[Compensation for disordered functions and the problems of rehabilitative treatment of disabled veterans of World War II who suffered gunshot wounds of the upper extrememities]. The data of dynamic observations and clincal examination of 128 invalids of the Great Patriotic War having gunshot wounds of the upper extremities after 20 years and longer evidence considerable improvement of the wounded extremity function and a reduced degree of disability in the late period due to compensatory phenomena under the influence of active labour life.


Prophylactic use of hyperimmune serum in experimental colisepticaemia in calves. Evidence is presented to demonstrate the efficacy of an intravenously administered polyvalent hyperimmune serum prepared from bovine serum, in the prevention of experimental colisepticaemia produced by oral challenge with E coli O78: K80(B) in colostrum deprived calves. It is suggested that the protection afforded by this hyperimmune serum is due to high levels of specific antibody demonstrable in the serum of calves post treatment and that protection is given in this instance by antibodies contained in the IgG class of immunoglobulins.


[Action of ftorafur and 5-fluorouracil on the chromosomes of normal and tumorous cells in vivo]. No chromosome aberrations were found in the bone marrow cells and Djungarian hamster tumor cells and bone-marrow cells of thymectomized mice receiving different doses of fluorafur and 5-fluoruracil in vivo. The time of exposure to these antitumor drugs varied from 2 to 72 hours. 12% of aberrant metaphases under 400 mg/Kg of fluorafur and 38%--under 200 mg/Kg of 5-fluoruracil were found in cells of human colonic tumor trasplanted into thymectomized mice.


'VA', a new type of erythrocyte polyagglutination characterized by depressed H receptors and associated with hemolytic anemia. II. Observations by immunofluorescence, electron microscopy, cell electrophoresis and Biochemistry. With help of immunoflorescence, best with anti-AHP from Helix pomatia, a stippled structure could be demonstrated on the patient"s red blood cells. Thus an "A-like" receptor could be detected on the erythrocyte membrane of this group O patient. The reactive antigen was proved not to be a crypt antigen exposed by the action of neuraminidase. The same stippled fluorescence with antiAhp was observed on the red blood cells of a patient suffering from hemolytic anemia induced by influnza A2 virus. In this case this virus was shown not to be responsible for polyagglutination. No virus or microorganism could be isolated from the patient"s blood. Also by immunofluorescence the weak expression of the H antigen could be demonstrated with an extract of Evonymus europaeus. Electron microscopy of erythrocytes was normal. The neuraminic acid content and the electrophoretic mobility were found to be decreased to a minor degree. No distinct cell populations could be observed.


[Cytostatic therapy of metastasizing cancers: therapeutic indications and limitations (author's transl)]. The role of cytostatic drugs in the treatment of patients with advanced, metastasizing tumours and certain-therapeutic regimes are discussed in respect to the following tumours: breast cancer, gynaecological tumours, urinary tract cancers, tumours of the  head and neck, lung cancer and bone and soft tissue sarcomas. Recent progress in the management of these patients is outlined, whilst the limitations of cytotoxic treatment, with the inherent possibility of potentially fatal complications, are emphasized.


[Behaviour of serum and urinary lysozyme after renal transplantation (author's transl)]. The behaviour of serum and urinary lysozyme was investigated before and after renal transplantation in 20 patients. The mean postoperative observation time was 67.8 (10 to 212) days. In 11 patients with reversible olig-anuria due to prolonged preoperative ischaemia, lysozymuria lasted for a period of 17 days after surgery, whereas in 8 patients with immediate transplant function lysozymuria disappeared 7 days after transplantation. Serum lysozyme concentrations were markedly elevated before transplantation in all patients. In patients with transplant failure due to ischaemia, normalization of serum lysozyme levels was achieved 28 days after surgery; patients with immediate function showed normal serum lysozyme levels already 7 days after transplantation. Prolonged lysozymuria was also noticed in 2 cases with irreversible ischaemic transplant failure, in 1 case with recurrence of glomerulonephritis and in 1 further case with acute pyelonephritis in the transplant. In 7 cases with an acute renal rejection crisis, lysozymuria was evident 0.7 days before clinical diagnosis of rejection. Serum lysozyme levels showed a strong correlation with serum correlation with serum creatinine concentrations. Therefore, lysozymuria in renal transplant patients indicates tubular transplant damage of varied aetiology. Elevated serum lysozyme levels, on the other hand, seem to reflect a reduced glomerular filtration rate.


[Bistability of pyruvate production by E. coli ML30 in continuous culture]. The pyruvate production of E. coli ML30 in continuous cultures was investigated. In a glucose mineralsalt medium with ammonium as the limiting substrate two stable stationary states (bistability) of pyruvate concentration were obtained. The bistability was limited to dilution rates lower than 0.3 h-1 and connected with a decrease of the yield coefficient (Y Glc) from approximately 0.45 to approximately 0.1.


[Laboratory diagnosis in rheumatology].

[Laboratory diagnosis in rheumatology]. The laboratory diagnostics essentially contributed to the pathogenetic clarification of rheumatological problems and gives multifarious support to the rheumatologist in differential and activity diagnostics and thus also decisively contributes to early diagnostics and therapy. When the acute-phase-reactions serve for the differentiation of inflammatory-rheumatic diseases and degenerative diseases and for the establishment of the degree of activity, so the ASR further the diagnostic ascertainment of a rheumatic fever, the agglutination tests for proving the rheumatoid factor further the differential diagnosis of the rheumatoid arthritis, the LE-phenomenon and the ANF further the differential diagnosis of the LEV, the proof of cardiac auto-antibodies essentially furthers the diagnostics of carditis, the increase of uric acid the early recognition of gout, the synovial diagnostics at length became necessary for the clarification of clinically unclear mon- or oligoarthritides and the determination of the local activity for the observation and judgment of the course. Notwithstanding the primate of the clinic without an effective laboratory diagnostics a modern rheumatology can no more be performed nowadays.


[Multivariant discriminance analytical computation methods for the evaluation of clinico-chemical parameters in liver and biliary tract diseases]. Multivariate variance and discriminance-analytic investigations on the value of evidence of clinico-chemical tests in the diagnostics of diseases of the liver and the biliary tract gave the following results: 1. By means of clinico-chemical methods and discriminance-analytic functions we succeed in 50% of the cases in formulating a correct diagnosis, in more than 75% of the cases a correct probability diagnosis (3 first places in the rank of diagnoses). Sensitivity and specificity of discrimination were established for 15 classes of diagnoses. 2. Due to the intercorrelations of test results biochemical maximum programmes contain numerous redundant parameters measured on diagnostic information values. With the help of a test for indispensability (redundance test) among 20 parameters owy 5-6 were characterized as indispensable. An optimal combination of parameters should not transgress an extent of 14 tests. 3. Results of reclassifications with discriminance analytic functions confirmed that the discriminance analysis is an extraordinarily suitable method for the computer-supported finding of a decision, on which basis aimed additional investigations might be performed.


[Leukocyte agglomeration as an activity criterion of inflammatory processes]. The agglomeration of leucocytes serves for the proof of activation of the leucocytic system, the so-called leucergia, which among other occurs in inflammatory diseases of different genesis. On the basis of 1,000 examinations in patients with rheumatoid arthritis the sensitivity of the method was tested compared with the usual criteria of inflammation. In agroup of patients with slight activity with the agglomeration of leucocytes an inflammatory activity could be proved in 67.5% (electrophoresis 53.5%, BSR 49.2%, CrP 35.4%, leucocytosis 27.9%). The chi2-test resulted in a significant correspondence between the examinations mentioned and the agglomeration (p less than 0.001). In contrast to the usual criteria of activity the proof of leucergy is a new principle ofthe diagnostics of activity. High sensitivity and simple methodics recommend the use of the agglomeration of leucocytes in routine diagnostics.


