[Hemodynamic effects and effects on plasma renin activity of injectable acebutolol in arterial hypertension]. The purpose of the study was to determine the early haemodynamic effects of injectable acebutolol and to study in parallel the changes in plasma renin activity (P.R.A.) in 11 patients, most of whom were affected with labile arterial hypertension. The haemodynamic measurements and P.R.A. determinations were carried out before and 5 and 15 mn after very slow intravenous injection of 10 mg acebutolol. The results obtained under these conditions were as follows: 1) Decrease in cardiac index (I.C.). It was particularly significant after 5 mn, since the I.C. decreased from 4.43 to 3.75 1/mm (p less than .01). It was essentially due to a decrease in heart rate, that fell from 90.45 to 77 beats/mn (p less than .001), while stroke volume changed virtually not. 2) Decrease in blood pressure, more marked on systolic blood pressure (110 mm Hg after 15 mn as against 154 mm Hg before injection; p less than .001), associated with a decrease in left ventricular work (4.7 kgm/mn/m2 after 5 mn as against 6.2 kgm/mn/m2 before injection; p less than .001), without significant changes in total systemic arterial resistances. 3) Increase in diastolic pulmonary arterial pressure (10.4 mm Hg after 5 mn against 8.09 mm Hg before injection; p less than .001), testifying to a slight left ventricular myocardial depression. 4) Decrease in supine P.R.A. level (0.72 nanogram/1/mn after 5 mn as against 1.15 nanogram/1/min before injection; p less than .01). A significant correlation was found between this decrease in P.R.A. and that in I.C., testifying to a close parallelism between the inhibition of cardiac beta-1 receptors and that of the receptors involved in renine secretion. 5) The tolerance of injectable acebutolol appeared to us to be excellent.


[Action of acebutolol on heart rate and FEV1 in asthmatic patients. Single intravenous administration and long term oral administration]. In 7 asthmatic patients, intravenous injection of acebutolol resulted in a slowing of the heart rate by blocking the cardiac beta-receptors. An aerosol of isoprenaline, which accelerated the heart, is without effect after intravenous injection of acebutolol. On the contrary, isoprenaline caused similar changes in the FEV1 before and after acebutolol injection in the same patients. This effect confirms the slight action of the compound on the beta2-adrenergic receptors. Prolonged oral administration did not cause any adverse clinical effects in 6 asthmatic patients.


[Acebutolol test in moderate arterial hypertension. Action on systolic time intervals]. The antihypertensive effect of acebutolol, a new cardioselective beta-blocking drug, is studied in 31 patients with mild essential hypertension. Administration of acebutolol (2,000 mg) in 48 hours produced a significant decrease in blood pressure, heart rate, plasma renin activity (P.R.A.) and an increase in systolic time intervals (pre-ejection period and isovolumetric contraction time). The blood pressure drop is highly correlated to the initial P.R.A. values, but is not related either to the initial heart rate, or to the systolic time intervals values.


[Controlled comparative trial of acebutolol and bendrofluazide alone or in association for the treatment of hypertension]. The hypotensive effects of acebutolol and bendrofluazide were studied comparatively, used alone or in association, using a permutation method over three consecutive six week periods, in 47 patients aged over 21 whose diastolic pressure prior to treatment was in excess of 100 mm Hg. Whether used alone or associated, the drugs were prescribed at the following daily doses: acebutolol 500 mg, bendrofluazide 5-15 mg. After six weeks and at the end of the trials (18 weeks), acebutolol proved to have an hypotensive effect, less marked when given alone than in association. It provided significant relief from anxiety, especially when prescribed alone during the latter part of the test. Side effects were unfrequent on the whole and without marked predominance for any type of treatment.


[Results of the treatment of essential arterial hypertension following prolonged (24 months administration of acebutolol)]. Acebutolol, a new cardioselective blocking agent, has been used to treat essential hypertension during two years in 56 patients. The initial dosage was 600 mg a day and was sufficient in the majority of patients. We have observed a perfect control of arterial blood pressure in 69 p.cent. In 10 p.cent of our patients arterial blood pressure decreased and the mean decrease was 25 mm Hg. In 21 p.cent there was no effect of the treatment. Tolerance was very good.


[Acebutolol in the treatment of arterial hypertension. Clinical study]. Fifty hypertensive patients were given a beta-blocker, acebutolol, alone or in association with other hypotensive drugs, in an open therapeutic trial lasting for a year. The results of treatment were considered to be good or moderate in 74 p.cent of the patients. Treatment failures were recorded in 26 p.cent. The mean dosage of acebutolol was 10 mg/kg (maximum 22 mg/kg) and the drug was very well tolerated. Hypertension with an increased cardiac index and reno-vascular hypertension with increased plasma renin activity are good indications for acebutolol.


[Treatment of arterial hypertension with acebutolol. Clinical results]. Acebutolol was given to a group of 23 subjects with essential arterial hypertension associated with tachycardia at rest. In 70 p.cent of the cases, arterial blood pressure was rapidly influenced by the treatment. The favorable results are mostly-but not exclusively-found among the subjects with the highest initial sympathetic reactivity and renin plasmatic activity. However, there is no correlation between the quality of the result and the degree of reduction of renin activity or heart rate.


[Comparative study of acebutolol and propranolol in the treatment of arterial hypertension]. This double-blind clinical study was carried out in order to compare the therapeutic activity of propranolol, and a new beta-adrenergic blocker, acebutolol, in essential hypertension. The hypotensive activity of acebutolol was confirmed when a dosage of 600 mg/day was used, with en absence of side effects.


[The induction of labor by prostaglandin F2alpha Clinical, tocographic and electrohysterographic study]. Induction of labor was performed in 65 patients by intravenous infusion of PgF2alpha. 55 patients were near term and induction made electively. 5 cases failed. No correlation was found between the stade of the cervix and the probability of success nor the length of the induction time. PgF2alpha induced labor needs to be closely monitored (electronical pumps and monitoring) because of the risk of hypertonus. With such a technique the side effects are minimal and no undesirable consequences were observed concerning either the mother or the child. During the course of this investigation a study was performed for the first time of the electrical activity of the human myometrium subjected to PgF2alpha stimulation. (26 recordings through the extra-amniotic intrauterine technique). The pattern of this activity is quite similar to spontaneously occuring alectrical activity.


Oviduct patency control by means of 133Xe-solution. The authors describe a radioisotopic method for the oviduct patency control in patients suffering from primary or secondary sterility. The application of 133Xe causes at least about 3-4 times less radiation than hysterosalpingographical tests. Ease of interpretation facility, painlessness and comparability of the results were noticed.


[Minimal cardiac transit times in the diagnosis of heart disease: measurements with the gamma retina V and indium-113m. The influence on central volume relationships of long-term digitalis therapy in patients with latent and manifest coronary insufficiency]. Using Indium-113m and the Gamma Retina V (Fucks-Knipping Camera), the minimal cardiac transit times (MTTs) were measured radiocardiographically from the right auricle to the aortic root. This analysis served to determine the relation between stroke volume and the segment volume of the part of circulation between the right auricle and the aortic root. In 39 patients with myocardial insufficiency of different clinical degree the effectiveness of digitalization was, up to a period of 5 years, measured by means of the volume relation mentioned above. The following conclusions can be drawn from the results: digitalization of patients with myocardial insufficiency leads to an improvement of the impaired relation of central volumes. In patients with diminished cardiac reserve the improvement is drastic and often results in a nearly complete normalization. The data remain constant during therapy even for an observation period of 5 years. Digitalization of patients with congestive heart failure only leads to a partial improvement. In contrast to patients with diminished cardiac reserve this effect is temporary. The different behaviour of the relation between stroke volume and segment volume in patients with diminished cardiac reserve and congestive heart failure under prolonged administration of digitalis points to the necessity of treatment with digitalis in the early stage of myocardial disease.


The isolation and partial characterization of a new restriction endonuclease from Providencia stuartii. We describe the isolation of a new class 2 restriction endonuclease from Providencia stuartii 164. Using the procedure of osmotic shock treatment, we have partially purified this enzyme (Pst 1) and have begun preliminary work to characterize its specificity and requirements. Pst 1 requires Mg++ as the only cofactor and produces more than 18 cleavages in wild type lambda. We have determined the location of 7 of these cleavages by the use of deletion and insertion mutants of lambda.


A modified uridine in the anticodon of E. coli tRNA I Tyr su + oc. The anticodon of an ochre-suppressing derivative of E. coli tRNA I Tyr, previously identified as UUA, can contain a modified uridine (U+) in the first position. The novel modified nucleotide has been identified by two-dimensional thin layer chromatography following RNase T2 digestion of anticodon-containing fragments. Up+ is found in less than stoichiometric molar yields in preparations of tRNA I Tyr su + oc. The electrophoretic mobility of Up+ is the same as Up at pH 3.5 and pH 7.5. U+ probably does not contain sulfur since it cannot be labeled with 35S in vivo incorporation experiments.


Comparison of the fine structure of mitochondrial DNA from Saccharomyces cerevisiae and S. carlsbergensis: electron microscopy of partially denatured molecules. Denaturation-maps of mitochondrial DNA from Saccharomyces cerevisiae and S. carlsbergensis have been derived from electron microscopic observations of partially denatured complete circular molecules and large fragments of these circles. The mitochondrial DNA from the two species differ by 6% in total length, but seems from the maps to contain some regions of apparent close homology. The cleavage pattern of the two DNAs by the restriction endonuclease EcoRI is compared by gel electrophoresis.


Late psychologic effects of a serious illness in childhood. The results of psychologic testing and parent interviews showed that children who experience catastrophic illness between 2 and 5 years of age do not necessarily have severe adjustment problems at a later date. Only 2 of the 18 children studied, who are long-term survivors of childhood cancer, have been found to have moderately severe adjustment problems. The problems of these two children could be related to continuing stress within the family and are not necessarily caused by the child's illness.


[Changes in the concentration of estradiol in the peripheral blood of immature female rats following intrahypothalamic administration of a factor liberating luteinizing hormone]. Administration of a synthetic luteinizing hormone-releasing factor (LH-RF) into the area of the medial eminence and the third ventricle of the sexually immature female rats, aged 20-22 days, caused a distinct increase in the estradiol concentration in the peripheral blood of the majority of these animals. Administration of physiological solution produced a reaction (much weaker) only in a small percentage of the animals. There was no increase in estradiol level when LH-RF got into the other areas of the hypothalamus.


