizes and bulge into the lumen. Long protrusions connect these cells to the IEL through a layer of granular and fibrillar material that separates the IEL from the endothelium. This material is PAS and Alcian blue positive and increases with age. There are twice as many pinocytic vesicles on the luminal front of endothelial cells of old rats as compared to the tissue front. Endothelial cells of young rats have similar numbers of vesicles on the two fronts. No significant difference was found between the charge density of the luninal plasmalemma of young and old rats; however, significantly less sialyl groups were found on endothelial cells of old rats. A marked difference in the labeling pattern of the IEL by cationized ferritin (CF) was observed between young and old rats.


The development and assessment of a bacteriocin typing method for Klebsiella. Klebsiellas are generally typed by the method of capsular serotyping but, although this is a reliable method, it is time consuming, requires the production of a large number of antisera and is not generally available. For this reason another method for typing klebsiellas was sought. A bacteriocin typing method involving mitomycin C induction was developed and the cultural conditions giving optimum klebecin production and the best methods of testing the sensitivity of the organisms to klebecins were determined. Of 190 klebsiella strains screened for bacteriocinogeny, only 68 (35.8%) produced klebecin and after calculation of similarity values by computer analysis, a typing set of 15 producers was selected. This typing set allowed over 96% of klebsiella strains to be typed and tests of the reproducibility of the method and the variability of typing patterns in natural populations of klebsiella indicated that results of acceptable accuracy could be obtained, while retaining good discrimination if two or more differences were required between patterns before they were regarded as distinct. A complete set of capsular antisera were prepared, enabling the results obtained from klebecin typing to be compared with those from serotyping. There was generally close agreement between the results from the two typing methods and greater discrimination was obtained between similar strains when the two methods were combined. Klebecin typing and serotyping revealed relationships between strains from five outbreaks of infection, and strains of the same serotype from different hospitals could frequently be distinguished by their klebecin typing patterns.


Complex surveillance of Streptococcus pyogenes. IV. The phenomenon of interference of human serum under the conditions of the bactericidal test. The phenomenon of interference of human sera under the conditions of the bactericidal test was described. In the presence of these sera, secondarily non-resistant strains of Streptococcus pyogenes were capable of vigorous growth and anti M 12 bactericidal activity was impaired. The factor was found in the albumin fraction and has probably the character of a blocking cytophilic lymphokin. It can markedly distort the interpretation of the bactericidal test.


Enterotoxigenic E. coli in humans.

Enterotoxigenic E. coli in humans. E. coli strains isolated from persons having diarrhoeal disease were tested for the production of TS enterotoxin. The production of TSE was demonstrated in 2.5% in a series of 80 strains isolated from children under one year of age, having acute diarrhoea. TSE was produced by 8.4% of E. coli strains out of 59 strains isolated from patients over one year of age. Among these strains, an interesting E. coli strain was isolated from the patient T. J., which produced TSE for more than 15 months. The production of TLE was tested though not proved in all strains by experiment on an isolated intestinal loop of an adult rabbit. The test on suckling mice so far appears to be the most suitable test for the demonstration of TSE. The results were considered positive when the index (the ratio of the weight of the whole intestine to the weight of the rest of the body) was higher than 0.08 while indices up to 0.078 were considered negative. E. coli strains with indices of intermediate values and strains with temporary production of TSE, occurring particularly in very small children, deserve special attention. The height of the indices was not influenced by a 30-minute exposure at 60 degrees C, but a decrease in the values of the indices was observed after boiling for a period of 15 min. The occurrence of E. coli strains producing TSE is evidently small in humans in European countries but, without doubt, they are important in the aetiology of diarrhoeal diseases.


A comparison of labelled antibody methods for the detection of virus antigens in cell monolayers. A number of labelled antibody methods have been applied to the detection of Semliki Forest virus antigens after replication of the virus in monolayers of host cells in multi-wellpolystyrene plates. The importance of several reaction variables has been investigated and the sensitivity of the methods compared for different periods of virus replication. Direct assays with radio-labelled antibody (RLA) and indirect assays using peroxidase-antiperoxidase complexes (PAP) were equally sensitive. Direct and indirect assays using enzyme-linked antibodies (ELA) were slightly less sensitive than direct RLA and PAP methods but were more sensitive than the indirect RLA or fluorescent antibody (FLA) methods. Direct assays using ELA were more rapid and easier to perform than the other assay methods.


Detection of antibody-forming cells and humoral antibody to horseradish peroxidase. Two new simple methods for detecting antibody-forming cells by hemolytic plaque assay and hemagglutinating antibody to horseradish peroxidase have been developed in mice. Both techniques utilize as target, sheep erythrocytes coupled directly with horseradish peroxidase. These assays are sensitive, antigen-specific and are useful to quantitate both direct and indirect antibody-forming cells and humoral antibodies.


The effects of organic solvents and temperature on the desorption of yeast 3-phosphoglycerate kinase from immunoadsorbent. Physicochemical parameters governing the elution of yeast 3-phosphoglycerate kinase from its immunoadsorbent were studied. Non-denaturing elution conditions were determined (alkali medium containing 50%, v/v, ethylene glycol) and the method was applied to one-step isolation of enzyme from a crude yeast preparation.


The leukocyte adherence-inhibition assay as a diagnostic test for multiple sclerosis: study of a substance found in MS blood. We have modified and adapted two well-accepted cancer immunology research techniques to study blood leukocyte phenomena of MS patients. The LAI test of Halliday and Miller and the 3 molar potassium chloride (3M KCl) tumor antigen extraction technique of Dean and McCoy were adapted to extract from pooled MS whole blood an MSRM. The LAI test results of 53 of 58 MS patients (91%) were considered positive, but only three of 75 control subjects (4%) were positive when tested against the MSRM. This indicates that patients with MS had a greater specific reactivity to the MSRM than did the control subjects (healthy individuals and patients with disease other than MS). The specificity and reproducibility of this reaction were tested with materials prepared from various malignant diseases. Sensitized leukocytes showed consistently higher reactivity to antigen extracts prepared from corresponding types of tumors than to extracts prepared from tumors of other histological types. Our results indicate that (1) the LAI test is able to corroborate the neurological diagnosis of MS and (2) there is a blood constituent found only in the MS patient.


David Edward Hughes and his audiometer.

David Edward Hughes and his audiometer. A brief biography of David Edward Hughes is outlined. His Audiometer and its presentation are described. The response of clinicians to the device is discussed.


Differential control of luteinizing hormone and follicle-stimulating hormone by luteinizing hormone releasing hormone in the ram. Adult Soay rams with low concentrations of gonadotrophins in the circulation as a result of 12 weeks of exposure to long daylengths (16 h light : 8 h darkness) were given small doses (100 ng) of synthetic luteinizing hormone releasing hormone (LH-RH) into the jugular vein two, four or seven times/day for 10 days. Each injection of LH-RH induced a transitory increase in the concentration of LH and testosterone in the plasma, whereas the concentration of FSH showed little immediate change. After repeated treatment with pulses of LH-RH, the responses of LH and testosterone became slightly enhanced and the plasma concentration of FSH became permanently raised; these changes were most conspicuous in the animals receiving the most frequent injections. At the end of the study when the injections of LH-RH were stopped, the concentrations of LH and testosterone remained low but the concentrations of FSH continued to be maintained at a high level for at least 24 h.


Relative activity, plasma elimination and tissue degradation of synthetic luteinizing hormone releasing hormone and certain of its analogues. The abilities of three nonapeptide analogues of synthetic luteinizing hormone releasing hormone (LH-RH) to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in anoestrous and cyclic ewes were examined, as were their elimination from the plasma in vivo and degradation by extracts of the hypothalamus, anterior pituitary gland, lung, kidney, liver and plasma in vitro. In all cases, comparisons were made with synthetic LH-RH. When injected i.v. into mature ewes as a single dose, the potencies of the analogues were graded and Des Gly-NH2(10) LH-RH ethylamide was found to be the least potent. It was not possible to demonstrate any significant increase in the potency of this analogue over LH-RH, although a trend was apparent with each parameter examined. [D-Ser(But)6] Des Gly-NH2(10) LH-RH ethylamide had the greatest potency. There were no differences between the responses of anoestrous ewes and those of ewes treated on day 10 of the oestrous cycle. None of the analogues had a rate of elimination from the plasma different from that of LH-RH during either the first or the second components of the biphasic disappearance curve. The incubation of LH-RH with tissue extracts showed that extracts of the hypothalamus and anterior pituitary gland degraded LH-RH to a similar extent. Both the hypothalamic and anterior pituitary gland extracts degraded more LH-RH than did lung extract, which in turn destroyed more LH-RH than did extracts of kidney or liver tissue. The degradative abilities of kidney and liver extracts did not differ from each other. Plasma failed to degrade LH-RH or the analogues. Although LH-RH was rapidly destroyed by hypothalamic extract in vitro, of the analogues, only Des Gly-NH2(10) LH-RH ethylamide was degraded. The anterior pituitary gland and kidney extracts failed to degrade [D-Ser6] Des Gly-NH2(10) LH-RH ethylamide and [D-Ser(But)6] Des Gly-NH2(10) LH-RH ethylamide as rapidly as LH-RH. Extracts of liver and lung were incapable of catabolizing any of the analogues. There was an inverse correlation between the LH- and FSH-releasing potency of an analogue and its rate of degradation by anterior pituitary gland extract. The slower rates of catabolism of certain analogues of LH-RH by the anterior pituitary gland may explain their increased LH- and FSH-releasing potency.