[Technics for B-cell determination in lymphocytes]. The conception of the subdivision of lymphocytes into T- (dependent on thymus) and B- (dependent on bone marrow or bursa) cells which was transferred from animal experiments on mice to man has already clinical significance despite some deficiencies. For immunoproliferative clinical pictures, immune defects and autoimmune diseases a determination of the B- and T-lymphocytes in the peripheral blood is important. As methods for the determination of T-lymphocytes the rosette-test with erythrocytes of sheep (E-rosettes) as well as the immunofluorescence labelling of anti-T-lymphocyte globulin are used. For the demonstration of B-lymphocytes to-day the immunofluorescence microscopy, the autoradiography, the immune enzyme technique and the rosette tests for the determination of the Fc-receptor (EA-rosette) and the complement receptor (EAC-rosette), respectively, are used. Possibilities of differentiation between the two populations of lymphocytes are furthermore obtained by the grid electron microscopy and the important functional tests of the transformation of lymphocytes by means of unspecific and specific stimulants. In own investigations by means of the direct and indirect immunofluorescence and immune enzyme technique of the peripheral blood and from lymphatic nodes were tested. In normal persons a large proportion of IgM-receptors on the lymphocyte membrane was established. Patients with chronic lymphadenosis had a high number of B-lymphocytes, which clearly decreased under cytostatic therapy. In plasmocytoma, Waldenström's disease and primary immune defects the connections between the dominating classes of immunoglobulins on the membrane and in the serum. Investigations of the different populations of lymphocytes in there are peripheral blood and in the lymphatic nodes are suited to develop new conceptions on pathogenetic intergrades, therapeutic influences and variants of the course of immunoproliferative and immunodefective clinical pictures.


[Standardized indirect immunofluorescence. Differentiation of mitochondrial, microsomal and ribosomal antibodies]. By an extensive standardisation of the indirect immunofluorescence for the demonstration espeially of mitochondrial antibodies we succeeded in recognizing atypical fluorescence patterns and in describing their exact localisation. On the basis of absorption studies with mitochondrias, microsomas and ribosomas by comparative observation of sections of liver, stomach and kidneys of rats the preferred sort of reaction and the intensity of fluorescence of antibodies against mitochondria, microsomas and ribosomas were empirically established. Antimitochondrial antibodies react above all with the parietal cells of the stomach and the distal epithelia of the tubulus of the kidney. Antibodies against microsomas of liver and kidney are characterized by a brilliant diffuse cytoplasmatic fluorescence of the hepatocytes and by a comparatively weaker fluorescence of exclusively proximal tubuli of the kidneys of rats. Antibodies against ribosomas lead to a fluorescence especially of the main cells of the stomach. The differentiation of several cytoplasmatic antibodies is among others of interest for the diagnosis of certain autoimmune diseases. Although there are numerous still unclear findings and "overlap" phenomena the existence of high titre antibodies against mitochondrias speaks for a primarily biliary cirrhosis or a pseudo-LE-syndrome, the existence of antibodies against microsomas of kidney and liver of rats for a special form of a chronically active hepatitis and the existence of the very rare antibodies against ribosomas for an active lupus erythematodes disseminatus.


[Natural history in patients with mitral- and aorticvalve-disease (author's transl)]. Knowledge and due consideration of the natural history of valvular heart disease are prerequisites for their operative therapy. Presumptive mortality and morbidity of the surgical intervention must be weighted against the expected prognosis under medical treatment alone. The timing of the operation depends on these considerations. Mitral stenosis and the chronic forms of mitral and aortic incompetence have similar natural histories and for both signs and symptoms are good indicators for an eventual progression of the condition. The length of the period during which the patient is free of complaints may be quite variable but a critical change in the natural history comes about once the disease causes signs and symptoms. Surgical repair is indicated when the patient reaches stage III according to the NYHA-classification. The prognosis is worst for aortic stenosis, in particular due to the danger of  sudden death. Patients with high pressure gradients are at particularly high risk; this holds even true for those patients which are not yet suffering from any complaints. The prognosis becomes even more serious, when signs such as dyspnea, anginal pain, or syncopal attacks occur. Prognosis and indication for surgical intervention cannot be evaluated reliably by considering only the clinical signs without knowledge of hemodynamic parameters. Acute mitral and aortic incompetence, in paricular when they occur during baterial endocarditis, must be observed very closely because of their most serious prognosis; if necessary, emergency surgery must be carried out in these cases.


[Bone tuberculosis of the bovine type after BCG-vaccination (author's transl)]. It is reported about the BCG-osteomyelitis in early childhood. A long intervall between BCG-vaccination and the onset of clinical symptoms, the good general condition of the patient, nearly unrestricted joint function, often negative bacteriological culture for the tubercle bacillus and negative guinea-pig test are characteristics. Even with extensive lesions of the epiphysis and metaphysis of the long bone and formation of an abscess, the course of the disease seems to be fairly benign. Operation is recommended for getting biopsy material for histological proof of the tuberculous process and for quicker healing.


Application and standardization of various procedures for inoculation of maize by Erwinia carotovora f. sp. zeae. Hypodermic syringe and toothpick methods were best for evaluating pathogenicity of the maize plant against Erwinia carotovora f. sp. zeae, both in glass house and in the field. The portion of the stalk above the ground was best suited for reproducing the disease symptoms. Leaf and leaf whorl did not show any rotting hero. Seed inoculation showed least mortality percentage. Root inoculation was suitable only for young seedlings. Cotyledons, as an organ for inoculation for getting best reproducible infection, were not at all suitable.


[Mapping the fucidin resistance marker in S. typhimurium and a study of the properties of its transductants]. The fusidic resistance marker in S. typhimurium is contransduced in 95% of cases by means of P 22 phage with the streptomycin resistance marker. The transfer of the fusidic acid resistance gene doesn't lead to any significant alterations in the tranductants' properties (morphology, antigenic structure, growth rate, biochemical activity, sensitivity to other antibiotics). The fusidic acid resistant mutants and transductants studied displayed a significantly decreased virulence to albino mice. The rate of this decrease, however, doesn't correspond to the degree of transductants' resistance. Virulent variants are also possible.


[Reactogenicity and immunologic activity of live enteric Sonne dysentery vaccine from a spontaneous mutant]. Live dysentery Sonne vaccine from a spontaneous mutant proved to be practically areactogenic and specifically harmless in oral immunization of children aged from 7 to 13 years, in doses of from 3 to 25 milliard live microbial cells and in single and triple immunization schemes. Weak reactions of the gastro-intestinal tract were noted with the same frequency (1.7%) in children immunized with the vaccine and in children given placebo (2.2%). There proved to be a significant increase in the serum of the immunized persons of the level of specific hemagglutinins, and also of the IgA-and IgM-titers in 82% of the persons vaccinated; they persisted at a high level for 2 months. The appearance of IgA-antibodies in high titres in the persons vaccinated orally pointed to a marked local and general immunological activity of the live dysentery Sonne vaccine from the spontaneous mutant processing the capacity to survive in the intestine of children for a long time.


[Quantitative characteristics of the T- and B-systems of immunity in healthy persons of different age groups]. The authors carried out a complex immunomorphological study of the peripheral blood lymphocytes in 160 healthy persons of different age groups. The tests of spontaneous and complementary rosette formation of lymphocyte blasttransformation with PHA were used, assessing it by the H3-thymidine incorporation, lymphocyte straining by Coon's direct and indirect methods for detection of surface immunoglobulin receptors; G, A, and M immunoglobulins blood serum content was studied by Mancini's method. Mean indices characterizing the T- and B-populations of lymphocytes in persons of different age were calculated on the basis of these studies.


[Study of streptococcal L forms in the scanning electron microscope. II. Dynamics of the development of structural elements of L colonies at different stages of growth]. The method of scanning electron microscopy showed that the L-colonies of streptococcus were formed by the spherical structures 0.1--1.5 micronm in diameter, elements of polygonal shape (large bodies) 10--30 micronm in size, filamentous structures 01--7 micronm in diameter and structureless matrix. A regular replacement of one form by another was observed in the process of the L-colonies development. Thus, the spherical elements appeared in the lag-phase, and polygonal elements were found mostly at the initial stages of the L-colonies formation; as to the filamentous structures -- they were present at all the developmental stages, but their diameter increased, and their structure and number changed at different growth phases. The spherical elements of the L-colonies formed evenly both on the structureless depth matrix of the colonies, on the filamentous structures in the form of buds on the "large bodies", and the disintegration of the latter. The role of the filamentous structures in the development of the L-colonies is discussed.