Identification of biological molecules in situ at high resolution via the fluorescence excited by a scanning electron beam. Proteins, nucleic acids, and fluorescein-conjugated antibody are shown to be identifidable in situ via the fluorescence excited by the focused electron beam of a canning electron microscope. A molecular species is identified by its characteristic fluorescence spectrum and by a characteristic alteration of the spectrum with time under the electron beam. Primary protein fluorescence is relatively rapidly destroyed by the beam, but protein photoproduct fluorescence is more rugged and will in some cases permit detection of small numbers of protein molecules. Nucleic acid fluorescence is extremely long-lived and will permit detection of small numbers of nucleic acid residues. The theoretical resolution limit for localization of a particular molecular species -- about 20 A--is determined by the known maximum distance for molecular excitation by fast electrons. Drect extapolation from an observed resolution of 900 A in the localization of nucleic acid using a low-efficiency detector leads to an experimental resolution limit of less than 60 A. Fluorescence is strongly quenched by residual water in the specimen. Similar quenching is produced by some macromolecular associations and so may serve to localize such associations.


Cloning of Escherichia coli DNA that controls cell division and capsular polysaccharide synthesis. A 2 x 10(6) dalton DNA fragment that controls cell division, capsular polysaccharide synthesis, and enzymes of capsular polysaccharide synthesis has been cloned.


Specific in situ cleavage of 16S ribosomal RNA of Escherichia coli interferes with the function of initiation factor IF-1. Specific in situ cleavage of 16S rRNA of E. coli has been accomplished by in vitro treatment of 70S ribosomes ("tight couples") with the bacteriocin cloacin DF13. The defective ribosomes, which have fully lost their ability to sustain polypeptide synthesis, are still able to form initiation on complexes with MS2 RNA, but the kinetics are altered. This is apparently due to an improper functioning of initiation factor IF-1, for the defective ribosomal couples respond normally to dissociation by IF-3 but the dissociation is not stimulated by IF-1. The initiation complexes formed with defective ribosomes are fully reactive with puromycin. Their ability to bind alanyl-tRNA is reduced by about 50% at all concentrations of elongation factor Tu studied. Cleavage of the 16S rRNA, not the release of the terminal fragment from the ribosome, causes the block of protein synthesis and the aberrations observed during initiation and elongation.


Stringent factor from Escherichia coli directs ribosomal binding and release of uncharged tRNA. Uncharged tRNA is preferentially bound to the peptidyl site of the ribosome in the absence of stringent factor ,but in its presence is directed to the acceptor site. The synthesis of pppGpp and ppGpp is initiated by tRNA bound in the acceptor but not in the peptidyl site. In this reaction, tRNA is not permanently attached to the acceptor site. Uncharged [32P] tRNA but not 3H-labeled stringent factor is released from the ribosome after each round of stringent factor-dependent hydrolysis of ATP. ATP-32PPi-exchange experiments reveal that exchange is independent of the presence of GTP but strongly enhanced by the addition of stringent factor and tRNA. The tRNA release is suppressed when ATP is replaced by beta, gamma-imido adenosine 5'-triphosphate, 5'-AMP, or GTP.


Isolation of an intermediate which precedes dnaG RNA polymerase participation in enzymatic replication of bacteriophage phi X174 DNA. Conversion of phi X174 single-stranded DNA to the duplex replicative form (RF) in vitro requires at least 10 purified proteins. Three stages - strand initiation, elongation, and termination - comprise this conversion. We now identify a separate stage in strand initiation which precedes dnaG RNA polymerase participation. Incubation of five proteins - protein i, protein n, DNA unwinding protein, dnaB protein, and dnaC protein - with ATP and phi X174 DNA forms an intermediate which enables subsequent stages measured by DNA synthesis to proceed 20 times faster. The intermediate can be isolated in quantitative yield by gel filtration or by ultracentrifugation. Protein i and protein n are required in less than stoichiometric amounts and appear to be absent from the isolated intermediate. Whereas formation of the intermediate is sensitive to antibody to protein i and to N-ethylmaleimide (an inhibitor of protein n and dnaC protein), the intermediate itself is resistant to these reagents. DNA unwinding protein complexes the DNA in a ratio of 60 molecules per circle. Synthesis of the intermediate appears to require stoichiometric quantities of dnaB protein and dnaC PROTEin but their presence in the intermediate has not been established as yet.


Receptor interactions in a signalling system: competition between ribose receptor and galactose receptor in the chemotaxis response. Galactose and ribose receptors are shown to compete for a common site by comparing the specificities of the purified receptors with the specificity of the whole organism response. Ribose does not bind to the purified galactose receptor but inhibits the in vivo galactose response. A mutant lacking the ribose receptor shows no inhibition of the galactose response even at very high ribose concentrations. The results can be explained by a mechanism involving (a) a ligand-induced conformational change in the receptor which produces a combining site with affinity for the molecule that serves as a first component of the signalling system and (b) a limited number of such first component molecules that cannot bind both receptors simultaneously. The mechanism may have considerable generality for sensory, hormonal, and transport systems.


Escherichia coli thioredoxin: a subunit of bacteriophage T7 DNA polymerase. T7 DNA polymerase (DNA nucleotidyltransferase; deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase, EC 2.7.7.7) is composed of an 84,000 dalton protein specified by the gene 5 of the phage and a 12,000 dalton protein (TsnC protein) specified by the tsnC gene of E. coli [Modrich, P. & Richardson, C. C. (1975) J. Biol. Chem. 250 5515-5522]. Both proteins are necessary for T7 DNA polymerase activity and for the replication of T7 DNA. The TsnC protein is identical to thioredoxin of E. coli by the following criteria: (1) Homogeneous preparations of both proteins have TsnC and thioredoxin activity. (2) Both proteins show similar stability to heat. (3) They have identical mobilities, corresponding to a molecular weight of 12,000, on polyacrylamide gels containing sodium dodecyl sulfate. (4) Their amino-acid compositions are indistinguishabe. (5) Antibody prepared against thioredoxin inhibits TsnC activity. (6) TsnC protein isolated from purified T7 DNA polymerase has thioredoxin activity. In addition, preparations of T7 DNA polymerase itself exhibit thioredoxin activity and are partially inhibited by antibody to thioredoxin.


Influence of polyunsaturated fatty acids on survival of skin allografts and tumor incidence in mice. Subcutaneous or oral administration of the polyunsaturated fatty acid linoleic acid prolongs survival of skin allografts in mice. Mice fed on a diet deficient in polyunsaturated fatty acids show a relative immunopotentiation, as indicated by accelerated skin allograft rejection and decreased incidence and rate of development of methylcholanthrene-induced tumors. These observations support the hypothesis that polyunsaturated fatty acids take part in immunoregulatory mechanisms.


Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals: discussion. About 300 carcinogens and non-carcinogens of a wide variety of chemical types have been tested for mutagenicity in the simple Salmonella/microsome test. The test uses bacteria as sensitive indicators of DNA damage, and mammalian liver extracts for metabolic conversion of carcinogens to their active mutagenic forms. There is a high correlation between carcinogenicity and mutagenicity: 90% (157/175) of the carcinogens were mutagenic in the test, including almost all of the known human carcinogens that were tested. Despite the severe limitations inherent in defining non-carcinogenicity, few "non-carcinogens" showed any degree of mutagenicity [McCann et al. (1975) Proc. Nat. Acad. Sci. USA 72, 5135-5139]. In the present paper, carcinogens negative in the test andapparent false positives are discussed. We also discuss evidence that chemical carcinogens and radiation, likely to initiate most human cancer and genetic defects do so by damage to DNA. The Salmonella test can play a central role in a program of prevention: to identify mutagenic chemicals in the environment (all indications are there are many) and to aid in the development of non-mutagenic products to prevent future human exposure.


Turnover of tritiated-thymidine-labeled mononuclear cells in tuberculous lesions of rabbits: a comparison of primary dermal BCG lesions and those of reinfection. Rabbits were infected or reinfected intradermally in multiple sites with BCG. One day before the BCG infection they were injected iv with a single pulse of tritiated thymidine (3HT). At various times thereafter, the BCG lesions were biopsied and evaluated for 3HT-labeled mononuclear cells (MN), which are mostly macrophages but include some lymphocytes. Periodically Old Tuberculin (OT) was infected intradermally, creating MN traps, which were biopsied and evaluated 1 day after their onset. These traps monitor the population of 3HT-labeled MN in the blood stream that readily enters sites of inflammation. During the first 5 days after the 3HT pulse, a higher percentage of labeled MN accumulated in tuberculin traps on rabbits reinfected with BCG than in traps on rabbits with primary infection. The high percentage of labeled MN in the former was probably due to the more intense inflammation cuased by preexisting tuberculin hypersensitivity. By 8 days after the 3HT pulse, a lower percentage of labeled MN had accumulated in BCG lesions of reinfection than in primary BCG lesions. Evidently the presence of delayed hypersensitivity increased the turnover of MN in tuberculous lesions. By 15 days after the 3HT pulse, the percentage of 3HT-labeled MN was much higher in BCG lesions than in 1-day traps, suggesting that such MN had accumulated in the lesions over a period of several days.


The bacterial flora of the female rat genital tract. A study of the genital microflora in virgin female rats of reproductive age has demonstrated that alpha and nonhemolytic streptococci, Pasteurella pneumotropica, diphtheroid bacilli, Staphylococcus epidermidis, and Proteus mirabilis are the predominant genital organisms. The pH of the rat vagina was demonstrated to be near neutrality. It is suggested that the higher pH in the rat vagina as compared to the human vagina may account for some of the differences between human and rat genital microflora.


Serum and blister fluid anticomplementary activity in pemphigus and bullous pemphigoid. Sucrose density gradient studies. By sucrose density gradient ultracentrifugation and standard hemolytic complement assays, complement fixing activity of about 19 S and greater was found in blister fluids of one patient with pemphigus and three of five patients with bullous pemphigoid. Control blister fluids, including experimentally induced blisters, lacked such activity. Complement fixing activity was apparent, however, in 6 of 10 pemphigus sera and in two of five bullous pemphigoid sera tested. The material present in both pemphigus and bullous pemphigoid appears to activate the classical complement pathway.