Evidence to suggest that rat growth hormone is modified when secreted by the pituitary gland. The relationships were examined between the concentrations of GH determined by bioassay (rat tibia test) and radioimmunoassay in homogenates of rat adenohypophysial tissue and in the incubation medium in which the tissue had been maintained. Adenohypophyses from young male rats were incubated in Medium 199 with or without a putative synthetic GH-releasing factor (GRF) to achieve a dynamic state of GH secretion, but the GRF did not consistently stimulate the release of GH as measured by either bioassay or radioimmunoassay. Both assays gave closely similar values for the concentration of GH in homogenates of the adenohypophyses of undisturbed rats. When the two assays were used to measure the concentrations of GH in incubated pituitary tissue, the values showed no correlation, although the concentrations of GH in the incubation medium were again highly correlated. However, the bioassay : radioimmunoassay ratio for the secreted hormone [2.14 +/- 0.09 (S.E.M.)] was significantly higher than that for the intrapituitary form from the unincubated gland (0.93 +/- 0.06). By radioimmunoassay, secreted rat GH was found to be less stable than purified rat GH when the two forms were incubated in vitro with slices of various rat tissues. Similarly, the rate of clearance of secreted rat GH from the plasma of hypophysectomized rats, as determined by radioimmunoassay, was much faster than that of the purified GH. The biological activity of purified bovine GH was blocked by aprotinin, an inhibitor of proteolysis, but the drug had no inhibitory effect on the bioactivity of rat GH secreted into the incubation medium. Overall, these results indicate that secreted rat GH has properties intermediate between those of the intrapituitary form and the form found in the circulation.


Bioassay of inhibin-like activity using pituitary cells in vitro. The secretion of follicle-stimulating hormone (FSH) by the pituitary gland appears to be partially regulated by a protein hormone, inhibin, which is produced in the Sertoli cells of the testis and is also present in ovarian follicular fluid (FF). The aim of the present study was to develop a sensitive method for the detection and estimation of inhibin-like activity, using dispersed pituitary cells in culture. Pituitary cells from adult male rats were dispersed and precultured for 3 days. After renewal of the medium (2 ml), samples to be tested for inhibin-like activity were added and culture was continued for a further 3 days. A dose-dependent suppression of the concentration of FSH in the medium (lambda = 0.17--0.22) was observed after addition of FF (0.05--1 microliter) or Sertoli cell culture medium (SCCM, 0.05--1 ml). Luteinizing hormone (LH) concentrations were not affected with these doses of FF, but SCCM and higher doses of FF caused a significant increase in the concentration of LH in the medium. During an additional 6 h of culture in the presence of luteinizing hormone releasing hormone (LH-RH), FF and SCCM suppressed the release of both FSH (lambda = 0.07--0.11) and LH in a dose-dependent way. Cellular content of FSH, but not of LH, was decreased after these treatments. These results could not be explained by damage to the pituitary cells, by degradation of FSH or LH-RH, or by effects of steroids. It is concluded that this pituitary cell culture system can be used as a sensitive method for the estimation of inhibin-like activity in FF and SCCM.


Form variation in Escherichia coli K1: determined by O-acetylation of the capsular polysaccharide. The chemical basis for the alternating antigenic change called form variation noted for the Escherichia coli K1-capsular polysaccharide has been shown by 13C nuclear magnetic resonance to be a result of random O-acetylation of C7 and C9 carbons of the alpha-2-8-linked sialic acid homopolymer. A serologic method (antiserum agar) was developed to identify and isolate the form variants. The O-acetyl positive and O-acetyl negative K1 polysaccharides had unique biochemical and immunologic properties. The O-acetyl-positive variants resisted neuraminidase hydrolysis in contrast to the susceptibility of the O-acetyl negative variant to this enzyme. In addition, O-acetylation altered the antigenicity of the O-acetyl polysaccharides. When injected as whole organisms, O-acetyl positive organisms produced anti-K1 -antibodies in rabbits specific for this polysaccharide variant. O-acetyl negative organisms were comparatively less immunogenic; however, antibodies induced by these organisms reacted with both K1 polysaccharide variants. Burros, injected with either variant, produced antibodies reactive with both K1 polysaccharides.


Cellular requirements for lipopolysaccharide adjuvanticity. A role for both T lymphocytes and macrophages for in vitro responses to particulate antigens. By employing primary cultures of purified spleen cells from lipopolysaccharide (LPS) responder (C3H/HeN or C57BL/10Sn) or nonresponder (C3H/HeJ or C57BL/10ScN) mice incubated with particulate antigen and LPS prepared by phenol-water extraction (Ph), we have presented evidence that both T cells and macrophages (MO) are required for LPS-induced adjuvanticity. First, MO derived from C3H/HeN spleen cells, when mixed with responder, C3H/HeN lymphocytes and Ph-LPS, elicited enhanced antibody responses to sheep erythrocytes (SRC) antigen, whereas lymphocytes from the nonresponder, C3H/HeJ mouse strain did not evoke this response. Similarly, purified T cells from C3H/HeN spleens, when cultured with responder, nu/nu spleen cells, and Ph-LPS yielded enhanced anti-TNP PFC responses; whereas, C3H/HeJ T cells did not potentiate immune responses when mixed with optimal concentrations of Ph-LPS. LPS prepared by butanol-water extraction elicited significant adjuvant effects with all cell combinations. Finally, purified responder T cells and MO enabled either responder or nonresponder B cells to elicit LPS potentiation. These data indicate that T cells and MO are controlling LPS-induced augmentation of B-cell responses.


Bactericidal activity of the alternative complement pathway generated from 11 isolated plasma proteins. Exposure of E. coli K12 W1485 to the cytolytic alternative pathway assembled from the 11 isolated pathway proteins resulted in killing of the bacteria, as evidenced by loss of viability. Lysis of the bacteria required introduction of lysozyme into the reaction mixture. The time-course and dose dependency of bacteriolysis in the isolated system were identical to those in C4-depleted serum. The bacteriolytic activity of the pathway was highly dependent on the concentration of the pathway proteins and became insignificant at 1:16 physiological concentration. Electron microscopic visualization of killed and of lysed bacteria revealed numerous complement membrane lesions and partial disintegration of the outer phospholipid membrane. Scanning electron microscopy showed that killed bacteria were enlarged, partially collapsed and exhibited irregular surface protrusions. Lysed bacteria were fragmented and appeared polymorphic. This study demonstrates that the alternative pathway, in absence of immunoglobulins, has the potential or eradicating gram-negative bacteria.


Metabolic similarities between fertilization and phagocytosis. Conservation of a peroxidatic mechanism. At the time of fertilization, sea urchin eggs release a peroxidase which, together with H2O2 generated by a respiratory burst, is responsible for hardening of the fertilization membrane. We demonstrate here that the ovoperoxidase of unfertilized eggs is located in cortical granules and, after fertilization, is concentrated in the fertilization membrane. Fertilization of sea urchin eggs or their parthenogenetic activation with the ionophor A23187 also results in (a) the conversion of iodide to a trichloroacetic acid-precipitable form (iodination), (b) the deiodination of eggs exogenously labeled with myeloperoxidase and H2O2, (c) the degradation of thyroxine as measured by the recovery of the released radioiodine at the origin and in the inorganic iodide spot on paper chromatography, and (d) the conversion of estradiol to an alcohol-precipitable form (estrogen binding). The iodination reaction and the binding of estradio occurs predominantly in the fertilization membrane where the ovoperoxidase is concentrated. From the estimation of the kinetics of incorporation of iodine, we determine that the peroxidative system is active for 30 min after fertilization, long after hardening of the fertilization membrane is complete. Most of the bound iodine is lost during the hatching process. Iodination of albumin is catalyzed by the material released from the egg during fertilization, when combined with H2O2 and iodide. Iodination, thyroxine degradation, and estradiol binding are inhibited by azide, cyanide, aminotriazole, methimazole, ascorbic acid and ergothioneine, all of which can inhibit peroxidase-catalyzed reactions. These responses of the sea urchin egg to fertilization are strikingly similar to the changes induced in polymorphonuclear leukocytes by phagocytosis and, in both instances, a peroxidative mechanism may be involved.


Sexual dysfunction associated with diabetes mellitus. Sexual dysfunction associated with diabetes mellitis has been reviewed. The prevalence of impotence among diabetic males ranges between 50 and 60 percent. Duration of diabetes does not correlate with the increasing incidence of impotence, but increasing age of the male is associated. The etiology of impotence is generally assumed to be autonomic neuropathy; the role of vascular pathology is moot. Retrograde ejaculation is present in one to two percent of the cases. Nocturnal penile tumescence monitoring during periods of rapid eye movement (REM) sleep will aid in the differential diagnosis of organic vs psychogenic etiology. Penile prostheses should be considered in the treatment of organic impotence, while sex counseling is indicated for psychogenic cases. The effect of diabetes on female sexual response is conflicting. Further research in needed.