[Hyaluronic capsule as one of the factors of hemolytic streptococcal pathogenicity]. Experiments were conducted on albino mice. It was shown that treatment of streptococci with testicular hyaluronidase or a single administration of the enzyme to infected animals failed to inhibit the infectious process. Injection of hyaluronidase solution to every 3 or 4 hours depressed the development of the process and increased the percentage of survived animals during its first stages. A marked intensification of the hyaluronidase action inhibiting the infectious process was observed under conditions of a moderately active or passive immunity and also in the case of preliminary treatment of streptococci with homologous immune serum. The data obtained permit to regard the hyaluronic capsule in the hemolytic streptococci as one of the pathogenicity factors of this microbial species providing survival of the causative agent after its entrance into the macroorganism.


[Interaction of group A streptococci with a culture of HEp-2 cells]. An initial stage of the interaction of the virulent (matt) and avirulent (glossy) strains of group A streptococcus with the human epithelial tissue (Hep-2) was studied. M+ and M- variants of three strains of group A streptococcus belonging to serological types 2 and 4 possessed different biological activity against the Hep-2 epithelial cells in the monolayer. M+-variant actively affected the great majority of the cells of the monolayer, multiplied of their surface and formed microcolonies. M--variant affected only an insignificant number of cells and failed to multiply on them. In difference from M+-streptococci, the activity of M+-variants is explained by their capacity to adhere to the surface of the animal cells irreversibly. This process started immediately and terminated by 1 1/2 hours of the microbial incubation in vitro with the Hep-2 monolayer. Trypsin treatment of M+-streptococci sharply diminished their capacity to adhesion, this apparently being the result of M-protein digestion. The data presented point to the important role played by M-protein in the phenomenon of the streptococci adhesion to the epithelial cells.


[Increasing the non-specific resistance of animals to pathogenic E. coli with preparations of RNA]. Yeast RNA and sodium nucleinate considerably increased the nonsusceptibility of mice to pathogenic escherichia and typhoid salmonellae. Ineffective single nucleonate doses created an intense resistance in repeated use; prolonged application was not accompanied by the appearance of tolerance to the preparation. The principal mechanism of the induced phenomenon consisted in the intensification of the bacterial elimination and the endotoxin detoxification chiefly realized by the activity of the mobile phagocytes.


[Experimental study of the pulmonary form of plague, tularemia and pseudotuberculosis]. There was revealed a regular reduction of plague, tularemia and pseudotuberculosis bacteria count in the lungs of guinea pigs the first 12 hours after aerosol infection. Generalization of the infectious process and associated septicemia occurred in pulmonary plague and pulmonary tularemia on the 1st-2nd day, and in pulmonary pseudotuberculosis - on the 4th-5th day. Limits of accumulation of the causative agents in the organs and the blood at various stages of the infectious process were established.


[Characteristics of the virulence of a strain of S. typhimurium and its glycerin mutant in a HEp-2 cell line model]. Sensitivity of the HEp-2 cell culture to the infection with the virulent salmonella strains was shown; active penetration and multiplication of bacteria in the monolayer cells indicated this. Gly 90, a glycerine mutant defective by glycerokinase, obtained under the action of ethylmethanesulphonate, displayed a distinct difference from the initial virulent strains of salmonella by decreased invasive properties and the absence of any capacity to multiplication in the epithelial cells. The data on the avirulence of the glycerine mutant obtained on a model in vitro confirmed the observations carried out in vivo in intraperitoneal infection of albino mice (LD50 = 1-10(7) cells) and in keratoconjunctival infection of guinea pigs.


[Successes in the control of childhood droplet infections in the UkrSSR during the 60 years of Soviet government]. Marked achievements in reduction of morbidity and mortality from the main child infections were reached as a result of radical social changes during the years of Soviet power improvement of welfare of the population, science development, proper organization of antiepidemic measures, creation of effective prophylactic preparations and mass immunization. Poliomyelitis is practically wiped out in the Republic, diphtheria incidence fell sharply and whooping cough and measles incidence decreased considerably.


[Immune response of rats of inbred strains to the polysaccharide of group A streptococci]. Immune response to polysaccharide of group A streptococcus was studied in rats of inbred strains MCY, VAG and August. Pure antibodies to beta-N-acetylglucosamine were isolated; their chromatography (by affinity) was conducted, and the content of the molecules of the IgG and IgM classes was established in each antibody fraction. Interlinear differences were revealed by each of the signs under study, this pointing to the role of genetic factors in the formation of antibodies to polysaccharide of group A streptococcus.


[Experimental evaluation of a double-layer anastomosis of the large bowel in the dog following irradiation]. In our experiments on dogs we study the influence of irradiation on large bowel surgery. 24 dogs were divided in two groups: the control and the irradiated group. The dogs were irradiated and after 4 months the resections of 5 cm of the irradiated large intestine was performed. We used single and double layer anastomosis. Two weeks after the operation the dogs were sacrified and morphological, tensiometric and histological studies were applied to the operated and irradiated large intestine. Conclusion of our experiments is the statement, that the single layer intestinal suture satisfies in a greater degree the requirements of an ideal suture in the irradiated bowel than the double layer intestinal suture.


[Combined stereotaxic surgery (methodologic remarks)]. The experience in stereotaxic operations performed in two neurosurgical institutions (Madras, India, and Bratislava, CSSR) indicated that an important part of them were combined interventions. From a methodological point of view the stereotaxic operations can be classified as one- and multi-stage, symmetrical, asymmetrical and unilateral procedures. A stereotaxic intervention differs from the traditional concept of an operation that is expected to lead to a recovery after a single procedure. Stereotaxic treatment, as a rule, comprises a succession of such interventions that form the strategy of the whole therapy.


[Pancreatic injuries].

[Pancreatic injuries]. Within a constant increase in the number of injured in the last ten years a significant rise in the number of abdominal injuries has been noticeable. From 1,2% of ten years ago, abdomeninal injuries have risen to 4,6% of the total number of treated patients. While in earlier years pancreatic injuries were a rarity, in 1974 there were six patients with an injury to the pancreas due to either a blunt or penetranting wound of the abdomen. Out of altogether (21) treated patients only in one was an isolated injury to the pancreas found. We have never been able to recognise with certainty the injury to the pancreas with clinical methods, but only surgical exploration enabled us to make an accurate diagnosis. In all surgically treated pancreatic injuries a suture of the capsule of the pancreas was done after débridement and minute hemostasis. Only in one case of complete transversal rupture of the corpus we decided upon a resection and a blind closure of the truncus. The site of the injury was obligatorily repeatedly drained in order to remove pancreatic secretions from the abdominal cavity. Out of the total number of patients surgically operated were 12, of whom 7 died. Other patients could not be operated upon because of the traumatic shock, so that pancreatic traumas in these patients were discovered at a postmortem examination.


[The use of mesh skin grafts in wide-spread deep burns]. The author discusses the problem of the treatment of wide-spread deep burns by describing different procedures, the history of the use of mesh skin grafts, a comparison with micrografts, tehnicalities in these procedures, the equipment used, indications, and the results. Optimum results obtained by mesh grafts in combination with early tangential excisions, as a further step in a quicker and more successful treatment of wide-spread deep burns, are pointed out.


[Our experiences in the treatment of burns using the technic of early necrectomy]. In the last 10 years there were enough oppositions as regards time when to undertake surgical treatment. The tendency existed that the operation should be undertaken earlier. Tangentional excision and immediate covering of transplantations for deep dermal burns and burns the full thickness of the skin is surely the right method. Our work on 123 cases during the last six years treated in this method, that is with the early closing of the wound, resulted in abbreviating the treatment and providing as better functional and aesthetical sight.


Noradrenergic mechanisms in hemorrhagic shock of the rat. The effects of hemorrhagic shock on the noradrenergic nerves of the rat were studied. Fluorescence microscopy of these nerves combined with biochemical determination of noradrenaline revealed a highly selective activation of certain adrenergic nerves, especially the nerves of the arterioli. Under the present experimental conditions transmitter mechanisms such as uptake and release of noradrenaline were not severely impaired by shock.