Functional imaging of lung ventilation using the concept of mean transit time. This paper describes a new way of expressing local ventilation using a scintillation gamma camera interfaced to a digital computer. From the ratio of the first to the zeroth moment of the lung clearance curve for 13N gas, a mean transit time is calculated and displayed for different regions of the lung. Lung clearance curves following intravenously administered 13N solutions, or after equilibration with 13N gas, are measured during normal breathing. Describing regional ventilation by mean transit time during clearance uses all the counts in the lung clearance curve and the improvement in statistical accuracy compared with the height over area method using a Stewart-Hamilton equation is significant. In normal subjects the average mean transit time for clearance from the total lung field is t = (61 +/- 4) s, from the upper zone tuz = (64 +/- 4) s and from the lower zone tlz = (54 +/- 5) s. These results show uneven ventilation between regions of the normal lung in general agreement with that described by previous authors. In addition, the functional image gives the mean transit time for each cell of the 64 X 64 matrix of the computer display. The fractional error in mean transit time is 3% for an area of 2-2 cm2 corresponding to 12 cells in the display. This display provides a sensitive method, functionally and spatially, of investigating local differences in ventilation, including vertical and horizontal gradients in narrow strips of lung.


The free musculocutaneous flap.

The free musculocutaneous flap. We report the transfer of a free musculocutaneous compound flap, including the gracilis muscle, in one stage by microvascular surgery. The advantages of this free flap are discussed.


Thumb reconstruction in the severely burned hand. The standard techniques have generally been adequate for thumb reconstruction in the severely burned hand. The basic principles of preservation of length, prevention of malposition and contracture by appropriate splinting, early motion, and early skin coverage are all applicable. The nature of the tissue changes wrought by the burn wound, however, frequently necessitates certain modifications in the approach to surgical reconstruction. We have described these and our methods used in handling 9 specific cases.


Free skin flap from the retroauricular region to the nose. We present two new, one-stage methods for resurfacing a part of the face-- (1) the microvascular transfer of a free retroauricular flap, and (2) an island flap from the galea covered by a full-thickness skin graft from the retroauricular region. Both procedures provided the same good color match, without leaving a readily visible donor scar.


[Subcutaneous phlebopathic calcifications]. A detailed history of 3 cases of subcutaneous calcifications. A review of the present therapeutic alternatives (other than surgery). A discussion of Selye's theory of calciphylaxis. Its application to one clinical case.


The hand sandwich: adjacent flaps from opposing body surfaces. An anteriorly-based lateral chest flap gives volar coverage to the opposite denuded hand, while a flap from the adjacent inner arm gives dorsal coverage. While transferring the flaps, the donor sites are joined together to form a temporary chest-arm adhesion, which is separated later with skin grafting.


[Possible recourse to plastic surgery in the treatment of subcutaneous calcinosis]. The authors report three cases of subcutaneous calcinoses of the leg, one after burns, the other two after voluntary injection of essence of terpentine. The evolution and recurrences after tentative surgical treatment prove that excision is indicated when a calcareous plaque has led to cutaneous ulceration. This resection must be complete and may thus involve skin grafts or cover flaps.


Urate kinetics in hypoxanthine-guanine phosphoribosyltransferase deficiency: their significance for the understanding of gout. Urate production (miscible urate pool and turnover, daily production, glycine incorporation into urate) and urate excretion (24 hour urinary urate excretion on a purine free diet, renal clearances of urate and creatinine, per cent renal excretion of labelled urate, extra-renal elimination of urate) were measured in members of five families who demonstrated varying degrees of deficiency of the X-linked condition hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency. The hemizygous males, all of whom eventually developed symptoms, showed consistent overproduction of urate with a renal excretion of urate that varied from moderately to considerably increased. The nine heterozygotes, of whom seven were asymptomatic, also showed abnormalities of urate production, although all but two had normal serum urate concentrations. The one heterozygote who had developed gouty arthritis had the lowest renal excretory capacity for urate, whereas the one heterozygote who had developed an episode of renal colic had the highest urate clearance. In the heterozygotes with normal serum urate concentrations, the increase urate production was balanced by the renal excretion of urate. This demonstrates the importance of the relation between urate. This demonstrates the importance of the relation-between urate production and urate excretion in determining the clinical expression of abnormal urate metabolism.


A study of the endocrine manifestations of hepatic cirrhosis. The clinical features and hormonal abnormalities were surveyed in 117 men with cirrhosis of the liver. Compared with healthy men of similar ages, the patients had significantly lower metabolic clearance rates, plasma production rates and total and free levels of testosterone, reduced testosterone responses to human chorionic gonadotrophin stimulation, higher oestradiol, luteinizing hormone and follicle stimulating hormone levels and higher binding capacities of sex steroid binding globulin. The peripheral conversion of testosterone to oestradiol was also found to be significantly increased. However, the metabolic clearance and plasma production rates of oestradiol were not significantly different from those of healthy men. Patients who were severely ill with liver failure and one with haemochromatosis had low levels of luteinizing hormone and follicle stimulating hormone and sub-normal responses to clomiphene and luteinizing hormone-releasing hormone. Higher plasma oestradiol levels were found in patients with gynaecomastia and spider naevi than in those without these signs. However, the clinical features of androgen deficiency--that is, testicular atrophy, impotence and loss of secondary sex hair--were only poorly related to the low testosterone levels, and production rates and longtitudinal studies indicated that the hormonal levels, endocrine features and severity of the liver disease could change independently. It is concluded that the clearance of oestradiol from plasma is not limited by liver disease in all patients, and that reduced degradation of oestrogens is not the initial event in the sequence leading to the hormonal abnormalities of cirrhosis. While gonadotrophin deficiency occurs with liver failure and in some patients with haemochromatosis, the more usual findings are of elevated gonadotrophin levels and a poor Leydig cell response to chorionic gonadotrophin. These suggest that the hypogonadism is primary in most patients with cirrhosis. The causes of the high oestradiol levels were not discovered. Increased peripheral conversion of precursors to oestradiol or increased testicular secretion of oestradiol are possibilities. The high binding capacities of sex steroid binding globulin were not significantly correlated with either the low testosterone or high oestradiol level and the cause of this abnormality remains uncertain. The low metabolic clearance rates of testosterone appeared to result from the increased plasma protein binding of testosterone. The discrepancies in the expected relationships between the hormone and clinical changes suggest that factors other than those studied are also involved in the genesis of the endocrine features of hepatic cirrhosis.


Reflections on fifty years of publications on the history of general biology and special embryology. The publications of fifty years (1925-1974) of the histroy of biology and embryology are surveyed. In America, the earliest background for work during this period was provided by the collectors, mainly physicians, of books into extensive private libraries. The collectors, for instance Osler, Cushing, and Fulton in this country and Geoffrey Keynes abroad, became expert technical bibliographers during the early part of the half-century under consideration. High standards for medical, thus biological history, insofar as these fields overlap, were also set earlier by Sudhoff's Institut für Geschichte der Medizin in Leipzig, and American historical studies benefited when Sigerist came from Leipzig to Baltimore in the early 1930's. Textbooks of medical history are omitted from discussion here, but a number of more or less general histories of biology published within the specified period are briefly evaluated. The discussion next turns to histories of embryology, general and special. Recent monographs on the classical embryologists, Wolff and von Baer, are enumerated, as are a number of biographies and autobiographies of important embryologists published here or abroad during our half-century. Then general histories of embryology are discussed, and finally some specialized ones. Needham, Roger, and Adelmann are singled out as the most important contributors to the history of embryology, in the West, during the period covered. Few of the contributors to the history of biology and medicine during the years of 1925 through 1974 were trained as historians while students. It is concluded that the History of Science Society has performed an important contribution in professionalizing the history of biology and embryology, but it is pointed out that a great new challenge faces it in the necessity to counteract anti-historical and anti-intellectual moods and movements of today.


[Value of TPHA in the serological screening of lues]. In the present work, 21,400 not selected sera were tested with hemagglutination test (TPHA) and flocculation test (VDRL) with cardiolipin for screening of syphilis; sera that gave negative results against both tests showed remarkable agreement (97,81%). 468 sera gave positive results to least one of the tests employed in screening and were tested with the following procedures: fluorescent Treponemal antibody-absorption (FTA/ABS) test, complement fixation (by Kolmer, modified) with proteic (KP) and lipidic (KL) antigen; 100 of these sera were also tested with T. pallidum immobilizaiton (TPI) test. The agreement among the before mentioned tests and sera that gave positive results only to VDRL was significatively low; on the contrary, the agreement was remarkable in the case of those positive only to TPHA (99% with FTA/ABS, 83% with TPI, 52,5% with KP and 21,5% with KL). The results obtained in attesting sensitivity and specificity of TPHA indicate that it is a very valuable screening test, and suggest to the AA. to emphasize that TPHA/VDRL association a definitive conclusion in syphilis serological negativity.


[Abolition of capital punishment in public in England]. The Author, following a critical approach focussed on society's response to deviance and on the means of social control which society applies to defend itself from crime and criminals, confutes the thesis according to which the demise of public execution is generally considered as a step in the evolution of the humanitarian ideal of total abolition of the death penalty. By means of a detailed historical analysis of the socioeconomic and political climate which gave rise to the campagning for the demise of public execution in England, the Author gives evidence that such abolition cannot be seen as a linear descendant of a long line of criminal law reforms but rather as a successful manoeuvre to ensure the continuance of the use of the dealth penalty in order to reaffirm the power of the elite which represented itself as the moral guardian of society.