Induced quantitative variation for penicillin titre in clonal populations of Aspergillus nidulans. The variation in penicillin titre within populations of cultures of Aspergillus nidulans derived from untreated conidia and from conidia treated with ethyl methanesulphonate (EMS), near-ultraviolet light in the presence of 8-methoxypsoralen (8MOP) or N-methyl-N'-nitro-N-nitrosoguanidine (NTG), each at several dose levels, was determined. Both mutagentreated and untreated populations showed a continuous distribution of pencillin titres. The population mean titre of the mutagenized populations was decreased and the range of titres was increased relative to those of the control populations. No differences between sister cultures could be detected in three untreated populations, but nine out of ten populations derived from mutagenized conidia showed significant variation for penicillin titre. In general the magnitude of this induced variation increased with increasing dosage of the mutagen. Comparisons at fixed survival levels indicate that 8MOP mutagenesis is less effective for the induction of variation in penicillin titre than EMS or NTG mutagenesis. A statistical procedure was adopted to classify the survivors as unchanged cultures ('0'), titre-increasing mutants ('+') or titre-decreasing mutants ("-"). The frequency of both '+' and '-' mutants increased following mutagenesis, with NTG being the most active of the three mutagens. Over all treatments, these two mutant classes were recovered with equal frequency. The frequency of "+" mutants was largely independent of mutagen dose, within the ranges used, and moderate treatments (around 10% survival) gave as high or higher frequencies than more extreme doses. All three mutagens, and in particular NTG, produced morphological mutants. These contained an increased frequency of titre-decreasing mutants, but increases in titre appeared to be independent of changes in colony morphology. Estimates based on the observed frequencies of penicillin titre mutants suggest that several hundred genes are potentially capable of affecting this continuous variable.


Genetic circularity of the Proteus mirabilis linkage map. The T incompatibility group plasmid R394 can mobilize the chromosome of Proteus mirabilis strain PM5006. It transferred relatively large segments, corresponding to at least 20 min on the D plasmid chromosomal map of the organism. The frequency of recombination for a large number of selected markers was nearly constant at 5 X 10(-6) per donor cell and it is concluded that mobilization takes place from a number of chromosomal sites. All recombinants were R+ and displayed all properties of the plasmid. By analysing crosses for co-inheritance frequencies of unselected markers, a number of chromosomal loci were assembled in linear array. Linkage between markers at the ends of this linkage group was established to markers at the respective termini of the existing D plasmid linkage group. This established a composite circular linkage map of genes of the P. mirabilis strain PM5006 chromosome.


Effects of phosphate limitation of growth on the cell-wall and lipid composition of Saccharomyces cerevisiae. The phosphorus content of phosphate-limited Saccharomyces cerevisiae was only 71% of that of non-limited yeast. Walls prepared from phosphate-limited cells contained slightly less phosphorus than control walls. No evidence was obtained for the presence in these walls of uronic acid or succinyl residues. The carbohydrate content of walls of phosphate-limited yeast was less than that of non-limited walls, and this was reflected in a decreased glucan content. There was only a slight decrease in glucosamine content while the protein content increased. The major change in the lipid composition of phosphate-limited yeast was a decrease in both sterol esters and triacylglycerols. There was a decrease in total lipid content, but increased production of phosphatidylethanolamine and phosphatidylcholine. The phosphatidylserine content was decreased. These results suggest that there are fewer intracellular low-density vesicles in phosphate-limited yeast.


Protein II influences ferrichrome-iron transport in Escherichia coli K12. Ferrichrome-promoted iron uptake in Escherichia coli K12 is strictly dependent upon the tonA gene product, a 'minor' outer membrane protein. By selection for mutants of E. coli resistant to phages which require 'major' outer membrane proteins as receptors, strains with pronounced protein deficiencies were constructed. Such strains were tested for anomalous behaviour of ferrichrome transport. No significant differences in iron uptake were detected in E. coli K12 strains with markedly reduced amounts of protein I. However, a reduction in the initial velocity (up to 40%) was observed in E. coli deficient in outer membrane protein II. This difference was only evident when cells were grown under iron-starvation conditions; it was abolished when cells were grown in rich medium. Kinetic parameters for ferrichrome transport were determined for maximum velocity but for Km; double reciprocal plots showed a biphasic nature, probably attributable to a limited number of outer membrane binding sites and to the multi-component nature of the ferrichrome-iron transport system.


Transfer of a gene for sucrose utilization into Escherichia coli K12, and consequent failure of expression of genes for D-serine utilization. As the first stage in investigating the genetic basis of natural variation in Escherichia coli, the gene(s) conferring the ability to use sucrose as a carbon and energy source (given the symbol sac+) was transferred from a wild strain to K12, which does not use sucrose. The sac+ region was transferred by two different methods. On both occasions it took a chromosomal location at minute 50.5 on the linkage map, between aroC and supN, in the region of the dsd genes, which confer the ability to use D-serine as a carbon  and energy source. When the sac+ region was present in the K12 chromosome the bacteria were unable to use D-serine as a carbon and energy source. In F' sac+/dsd+ diploids, the dsd+ genes were similarly not expressed. Strain K12(sac+) bacteria were sensitive to inhibition by D-serine; they mutated to D-serine resistance with much greater frequency than did a dsd mutant of K12. Such bacteria also mutated frequently to use raffinose. Strain K12(sac+) bacteria did not utilize sucrose when they carried a mutation affecting the phosphotransferase system.


Uroporphyrin- and coproporphyrin I-accumulating mutant of Escherichia coli K12. A new type of haem-deficient mutant was isolated in Escherichia coli K12 by neomycin selection. The mutant was deficient in uroporphyrinogen III cosynthase activity as indicated by the accumulation of uroporphyrin I and coproporphyrin. The mapping of the corresponding hemD gene by P1-mediated transduction showed that the new gene was located between ilv and cya, at min 83 on the chromosomal map of Escherichia coli K12.


Rapid diagnosis of tick-borne encephalitis by means of enzyme linked immunosorbent assay. An enzyme-linked immunosorbent assay was applied for determining separately IgM and IgG antibodies against tick-borne encephalitis virus. A micro-modification in microtitre plates proved to be at least as sensitive as the HI test. However, more precise information could be achieved by a macrotest using antigen coated polystyrene balls. False positive results in IgM antibody determinations could be caused by a rheumatoid factor. A high content of IgM antibodies in a serum could impair the determination of its IgG antibodies but not vice versa. Titres were expressed in comparison to a positive control serum.


Demonstration of hepatitis B e antigen in hepatitis B core particles obtained from the nucleus of hepatocytes infected with hepatitis B virus. Liver tissue infected with hepatitis B virus was homogenized and nuclei were separated by centrifugation. Hepatitis B core particles were obtained from the nucleus by the digestion with pronase followed by ultracentrifugation in a sucrose density gradient. Hepatitis B core particles were then treated with sodium dodecyl sulphate and 2 mercaptoethanol and tested for hepatitis B e antigen (HBeAg) by the haemagglutination method. The antigenicity of HBeAg was clearly demonstrated in hepatitis B core particles so treated, although untreated core particles did not reveal any detectable HBeAg activity. The localization of HBeAg in hepatitis B core particles was further supported by the results of a fluorescent antibody technique. When a frozen section of the liver infected with hepatitis B virus was stained with the specific rabbit antibody against HBeAg labelled with fluorescent isothiocyanate, only nuclei of hepatocytes were stained, in a similar distribution to hepatitis B core antigen visualized by fluorescent antibody against hepatitis B core antigen in a nearby section.


Cyclic expression of antigen and infectious virus in a BHK cell line (0-853) persistently infected with an SSPE strain of measles virus. Establishment and characteristics of a baby hamster kidney cell line (BHK 0-853) persistently infected with a subacute sclerosing panencephalitis (SSPE) strain of measles virus (Lec strain) is described. The persistent infection was easily and repeatedly established and no special conditions were required. There was a predictable fluctuation in expression of virus intracellular and membrane antigens which varied from greater than 90% to less than 1% of the cells demonstrating these antigens during the first 6 or 7 passages. Thereafter, fluctuation of antigen and infectious virus expression continued in an unpredictable fashion.


Glial fibrillary acidic protein in ependymomas and other brain tumors. Distribution, diagnostic criteria, and relation to formation of processes. Glial fibrillary acidic protein (GFAP) was studied in ependymomas by the three-step immunoperoxidase method and compared to results in astrocytomas and normal tissues. An order of reactivity for GFAP is presented. Diagnostic criteria, based on GFAP content, are proposed. In ependymomas GFAP-positive cells give rise to only some of the tumor cells, usually those forming tubules and perivascular arrangements. It is hypothesized that the same GFAP-positive cells may form tubules at their luminal poles and may produce perivascular arrangements at their other poles. The aberrant regulation associated with neoplastic transformation in glia is often, but not always, reflected in increased GFAP content. In both astrocytes and ependymal cells GFAP may have a similar function since in both cells the increase in GFAP appears to be related to the development of fibrillary processes.