Pituitary gonadotrophin secretion during the first weeks of pregnancy. A longitudinal study of basal plasma LH and FSH and their responses to 25 microng LRH iv as well as basal levels of oestradiol, progesterone, prolatin and HCG was performed every week in 3 women, pregnant after heterologous insemination, from conception until the 6th week of gestation. A comparative study was carried out in 7 women in cycles in which no conception occurred after insemination. All hormones were assayed with radioimmunoassay. LH was measured with a specific assay for native HL, which did not cross-react with HCG. A decrease in basal levels of LH and FSH as well as decreasing responses to LRH was found during the first 2 weeks of gestation. These changes did not differ from what was observed during the luteal phase in the non-conception cycles. One week later the basal FSH levels and the FSH response in the pregnant women showed a further decrease, while in the non-pregnant women, now reaching the early follicular phase, a rise in FSH basal levels occurred. The basal levels of LH and the LH response, however, did not differ from that found in the non-pregnant woment at this time. FSH basal levels remained below the lower normal limit in eumenorrhoic women from the 3rd week of gestation. By this time the FSH response was almost completely inhibited. The LH basal levels, however, remained above the lower normal limit in eumenorrhoic women, but the LH response to LRH progressively decrease and was completely inhibited by the 5th week of gestation. In the non-conception cycles the LH response varied with the levels of oestradiol in plasma. This was not found in the pregnant women as the decrease in gonadotrophin response occurred while oestradiol remained at mid-cycle levels during the first 4 weeks of gestation. Rather it seems that the increasing and continuously elevated level of progesterone, in the presence of appropriate levels of oestradiol, might be the main go nadal steroid responsible for the diminishing pituitary secretion. The contribution of HCG to the further decrease in gonadotrophin secretion after the 2nd week of pregnancy cannot be answered by the present studies. Prolactin remained at non-pregnant levels until the 6th week of gestation, and appeared to have no influence on the secretion of gonadotrophins during early pregnancy.


Clearance of viable Calmette-Guèrin bacillus by the in vitro isolated and perfused rat liver. Liver efficiency in clearing circulating BCG (Clamette-Guèrin bacillus) was studied using the isolated rat liver. Bacteria were added to the perfusate at a concentration of 1 X 10(6) cells/ml, and the medium was then sampled at subsequent intervals for 6 hours in 2 perfusions and for 1 hour in 7 perfusions. At the end of all perfusions, liver and bile samples were obtained and used for viable bacterial counts. For each perfusion the bactericidal activity which might have been exerted by serum present in the perfusate was also investigated. About 95% of BCG disappeared from the perfusate after 6 hours of perfusions, and 90% after 1 hour. Recovery of viable bacteria in the liver at 60 minutes averaged 80% of the inoculum. Recovery in bile was negligible. Control experiments indicated that extrahepatic factors in possible reduction of bacterial concentration in the perfusate did not interfere with hepatic removal, per se.


Computer analysis of atypical urothelial cells. I. Classification by supervised learning algorithms. Computer discrimination of atypical (ATY) urothelial cells from the urinary sediment by means of supervised learning algorithms discoled that these cells form a distinct, although ill-defined, family of cells which differs from normal (NEG) and malignant (POS) cell groups. The clinical significance of this observation must await long-term clinical follow-up. The possibility of issuing computer displays on individual patients with possible diagnostic and prognostic implications is discussed.


Effects of lymphokines on fibrinolysis and kinin generation in human plasma. Supernatants from Con-A-stimulated human lymphocytes containing leukocyte migration inhibitory factor, skin reactive factor and procoagulant activities were tested for their effect on fibrinolysis and kinin generation. The supernatants of stimulated lymphocytes activated the fibrinolysis and generated kinin in human plasma. These results are discussed from the aspect of cell-mediated (type IV) immune inflammation.


Phase microscope study of the giant cells from the normal testes of  the Indian hedgehog, Paraechinus micropus. The phase-optic study of the germinal cells from the testes of the hedgehog, a seasonally breeding mammal, reveals the multinucleate giant cells in the natural state in late August, at the beginning of winter regression without subjecting these animals to any type of experimental stress. The participation of primary spermatocytes and spermatogonia, in addition to spermatids, in the formation of these giant cells has been observed. The nuclei at similar stage of spermatogenesis are identifiable in a single giant cell. The possible mechanism of their formation is discussed.


A simple method for demonstrating cells in the cerebrospinal fluid by scanning electron microscopy. A combination of forced sedimentation and air-drying has been used to prepare cerebrospinal fluid cells for scanning electron microscopy. On the basis of surface morphology, the similarity of CSF cells to blood cells is emphasized. Various types of cells were demonstrated in bacterial meningitis, multiple sclerosis and CNS leukemia.


The contractile nature of the tubular-like cells of the parietal layer of the Bowman's capsule in male mice. An immunochemical and ultrastructural study. The tubule-like cells (TLC) of the parietal layer of the Bowman's capsule of the renal corpuscle in normal male mice are provided with bundles of thin microfilaments (50-70 A). Moreover, the ultrastructural observations demonstrated that similar thin filaments (50-70 A) are located in the flattened cells of the parietal layer of the Bowman's capsule and in the tubular cells. All the above cells bind antimyosin-like antibodies. Considering the correspondence between the immunochemical and ultrastructural findings, it is suggested that the microfilaments located in TLC contain a 'myosin-like' protein.


[Experimental analysis of cardiac regulation in the chick embryo]. Homochronous homografts of prospective cardiac area labeled with 3H thymidine have been carried out in chicken embryos at stages 5 and 6 of Hamburger and Hamilton. It has been observed how a heart tube or a vesicle, sometimes contractile, is developed by the graft. This vesicle, which is partly joined or not joined, to the receptor's heart, is always in close dependence on the pharynx normogenesis.


Type II Arnold-Chiari malformation with normal spine in trisomy 18. A variety of anomalies of the central nervous system are observed in trisomy 18. The present case describes an infant having a type II Arnold-Chiari malformation without spina bifida. One previous case of an Arnold-Chiari malformation was reported in trisomy 18 but that infant also had a lumbar meningomyelocoele. Abnormalities of cerebral gyration, hydrocephalus, and agenesis of the corpus callosum were also found in the present case.


The suppression of puerperal lactation with bromocryptine. The therapeutic value of 2-Br-alpha-ergocryptine for the suppression of puerperal lactation was studied in 30 normal women; 16 received the drug, 14 were controls. In six women plasma levels of FSH, oestradiol and alpha-lactalbulmin were measured in labour and in the early puerperium. Brom-ergocryptine was found effectively to suppress milk production and alleviate breast pain and congestion, with no side effects and minimum rebound lactation. The inverse relationship between prolactin and FSH levels reported elsewhere in non-pregnant women did not appear to occur in the early postpartum period. Although there was a significant rise in alpha-lactalbumin levels in labour and the puerperium over non-pregnant levels, there was no difference between lactating and non-lactating women.


An autopsy case of Creutzfeldt-Jakob disease with kuru-like neuropathological changes. An autopsy case of Creutzfeldt-Jakob disease with Kuru-like neuropathological changes which revealed clinically extrapyramidal, pyramidal and psychic symptoms is presented in this report. On microscopic examination, status spongiosus, neuronal degeneration, proliferation of hypertrophic astrocytes and numerous plaques were observed in the cerebrum and cerebellum accompanied with widespread demyelinization. These plaques which suggested Kuru plaques measuring 10 to 60 micron were strongly PAS positive and had a dense central core surrounded by a halo of fine radially arranged fibrils. As for the relationship between Creutzfeldt-Jakob disease and Kuru, the significance of these morphological changes is discussed.


Effects of ampicillin on intracellular levels of adenosine triphosphate in bacterial cultures related to antibiotic susceptibility. Short time effects of ampicillin on viability and levels of intracellular ATP were studied in bacterial cultures and a close relationship between intracellular ATP levels and viability was demonstrated. The connection between the effects observed and MIC values is discussed. The possibility of using the phenomenon for rapid antibioitc susceptibility testing was studied in clinical isolates incubated for 2 hours followed by luciferase assay of intracellular ATP. A positive correlation was demonstrated between ampicillin-induced decreases in intracellular ATP and inhibitory zone diameters, as measured by the agar diffusion technique.