Vaginally administered 16, 16-dimethyl-PGE2 for the induction of midtrimester abortion. Thirty patients in the 13th-20th week of gestation underwent therapeutic abortion utilizing vaginally administered 16, 16-dimethyl-PGE2 (free acid) suppositories. The first 15 patients obtained individual doses in the range of 400-1200 mug given every three hours (mean total dose 4.2 mg). In the following 15 patients a fixed dose schedule was used (800 mug followed by 1000 mug every three hours; mean total dose 5.3 mg). All but one of the 30 patients aborted. The mean induction-abortion interval for all patients was 16.8 +/- 6.9 hours (mean +/- S.D.) With the fixed dose regime the success rate was 100% and the induction-abortion interval 16.0 +/- 5.9 hours. Because gastro-intestinal side effects were minimal, neither anti-emetic nor anti-diarrheic medication was required. A slight elevation of temperature was noted in five patients. The uterine response to the vaginal administration of this compound was characterized by a gradual increase in uterine tonus followed by sustained stimulation. The results are interpreted to suggest that the vaginal administration of 16, 16-dimethyl-PGE2 is a useful alternate method for the induction of second trimester abortion. Moreover, this compound seems to cause fewer gastro-intestinal side effects than other prostaglandins administered by the vaginal route at our department.


Determination of prostaglandin F2alpha and E2 contents in human cerebrospinal fluid by the radioisotope dilution method. Prostaglandin F2alpha and E2 contents in human cerebrospinal fluid were determined by the radioisotope dilution method. The mean values of PGF2alpha and PGE2 of men were 9.8+/-0.87 ng/ml and 6.5+/-1.39 ng/ml, respectively. Those of women were 8.3+/-1.4 ng/ml and 6.9+/-1.72 ng/ml, respectively. The correlation between age and PG was significantly with PGE2 of men and with PGF2alpha of women.


Anticoagulants and cancer. A review.

Anticoagulants and cancer. A review. Anticoagulants (heparin, warfarin, fibrinolysin and others) reduced incidence of cancer metastases by inhibiting the formation of a fibrin matrix indispensable for peripheral fixation of circulating cancer cells. Apart from their specific anticoagulant activity most of these substances interfere directly with cell growth and metabolism, stimulating also immunologic anticancer mechanism. In clinical cases, favourable results have been obtained in various forms of metastasizing cancer, and especially in Hodgkin's disease and leukemias, by combining anticoagulant and cytostatic treatment. The results observed in other forms of cancer, though promising, are still controversial. The potential dangers and side effects of anticoagulant treatment in cancer are discussed.


EEG and evoked potentials in the psychoses. EEG and evoked potential (ER) findings in schizophrenic and affective psychoses were selectively reviewed. Both groups of psychoses appear to differ from normal in a number of EEG and ER characteristics; however, diagnostic specificity was suggested by relatively few findings. More encouraging result with respect to specificity have been obtained by subtyping the psychotic groups, e.g., process versus reactive schizophrenic, unipolar versus bipolar depression. Methodologic issues and directions for future research were discussed.


Protection against acute toxicity of acetaldehyde in mice. The ability of several compounds to protect against acetaldehyde-induced loss of righting reflex was studied in mice and compared with previously published results in rats. L-cysteine (3 mMoles/kg), L-ascorbic acid, DL-thioctic acid, or DL-homocysteine (2 mMoles/kg each) was administered orally 30 minutes prior to an intraperitoneal ED90 of acetaldehyde (415 mg/kg). Cysteine, ascorbate, and thioctic acid caused a statistically significant reduction in acetaldehyde-induced toxicity, while homocysteine afforded only little protection. These results are qualitatively, but not quantitatively, similar to those reported for rats.


Tissue distribution of 14C-labeled ethylene disbromide in the guinea pig. A study was undertaken to determine the tissue distribution of uniformly 14C-labeled ethylene dibromide in guinea pigs following intraperitoneal administration. Organs containing the greatest concentration of radioactivity per unit weight (kidneys, liver, adrenals, pancreas, and spleen) were the same organs in which pathologic changes have been reported by other investigators, indicating a direct correlation between tissue levels and target organ toxicity. The principal route of excretion was via the kidneys, 66% of the dose appearing in the urine within 72 hours of administration. Fecal excretion for the 72 hour period was relatively insignificant, representing less than 3% of the dose.


Effect of isolation media on recovery of rough variants of Salmonella. Preferential inhibition of rough variants of Salmonella was observed with tetrathionate and selenite-F broths and with Salmonella Shigella agar. These results suggest that rough strains of Salmonella may be more prevalent in nature than previously suspected.


The specificity and sensitivity of the fluorescent antibody test for Mycobacterium johnei infection in abattoir and culled cattle. In a series of 100 cattle in which there was no bacteriological or histopathological evidence of Mycobacterium johnei infection there were four positive reactions to the fluorescent antibody (FA) test with M johnei antigen and 20 to the complement fixation (CF) test. In a second series of 118 culled adult cattle M johnei infection was found in 26. The FA test was positive in 16 and the CF in 12 of those infected cattle. In 92 cattle with no evidence of M johnei infection the FA test was positive in seven and the CF test in 22.


The specificity and sensitivity of the fluorescent antibody test in cattle experimentally infected with Mycobacterium avium and Mycobacterium johnei. In five calves experimentally infected with Mycobacterium avium and in 10 with M johnei it was shown that the serological response by the fluorescent antibody (FA) test was specific. The serological response in the M avium infected calves was transitory and lasted up to five months. The first evidence of a serological response with the FA test in the M johnei dosed calves occurred at four months, and all calves had reacted by nine months after dosing. At the 23 tests carried out between four and 32 months after dosing, when the experiment was terminated, an average of 5-8 animals was positive at any one test. Johne's disease was confirmed bacteriologically and histologically in six of the 10 calves though none had shown clinical signs.


Metabolic fates of herbicides in animals. Many general aspects of the subjects were covered by the two previous reviews. Important recent changes in handling harvested cereal grains include more bulk transportation--particularly containerisation,processing closer to the site of production, resistance topesticides in many granivorous insects and the alarmingly unpredictable cross-resistance spectra in some sppecies, and a hardening in the attitude of governments and the food industry to the use of pesticides. Pesticide manufacturers arecurrently restricting their involvement in the stored grain area. The market is small and unpredictable due to crossresistance. However, a number of interesting and potentially useful compounds have appeared, notable )(bio)  resmethrin, pirimiphos-methyl, andDursban-methyl, which reflect attempts to provide somewhat morepersistent compounds under adverse storage conditionnnnns than ismalathion--currently the most widely-used control agent.Inevitably, there is interest also in alternative methods, of control, from the obvious physical methods (drying, cooling, air-tight storage)to use of pheromones, insect hormone anaogues, and larvicides, all of which may have some future potential...


Measurement of cardiac output by impedance cardiography in patients with myocardial infarction. Comparative evaluation of impedance and dye dilution methods. The cardiac output was measured simultaneously by the impedance cardiography and dye dilution methods in 10 patients with acute myocardial infarction 2-3 weeks after admission to the Coronary Care Unit. The impedance cardiac output was on the average 9.7% higher than the dye dilution cardiac output. The reproducibility of impedance cardiac output 4.1%, compared with 5.1% for the dye dilution method. The study showed a satisfactory reliability of impedance in predicting the relative changed of cardiac output in response to tilting from the supine to the 30 degrees head-up position, to a 10 degrees head-down position, and to the intravenous administration of propranolol.


Serum zinc and urinary zinc excretion after renal allotransplantation. In nine kidney-transplanted patients, receiving prednisone as part of the immunosuppression, serum zinc and urinary zinc excretion were measured for a period of 5-7 weeks after the transplantation. Serum zinc decreased significantly from normal pretransplant values to subnormal vaues 1-5 days after the transplantation. Thereafter, the serum zinc rose again, and after 2-3 weeks, before start of reduction of prednisone, the serum zinc had risen to a level that was not significantly lower than the pretransplant level. Urinary zinc excretion was generally elevated, especially just after the transplantation. In patients with initially good kidney function function the zinc clearance to creatinine clearance ratio was significantly higher during the first week after the transplantation than in the rest of the observation period. Similar findings have been reported after major surgery, and no correlation between serum zinc and the corticosteroid dose was demonstrable. Therefore, in renal allotransplantation, no special supplementation of zinc seems necessary beyond what may be justified by the effect of the surgical trauma.


Human granulocytopoietic colonies in diffusion chambers in mice: growth of colonies and the effect of host irradiation. Normal human non-separated bone marrow cells were cultured in fibrin clots in diffusion chambers implanted intraperitoneally in mice, and harvested at different intervals by a previously described chamber centrifugation technique. This method demonstrates the presence of cell aggregates in the diffusion chambers. When the chambers are implanted in irradiated mice (450 R) and retransplantated into newly irradiated mice every seventh day, a continous increase in number of cells per granulocytopoietic aggregate is observed from day 8 to day 21. This is compatible with the view that the aggregate is observed from day 8 to day 21. This is compatible with the view that the aggregates are colonies. The term 'colony forming unit diffusion chamber' (CFUD) is suggested to denote the ancestor(s) of the colonies. However, formal proof that one colony is derived from one cell is lacking. Preirradiation of mice with 450 R significantly increases the number of neutrophilic granulocytopoietic colonies at day 14, provided the chambers are retransplantated to newly irradiated mice at day 7, indicating that the neutrophilic colony forming unit or its progeny is involved as at least one of the targets of the stimulating effect of host irradiation. In contrast, no effect of host irradiation on the numbers of eosinophilic colonies was observed.


Monoclonal B-lymphocytes in peripheral blood of patients with plasma cell myeloma. Relation to activity of the disease. Antisera were produced in rabbits against idiotypic determinants of the myeloma protein from 3 patients with IgG-k myeloma. The antisera did neither cross-react nor react with normal immunoglobulin (Ig). Idiotypic Ig-structures were demonstrated by indirect immunofluorescence (IFL) on 70-94% of peripheral B-lymphocytes inuntreated patients. The total numbers of circulating B-lymphocytes were increased with a simultaneous decrease of T-lymphocytes. Only one of the patients had blood lymphocytes which stained for cytoplasmic Ig with idiotypic antiserum. The monoclonal lymphocyte population decreased gradually during treatment. Plasma cell counts in bone marrow, IgG concentration in serum and erythrocyte sedimentation rate decreased simultaneously, whilt the haemoglobin concentration increased. Very few monoclonal lymphocytes were present during remission. Later, the monoclonal lymphocyte population began to increase in 2 of the patients in parallel with clinical signs indicating relapse. It is concluded that presence of monoclonal B-lymphocytes indicates dissemination of the disease and that they may belong to the malignant cell clone.