Human brain growth in the 19th and 20th century. Data of 2399 brain weights and ages from populations before 1880, 1885 to 1900 and 1966 to 1976 were obtained from German anatomical and pathological institutes, analyzed with non-linear and multiple linear regression analyses and the results compared. The influence of the absolute age (sample period) on brain weights of adults (age of at least 10 years of ontogenesis) could not be verified. Different averages in the different samples seem to be stipulated by inhomogeneities of the age distributions. Sex differences were confirmed for the different periods. There is an accelerated degree of maturity of brain weights between the population sampled from 1966 to 1976 and the two older populations. The growth rate of the degree of maturity reveals the same fact, i.e., the growth rate is more rapid than 100 years ago. These differences may be explained by changed causes of death in the autopsy samples, but it is possible that they are at least partly caused by an acceleration of brain development in the early postnatal period. In all populations analyzed brain weights in females develop faster than in males. The development of the brain weight in 6 more samples is compared with the results for the Medical School Hannover sample.


Uveitis and cerebral reticulum-cell sarcoma (large-cell lymphoma). Case report. A patient with a peculiarly refractoy uveitis and vitritis was later found to have an infiltrative mass lesion of the posterior portion of the corpus callosum. The histopathological diagnosis of reticulum-cell sarcoma (large-cell lymphoma) was made after study of vitreous tissue obtained by pars plana vitrectomy of the right eye. Intraocular involvement with cerebral reticulum-cell sarcoma has been reported previously.


Computer-assisted liver-mass estimation from gamma-camera images. We have devised a computer-assisted method for objective estimation of liver mass from the right lateral projection of radiocolloid images of the liver. Gamma-camera images were digitized, preprocessed, and stored in computer memory. The definition of liver for area measurement was adaptively determined by means of a Laplacian operator that measures change in radioactivity slope associated with the liver margin. Individual thresholds were calculated for each of 16 subregions. A liver-mass index was derived from a linear regression model correlating the area of the right lateral projection with liver weight at autopsy in 50 patients whose livers weighed between 0.8 to 3.0 Kg. The correlation coefficient found for this method was 0.83 using the equation: Liver Mass [kg] = Area [cm2]/275 [kg/cm2]--0.215 [kg]. Liver-mass estimates using an alternative computer-assisted method or representative manual methods adapted for gamma-camera images showed lower correlation with liver weight at autopsy.


Simple computer quantitation of spleen-to-liver ratios in the diagnosis of hepatocellular disease. Increased splenic uptake of radiocolloids is a helpful sign in the scintigraphic diagnosis of various hepatocellular diseases, but little attempt has been made to quantify this physiologic phenomenon. We have devised a simple computer method that compares average splenic activity to average right-lobe liver activity. The method is reproducible (r = 0.97) and exhibits little interobserver variation (r = 0.99). One hundred clinically normal subjects were found to have a nearly symmetrical distribution of S/L ratios around a mean of 0.77, with a s.d. of 0.20. Fifteen subjects normal by biopsy were found to have a similar mean spleen-to-liver (S/L) ratio of 0.74. Based upon a normal range of 0.37 to 1.17 (0.77 +/- 2 s.d.), elevated S/L ratios were found in fatty metamorphosis (85%), cirrhosis (67%), and chronic hepatitis (43%). Abnormal S/L ratios in the range from 1.17 to approximately 1.4 were not visually obvious. Overall sensitivity of the S/L ratio in these three diseases is 69%. When combined with the other scintigraphic indications of hepatocellular disease (nonhomogenous colloid uptake, hepatomegaly, splenomegaly, and bone-marrow colloidal uptake), the liver scan was found to have a sensitivity of 93%.


Retrospective evaluation of reproductive performance of workers exposed to ethylene dibromide (EDB). An attempt has been made to examine retrospectively any antifertility influence of ethylene dibromide (EDB) by studying the reproductive performance of men exposed to EDB, exclusively on the basis of their reproductive histories in terms of live births to their wives, subsequent to their occupational exposure to EDB. The number of live, putatively legitimate, natural children born to the wives was compared to the expected number derived from national fertility tables published for successive birth cohorts of U.S. women by the National Center for Health Statistics. The indirect standardization method was used to adjust for the confounding effects of maternal age, parity, race and calendar year in deriving the expected births. The number of observed births was expressed as a percentage of the expected in assessing the workers' reproductive performance. One of the four plants studied showed a significant decrease in fertility.


Short-range shotgun wounds to the face.

Short-range shotgun wounds to the face. To efficiently treat short-range shotgun wounds to the face, it is imperative to have a basic understanding of the causes, pathogenesis, probable extent of initial injury, primary treatment principles, and secondary reconstruction problems associated with these injuries. This paper deals with these basic principles in an attempt to provide a guide to the treatment of these devastating injuries.


Normal human glomerular cells in culture. Reproducible patterns of cell outgrowth have been observed from isolated normal adult, human glomeruli grown in tissue culture. Three morphologically distinct cell populations designated Types I, II, and III have been observed in culture from 15 normal human kidneys. Assessment of the morphology and behaviour of these cells has been made by phase contrast, time-lapse cinemicroscopic, transmission and scanning electron microscopic examination. The phagocytic capacity of these cells has been determined. The Type I cell appears in culture by migration from the capillary loops, its branched cytoplasm and ultrastructural features confirming its origin as a visceral epithelial cell. In keeping with the highly specialised nature of this cell, division was rare, movement was not observed, and differentiation was progressively lost in culture. The Type II cell was mobile and capable of active division. Ultrastructural features were those of mesangial cells. The Type III cell which was seen only rarely, had the features of a macrophage. Endothelial outgrowth was not observed.


Idiopathic rapidly progressive glomerulonephritis with C3 nephritic factor and hypocomplementemia. A 7-year-old boy with mild renal failure and signs and symptoms of acute poststreptococcal glomerulonephritis including severe hypocomplementemia had, by renal biopsy, numerous crescents but no deposits in the glomerular capillary loops. Instead, deposits identical in location and composition to those described for children with idiopathic rapidly progressive glomerulonephritis were present. The severe hypocomplementemia was found to be due to high levels of C3 nephritic factor; niether nephritic factor nor hypocomplementemia has been reported in rapidly progressive glomerulonephritis of the idiopathic type. Following prompt therapy with methylprednisolone intravenously, serologic abnormalities disappeared and renal function greatly improved, but a later biopsy showed 50% of the glomeruli obliterated by scarring. The case is of importance not only in indicating that severe hypocomplementemia does not rule out idiopathic rapidly progressive glomerulonephritis but also in adding to the list of diseases in which nephritic factor can be found.


The effect of synthetic androgens on the hypothalamic-pituitary-gonadal axis in boys with constitutionally delayed growth. Serial concentrations of basal serum LH, FSH, testosterone, and LH and FSH responses to intravenous gonadotropin-releasing hormone were measured before and during six months of administration of fluoxymesterone or oxandrolone in 14 boys with constitutionally delayed growth and adolescence, in order to assess the effects of these androgens on maturation of the hypothalamic-pituitary-gonadal axis. Before therapy all boys had normal hormonal responses based on bone age. At the end of six months therapy 10 of the 14 boys had lower LH responses (34 to 89% reduction) to GnRH without consistent changes in FSH responses. With both androgens, there there was significant suppression of both basal serum FSH and testosterone. Eleven boys were restudied six months after completion of therapy; basal serum LH, FSH, and testosterone and responses to GnRH were equal to or greater than pretreatment levels, indicating recovery or progressive maturation of the HPGA. All boys had increased growth velocity and imporved weight gain without excessive bone age advancement; all had improved psychosocial adjustment.


Factor and cluster analyses with the Rosenzweig Picture Frustration Study. The Rosenzweig Picture Frustration (P-F) Study data of 104 psychiatric hospital patients, 56 males and 48 females, were subjected first to a Factor Analysis and then to a Cluster Analysis. In the former, five factors were extracted which showed some similarity to other Factor Analyses reported in the literature. The Cluster Analysis turned up one very large group (42% of the sample) characterized by depression and P-F profiles with elevated i and very low E scores. Seven other clusters are described in the article. The factors and clusters found are clinically meaningful and can provide assistance in interpreting P-F profiles. Recommendations for a revised P-F manual to enhance the usefulness of the test are made.


The current state of process-reactive schizophrenia. Current developments in the process-reactive classification of schizophrenia are examined in the light of diagnosis, paranoid-nonparanoid status, premorbid adjustment, demographic factors, and outcome. Recent studies are reviewed as suggestive of a present focus, and theoretical possibilities are explored. Recommendations are made to include a broader, more complex view of the process-reactive conception,  methodological improvements, further theoretical development, and increased research into a variety of promising areas utilizing this framework and facilitating its useful growth as an approach to understanding the totality of schizophrenia.