Effect of experimental trichinosis on unrelated humoral and cell mediated immunity. Immune responses to unrelated antigens were studied during the course of Trichinella spiralis infection in mice. A transitory depression of the IgM response to the thymus dependent antigen, sheep erythrocytes, was seen three weeks after infection and this effect was more pronounced after challenge. A depression of the IgG response also was observed, however, not until 6 weeks after infection. The humoral response to the thymus independent antigen, polyvinyl pyrrolidone showed a slight increase which was most evident in challenged mice. The nonspecific cellular immune response, as measured by the split heart allograft technique, showed a profound and longlasting depression. This effect was mot pronounced one week after inoculation, when the parasite resides mainly in the intestine. The time at which the nonspecific cellular immunity was most depressed coincides with the period of strong specific cell mediated immunity. It is also shown that experimental trichinosis in CBA mice is accompanied by profound but transient changes in the thymus reflected mainly as a depletion of cortical thymocytes. These changes were not due to corticosteroids or malnutrition. There is reason to believe that thymic depletion is of significance for the depressed antibody response, but not for the prolonged survival of allografts. These findings indicate that T. spiralis affects the nonspecific immunity at different levels.


Antiparkinsonian agents and long-term neuroleptic treatment. Effect of G 31.406, orphenadrine, and placebo on parkinsonism, schizophrenic symptoms, depression and anxiety. The need for medication with anticholinergic antiparkinsonian drugs was examined in 118 schizophrenic patients under long-term neuroleptic treatment. It was found that 1) none of 18 patients under treatment with low mg potency neuroleptics (chlorprothixene, clozapine, and thioridazine) had any need for anticholinergics; 2) of 60 patients under treatment with short-acting high mg potency neuroleptics (perphenazine greater than 16 mg daily and haloperidol greater than 2 mg daily) nine patients (15%) required medication with anticholinergics, whereas 3) of 40 patients under treatment with long-acting (depot) neuroleptics, 17 (43%) had a need for anticholinergic medication; and 4) no patient factors predisposing to the need for continued antiparkinsonian treatment could be identified. In an additional double-blind cross-over study of 12 patients presenting persisting neuroleptic-induced parkinsonism, it was found that G 31.406 (a new potentially antiparkinsonian drug), compared with placebo, had an antiparkinsonian effect (P less than 0.01) as well as an antidepressant effect (P less than 0.05). G 31.406 resulted in an improvement in anxiety and schizophrenia-score in some patients. Compared with placebo, orphenadrine had a more questionable effect on parkinsonism (0.05 less than P less than 0.01) and no significant effect on mental symptoms. There were no significant differences between the effects of G 31.406 and orphenadrine.


Antiaggressive effect of lithium ion in man. In studies of the psychopharmacology of human aggression, 'aggression' should be related to easily identifiable behavior: angry threats or actual assaults. Aspects of behavior not meeting these criteria but relevant to a study of aggression should be described using appropriate terms such as social dominance, initiative, etc. With these conventions, examination of the heterogeneous literature on lithium treatment of aggression demonstrates that lithium ion exerts an antiaggressive effect in man. A number of hypotheses for the antiaggressive effect are examined using previous studies and new behavioral and biochemical data. It is concluded that the anti-aggressive effect is not due to any of the following: lithium toxicity or side effects; subjective or objective weakness; increased reaction time; reduced coordination or motor performance; frank cognitive deficits; hypothyroidism; reduction of serum testosterone; placebo effect; or underlying manic-depressive illness. Putative "thymoleptic" properties of lithium are too ambiguous to constitute an explanation of lithium's actions in man.


Angiography in reticulum cell sarcoma.

Angiography in reticulum cell sarcoma. Angiography was performed in 14 patients with reticulum cell sarcoma. When located in the retroperitoneal tissues, the spleen or the pancreas, the tumor is hypervascular with encasement of arteries and compression or invasion of veins. Tumors of the kidneys may have a similar appearance. A gastric tumor displays slight abnormalities, mainly hypervascularity, the lesion being better demonstrated by barium examination. A case of reticulum cell sarcoma in the small bowel demonstrated arterial encasement and arteriovenous shunting.


Effect of minoxidil on blood pressure and hemodynamics in severe hypertension. Eighteen patients with diastolic hypertension (100 to 120 mm Hg), in addition to propranolol, 160 mg daily, and hydrochlorothiazide, 100 mg daily, received progressively increased doses of either minoxidil or placebo in a double-blind crossover study. With minoxidil (average dose 19.7 mg) blood pressure decreased from 165/109 to 138/89 mm Hg without the appearance of orthostatic hypotension. Hypertrichosis and fluid retention did occur, with an average weight gain of 1.8 kg, concomitant with an increased plasma volume. Pulse rate and cardiac output increased; no significant changes were observed in plasma renin activity, renal plasma flow, glomerular filtration rate or excretion of catecholamines or aldosterone. Minoxidil appears to be a useful antihypertensive drug for treating patients who do not respond adequately to therapy with diuretic and beta adrenergic blocking agents.


Sodium intake and furosemide administration in hypertensive patients with renal insufficiency. The effects of various levels of sodium intake and loop diuretic (furosemide) administration upon arterial pressure and renal function were studied in 11 patients with impaired renal function and essential hypertension. The patients were hospitalized in a metabolic ward and continued taking their usual antihypertensive medications. After a stabilization period, all patients followed the following regiments for 5 to 7 days: period I, 20 mEq sodium diet without diuretic administration; period II, 80 mEq sodium diet and furosemide, 80 mg daily; and period III, 200 mEq sodium diet and furosemide, 240 mg daily. Supine diastolic pressure was lower (P is less than 0.05) during period II than during period I and both supine and standing systolic and diastolic pressures were significantly lower in period III than in period I (P is less than 0.01). No significant differences in the renal clearance of inulin were noted between any of the study periods. In patients with essential hypertension and impaired renal function, consumption of a moderate or liberal sodium diet combined with administration of a loop diuretic agent (furosemide) appears to result in better control of arterial pressure without significant changes in renal function than does strict sodium restriction without diuretic administration.


Improved longevity due to reduction of sudden death by aortocoronary bypass in coronary atherosclerosis. To evaluate the efficacy of coronary bypass surgery in reduction of sudden death, the prognosis of 286 similar patients with multivessel coronary stenosis was studied prospectively and the results of medical therapy (Group I, 114 patients) were compared with those of surgical therapy (Group II, 172 patients) after cardiac catheterization and coronary arteriography. During 39 months' evaluation of both groups, mortality from congestive heart failure and noncardiac causes did not differ (Group I, 14 percent; Group II, 8 percent) (P greater than 0.05). Sudden was evaluated in the remaining 217 patients (Group I, 96; Group II, 121 patients) who were matched for age (Group I, 52 years; Group II, 51 years); duration of overt coronary disease (Group I, 3.8 years; Group II, 4.0 years); angina pectoris (Group I, 83 percent; Group II, 95 percent); prior myocardial infarction (Group I, 77 percent; Group II, 74 percent); and congestive heart failure (Group I, 30 percent; Group II, 23 percent) (all P greater than 0.05). In addition, the prevalence of coronary risk factors was the same (P greater than 0.05) in both groups (hypertension, cigarette smoking, diabetes mellitus, lipid abnormalities and family history of coronary disease). Importantly, arteriography and catheterization established a similar extent and location of major coronary arterial stenoses and of ventricular dysfunction; two vessel disease (Group I, 32 percent; Group II, 33 percent) and three vessel disease (Group I, 68 percent; Group II, 67 percent); left ventricular end-diastolic pressure (Group I, 13; Group II, 14 mm Hg);cardiac index (Group I, 2.85; Group II, 2.91 liters/min per m2); and coronary collateral vessels (Group I, 58 percent; Group II, 61 percent) (all P greater than 0.05). Fifty-six percent of patients in Group II had multiple bypass grafts and a late patency rate (average 21 months) of 87 percent of one or more grafts. During subsequent prospective evaluation of over 3 years, bypass surgery provided greater symptomatic benefit of improved functional capacity (Group I, 12 percent; Group II, 69 percent) (P less than 0.05) and complete anginal relief (Group I, 30 percent; Group II, 60 percent) (P less than 0.05). Moreover, bypass surgery was associated with marked reduction in sudden death (Group I, 24 percent; Group II, 6 percent) (P less than 0.05). Thus, in patients with multivessel coronary disease carefully matched for clinical factors, hemodynamics, atherogenic precursors and coronary pathoanatomy, effective aortocoronary bypass surgery appeared to prolong survival by decreasing the incidence of sudden death, possibly by a decrease of unexpected fatal arrhythmias.