A trial of a phase-release aspirin preparation in rheumatoid arthritis. Thirty-six patients with active rheumatoid arthritis were treated in a double-blind cross-over study of phase-release aspirin tablets and aspirin B. P. tablest. Twenty-nine patients completed the study. The phase-release preparation given twice daily proved as effective as aspirin B.P. given four times daily. Better results were produced by the phase-release aspirin in respect of the degree and duration of morning stiffness, grip strength and joint size, although the differences did not reach the level of statistical significance. The E.S.R. was significantly reduced by the B. P. preparation but this result was thought to be due to an order effect in the weeks of therapy.


[Multiple sclerosis. Etiopathogenetic review]. This is a synthetic report about multiple sclerosis: there is described the neuropathology (by optic and electronic microscopy) of this disease, the changes in the protein metabolism, above all in basic protein content, in lipids, in enzymes of the plaques and of the apparently normal white and gray matter. There are afterwords described the relationship between viruses and multiple sclerosis, the probable action mechanism of the virus-determined demyelination, and the changes of the immunitary system (increase of gamma-globulins, serum myelotoxicity, lymphocitary changes).


[Rejection of a kidney graft after pregnancy and delivery]. Eighteen months after cadaver kidney transplantation a 22-year-old woman was successfully delivered of a healthy female child. Onset of allograft rejection in the third trimenon was followed three weeks after delivery by progressive renal failure and resumption of regular dialysis treatment. Pregnancy risk factors after successful renal transplantation and immunosuppressive therapy are discussed.


[Chronic juvenile kidney insufficiency. Results of a Swiss questionnaire]. From 1972 to 1974 a collaborative prospective study was undertaken to determine the incidence, causes and clinical course of chronic renal failure (CRF) in pediatric patients (age 1/2-16 years) in Switzerland. In addition, information concerning the occurrence of terminal CRF observed between 1967 and 1971 was obtained. CRF is defined as persistently elevated serum creatinine greater than 2 mg/100 ml. The small size of Switzerland (population 6.27 million) and the availability of specialized medical care favoured relative completeness of data. a) Non-terminal CRF. - Prevalence was 4.5 per million total population = 18.5 per million children (1/2-16 years old) (n = 28 at 31. 12. 1974). Causes: renal disease was acquired in 14% and congenital in 86% (hereditary nephropathies excluding polycystic kidneys 4%, polycystic kidneys 14%, hypoplasia 14%, urinary tract abnormalities 54%). Progression of CRF: mean time interval in which serum creatinine doubled was, in the group of acquired renal diseases, 8.3 months (n = 6); in hereditary nephropathies 14.3 months (n = 4); in the group of polycystic kidneys and hypoplasia 41.2 months (n = 6), and in patients with urinary tract abnormalities 35.8 months (n = 15). Body height was reduced in all groups as compared with normal children: 1.0 SDS (standard deviation scores) in acquired renal diseases (n = 9), 5.1 SDS in cystinosis (n = 2), 0.4 SDS in polycystic kidneys (n = 4), 1.6 SDS in hypoplasia (n = 5), and 2.3 SDS in urinary tract abnormalities (n = 16). b) Terminal CRF. - Mean yearly incidence (1967-1974, n = 68) was 1.36 per million total population = 5.6 per million children (1/2-16 years). Causes: In contrast to the situation in non-terminal CRF, acquired diseases were observed in 56% of all patients. Hereditary nephropathies were found in 12%, polycystic kidneys in 1.5%, hypoplasia in 4.5%, and urinary tract abnormalities in 26%. Between 1970 and 1972 , 7 of 21 patients, and during 1973/1974 13 of 16 pediatric patients, were treated by intermittent hemodialysis and renal transplantation. On 31. 12. 1974, 18 of these 20 treated patients were alive, and of these 14 had a functioning graft.


[Around the sphincter: problems of continence in surgery of the large intestine]. Anatomy and physiology of anal continence and incontinence are described. The surgeon's first main task is the prevention of incontinence, e.g. in the treatment of the small and mobile carcinoma of the rectum, the wide pedunculated papilloma, the fistula in ano, haemorrhoids and anal fissure. The second main task is the reconstruction of continence of rectal prolapse, ectropion, third grade rupture of the perineum and perineal injuries. The possibilities for reconstruction, reinforcement and replacement of the sphincter are described.


[Organ transplantations in intestinal tract surgery: history or future?]. In the case of three gastrointestinal organs - the esophagus, the stomach, and the colon - no indication for clinical transplantation is conceivable today or in future. On the other hand, experience with transplantation of the small bowel, the liver and the pancreas has already been gained, though up to now the results have been rather poor. Nevertheless, some clear indications exist which justify these transplantations in highly specialized centers. They include total loss, of the small bowel, multiple small bowel atresias, acute liver necrosis, congenital biliary atresia, Echinococcus alveolaris, in future some enzyme defects and finally, juvenile diabetes with nephropathy. Whether, and when, transplantation in these diseases becomes routine will depend on progress in immunology.


[Digestive complications and kidney transplantations]. A survey of 54 patients who had received one or two renal homografts revealed that 15 presented 18 types of serious digestive complications. A relation between immunosuppressive treatment and subsequent appearance of a complication is frequently encountered. Gastrointestinal bleeding constitutes a real danger for the transplant recipient. The importance of early detection of peptic ulcer and treatment by major surgery are stressed. Out of the 12 deaths registered among the total number of patients, 2 were caused by one of the digestive complications.


[Direct bonding in orthodontics].

[Direct bonding in orthodontics]. Composite materials have been used to attach orthodontic brackets on the conditioned enamel surface. A method of direct bonding with Enamelite of metal brackets with a mechanical retention on the basis is described. Clinical experience with the adhesive technique, its range of indication and possible failures are discussed in several case reports.


Effect of histamine H2-receptor blockade on gastric emptying and serum gastrin in man. The effect of orally administered metiamide, a Histamine H2-receptor antagonist, on the rate of gastric emptying was assessed in 24 uncomplicated duodenal ulcer patients given a standard meal containing indium 113m D.T.P.A. chelate. Metiamide produced significant slowing of gastric emptying when compared with control studies performed on the same patients following oral administration of a placebo. In a further study the effect of metiamide on the serum gastrin response to a protein meal was assessed in seven healthy male volunteers. Paired experiments demonstrated that a significantly greater elevation of serum gastrin occurred after metiamide than after placebo. The delay in gastric emptying produced by metiamide may be mediated by an elevation of the serum gastrin concentration.


Metal ions in enzymes using ammonia or amides. In an attempt to understand the role of nickel in jack bean urease (1), we turned to a variety of other enzymes important in the utilization, production, or transfer of ammonia. We found several, including the L-histidine and L-phenylalanine ammonialyases and some enzymes that utilize glutamine or ammonia in amidotransferase reactions, all of which show evidence for the involvement of as yet unreported transition metal ions in their mechanism of action. We support the view that catalysis by metalloenzymes may be a reflection of the chemistry of the metal ion itself as a Lewis acid, and that perhaps too much emphasis has been placed on supposed special characteristics (such as strains, "entasis") of the enzyme-metal ion association. In this context, we have discussed the mechanism of catalysis of hydrolysis of specific substrates by carboxypeptidase A, and have returned to urease to examine the role of nickel in its mechanism of action.


Phylogeny of DNA polymerase-beta.

Phylogeny of DNA polymerase-beta. Analyses of various organisms for DNA polymerase-beta activity show that the enzyme is widely distributed in cells from multicellular animals but absent in bacteria, plants, and protozoa. These results suggest that DNA polymerase-beta may have evolved with the development of metazoan forms. Further evolutionary changes of the enzyme protein may account for some of the minor differences in properties of the enzyme in various organisms.


Insulin-dependent diabetes: a disease of autoaggression. Lymphocytes from patients with insulin-dependent diabetes demonstrated significant cytoadherence and cytotoxicity against human insulinoma cells in vitro as compared to lymphocytes from normals. Complement was not involved in insulinoma cell destruction. The findings suggest that insulin-dependent diabetes may be a disease of autoaggression.


Human babesiosis: reservoir in infection on Nantucket Island. Examination of blood films from six species of rodents and lagomorphs on Nantucket Island disclosed infections with Babesia microti in all of five Microtus pennsylvanicus (field mice) and 31 of 39 Peromyscus leucopus (white-footed or deer mice). Six human cases of clinical babesiosis have recently been diagnosed on the island.


Lymphocele following renal transplantation: value of ultrasonography in diagnosis and follow-up studies. The case of a perirenal lymphocele complicating renal homotransplantation and simulating early rejection is presented. Multiple aspirations of the lymphocele combined with open drainage resulted in cure and return of good renal function. Ultrasonography allowed identification of the lymphocele and an assessment of its response to treatment.


Treatment of aseptic necrosis of the femoral head with Phemister-type bone grafts. This study was performed in order to assess the success and failure of bone grafting in early aseptic necrosis of the hip. Ten patients (11 hips) with a minimum of two years follow-up were evaluated by radiographic and clinical parameters. Seven of the 11 hips had good or excellent results. The criteria for a successful result were proper patient selection and exact placement of the bone grafts. The Phemister bone grafts appear to be the treatment of choice in early aseptic necrosis of the femoral head.


Electroencephalographic findings in patients with mild Parkinson's disease treated with L-dopa and placebo. The prognostic value of electroencephalograms in patients with early or mild Parkinson's disease treated with L-dopa is discussed. Fifteen patients with early or mild Parkinson's disease were studied clinically and electroencephalographically while receiving L-dopa or placebo treatment. Only a low incidence (four patients, 27%) of EEG abnormality was found. These patients showed only mild improvement: in three cases, the improvement followed an initial worsening in the first three months. Only one (13%) of the patients with a normal EEG became worse or failed to improve. The potential use of EED data in parkinsonism is discussed.


The variant form of angina pectoris.

The variant form of angina pectoris. Variant angina pectoris, usually not precipitated by exertion or emotional stress, often is more severe and lasts longer than classic angina. The pain tends to recur at about the same time each day. Arrhythmias, usually ventricular, occur in about 50% of cases during the peak of pain. Electrocardiograms show a characteristic ST segment elevation during pain, which is in contrast to the ST segment depression of classic angina pectoris. Pain may be due, at least in some cases, to a temporary increase in tonus of a single, large, narrowed coronary artery. Chemical changes in the myocardium and plasma catecholamine changes differ from those occurring in classic angina pectoris. The course of the disease is highly variable but the prognosis must be regarded as grave, since single large vessel disease, present in most cases, is associated with severe myocardial ischemia. Patients with variant angina pectoris should be studied early with coronary arteriography and considered for coronary artery bypass surgery if appropriate.