[Hyperfractionated radiotherapy in 56 patients with tumors of the head and neck (author's transl)]. A new method of irradiation known as hyperfractionated radiotherapy was studied in 56 patients with cancers in the region of the ear, nose, and throat. The dose was 72 grays given during 80 sessions over a period of 28 days, with a rest period of two weeks at the half-way point. Each session lasted 2 hours. The results (complications and survival rate) were compared with those obtained in a control group treated with 70 grays in 35 sessions over a period of 7 weeks. The complication rate was 21% in the series treated with hyperfractionated radiotherapy, against 19% in those given classical treatment (results not significant). The survival rate was better, however, (63% against 33% after 18 months), for the patients treated with this new method of irradiation.


Longterm survival of lupus nephritis patients treated with azathioprine and prednisone. Forty-seven SLE patients with severe renal disease characterized by renal biopsy documentation of diffuse proliferative or membranous glomerulonephritis or the nephrotic syndrome have been treated with azathioprine and prednisone in combination and followed for up to 12 years. Survivorship was 82% +/- 6% for five years and 74% +/- 8% for 10 years. There have been eight deaths and two patients have gone on hemodialysis. Five of the eight deaths are attributable to superinfection. Improvement in creatinine clearance was documented in 21 and decreased proteinuria in 35 of the patients. A therapeutic program, which included high dose corticosteroids initially, the combinations of azathioprine with corticosteroids chronically, and the rapid reduction in corticosteroid dosage to an alternate day schedule, appears to contribute to improved survivorship.


Immune complexes in psoriasis with and without arthritis. Two different assays were employed to detect soluble immune complexes in the serum of a large group of patients with psoriasis and psoriatic arthritis. Using a Raji cell assay no evidence of complexes was found. However, with the Clq deviation method, sera from 29% of the patients with psoriasis alone and 35% of those with associated arthritis, exhibited Clq reacting material.


Naproxen vs. aspirin in osteoarthritis of the hip and knee. This 12-week double-blind trial compared the efficacy and tolerance of naproxen (750 mg/day) with that of aspirin (3.6 gm/day). There was no statistical difference in efficacy between the two trial drugs for any of the objective (e.g., 25-foot walking time) or subjective (e.g., overall severity of symptoms) variables measured. No side effects were experienced by 69% of the naproxen patients and 37.5% of the aspirin patients. There were a statistically greater number and more severe side effects during aspirin therapy than during naproxen therapy (p = 0.002). The results show naproxen to be a potentially useful drug for the treatment of osteoarthritis.


Chernogubov's syndrome: a translation of the first modern case report of the Ehlers-Danlos syndrome. The heritable disorder of connective tissue, now termed Ehlers--Danlos syndrome, was described by Chernogubov, a Russian dermatologist, in 1892. His graphic description of the first modern case with multisystemic features is presented in English translation. Chernogubov attributed the development of this disorder to a generalized defect in the embryological formation of connective tissue fibers. Chernogubov's observations were recognized by his colleagues as providing new insights in explaining an interesting and puzzling case. In the literature of the Soviet Union this syndrome is known as Chernogubov's syndrome. This work is justifiably recognized as a seminal publication in rheumatology.


Quantitative structure-activity relationships in 1-aryl-2-(alkylamino)ethanol antimalarials. A quantitative structure-activity relationship has been formulated for 646 antimalarials acting against P. berghei in mice. The equation developed has 14 terms, 9 of which are indicator variables. The correlation coefficient for the QSAR is 0.898 and the standard deviation is 0.309. The antimalarials are all arylcarbinols of the type X-ArCHOHCH2NR1R2. Sixty different aryl structures, including a variety of heterocyles, are contained in the study. The most important determinate of activity is found to be the electron-withdrawing ability of the substituents X; the hydrophobic character of X and R plays less important roles. Suggestions for more potent analogues are made and the lack of activity of about 100 additional analogues is also considered.


The donation and transplantation of kidneys: should the law be changed? It is now eighteen years on since the Human Tissue Act 1961, but this legislation is still unchanged in England, Scotland and Wales. Ian Kennedy, in this paper, lays before us the law as it is, the problems of its interpretation and his opinion of what government should be doing to help clarify the situation and remove some of the problems which exist daily for the doctors who face the dilemma of seeking consent for transplants at the moment of extreme grief for the surviving spouses or relatives of the patient who has been in his care only moments before. Ian Kennedy suggests that by doing nothing the Department of Health and the government are being both callous and less than honest.


What is medicine?: towards a philosophical approach. The failure of Western medicine to deal with many of the problems it is currently facing has led to an awareness of the need for a fundamental reappraisal. The way in which medical concepts derived from the nineteenth century have brought technical medical advances in this century and the alliances that medicine has made with statistics and more recently the social sciences, have prevented a questioning of medicine's underlying assumptions. Thus, despite a number of critical initiatives from both within and outside medicine, there has been no coherent development to seriously confront the question 'what is medicine?'. It is suggested that the basis for such a development depends on the return to a philosophical questioning of our conceptual understanding of disease, a subject which has largely been ignored during the past hundred years.


The special affinity of particular types of Proteus mirabilis for the urinary tract. The strains of Proteus species found in significant numbers and as pure cultures in urine from 217 individuals were isolated, identified to species level and typed for proticine production (P type) and proticine sensitivity (S type) to give their P/S type. Urinary-tract infections with Proteus, principally P. mirabilis, were associated with the elderly. Ninety seven distinct P/S types were found but three P/S types P3/S1,8, P3/S1,8,13 and P3/S1,13 were isolated at a much higher frequency (14%) then could be explained from their faecal carriage rate. These types were almost without exception restricted to patients with clinical symptoms of urinary-tract infection and it is suggested therefore that they have some special affinity for the urinary tract.


Escherichia coli K antigen in relation to serum-induced lysis and phagocytosis. The presence of capsular polysaccharides (K antigens) and their relation to phagocytosis and sensitivity to the lytic action of serum of 26 strains of E. coli isolated from stools of healthy volunteers and from blood cultures were studied. Four of 12 strains isolated from stool cultures and 12 (86%) of the 14 strains isolated from blood cultures possessed K antigen. Three of the 12 strains isolated from stool cultures and seven of the 14 isolated from blood cultures were resistant to uptake by polymorphonuclear leucocytes; these resistant strains contained large amounts of K antigen. By contrast 10 strains, three with low amounts of K antigen and seven without detectable amounts of K antigen, were readily phagocytosed. Thus it appears that K antigen renders E. coli resistant to phagocytosis. Only four (15%) of the 26 strains were sensitive to serum lysis and there was no correlation between the presence of K antigen and the resistance to serum lysis.


Experience with radial haemolysis for rubella antibody screening. Twelve hundred and thirty three sera were tested in parallel by the single radial haemolysis (SRH) and by the simplified haemagglutination inhibition (HAI) technique in routine use in this laboratory. In 1203 (97.6%) of these sera the results were in agreement. The remaining 30 (2.4%) sera were re-tested by both methods because on initial testing the results obtained by the two methods did not agree; only three specimens remained discrepant. The SRH is a simple test to perform and discriminates clearly between positive and negative sera. It is particularly suitable for screening large batches of sera.


The effect of freezing and storage in liquid nitrogen on the viability and growth of Mycobacterium leprae. The effects of rapid and slow rates of freezing in liquid nitrogen, storage in liquid nitrogen for 12 months, and the rate of subsequent thawing on the viability and growth of M. leprae in the mouse footpad were studied. Some loss of viability of M. leprae was detected, and this was found to be associated with the freezing process, rather than with storage or thawing. Slow freezing was less deleterious than quick freezing, with a loss of viability of 90% compared with 98%. The growth pattern of M. leprae was unaffected except for a delay in the appearance of growth caused by the loss of viability, though there was some evidence of an increased lag phase of one strain, possibly due to the repair of sub-lethally damaged organisms.


The variable response of bacteria to excess ferric iron in host tissues. The enhancement by exogenous ferric iron, both systemic and local, of the infectivity of 120 strains of bacteria, representing 17 genera, was measured in the skin of guinea-pigs. Systemic iron enhanced only 23% of 115 strains, and local iron 49% of 71 strains. Systemic iron, by an apparently anti-inflammatory action, depressed the size of lesions produced by 27 of the non-enhanced strains from nine of the genera tested. For most strains, the degree of enhancement was small, ranging from 2- to 8-fold, and often evident only with the more effective local iron; among these were some near-saprophytes like Mycobacterium phlei, M. smegmatis, Bacillus cereus and Clostridium bifermentans. Substantial enhancement, from 14- to 50-fold, was observed with the more pathogenic among the strains tested: namely BCG, Corynebacterium ovis, C. murium, Listeria monocytogenes, Erysipelothrix rhusiopathiae, Cl. perfringens, Cl. septicum, Cl. oedematiens, and some strains of Klebsiella spp., Proteus spp. and Aeromonas hydrophila. The enhancement of BCG by a single dose of iron given locally with the inoculum was only feebly manifest after 7 days, but substantial after 14--19 days, indicating the decisive effect of interference with an early humoral defence on the establishment of chronic infection some time later. Insofar as guinea-pigs whose antibacterial defences are lowered by substantial amounts of exogenous iron in the circulation represent human subjects at risk of infection because of clinical states characterised by excess of available iron, the results of the survey suggest that only a minority among the environmental bacteria can take advantage of the decreased resistance associated with such states; but that this minority is likely to include the more virulent strains in the environment.