Metabolic regulation as a control for lipid disorders. I. Influence of (--)-hydroxycitrate on experimentally induced obesity in the rodent. The feasibility of treating obesity by metabolic regulation has been explored in this study by examining the effect of (--)-hydroxycitrate on three types of experimentally induced obesity in the rodent.(--)-Hydroxycitrate was utilized because it depressed fatty acid and cholesterol synthesis in vivo through its activity as a potent competitive inhibitor of APT citrate lyase. In all models, the mature rat, the goldthioglucose-induced obese mouse, and the ventromedial hypothalmic lesioned obese rat, food intake and body weight gain were reduced signficantly by the chronic oral administration of a nontoxic dose of (--)-hydroxcitrate. Body composition analyses of mature rats treated with (--)-hydroxycitrate demonstrated a significant depression of body lipid levels and an unaltered body protein content. However, a citrate administration produced no significant effects on weight gain, food intake, or body lipid or protein levels when compared to controls.


Reliability of the microdilution technic for detection of methicillin-resistant strains of staphylococcus aureus. To determine whether the microdilution technic for antimicrobic susceptibility testing could detect the hetero-resistance of "methicillin"-resistant Staphylococcus aureus, 100 stock cultures (54 methicillin-susceptible and 46 methicillin-resistant) were tested against methicillin, oxacillin, nafcillin and cephalothin. Each drug was diluted in Mueller-Hinton broth and in Mueller-Hinton broth with 5% NaCl. Minimum inhibitory concentration (MIC) determinations were made after 20-24 hours at 35 C and again after 48 hours of incubation. With one exception, methicillin resistance was detected in Mueller-Hinton broth when the trays were reincubated and read after 48 hours. Earlier detection of methicillin resistance was possible when the penicillinase-stable penicillins were diluted in broth containing 5% NaCl. Further studies suggest that the addition of NaCl to the broth medium might improve the stabilities of methicillin, oxacillin, and nafcillin during storage of the frozen microdilution trays. Either nafcillin or oxacillin would appear to be the best representative of the penicillinase-stable penicillins. Standardized disk-diffusion tests with cephalothin disks indicated that most methicillin-resistant strains are susceptible to cephalothin. However, there is reason to believe that such in-vitro test results might be inappropriate. With microdilution tests, most methicillin-resistant isolates were more resistant to cephalothin than were the methicillin-susceptible strains, but the MIC's for both types of staphylococci were generally within the range of concentrations that can be obtained during therapy. The addition of NaCl to the microdilution tests with cephalothin did not alter the test results significantly.


Isolation of Klebsiella ozaenae and Klebsiella rhinoscleromatis in a general hospital. Klebsiella ozaenae and Klebsiella rhinoscleromatis are uncommon organisms usually associated with granulomatous or necrotizing disease of the upper airways. Seven patients are described, non of whom had characteristic clinical manifestations of infection with these species. The organisms were recovered from mixed wound infections or sputum of five patients, and from the blood of three patients. Antibiotic sensitivity patterns were unusual and included susceptibility to both ampicillin and carbenicillin.


The placebo effect. Is it important in diverticular disease? Thirty patients with diverticular disease confirmed by barium enema examination were entered into a three-month double-blind trial of two tablets of methylcellulose (Celevac) daily or two placebo tablets daily. As these tablets were indistinguishable it was possible to cross over nine of the patients and follow them for a further three-month period. The placebo effect was sufficient for 11 patients who completed the trial on placebo to show a small mean improvement. A greater mean clinical improvement was shown, however, by the 16 patients who completed the trial on methylcellulose and in those who were crossed over, most of the improvement occurred during the time the patients were on methylcellulose.


Anencephalus and drinking water composition. The mortality rate (stillbirths and infant deaths) from anencephalus from 1950-1969 in 36 cities of over 50,000 population in Canada showed a negative association (r = -.39) with the concentration of magnesium in water sampled at domestic taps. The mortality rates showed negative associations with mean income and longitude, and a multiple regression model using the three factors showed significant effects of each and accounted for 69% of the intercity variation in rates. There were no significant associations seen with water calcium concentration or total hardness. Income, magnesium and longitude were also negatively  associated with mortality rates from spina bifida, hydrocephalus, other congenital abnormalities, and total stillbirth and infant death rates, but the association with magnesium was significant only for total stillbirths. The negative association of anencephalus mortality and magnesium levels was also seen in a sample of 14 smaller towns in Ontario.


Use and abuse of laxatives.

Use and abuse of laxatives. Colon physiology, the causes of constipation, an approach to management of constipation, and the features of various laxatives are reviewed. The categories of individual agents discussed include the bulk-forming laxatives, stimulant cathartics, saline laxatives, hyperosmotic laxatives, surfactant laxatives, emollient laxatives, enemas and suppositories. Dietary change and attention to proper bowel habits are frequently the only therapy necessary for the treatment of constipation. When laxative intervention is necessary, one of the milder agents should be employed over a short period of time. The chronic abuse of stimulant cathartics, often deeply rooted in family or ethnic traditions, is a significant problem and difficult to treat.


Review of current knowledge of plastic intravenous fluid containers. A review of the features of plastic intravenous fluid containers is presented. The following topics are discussed: (1) handling and storage; (2) environmental and human contamination; (3) particulate matter; (4) water vapor transmission; (5) drug additives; (6) leaching and adsorption; (7) possible toxicity; and (8) cost. It is concluded that various justifications can be presented for both glass and plastic containers.


Hazards of mechanical ventilation--therapeutic implications. The side effects and adverse reactions associated with the use of positive pressure volume cycle ventilators are described with a focus on information the pharmacist needs to know to monitor patient drug therapy. Mechanical ventilation is discussed with regard to pulmonary and blood gases, infections, cardiovascular effects, renal-fluid status, metabolic considerations, central nervous system effects, gastrointestinal effects, musculo-skeletal reactions, discontinuance of mechanical ventilation and the use of inhalation drugs.


Preexcitation.

Preexcitation. Recent increase in our knowledge of the basic features involved in ventricular preexcitation has moved it from being a somewhat rare curiosity for which there was no cure to an important medical condition requiring careful therapeutic planning. This review summarizes a body of information concerning mechanisms, various forms of preexcitation, embryologic features, electrophysiology and special testing maneuvers, treatment, prognosis and aviation plus insurance aspects of the syndrome. A new classification of the locations of the Kent bundles in the Wolff-Parkinson-White form of preexcitation is also offered.


Failure of bacterial growth inhibition by amniotic fluid. The bactericidal properties of amniotic fluid normally protect fetuses from late gestational infections by bacteria. Recently, such infections were found responsible for nearly a third of the perinatal deaths in Addis Ababa, Ethiopia. This prompted an analysis of the antimicrobial activity of amniotic fluid in patients in that city. The antimicrobial activity of fluid from 53 women, collected at term, was measured by a semiquantitative plate-count technique. Only one of the fluid samples was bactericidal, 12 were bacteriostatic, and 40 were noninhibitory to bacterial growth.


Homocystinuria: pathogenetic mechanisms. Homocystinuria with elevated plasma homocysteine and methionine levels is the result of deficient activity of cystathionine synthetase, the enzyme catalyzing conversion of homocysteine to cystathionine. It is inherited as an autosomal recessive trait with a worldwide distribution. The major clinical manifestations result from the elevated plasma homocysteine level. The excitotoxic effect of homocysteic acid accounts for mental retardation and seizures. Interference with collagen cross-linking by sulfhydryl groups of homocysteine causes ectopia lentis and skeletal deformities. Sulfation factor-like effects contribute to disruption of vascular endothelium, which is followed by platelet thrombosis and widespread arterial and venous occlusions. Low methionine homocystinuria, with deficient remethylation of homocysteine, results from deranged vitamin B(12) metabolism and from deficient 5,10-methylene-tetrahydrofolate reductase. Administration of azaribine produces homocystinuria by mechanism not yet elucidated.


A serologic response in human infection with Enterobacteriaceae. Sera from patients infected with Escherichia coli, Proteus, Klebsiella, and Serratia were studied for precipitins to ultrasonic extracts of these organisms in gel-diffusion plates. Sera from 66 per cent of these patients contained precipitins when initially tested. Twenty-four per cent of sera tested in the first week after onset of infection contained precipitins, but this rose to 78 per cent by the third week. Cross-reactions of sera with Pseudomonas antigens were unusual, but were common with other enterobacterial antigen extracts. However, higher titers were usually present to homologous as compared to heterologus antigens. Sera from seven patients contained precipitins to a common enterobacterial antigen. Precipitins to E. coli, Proteus, Klebsiella, and Serratia were detected in only a small proportion of control sera.