Coagulation studies in falciparum and vivax malaria. Coagulation factors and serum fibrin degradation products (FDP) were studied in 31 cases of acute falciparum malaria with severe complications, 13 cases without severe complications, and 6 cases of vivax malaria. Seven of 13 cases of acute falciparum infection with severe complications died and the coagulation studies were markedly changed and there were high levels of serum FDP. The degree of changes in coagulation and serum FDP varied with the severity of the symptoms and signs and there were virtually no changes in the cases of vivax malaria. It was speculated that changes might be the result rather than the cause of pathogenic processes in falciparum malaria.


Skin cover in extensive hand injuries.

Skin cover in extensive hand injuries. The concept of 'axial-based' flaps has revolutionised the replacement of full-thickness defects of the skin and subcutaneous tissue of the hand. The groin flap provides extensive skin replacement, and has the advantage of allowing considerable mobility of the hand, elbow and should during the period of attachment.


Failure to demonstrate high concentrations of luteinising hormone-releasing hormone in the bovine pineal body. Six in vitro experiments were conducted to study the effects of the incorporation into the culture system of 10 bovine pineal bodies (or a similar mass of bovine hypothalamic tissue) on the secretion of luteinising hormone (LH) from bovine adenohypophyseal tissue (anterior pituitary - AP). When hypothalamic tissue was incubated with AP tissue, an increased amount of LH was released into the medium but no marked increase in LH secretion was observed when pineal bodies were included in the AP culture system. Additionally, the amount of radio-immunologically active luteinising hormone-releasing hormone (LHRH) contained in bovine pineal bodies was much less than that contained in an equivalent mass of hypothalamic tissue. Thus, present results do not support the concept that the pineal body contains comparatively large amounts of lhrh.


Gastric acid and serum gastrin secretion before and after bypass of the small intestine for morbid obesity. Six obese patients undergoing end-to-side jejunoileal bypass had gastric acid output and serum gastrin measurements performed preoperatively and within three months postoperatively. Meat extract stimulated acid output was higher in obese than in normal patients. Following the bypass procedure, basal and meat extract stimulated acid output significantly decreased. Basal and meat extract stimulated serum gastrin levels did not change following bypass. These studies demonstrate that after a small intestinal bypass, acid output decreases. Gastrin plays no role in this change.


use of F(ab')2 fragment in experimental skin transplantation for burns. In a series of experiments involving approximately 500 animals, burned rats were administered the F(ab')2 fragment of antidonor IgG to study the survival of incompatible skin allografts. No prolongation was noted when treatment consisted of antidonor F(ab')2 fragment alone. This was true whether the fragment was raised against donor spleen cells of donor skin, whether the skin allograft was partial or full thickness and whether the systemic treatment of the recipients was preceded by a period of incubation of the graft in F(ab')2 fragment or not. Significant prolongation of survival was noted when the fragment was raised against both donor and recipient histocompatibility antigen and when the donor skin was incubated in steroids as well as in F(ab')2 fragment prior to grafting. Additional findings included the confirmation of prolonged allograft survival by increasing burn size and the prolongation of allograft survival by the presence of intact eschar.


Experiences with the Linton-Nachlas and the Sengstaken-Blakemore tubes for bleeding esophageal varices. A controlled clinical trial was begun to compare the effectiveness of the Sengstaken-Blakemore tube with that of the Linton-Nachlas tube in the emergency treatment of bleeding esophageal varices. The investigation was prematurely terminated after two lethal complications with the Linton-Nachlas tube. At that time, 28 patients with 42 bleeding episodes were included. Twenty-seven were treated with the Sengstaken-Blakemore tube, with bleeding being controlled in 20; 15 were treated with the Linton-Nachlas tube, with bleeding being controlled in six. No significant statistical difference was found between the two tubes, 0.05 less than p less than 0.1, but the results encourage the use of Sengstaken-Blakemore tube in preference to the Linton-Nachlas tube, except in patients with a hiatal hernia or bleeding from fundic varices.


Abdominal hysterectomy in obese women.

Abdominal hysterectomy in obese women. During a 25 year period in a university hospital gynecology service, 300 obese women, weighing 200 pounds or more, underwent abdominal total hysterectomy. In comparison with nonobese controls, the overweight patients were more likely to have carcinoma of the endometrium, hypertension and diabetes mellitus. Postoperatively, the most striking difference between the obese and nonobese groups was in the incidence of wound complications, with no significant difference in the occurrence of other disorders. The incidence of wound complications was 29 per cent with obesity, seven times that in patients of normal weight, and all types of wound disorders, except evisceration, occurred more frequently in obese patients. Among identifiable factors potentially responsible for wound infection were an increased incidence of diabetes, longer operating time and greater blood loss in overweight patients. The increased incidence of wound infection was responsible for greater febrile morbidity and the more frequent need for prolonged hospitalization. The mortality rate was 1 per cent in the obese group and zero per cent in the control group, a statistically insignificant difference. Since abdominal hysterectomy in obese women is associated with increased risk of morbidity, although not necessarily of mortality, obesity per se should rarely, if ever, contraindicate necessary surgical therapy. In situations in which surgical treatment is more elective, its complications should be borne in mind.


An improved technique of excision and skin grafting for primary malignant melanomas. A technique is described which decreases the cosmetic defomity associated with excision of primary melanomas and split thickness skin grafting. The incised skin edges are beveled peripherally and sutured to underlying muscle. A complete take of the graft is routine. There is a smooth transition from the cut skin edges to the skin grafted area that contrasts sharply with the cosmetically inferior cookie cutter defect resulting from conventional techniques.


Anterior cervical fusion using homologous bone grafts: a comparative study. A comparative sutyd of homologous and autogenous bone grafts in Smith-Robinson type anterior cervical fusions reveals no significant difference between the two in clinical or radiographic results and no complications related to the use of the homologous grafts from the tissue bank.


Renal transplantation between HL-A haploidentical donor-recipient pairs: functional and morphological evaluation. Fifty-nine recipients received renal allografts from an HL-A haploidentical family member. Immunogenicity of the incompatible haplotype was measured by skin grafts exchanged within each family when possible, and renal allograft recipients were assigned prospectively to two groups depending on the skin graft survival time (Group 2A greater than 15 days; Group 2B less than 15 days). If skin grafts could not be accomplished, the patients were place in an unclassified group, Group 2. Renal function at one and 2 years following engraftment did not differ between the two groups. Mixed lymphocyte stimulation of recipient lymphocytes by mitomycin-treated donor lymphocytes also was comparable in the groups. Histopathological evaluation by light, immunofluorescence, and electron microscopy at least 6 months following allografting did not distinguish between the groups. The only differentiating characteristic was that Group 2A patients did not experience their primary rejection episode until an average of 18 days following transplantation, whereas Groups 2B and unclassified 2 had their initial primary rejection episode at average days 9 and 5, respectively. In our clinical program, matching for HL-A halotypes continues to be the best predictor for long-term renal function in consanguineous renal transplantation.


Renal transplantation in patients with urinary tract abnormalities. Patients with chronic renal failure and total diversion of the lower urinary tract have been considered poor transplant candidates, and post-transplant urinary diversion, i.e., Bricker loop, has been thought to be necessary. Our experience with nine patients clearly indicates that these patients are actually excellent transplant candidates and that post-transplant urinary diversion rarely is necessary. Ureteroneocystostomy of the allografted ureter was performed in seven patients with pretransplant total urinary diversion and all have completely normal bladder and renal function 10 to 66 months after transplantation; the two patients with Bricker loop procedures performed at transplantation died 7 months after transplantation of rejection and pancreatitis. The excellent results achieved with ureteroneocystostomy are attributed to (1) errors in diagnosis resulting in inappropriate bladder or ureteric surgery early in the course of the patient's disease; (2) confusion of immunologic of functional disorders with anatomic problems; (3) growth and development of the bladder, and (4) complete control of chronic bladder infection by pretransplant nephrectomy, ureterectomy, and antibiotics.


Microvascular techniques for polar artery reconstruction in kidney transplants. The complications of ureteral ischemia make revascularization of polar vessels attractive in cadaver and live-related transplants. Thirty-two patients underwent reconstruction of polar vessels of 1.2 to 2.5 mm, in diameter after revascularization of the major vessels as follows: (1) inferior epigastric artery to polar artery, ten patients - six cadaver transplants, four living-related transplants (The vessels are spatulated and sutured precisely by microvascular techniques with Nos. 7-0 or 8-0 Tevdek); (2) polar vessel with a patch of aorta to iliac artery, one patient - living relative donor; (3) polar artery to the main renal artery or branch, 17 patients - 14 cadaver transplants, three living-related transplants [A Waters "MOX"-100 machine is used with cryoprecipitated plasma (800 mg. of SoluMedrol and 80 U. of insulin added) for preservation.]; (4) autogenous saphenous vein graft, two patients - one child receiving on adult live-related kidney and one cadaver transplant with three arteries and a stenosis of the inferior polar vessel; (5) polar artery to vein patch in iliac artery, two patients - cadaver transplants. Follow-up was done by arteriography (18 patients), direct observation (two patients), and by use of ultrasound (one patient). The remaining 11 patients have exhibited no evidence of occlusion. Twenty of 21 patients exhibited patent vessels; one thrombosed at the time of the transplant operation. Long-term patency in those patients studied was 95%. We advocate small-vessel reconstruction in human renal transplantation, either during ex vivo preservation (workbench surgery) or at the time of transplantation.