The effect of 5-fluorocytosine on the blastospores and hyphae of Candida albicans. In Candida albicans the continued increase in dry weight, in cell volume and in hyphal length during 5FC treatment is mainly due to increased amount of carbohydrate despite the decreased amounts of nucleic acids. Incorporation studies with 32PO4 (for RNA) in C. albicans and with 3H-thymidine-monophosphate (for DNA) in a thymidine-utilising strain of Saccharomyces cerevisiae have shown that the decreased amounts of nucleic acids were due to an inhibition of synthesis of RNA and DNA by 5FC. Nuclear-staining techniques on the hyphal phase of C. albicans showed that 5FC inhibits nuclear division. The changes in amounts of protein during 5FC treatment do not wholly explain the changes in cell size although 14C-histidine incorporation experiments showed that protein synthesis continued in the presence of 5FC. 14C-glucose incorporation in the presence of 5FC showed an initial accelerated synthesis of carbohydrate with a maintained level of synthesis after 16 h. This abnormal pattern of synthesis correlates with the increase in amount of carbohydrate and in cell size and hyphal elongation. 5FC inhibits DNA synthesis, and all manifestations of unbalanced growth that culminate in the cell volume changes appear to be a consequence of that inhibition.


Histologic investigation of glycol methacrylate embedded chick embryonic tissue. Specific light microscopic investigations (i.e. histochemical) of early embryonic material have always been beset by difficulties in processing and obtaining tissue sections of good quality. The advent of glycol methacrylate (GMA) as an embedding medium now provides a means to overcome these inherent problems with this tissue. Investigations were carried out to assess the histological results produced by different fixatives and times of fixation of GMA embedded 5-day chick embryonic tissue. Optimum cellular preservation of all tissues occurred following fixation in a mixture of acetic acid, 95% ethanol and neutral buffered formalin (AAF). With the procedures described in this study, a new method is available for more comprehensive examination of all types of early embryonic material.


A technique for illuminating early chick embryos in ovo with a glass rod as a light guide. A glass rod mounted on a microscope condenser acts as a light guide through the yolk of a fertile hen's egg. Two apertures must first be made in the shell: the one below covered with plastic film which seals around the rod; the one above covered with a glass coverslip to allow microscopic observation of the embryo.


Serum immunoglobulin levels in Indonesians with bancroftian filariasis. Serum immunoglobulin (Ig) levels (IgA, IgM, IgG, IgE) were determined on 185 Indonesians mostly males with and without microfilaremia and with and without clinical disease (hydrocele and elphantiasis). No significant differences were found in IgA and IgE levels in any of the groups but significantly higher IgG levels were found in microfilariae positive persons than those without microfilaremia. Persons with microfilariae alone and symptoms alone, but not both, had higher levels of IgM. There were no correlations between disease category and Ig levels.


Muscle flaps in the head and neck.

Muscle flaps in the head and neck. Muscle flaps about the head and neck have signficant application in reconstruction and rehabilitation following radical ablative surgery. Nine such flaps are reviewed and the uses, advantages, and disadvantages in three major muscle falps cited. Their main applications include: 1) augmentation of a regional deficiency and preparation of a bed for skin grafting; 2) rehabilitation of the paralyzed face and so improved appearance in repose and animation; 3) protection for vital vascular structures such as the carotid or innominate artery; and 4) assistance in mastication and deglutition when transposed to a paralytic or deficient area.


Localization of Escherichia coli RNA polymerase binding sites on bacteriophage S13 and 0X174 DNAs by electron microscopy. Complexes between Escherichia coli RNA polymerase and bacteriophage S13 and phage phiX174 replicative form III DNAs have been shown to form at specific locations on the phage genomes. The major locations on S13 have been mapped at 8 to 10 and 92 to 96% of the genome length, starting from the unique Pst I cleavage site. The locations correspond to the beginnings of genes D and B, respectively. Four minor locations map at 18 to 22, 28 to 32, 50 to 56, and 70 to 74% of the genome. The 70 to 74% site corresponds to the beginning of the A gene. The major locations on phiX174 are at 8 to 10, 50 to 54, and 92 to 94% of the genome. The 50 to 54% site is at the start of the H gene and has an equivalent minor site on S13, but it is not a promoter site. Three minor sites on phiX174, at 20 to 24, 26 to 32, and 68 to 74% of the genome, correspond to sites on S13. The data confirm the locations of sites identified by restriction fragment binding experiments (E. Rassart and J. H. Spencer, J. Virol. 27:677--687, 1978) and the assignment of putative promoters at the start of genes A, B and D.


Involvement of DNA gyrase in replication and transcription of bacteriophage T7 DNA. Growth of bacteriophage T7 is inhibited by the antibiotic coumermycin A1, an inhibitor of the Escherichia coli DNA gyrase. Since growth of the phage is insensitive to the antibiotic in strains containing a coumermycin-resistant DNA gyrase, this enzyme appears to be required for phage growth. We have investigated the effect of coumermycin on the kinetics of DNA, RNA, and protein synthesis during T7 infection. DNA synthesis is completely inhibited by the antibiotic. In addition, coumermycin significantly inhibits transcription of late but not early genes. Thus, E. coli DNA gyrase may play an important role in transcription as well as in replication of T7 DNA.


Chromosomal location of the attachment site for the PA-2 prophage in Escherichia coli K-12. The chromosomal attachment site for the PA-2 prophage is located between dsd and aroC at the approximately 50 min on the Escherichia coli K-12 genetic map. The attachment site is designated attPA-2.


Construction and characterization of the hybrid bacteriophage lambda Charon vectors for DNA cloning. Twenty hybrid lambda phages especially designed for molecular cloning have been constructed and named Charon phages. These phages differ in the ranges of sizes of DNA fragments that may be inserted, by the selections and screens which may be used to isolate and detect the incorporation of cloned fragments, by the way transcription of the cloned fragment may be controlled, by the different restriction enzymes that can be used for cloning, by the phage immunities that may be employed for controlling replication and transcription, and by the biological safety features that they contain. The crosses used to produce the vectors are described, and their genealogy is discussed. The structure of each vector has been verified by genetic tests, by DNA length determinations, by electron micrographic analysis of DNA heteroduplexes, and by gel electrophoresis of restriction enzyme digests. In the course of these constructions, a new EcoRI site was found in a derivative of lambda Aam32Bam1 which maps very near the left cohesive end of lambda.


In situ flushing of donor kidneys: its technique and rationale. In situ flushing of kidneys through an isolated segment of aorta was done on mongrel dogs. The 500 cc cold perfusate at 3 to 4C (delivered in 6 minutes) effectively cooled the kidneys to about 15C. This simplified technique of in situ flushing, its usefulness and rationale are discussed.


Free full thickness skin graft urethroplasty: current technique. We present details of our current techniques for skin graft urethroplasty. We believe that careful attention to the details of these operative techniques is important to their success. The changes from our previous reports include: 1) preparation of patch grafts with rounded ends, 2) preparation of tube grafts with fishmouth spatulation, 3) fixation of the stent catheter to the anterior abdominal wall, 4) leaving a stent catheter inlying for 2 weeks and replacing with a smaller catheter if a voiding cystourethrogram shows extravasation, 5) fixation of the graft during preparation by dermatome adhesive, 6) irrigation of the wound with irrigant before closure and 7) urodynamic flow study for non-invasive postoperative followup.


Intercostal nerve block with thoracoabdominal incision. A double-blind study was done on 30 patients undergoing thoracoabdominal incisions for retroperitoneal lymphadenectomy in testicular carcinoma to determine the effect of intraoperative intercostal nerve block with bupivacaine. The postoperative pain, day of ambulation and day of oral fluid intake were analyzed. In this homogeneous group we found a significant reduction in the amount of postoperative analgesia required but no difference in the day of ambulation or fluid intake.


Massive renal angiomyolipoma: preoperative infarction by balloon catheter. A case of a renal angiomyolipoma supplied by 2 renal arteries is reported. Preoperative, percutaneous transluminal infarction by a balloon catheter facilitated surgical removal of this massive neoplasm.


Analysis of costs and outcomes of renal transplantation at one center. Its implications. A cost increase of more than 900% for medical services to dialysis patients and transplant recipients has been projected during the decade 1974 to 1984. To evaluate the role of renal transplantation in the End-Stage Renal Disease Program, we analyzed direct costs and patient outcomes in 466 consecutive transplants at our center. A successful transplant from either a living related or cadaver donor cost less than +7,000 per year for two years of graft function. The cost of transplants rejected during the second year also proved cost-effective when compared with the yearly costs of maintenance-facility hemodialysis. Patient survival was 100% at two years for recipients of a transplant from a living related donor and 84% at two years for recipients of a transplant from a cadaver. Renal transplantation can reduce the rising costs for end-stage renal disease patient care, without reducing life expectancy.