Significance of antimicrobial synergism for the outcome of gram negative sepsis. Amikacin plus penicillin (A+P) was compared to amikacin plus carbenicillin (A+C) in a double-blind study. Therapy with one of these combinations was given, as soon as servere infection was suspected, to 117 patients with proved gram negative infection, none of whom was granulocytopenic. Gram negative bacteremia was documented retrospectively in 52 patients; 25 had received A+P and 27 had been treated with A+C. All the isolated gram negative pathogens were sensitive to amikacin (MIC less than 12 microng/ml). In the A+P group, 55 per cent of the patients responded favorably while in the A+C group 63 per cent did respond; the difference was more striking for bacteremic patients: 52 per cent responded in the A+P group and 70 per cent in the A+C group. This difference, however, was not statistically significant. The outcome of patients whose infection was treated by synergistic combinations against the offending pathogen was better (66 per cent) than that observed in patients who received nonsynergistic combinations (48 per cent) (p less than 0.05). Once again the results were more striking in the bacteremic patients (p less than 0.01). A favorable outcome was associated also with a high (larger than or equal to 1/8) bactericidal activity of the diluted serum of the treated patient against the offending pathogen (p less than 0.05). This study suggests that the optimal therapy in gram negative septicemia might be the administration of synergistic combinations of antibiotics.


Endocarditis due to enteric bacilli other than Salmonellae: case reports and literature review. The clinical and pathological findings in two recent patients with non-salmonella enterobacterial endocarditis are described, and those of 42 patients in the literature are summarized. Most of the patients acquired their endocarditis secondary to urinary tract infection and had an acute clinical course characterized by high fever and chills. Thirty-two of these patients died, and all except one had a postmortem examination. The most frequent pathological finding was the occurrence of very large vegetations which caused relatively little destruction of the underlying valve. Prompt diagnosis and antibiotic therapy chosen on the basis of bactericidal as well as bacteriostatic activity against the individual bacterium may improve the prognosis in this disease. Results of tricuspid and pulmonic valvulectomies for bacteriologic failure in pseudomonas and in a few cases of enterobacterial endocarditis appear to warrant a surgical approach in patients with right-sided enterobacterial endocarditis who fail to respond to vigorous medical therapy.


Effect of oral contraceptives on blood folate levels in pregnancy. An investigation was carried out to assess residual effects of oral contraceptives on the folate status of pregnant women who had discontinued intake of these drugs within six months of conception. The sample population of middle class women consisted of users and nonusers of oral contraceptives of similar age groups. Subgroups were those studied initially during the summer (May to July) or winter (October to January). Red blood cell folate values showed seasonal variability and were lower in the winter months. Oral contraceptive users had lower plasma and red blood cell folate values than did the respective control subjects. Red blood cell folate values were more affected by previous drug use in the winter group than in the summer group. Dietary folate was found to have a significant effect on plasma and red cell folate; such for any one level of intake, blood folate values were significantly lower in oral contraceptive users.


Effect of ampicillin administration on plasma conjugated and unconjugated estrogen and progesterone levels in pregnancy. The administration of ampicillin to three women in the last trimester of pregnancy caused a transient reduction in the plasma concentration of total conjugated estriol and of estriol-16alpha-glucuronide, as measured by a specific radioimmunoassay. Similar changes were seen in plasma conjugated estrone and estradiol levels, but the effect seemed to be more prolonged. In most cases, the reduction in plasma conjugated estrogens was greatest on the second and third day of ampicillin administration, the pattern being similar to that described previously for urinary estriol and other estrogens. There were no obvious differences in the ampicillin effect between the morning and afternoon plasma levels. Ampicillin caused no consistent change in the plasma levels of unconjugated estrone, estradiol, and estriol or in plasma progesterone. These results are discussed with consideration of our present understanding of the effect of ampicillin on the intestinal metabolism and enterohepatic circulation of steroids.


Single dose of two grams of metronidazole for Trichomonas vaginalis infection. In this study, 243 women with symptomatic trichomonal vaginitis were treated with eight 250 mg. tablets of metronidazole for themselves, and eight tablets were given to each of their male consorts. They were given instructions to ingest "all eight in a row" and "avoid alcohol for 48 hours." Ninety-five per cent of 203 women that returned for re-examination were cured. This single-dose treatment is effective, well tolerated, and less expensive than current recommended dosages.


The spermatozoan genome and fertility.

The spermatozoan genome and fertility. The strategy for effective reproduction by eliminating genetically unbalanced gametes during spermatogenesis and transport varies in degree of success within as well as among species, but in no animal has it been reported to be completely effective. In the human subject, for example, it is estimated that one in every 50 ejaculated spermatozoa is genetically abnormal. The causal basis of these anomalies is poorly understood. Meiotic accidents, environmental mutagens, and gamete senescence in utero are all implicated. However, many of these abnormal cells are fertile. This fact plus the weight of the evidence reviewed suggest that fertility differences among males which cannot be ascribed to measurable differences in semen characteristics reflect, in large part, the increased opportunity of nuclear defective gametes in the semen of some males to effect fertilization. The elimination of embryos arising from eggs fertilized by genetically defective spermatozoa through spontaneous abortions, although biologically costly, must be viewed as the final check for the elimination of genetic detritus of the species.


Computer-assisted eye examination. V. Preliminary evaluation of the refractor III system for subjective examination. A computer-assisted subjective eye examination was administered to 78 patients as they volunteered. They were also examined in the conventional, manual way, some before and some after the computer-assisted examination. Results of the computer-assisted examination were compared to those obtained by conventional subjective methods. For the distance prescription, satisfactory agreement was obtained for 83% of the patients. The 17% unsatisfactory prescriptions were subdivided into about 6% avoidable errors (caused by errors in software, hardware, or optometric flow charts), about 6% errors of undetermined cause, and 4% fundamental errors (caused by patient's physical and mental impairment or confusion). A similar analysis is made for the near add. With further development of the system it is expected that between 90 and 96% of patients in an optometric clinic can be successfully examined by this computer-assisted method.


Bonding metal brackets with a self-polymerizing  sealant-composite: a 12-month assessment. Data spanning 15 months and about 1,500 bands have been presented describing an effective procedure for bonding metal brackets to enamel by the acid-etch method. A sealant-composite combination for metal brackets, not previously reported, has been described. Data have also been presented showing that, for the method and material used, it did not seem to matter clinically if a 37 per cent acid were used or if, instead a 50 per cent orthophosphoric acid in a liquid or thixotropic form, applied for 2 to 2 1/2 minutes, and drying agent were used. A comparison with the Nuva system was made and a modification was described for a useful combination technique, namely, Enamel Bond-Nuva-Tach, which takes advantage of certain attributes of each.


The Southern California Sensory Integration Tests (Ayres) and the Bender Gestalt: a correlative study. The Southern California Sensory Integration Tests (SCSIT) and the Bender Gestalt are two measures used to evaluate children with suspected perceptual-motor deficits. Since these tests are used primarily by two groups of professionals, occupational therapists and psychologists, it was thought that studying the correlations between these two tests might help psychologists to know which children needed to be referred to an occupational therapist for sensory integrative evaluation, and might help the occupational therapist to understand the psychologist's use of the Bender Gestalt. The use of the Bender by the occupational therapist as a screening device for sensory integrative dysfunction was also investigated. The SCSIT and Bender were given to 26 children with suspected sensory integrative dysfunction. Scores on the Bender were found to be predictive of grouped scores on the Form and Space Perception and Praxis-Tactile sections of the SCSIT, but not of the Postural and Bilateral Integration section. It was concluded that when the Bender is used as a screening device for sensory integrative dysfunction, some measure of postural mechanisms must be included. Correlations between the Bender and individual tests of the SCSIT were also studied.