Sequential renal transplants: some surgical and immunological implications on management of the first homograft. Experience with 35 second grafts included in a total number of 310 renal transplants was analyzed to identify factors associated with success. The 2 year life-table renal survival rate of sequential cadaveric grafts is 42 percent compared in 54 percent for primary cadaveric grafts. The 2 year life-table patient survival rate for the same group is 68 percent compared to 72 percent for single cadaveric homotransplants. Twenty-one of 30 patients tested in the interval between grafts developed cytotoxic antibodies to greater than 5 percent of a random panel of cells; 43 percent of these kidneys functioned at least one year; 65 percent functioned for one year or more if the cytotoxicity was 5 percent or less. If the first graft functioned greater than 3 months, the second had a 67 percent chance of functioning for one year; if less than 3 months, the second had a 45 percent one year function rate. Removal of the first transplant at time of second transplantation resulted in an 88 percent one year life-table survival rate of the second kidney in nine patients. Removal prior to second transplantation resulted in a 25 percent one year survival rate in 23 patients. To further evaluate this significant finding, data was obtained through the American College of Surgeons/National Institutes of Health (ACS/NIH) Organ Transplant Registry from five major transplant centers. Thirty-two patients had their first graft removed at time of second transplantation with a 52 percent one year life-table kidney survival rate vs. 29 percent if the first were removed more than 90 days prior to second grafting. Statistical analysis shows this to be significant at the 95 percent confidence level.


Cryptococcosis after renal transplantation: report of ten cases. Ten cases of cryptococcosis have been identified in a 13 year experience with more than 650 renal transplants. Eight patients had meningitis, one patient had a cerebral granuloma, and in one patient the infection appeared to be limited to the lungs. The central nervous system infection often masqueraded as brain tumor and was not suspected initially. The most useful diagnostic test was cerebrospinal fluid examination including India ink preparation. Various ther apeutic regimens with amphotericin B and 5-fluorocytosine were effective in suppressing the infection. A combination of low doses of amphotericin B, not affecting kidney function, with 5-fluorocytosine for at least 3 months was associated with remission of disease in five patients who still are alive, including three patients without recurrence for longer than one year. Five deaths 3 weeks to 4 years after the beginning of treatment were not due to cryptococcosis; death resulted from vascular disease and septiciemia in three of the four patients with known causes of death. Central nervous system cryptococcosis, with the exception of the rare cerebral granuloma, is associated with little inflammation. If early death from increased intracranial pressure or cerebral edema is prevented, prolonged therapy with amphotericin B and 5-fluorocytosine may be expected to control the infection, even in immunosuppressed patients.


Cessation of immunosuppression after renal transplantation. Five recipients of successful living related donor kidney transplants stopped azathioprine and prednisone against medical advice. Two recipients who were nonidentical by human leukocyte (HL-A) serotyping and mixed leukocyte culture (MLC) became uremic again after cessation if immunosuppression for periods of 2 and 6 months. Both patients died while refusing to reinstitute iunosuppression and their kidneys showed severe rejection histologically. Three recipients of MCL and HL-A identical kidneys were off azathioprine and prednisone for periods of 7, 12, and 30 months, respectively. None developed changes in renal function. Two patients currently are back on immunosuppression. The third recipient remains stable although off immunosuppression for 36 months; her cessation of immunosuppression was elicited by a mailed questionnaire sent to all recipients following detection of the first four. In addition to these five patients, three recipients of cadaver kidneys lost graft function after lapses in immunosuppression. This represents a 4% incidence of major lapses in immunosuppression (excluding known cessation during sepsis). The clinical outcome depended on degree of histocompatibility as best measured by MLC.


Stephen H. Watts: A disciple of Halsted. Stephen Watts was one of Dr. William S. Halsted's 17 resident surgeons. He contributed much to experimental, clinical, and didactic surgery during his lifetime. Primarily, his experimental work was in vascular and transplant surgery modeled after Alexis Carrel's efforts. Clinically, he maintained the diversity and expertise propagated by Dr. Halsted. As a teacher he continued the education of young surgeons in the spirit of a true academician.


Use of plasma protein fraction in preservation of cadaveric kidneys. We have compared 23 cadaver kidneys preserved with cryoprecipitated plasma (CPP) with 23 consecutive cadaver kidneys preserved with plasma protein fractions (PPF). In both groups the MOX-100 Waters machine was used. The PPF solution does not contain any fibrinogen or gamma globulin. The harvesting characteristics of both groups were comparable. Pulsatile perfusion time in the PPF group was up to 46 hours and in the CPP group was up to 44 hours. In the PPF group, 20 kidneys achieved immediate function upon transplant (85 percent). Two underwent periods of acute tubular necrosis (ATN) and one kidney never worked. In the CPP group, 18 kidneys achieved immediate function (78 percent). Two underwent periods of ATN and three never achieved satisfactory function. From this clinical experience, PPF is as effective as CPP for the preservation of kidneys up to 44 hours prior to transplant. The advantages of the PPF are easy availability, long shelf life, simple preparation, low cost, freedom from risk of hepatitis, and theoretical absence of antibody against the kidney. Graft and patient survival at 6 months showed no statistical difference.


The adverse effect of high-dose steroids on renal autografts and homografts. We observed that canine renal homografts preserved for 5 hours with hypothermic pulsatile perfusion to which large doses of methylprednisolone were added showed obliteration of glomerular capillary loops by eosinophilic proteinaceous material immediately after revascularization. The lesion progressed to focal necrosis at 24 hours and diffuse necrosis by 5 days. Urine formation was present 7.8 (+/- 3.2 S.D.) days in eight control kidneys not exposed to methylprednisolone, 5.8 (+/- 3.8 S.D.) in 11 organs perfused with 1.0 Gm. of methylprednisolone added, and 3.0 (+/- 2.9 S.D.) in eight with 2.0 Gm. of the drug in the standard cryoprecipitated canine plasma perfusate. Autografts treated with the larger dose also showed a similar but temporally more variable lesion. Two kidneys ceased functioning at 4 and 7 days, and six still were functioning at 14 days. Ninety-four percent of human renal homografts from living related donors were functioning at one month and 82 percent at one year in 88 patients who had rejection crises treated with one gram of methylprednisolone or less intravenously. In 32 human recipients of living related donor grafts receiving 40 mg. per kilogram of methylprednisolone intravenously from days one to 3 postoperatively and for rejection crises, 69 and 59 percent were functioning at one month and one year, respectively. From this data we conclude that exercise doses of methylprednisolone are inadvisable in renal transplantation.


Perfusion time and the survival of cadaver transplants. Perfusion of cadaver kidneys up to 48 hours did not adversely affect the long-term renal allotransplant function and did not result in an increased rate of rejection. In fact, cadaver kidneys perfused for longer periods of time had a slightly better functional survival rate than did kidneys perfused for shorter periods. From 100 perfused cadaver kidneys, we can conclude that the length of perfusion had little if any effect on the immunogenicity of the renal allograft in the immunosuppressed transplant patient.


Possible active enhancement of a human cadaver renal allograft with antilymphocyte serum (ALS) and donor bone marrow: case report of an initial attempt. Nonspecific immunosuppression of transplant patients frequently leads to complications which might be circumvented by inducing donor-specific immune unresponsiveness. Such specific immunosuppression has been produced experimentally, with use of donor antigen and antilymphocyte serum (ALS) for active enhancement. A case is presented in which the recipient of a cadaveric renal allograft (zero antigen match, cross-match negative) was given ALS (first 14 days after operation) and 11 X 10(9) donor bone marrow cells (twenty-fifth postoperative day) along with conventional doses of prednisone and Imuran in an attempt to produce donor-specific immune unresponsiveness. There were no rejection episodes, and serum creatinine remained less than 1.0 mg. per 100 ml. By the second month after transplantation there was no evidence for the persistence of donor erythrocytes or white cells. The conventional immunosuppressive agents were tapered and renal function was normal 8 months after transplantation, when the patient developed fatal peritonitis secondary to perforated sigmoid diverticulitis. At autopsy the renal allograft showed only minimal evidence of rejection. The present case illustrates an attempt to use ALS and donor bone marrow cells for active enhancement of a human cadaveric renal allograft. The infusion of stored donor marrow cells after transplantation is a particularly applicable technique for human cadaveric organ transplantation. The rejection-free course of this patient suggests that attempts to produce active enhancement clinically deserve further trial.


Total and active T cell dynamics in renal allograft recipients. Serial determinations of human thymus-dependent (T) and bone marrow-dependent (B) peripheral blood lymphocytes were performed to detect changes in activity of these rosette-forming cells in five groups of patients: controls; chronic renal failure (CRF) patients; dialysis patients receiving pretransplant splenectomy; 5 days before transplant immunosuppression; and following 17 patient renal allograft implantations. Five cadaver recipients received ATG for 14 days. Patient follow-up was 27 to 215 days (M = 101) during which time four cadaver grafts were lost to rejection. Twenty clinical acute rejection (AR) episodes occurred. CRF patients had suppressed total T cells when compared to control patients (63.2 to 44.7 percent, P less than 0.01) without change in active T cells. Similarly, total T cells decreased in CRF patients following splenectomy (56.7 to 35.5 percent, P greater than 0.01), during prednisone-azathioprine immunosuppression (65.6 to 46.7 percent, P greater than 0.01), with no change in active T cells. Both active and total T cells declined profoundly during ATG administration, following allograft implantation, and during AR. Active and total T cells increased when ATG was discontinued, when AR subsided, and following transplant nephrectomy. B cell populations were suppressed in only the ATG group. These studies delineate that total T cells are influenced by many interventions and active T cells specifically reflect cellular-immune kinetics in renal allograft recipients.


Monitoring and modulation of immune reactivity in human transplant recipients. In this study parameters of humoral antibody (HA) and cell-mediated immunity (CMI) were measured before and after transplant in 44 renal transplant patients. The results indicated that, before transplant, CMI parameters but not HA measurements correlated with early graft rejection crises. In antithymocyte globulin (ATG)-treated patients, a striking loss of early rejection activity occurred which correlated with ablation of T cells in the peripheral blood. ATG-treated patients also had a marked loss of T cell reactivity, as measured by phytohemagglutinin (PHA) blastogenesis and these parameters also correlated with allograft reactivity. Concanavalin A (Con-A) reactivity, however, did not correlate well with early rejection activity. Triple drug therapy with ATG, but not prednisone-Imuran therapy, caused a marked fall of T cell levels and reactivity within hours of the first dose of ATG. None of the ATG-treated patients had irreversible or progressive rejection in the first month after transplant and only 32 percent of patients had rejections, of which more than 70 percent were Type I. A "permissive" level of T cells of about 20 percent of normal was associated with over 95 percent of acute rejection crises, whereas no correlation of a variety of humoral antibody parameters and rejection has been seen in our unit. These studies suggest a primary role of the T cell in early allograft reactivity and indicate that future immunosuppressive techniques for human transplantation should be directed toward effective monitoring and modulation of T cell levels and reactivity in the early post-transplant period.