Invasive pulmonary aspergillosis associated with influenza. Fatal invasive pulmonary aspergillosis may follow viral influenza infections. Two cases with verified influenza A infection were followed by fatal necrotizing pneumonia due to Aspergillus fumigatus. Both patients demonstrated cutaneous anergy and lymphocytopenia. Influenza and perhaps other viruses that depress T-cell function may result in increased susceptibility to infections in which T cells are important in host defenses.


Prophylaxis of streptococcal infections and rheumatic fever: a comparison of orally administered clindamycin and penicillin. Orally administered clindamycin and penicillin were compared for effectiveness in preventing streptococcal infections in 202 randomly assigned patients with previous rheumatic fever (RF). Among 143 patients aged 21 years or younger observed for 537 patient-years, the number of streptococcal infections (and number per patient-year) was 23 (0.084) in the penicillin group and 12 (0.045) in the clindamycin group. Excluding uncooperative patients, the rate of streptococcal infection remained less, though not statistically significant, in the clindamycin group than in the penicillin group. Two RF recurrences occurred in the penicillin group, and no recurrence occurred in the clindamycin group. Clindamycin was well tolerated except for possible mild gastrointestinal symptoms in six patients. Clindamycin can be substituted for penicillin for RF prophylaxis when there is allergy to penicillin or concern about the development of penicillin-resistant mouth organisms.


Respiratory failure in cancer patients.

Respiratory failure in cancer patients. A review of 180 cancer patients requiring mechanical ventilation disclosed that 26% survived to extubation, and 13% and 7% were alive at two and six months, respectively. Mortality was related to several factors individually and the cumulative number of organ systems dysfunctioning in a given patient. Compared with general intensive care patients, those with respiratory failure and neoplastic disease demonstrated a high incidence of drug-induced pulmonary disease, hematologic abnormalities, pneumothorax, and infections with multiple and unusual organisms--all of which alter the approach to management. Although the long-term survival was poor, immediate survival was comparable with that of many groups of patients with respiratory failure.


Ticrynafen and hydrochlorothiazide. A double-blind study of antihypertensive properties with an open crossover. Twenty-eight patients completed a double-blind study of the antihypertensive effects of ticrynafen compared with those of hydrochlorothiazide. The results of blood pressure reduction were comparable in the two groups. After six months, 12 patients were crossed over to ticrynafen therapy from hydrochlorothiazide. They maintained their blood pressure reduction. The most striking difference between the two groups was in the uric acid response. The uric acid level in the patients receiving hydrochlorothiazide therapy rose from a baseline of 5.9 to 7.5 mg/dL (normal range, 3.0 to 8.0 mg/dL). The uric acid level of those patients receiving ticrynafen therapy decreased from a baseline of 6.4 mg/dL to a low of 3.3 mg/dL. In view of ticrynafen's appreciable antihypertensive and uric-acid-lowering effects, it appears to be a useful new antihypertensive drug.


Kupffer cell sarcoma in rats after exposure to small doses of dimethylnitrosamine and N-2-acetylaminofluorene during hepatic regeneration. During experiments to study the evolution of hepatocellular carcinoma in adult male Wistar rats by exposing regenerating livers to the action of small doses of dimethylnitrosamine (DMN) or N-2-acetylaminofluorene (AAF), several primary sarcomas of the liver were incidentally observed. The morphology and behavior of the tumors suggest their origin from Kupffer's cells. Kupffer cell sarcomas occurred more frequently when 70% hepatectomy was used as the regenerative stimulus. None of the 36 animals treated with AAF alone and 2 of the 38 rats given DMN only had this tumor.


Reaction of immune complexes with Hodgkin's disease tissue cultures: radioimmune assay and immunoferritin electron microscopy. We examined the binding of soluble immune complexes in sera from patients with Hodgkin's disease to established tissue cultures derived from the tumor. Circulating immune complex levels were determined by the Raji cell assay, and the reaction of serum with cultured cells was examined with a radioimmune assay and by immunoferritin electron microscopy. Serum with elevated immune complexes was found to react with cells of Hodgkin's disease monolayers when tested with radioiodine-labeled antisera against human IgG heavy and light chains and the complement 3 (C3) component. When examined with the electron microscope, monolayers incubated with Hodgkin's disease serum containing immune complex and labeled with ferritin-conjugated antiserum to C3 contained surface-bound ferritin particles with a uniform but discontinuous pattern. Absorption of Hodgkin's disease serum with monolayer cells reduced immune complexes and decreased reactivity of the sample with cultured cells by radioimmune assay. Sera of patients with other disorders and aggregated gamma-globulin with complement, despite markedly elevated immune complex levels, did not react positively with monolayers derived from Hodgkin's disease tumors, and none of the sera reacted with normal cultured spleen. The approximate size of serum components reacting with Hodgkin's disease monolayers was estimated by sucrose density gradient centrifugation. Sedimentation fractions in the 19S region reacted with monolayer cells when tested with 125I-labeled antisera to both IgG and C3 and contained immunoglobulin-complement complexes by gel diffusion and immunoabsorption. A component sedimenting at 7-9S contained immunoglobulin not complexed with complement; this component reacted with monolayer cells when tested with anti-IgG antiserum but did not react when tested with antibody to C3. The reaction of Hodgkin's disease monolayers with serum containing immune complexes differed from that of two suspension culture lines composed of cells with surface complement and IgG Fc receptors. Inasmuch as cells of our long-term Hodgkin's disease monolayers do not contain these surface receptors, possibly the antibody component of the immune complex reacts with antigens on the surface of cultured cells.


Selection of carcinogens and related compounds tested for mutagenic activity. A list of 102 chemicals was prepared for subsequent mutagenesis assays in a National Cancer Institute program to determine the extent of correlation between carcinogenesis and mutagenesis in standardized assays. The chemicals were divided into five major categories: 37 aromatic amines, 11 polycyclic aromatic hydrocarbons, 8 nitrosamines and nitrosamides, 16 alkylating agents, and a miscellaneous category consisting of 11 heterocyclic compounds, 7 amides, ureas and acylating agents, 5 antimetabolites, 4 inorganic chemicals, and 3 promoters. The chemicals were further described as procarcinogens (requiring metabolic activation to exert their biologic activities), ultimate carcinogens (direct-acting chemicals not requiring metabolic activation), and noncarcinogens (compounds shown to be inactive in one or more adequate carcinogenicity tests). An extensive bibliography documents the selection and categorization of the compounds.


Evaluation of the mutagenicity and DNA-modifying activity of carcinogens and noncarcinogens in microbial systems. The mutagenicity of 99 chemicals was determined in a standard Salmonella typhimurium assay with the use of strains TA1535 and TA1538; the DNA-modifying capacity was determined with normal and DNA polymerase-deficient Escherichia coli strains. The following categories of chemicals were studied: alkylating agents (15); nitrosamines, hydrazines, and related substances (8); heterocyclics (10); aromatic amines (36); polycyclic aromatic hydrocarbons (11); amides, ureas, and acylating agents (7); antimetabolites (5); inorganics (4); and promoters (3). Of the substances studied, 21 were known noncarcinogens, 21 were ultimate carcinogens, and 45 were procarcinogens. Of the noncarcinogens, 35, 30, and 25% were positive in the Salmonella, E. coli, and both systems, respectively. All of the ultimate carcinogens were detectable as mutagens of DNA-modifying agents; 79, 100, and 79% gave positive tests in the Salmonella, E. coli, and both systems, respectively. Of the procarcinogens 72% were identifiable by these procedures: 52, 67, and 48% in the Salmonella, E. coli, and both assays, respectively. A tabulation of the combined data for ultimate carcinogens and procarcinogens indicates that 77% of the carcinogens gave positive results: 61, 74, and 59% in the Salmonella, E. coli, and both assays, respectively. We suggest that, for prescreening procedures with microbial assays, S. typhimurium strains TA98 and TA100 be included and the standard E. coli DNA polymerase-deficient assay be run in tandem with the Salmonella mutagenicity assay. When the standard E. coli DNA polymerase-deficient assay does not give interpretable results because of the lack of zones of growth inhibition, a modified assay with the use of liquid suspension should be performed.


In vitro mutagenicity assays of chemical carcinogens and related compounds with Salmonella typhimurium. The mutagenic activity of 101 chemicals was studied with the use of the Salmonella typhimurium-microsome system described by Ames. The tester strains were TA1535, TA1536, TA1537, TA1538, TA98, and TA100. Assays were conducted in the presence and absence of a metabolic activation system prepared from the livers of randomly bred Sprague-Dawley rats that had been pretreated with Aroclor 1254. The test chemicals were incorporated into the agar with bacteria and the metabolic activation system. Mutagens were defined as chemicals that induced a reproducible dose-related increase in the number of histidine-independent revertants. With the use of these procedures, 65% of the organic carcinogens and 25% of the noncarcinogens were found to be mutagenic.


In vitro assays for recombinogenic activity of chemical carcinogens and related compounds with Saccharomyces cerevisiae D3. A total of 101 carcinogens, noncarcinogens, metals, and promoters representing a wide variety of chemical classes was tested to determine whether they increased mitotic recombination in Saccharomyces cerevisiae D3. A metabolic activation system prepared from homogenates of livers from rats that had been pretreated with Aroclor 1254 (a mixture of polychlorinated biphenyls) was incorporated in the assay procedure. All of the ultimate carcinogens (20/20) and 38% of the procarcinogens (18/48) increased mitotic recombination. Of the noncarcinogens 29% (6/21) also increased mitotic recombination. A improved metabolic activation procedure appears to be required to increase the probability of detecting procarcinogens by this method. The carcinogens thioacetamide, natulan, auramine, safrole, and 1'-hydroxysafrole increased mitotic recombination in S. cerevisiae D3 (the last compound was marginally positive), but they were negative in assays with Salmonella typhyimurium.


Mutagenic activity of chemical carcinogens and related compounds in the intraperitoneal host-mediated assay. The mutagenic activities of 79 carcinogens, noncarcinogens, and structurally related compounds toward Salmonella typhimurium strains TA1530, TA1535, and TA1538 and toward Saccharomyces cerevisiae D3 were investigated in the intraperitoneal host-mediated assay. Fewer than half of the carcinogens were mutagenic toward the Salmonella strains. The insensitivity of the system was most marked with the aromatic amine and polycyclic hydrocarbon procarcinogens. Under the test conditions, fewer than 10% of the carcinogens showed clear mutagenic activity toward S. cerevisiae D3. However, none of the noncarcinogens was significantly mutagenic toward either S. typhimurium or S. cerevisiae D3. Overall, the intraperitoneal host-mediated assay does not seem suitable for routine preliminary screening of large numbers of potential carcinogens. The median lethal doses to mice of 46 compounds were determined.


Initial National Cancer Institute studies on mutagenesis as a prescreen for chemical carcinogens: an appraisal. The efficacy of several in vitro and in vivo assays to detect carcinogens from a list of compounds was evaluated. Salmonella and polymerase A-deficient Escherichia coli in vitro were the most effective systems studied. Together they detected 82% of the organic carcinogens tested. Potential prescreening systems, which were thought to be currently insufficiently sensitive for the routine screening of potential carcinogens, included a) the development of resistance to thymidine overloading, methotrexate, and cytosine arabinoside by L5178y cells, b) Saccharomyces cerevisiae D3, c) the intraperitoneal host-mediated assay, and d) thymidine uptake as a reflection of DNA repair.


[Use of the aldosterone antagonist, canrenoate potassium for treating chronic circulatory insufficiency]. The results of studying the clinical effect of the diuretic soldacton and its effect on a number of indices of water-electrolyte metabolism are discussed. The drug was used in 16 patients with IIB--III stage of circulatory insufficiency. It was found that soldacton possesses a moderate diuretic and natriuretic effect and produces a potassium-preserving effect. The drug is effective in various initial concentrations of plasma aldosterone which does not change significantly under its effect. Soldacton promotes improvement of tolerance to cardiac glycosides and diminishes the risk of the development of digitalis intoxication.


[Use of Visken-15 for treating hypertension]. The hypotensive effect of visken-15, a blocking agent of the beta-adrenergic receptors, was studied in 7 patients with stage IB hypertensive disease, in 18 with stage IIA, and in 8 patients with stage IIB under conditions of in- and out-patient establishments. A favourable effect was produced in 81.5% of patients who were given one tablet of the drug once or twice a day. Treatment with visken-15 led to a decrease in systolic, diastolic and mean arterial pressure, in the rate of cardiac contractions, and in the blood minute volume at rest, in the orthostatic position, and during physical load. Visken-15 is marked by low toxicity, it is tolerated well and seldom causes side effects. The drug is recommended for the treatment of patients with early stages of hypertensive disease.


[Absolute and relative volumes of the right ventricle normally and in pathological states measured by the dye dilution method]. In using the method of dye dilution improved by reflectometry by means of fibrooptic catheters the authors measured the volumes of the right ventricle in patients with hemodynamics close to normal, in patients with a tension load of the right ventricle, with a volumetric load, in decompensation and in pericarditis. The authors noted a constancy of the relative stroke volume in compensated work of the right ventricle (approximately 53%). They regard this index to be the criterion of normal pump function of the right ventricle. In deficiency of this function the relative stroke volume may be reduced by nearly half, to 28%.


Pulmonary response to glass fiber by inhalation exposure. Rats, hamsters, and guinea pigs were exposed to airborne glass fiber at a gravimetric concentration of 0.42 mg. per liter for 6 hours per day, 5 days per week for 90 days. The number of dust particles greater than 5 micron. in length was 0.73 x 10(6) per liter with an average diameter of approximately 1.2 micron. Most particles were less than 2 micron. in size and only 15% of the dust particles had a fibrous shape. Few fibers were longer than 10 micron. The pulmonary response was characterized by macrophage reaction with alveolar proteinosis at 90 days of inhalation. The light and ultrastructural alterations were similar to the other experimental or human alveolar proteinosis. The alveolar proteinosis disappeared at 1-year postexposure, but focal dust cell accumulation with proliferating granular pneumocytes persisted throughout the 2-year recovery period. No significant fibrosis or stromal changes were found in the dust-deposited areas. In hamsters and guinea pigs, most ferruginous bodies were developed from fibrous fibers but not from tiny dust particles. The tracheobronchial lymph nodes were markedly swollen and laden with dust cells.


Immunofluorescence studies of dense deposit disease. The presence of railroad tracks and mesangial rings. Immunopathologic analysis was carried out on renal tissue from patients with membranoproliferative glomerulonephritis, nine with type I and nine with type II (dense deposit disease). A specific finding in all patients with type II, but not type I, was the presence of C3 along the margin but not within the central portion of dense deposit material in the glomerular basement membrane giving a double linear appearance (railroad tracks); C3 was also present within the mesangium, outlining numerous circular structures (mesangial rings). By phase contrast, electron microscopy, and dual label fluorescence studies, the railroad tracks and mesangial rings were shown to outline dense deposit material. Mesangial rings contained properdin (four of nine patients); railroad tracks contained properdin (five of nine patients) and C4 (four of nine patients); no other complement components or immunoglobulins were present. Studies using rhodamine-conjugated rabbit antibody to human glomerular basement membrane demonstrated no reactivity with the dense deposit material itself. In type I and to a lesser extent in type II, granular deposits of C3, C4, properdin, IgM, and IgG were present along the glomerular basement membrane, suggesting that immune complexes play a role in both diseases. Dense deposit transformation of the glomerular basement membrane may be a consequence of a highly specific injury.


Effect of donor bronchial length on healing: a canine model to evaluate bronchial anastomotic problems in lung transplantation. Bronchial anastomotic complications in lung transplantation in man remain a major cause of failure. To study this problem in a canine model, we varied the length of the distal bronchial component in three groups of dogs that underwent hilar stripping, bronchial transection, and reanastomosis, The distal bronchial component was thus analogous to the donor in a transplanted lung. Anastomoses were performed, respectively, at the level of the main carina (long single anastomosis), at the midpoint between the main carina and the bifurcation of the left main-stem bronchus (short single anastomosis), and just distal to the bifurcation of the left main-stem bronchus (lobar anastomosis). Bronchial anastomotic damage and necrosis were evaluated by periodic examination with a fiberoptic bronchoscope and by gross and microscopic examination at sacrifice on the seventh postoperative day. The long single anastomoses demonstrated the most necrosis, and the labor anastomoses showed the least. The short single anastomoses showed an intermediate degree of damage. These findings support the hypothesis that shortening the distal or donor bronchial component reduces anastomotic damage, probably because of better pulmonary-to-bronchial collateral blood supply. This study provides a canine model by which to examine bronchial anastomotic complicatons and demonstrates the feasibility of performing labor anastomoses as a means for decreasing bronchial anastomotic problems in lung transplantation.


Surgical management of congenital vascular rings. Case histories of 53 patients with surgically treated vascular rings are presented. The diagnosis was strongly suggested in all patients by symptoms of tracheosophageal obstruction and was confirmed by barium esophagogram, which showed typical bilateral and posterior indentations in the esophagus. Angiography was rarely used although it is helpful in doubtful cases. Endoscopic studies were considered unnecessary and potentially harmful. A left posterolateral thoractomy afforded ample access for division of the ring in all patients. Two patients died who were operated upon during the early experience. There were no postoperative deaths among the last 45 consecutive patients. All survivors had excellent symptomatic relief although complete resolution of symptoms took several months in some patients. All survivors had excellent symptomatic relief although complete resolution of symptoms took several months in some patients. The importance of early diagnosis and prompt surgical division is emphasized.


New technique for repair of posterior left ventricular rupture. A case is presented of posterior left ventricular rupture occurring from resection of intramyocardial calcification during mitral valve replacement. The laceration was obvious on the operating table with discontinuation of cardiopulmonary bypass, but attempts at simple closure with buttressd sutures were unsuccessful. The ventricular defect was repaired by insertion of a low-porosity Dacron graft. A saphenous vein bypass graft was also placed between the aorta and circumflex coronary artery.