Forty-eight hour ice storage of kidneys: importance of cation content. The importance of the cation content of flush solutions used for simple hypothermic storage has been investigated in a 48 hour canine kidney preservation model. Uniformly successful 48 hour storage was achieved with solution C2. However, inclusion of procaine (0.1 Gm. per 100 ml.) in the flushing solution as in C3 produced significant kidney damage. Without procaine, Sacks solution was no better than was C2 and the latter proved significantly superior to a sodium-based solution having identical anion content and osmolarity. The magnesium content of the sodium appeared to favorably influence the outcome of the kidney storage experiments.


Perfusion-related injury in renal transplantation. The implantation and one hour post-transplant renal biopsies from three types of allograft recipients were compared with a blind grading system: (1) 25 cadaver kidneys preserved by pulsatile perfusion, (2) seven cadaver kidneys preserved by simple hypothermia following electrolyte solution flush, (3) 18 kidneys from living-related donors. Significant lesions were found only in cadaver kidneys which had received pulsatile preservation. Microscopic findings were correlated with perfusing agent, length of perfusion and its characteristics, and subsequent clinical course of the patient. Perfusion-related injury was found to be morphologically identical to hyperacute rejection, although the lesion is produced by quite different mechanisms. Pulsatile preservation appears to be associated with a spectrum of mechanical endothelial injury ranging from minute breaks visible only ultrastructurally to areas of complete denudation baring the basement membrane. The exposed collagen activates the clotting sequence resulting in platelet and fibrin deposition, whereas in classical hyperacute rejection the triggering mechanism is cytotoxic recipient antibody. The extent of perfusion-related injury correlates well with length of preservation, quantity of fibrin deposited, and, most importantly, with both the immediate and long-term post-transplant failure rate. In some patients the injury appears to be produced by cytotoxic antibodies in the plasma perfusate, which combine with antigens in the kidney ex vivo. The Ag-Ab complex activates complement and coagulation sequences in vivo after reimplantation. Early results with albumin or purified plasma fraction perfusates suggest this portion of perfusion-related injury can be eliminated. Comparison of pre- and postimplantation biopsies of the kidneys preserved by simple hypothermia or by pulsatile preservation suggests that perfusion-related injury is much more common than is true hyperacute rejection mediated by recipient cytotoxic antibodies. We suggest that the term "hyperacute rejection" be reserved for situations where significant endothelial drainage has been excluded by preimplantation biopsy and where recipient cytotoxic antibodies can be proved.


Practical considerations for the use of a pulmonary artery thermistor catheter. The use of a pulmonary artery thermistor catheter for pressure measurement and thermodilution cardiac output determination was evaluated in 11 dogs. Pulmonary artery wedge pressure was a reliable index of left atrial pressure at end-expiratory pressures less than 10 cm. H2O. Fluctuations in pulmonary artery temperature occurred at a frequency equal to the respiratory rate and an amplitude of 0.010 to 0.086 degrees C. Changes in amplitude were associated with changes in ventilatory waveform, respiratory rate, and level of anesthesia. Intermittent and continuous positive-pressure ventilation generally dampened and reversed the pulmonary artery temperature pattern exhibited during spontaneous breathing. This suggested that when end expiration is used to time indicator injection, cardiac output will be underestimated during spontaneous breathing and overestimated during continuous or intermittent positive-pressure ventilation. When indicator was injected at the same point in the ventilatory cycle, successive values of cardiac output deviated from one another by 0.0 to 6.7 percent. Deviations as large as 14 percent resulted if sequential injections were out of phase by half a respiratory cycle. These deviations can be minimized by injecting indicator at the same point in the respiratory cycle, if it is not feasible to measure cardiac output during apnea. The clinical utility of a pulmonary artery thermistor catheter can be optimized through appreciation of its specific strengths and limitations.


Beta-adrenergic function in airways of healthy and asthmatic subjects. We measured the short-term effects of beta-adrenergic blockade with propranolol (0.2 mg/kg iv), followed by stimulation with salbutamol (200 mug inhaled), on specific airway conductance (SGaw) heart rate, and systemic blood pressure (BP) in 11 healthy subjects, and 11 symptom-free asthmatics with normal lung function values. Propranolol induced a significant bronchoconstrictor effect in both groups, stronger in asthmatics than in normals: mean SGaw decreased 34.6 +/- 25% against 9.4 +/- 9% (p less than 0.01). Six of the 11 asthmatics exhibited a more pronounced bronchoconstriction than the most responsive healthy subject. Large individual variations were seen in both groups although they were greater in the asthmatics. A similar rise in SGaw was produced by salbutamol in both groups. The decrease of heart rate provoked by propranolol was similar in the two groups, averaging 18.6%, with no further change after salbutamol. The blood pressure was slightly decreased by propranolol in both groups. The results indicate that normal subjects have a weak and variable bronchodilator beta-adrenergic activity. In most asthmatics beta-adrenergic tone appeared more pronounced. The individual differences in response to propranolol observed in both groups suggest that asthmatic patients differ quantitatively rather than qualitatively from healthy subjects with respect to beta-adrenergic receptor function. There was no association between clinical findings and the degree of bronchomotor effect of propranolol in the patients with asthma. This study does not support the view that airways of asthmatic patients have a decreased beta-adrengeric receptor function.


No demonstrable effect of S-carboxymethylcysteine on clearance of secretions from the human lung. The mucolytic efficacy of S-carboxymethylcysteine has been assessed in a double-blind crossover trial in 16 patients with chronic obstructive bronchitis. No significant difference was found between drug and placebo after four or seven days' treatment in the rate of clearance of secretions from the lung. This was measured by external counting of previously inhaled polystyrene tracer particles tagged with technetium-99m (99mTc). Lateral scans across the right chest after inhaling the aerosol showed equal penetration of particles towards the periphery of the lung in drug and placebo runs; this indicated that the airways had not been cleared of mucus by the drug. There was no significant difference between drug and placebo runs in the number of coughs or the weight and radioactive content of sputum voided or raised at the end of the run by chest percussion and postural drainage. Ventilatory capacity was not significantly changed nor was there any subjective improvement in the patients as a result of taking the drug.


Abnormalities of lung function in hay fever. Twenty subjects with symptoms of hay fever were studied to see whether abnormalities could be detected in the function of small airways. The investigations included dynamic compliance at varying respiratory frequencies, closing capacity, residual volume, transfer factor, and maximal expiratory flow-volume curves. The tests were repeated in the winter when symptoms had resolved. Frequency dependence of compliance was found in eight subjects with symptoms (40%), closing capacities being abnormal in only two instances. Conventional pulmonary function tests, including expiratory flow rates at mid vital capacity, were within the predicted range of all subjects. When tests were repeated in the winter, frequency dependence of compliance was no longer present in subjects whose symptoms had resolved. The study suggests that reversible small airway abnormalities are present in a significant proportion of subjects with symptoms of hay fever and that such abnormalities are best detected by the measurement of dynamic compliance at varying respiratory frequencies.


[Rare localization of a reticulum-cell sarcoma in the clavicular epiphysis]. The unusual case of a reticulum cell sarcoma in the clavicular epiphysis gives occasion to discuss the problems of diagnosis and therapy of this tumor and to point out difficulties met with in the early identification of the clinical picture of this disease.


Stimulation and inhibition of erythropoiesis in donors and hematopoietic effect in irradiated recipient. Regeneration dynamics in bone marrow and spleen was studied in rats after irradiation of 800 R and transfusion of bone marrow cells from donors treated in different ways. Priority of the microenvironment of the recipient or of the information obtained in cell donors with respect to further hematopoietic cell differentiation was studied in irradiated recipients. Rats irradiated with 800 R were used as recipients in the experiments. The donors of marrow cells were the rats with stimulated or inhibited erythropoiesis. Stimulation of erythropoiesis was induced by bleeding and experimental polycythemia was provoked by packed erythrocytes. According to our results, it can be concluded that the processes of postirradiation hematopoiesis after transplantation of the bone marrow cells depend on the number and proliferative state of both donors and recipient stem cells, and microenvironment, not excluding the information introduced with the donor cell transplant.


Chloramphenicol antibody causing interference in antibody detection and identification tests. Investigation of the serum of three patients with positive antibody detection tests demonstrated the cause in each to be an antibody against chloramphenicol, a bacteriostatic agent used in commercial red blood cell reagents. Washing of these red cells prior to use prevented agglutination. All three examples of anti-chloramphenicol antibody were IgM and were in low titer when tested at room temperature and 37 C in saline. Two of the antibodies bound complement. The possibility of an antibody to an ingredient of the commercial preservative solution should be considered if problems are encountered in tests with unwashed commercial red blood cell reagents.


Orthotopic heart transplantation in the pig: the pattern of rejection. This paper describes the behavior of orthotopically allografted hearts in the pig. Rejection between littermate pigs varied from under 7 days to more than 5 mo in unimmunosuppressed animals.


Cardiac transplantation: review of seven years' experience. Over the past 7 years, the feasibility of human cardiac transplantation has been documented and proved to prolong useful human life. Ideal candidates are characterized by the relatively young vigorous patient who is otherwise healthy and optimistic about his long-term chances of survival. Survival statistics indicate over a 75% 1-year survival if the patient survived the first 3 months following transplantation, at which time the most severe rejection episodes occur. Allograft rejection in both acute and chronic form remain the single most challenging problem limiting the success of the transplant program. Despite this, there has been gradual improvement in survival statistics characterized by a 57% 1-year survival for the past 1 year. The early diagnosis of cardiac rejection has been facilitated by routine serial percutaneous transvenous endomyocardial biopsies of the right ventricle to confirm clinical evidence of rejection. Over 88% of patients have been vocationally and actively rehabilitated and the remaining 12% are not limited by cardiovascular function but by complications of immunosuppresive therapy. In conclusion, it appears that human cardiac transplantation has been successful and can be used to treat selected patients with end-stage cardiac disease.