Sodium ions, calcium ions, blood pressure regulation, and hypertension: a reassessment and a hypothesis. An attempt is made to elucidate the cellular mechanisms which may account for the well-documented correlation between sodium metabolism and peripheral vascular resistance. As a starting point, the evidence that the Na electrochemical gradient across the vascular smooth muscle cell plasma membrane (sarcolemma) plays an important role in cell calcium regulation is reviewed. Because there is significant resting tension ("tone") in most resistance vessels, the ionized Ca2+ level ([Ca2+]1) in the smooth muscle fibers in these vessels must be maintained above the contraction threshold. Consequently, the Ca transport system in the sarcolemma, presumably an Na-Ca exchange mechanism, must be set so as to hold [Ca2+]1 at this suprathreshold level. Any change in the Na gradient will then be reflected as a change in [Ca2+]1 and, therefore, in steady vessel wall tension and peripheral resistance. The correlation between Na metabolism and hypertension could then be accounted for if a circulating agent, perhaps the "natriuretic hormone," affects the Na gradient (across the sarcolemma) and, therefore, [Ca2+]1 and tension.


Involvement of a humoral factor in regulation of body weight in parabiotic rats. Excessive food intake and obesity was induced in one member of parabiotic pairs by electrical stimulation (three 30-min sessions/day for 2 wk) of the lateral hypothalamus (LH). The nonstimulated partners reduced spontaneous food intake the fatter the stimulated animals became. This reduced food intake resulted in a decreased body weight, fat content, and fat-free solid body mass. The decrease of food intake was not due to changed social behavior of the obese partner. It must be attributed to transmission of a humoral satiety factor. The very first stimulation of the LH in the stimulated partners resulted in a large increase in blood glucose and glucagon level without much change in the insulin level. These changes in blood parameters were probably due to strong sympathetic arousal. In the nonstimulated animals there were practically no changes in these parameters. One week of fattening resulted in increased basal glucose and insulin levels in the stimulated animals and decreased glucose levels in the nonstimulated partners, in which the basal insulin levels remained nearly normal. Basal glucagon levels were the same in both partners and did not differ from the prefattening situation. At that time during stimulation the obese animals showed a large increase in glucose and glucagon levels and a decrease in insulin level. On the other hand the nonstimulated animals showed a slow gradual increase in glucose and insulin level due to transmission from their fat partners because of the large gradient in these substances between the animals. These phenomena were still more pronounced after 2 wk of fattening. It is tentatively concluded that the humoral satiety factor is neither circulating insulin nor glucagon nor one of the major circulating nutrients.


Surgical repair of gastroesophageal reflux with sliding hiatal hernia. A controlled prospective study of forty-two patients shows it is feasible to correct gastroesophageal reflux complicating sliding hiatal hernia by modifying Allison's repair, using the technic of vertical mattress sutures and Dacron pledgets to approximate the crura and reattach the esophagus to the narrowed hiatus. There was no operative mortality and minimal morbidity. The follow-up period ranges from six to eighty-two months (mean, 38.5 months). One recurrence was noted clinically and verified by esophagogram, esophagoscopy, and motility studies. The remainder have no symptoms of gastroesophageal reflux, and no recurrence has been seen on repeat esophagograms.


Antimicrobial prophylaxis of contaminated tissues containing suture implants. Neomycin sulfate was the only antibiotic tested that significantly reduced the incidence of infections around suture implant sites. The therapeutic efficacy of this antibiotic was related to the chemical and physical configuration of the sutures.


Islet cell hyperplasia localized by pancreatic vein catheterization and insulin radioimmunoassay. A patient with organic hypoglycemia but with normal pancreatic arteriography was investigated with pancreatic vein catheterization for insulin immunoassay. Very high insulin concentrations (1, 130 micronU/ml) were found in a vein draining part of the pancreatic tail. Even though no tumor was found at operation, distal hemipancreatectomy was performed according to the assay findings. Histology and immunohistochemistry revealed a localized islet hyperplasia.


Effect of bowel preparation on small bowel microflora and postoperative wound infection. A method of wound closure utilizing continuous wound compression and suction decompression of the subcutaneous space is described. This method has reduced the incidence of wound complication in the diverse population of patients in whom it has been utilized.


The effect of age and strain on the amount of neurosecretion. The work carried on 4 groups of guinea pigs, each group consisting of five animals showed, that the age and strain may influence the amount of neurosecretion, with the older (except 6 month old animals which passed maturing stage) secreting more than that of younger. And the amount of neurosecretion in animals of the black strain is somehow lower than the ones of the grey.


Pulmonary wedge catheterization during positive end-expiratory pressure ventilation in the dog. In ten supine anesthetized dogs, recordings of left atrial (LA) and pulmonary-artery wedge (PW) pressures were simultaneously obtained at several levels of positive end-expiratory pressure (PEEP) ventilation with the thorax either open or closed. Lateral roentgenograms were taken to determine the relative vertical positions of the LA and PW catheter tips. When the wedge catheter tip was vertically above the left artrial catheter tip, mean PW followed airway pressure at PEEP of more that 5 cm H20. For PEEP 5 cm H20 or less, and for PW catheter tip positions vertically below the LA catheter tip at all levels of PEEP, mean wedge catheter pressure was close to left atrial pressure. Thus, it appears the LA pressure can best be estimated by PW catheter positions vertically below the left atrium during positive end-expiratory pressure ventilation.


Effects of ventilatory techniques during cardiopulmonary bypass on post-bypass and postoperative pulmonary compliance and shunt. Pulmonary compliance and shunt were evaluated preoperatively, 30 minutes after cardiopulmonary bypass, and two hours postoperatively in 132 calves undergoing open-heart surgery with halothane and oxygen anesthesia. The calves were divided into 11 groups with respect to maintenance of the lungs during bypass. In Group 1 the lungs were collapsed during bypass. In all other groups the lungs were mechanically ventilated, statically inflated, or both, with either pure oxygen or nitrous oxide, 50 per cent, in oxygen. All groups had similar compliance and shunt values before operation and sustained significant decreases in compliance and increases in shunt 30 minutes after bypass. Calves exposed to positive-pressure breathing during bypass had higher shunt and lower compliance values after bypass and postoperatively than those not exposed to mechanical ventilation, irrespective of the inflating gas or presence or absence of any amount of static airway pressure. Animals not ventilated during bypass had compliance and shunt values that were not significantly different from preoperative values, while calves that were ventilated had compliance and shunt values that were still significantly altered two hours postoperatively. These data demonstrate that positive-pressure breathing during bypass decreases pulmonary compliance after bypass and postoperatively and increases intrapulmonary shunt, but that the gas inflating the lungs during bypass does not influence either of these variables. The findings also suggest that static pulmonary inflation during bypass offers no advantage over allowing the lungs to remain collapsed.


Nonsurgical class iii orthodontic treatment. 1. Lower incisor angle was decreased due to the closing of the extraction sites and tipping of the incisors. 2. Maxillary incisor angle was increased. 3. Maxillary arch expansion was maintained. 4. The buccal segments remained in Class III occlusion. 5. Rotation of the mandible during treatment recovered as shown by the almost parallel lower borders of the mandible on the composite cephalometric tracing of the initial and final cephalograms. 6. Facial profile did improve. 7. The dental compensations were increased as the facial contour improved, however, most Class III characteristics are still present. 8. Periodontal tissues appear to be acceptable. 9. In select Class III malocclusions orthodontic treatment alone can accomplish an acceptable result without submitting the patient to surgical procedures.


72 kidney transplants at the Medical College of Georgia 1968-1976. Seventy-two kidneys have been transplanted-47 from related donors, and 25 from cadaver donors-into 63 recipients. No donor died or experienced a complication requiring more than one extra week of hospitalization. Six recipients died. Three of the six recipients died from complications. Two of the six died only because they declined to resume hemodialysis, and one died in prison of unusual circumstances after seven and one-half years of good health and kidney function. Five patients are surviving by virtue of a second transplant. Eight patients are now on hemodialysis. Seven patients with transplants are not in excellent physical health and five other patients with excellent health and renal function are nonetheless frequently depressed and easily upset over minor physical disabilities. A majority of the recipients have been rehabilitated to a gratifying extent.


Ultrastructural and physiological studies of the stalk-sectioned rat pituitary gland. A pituitary stalk-section rat model was prepared that would be suitable for the study of the direct effects of steroids on the pituitary gland. In this model, the hypophyseal stalk was severed surgically and metal foil was inserted to prevent regeneration of portal vessels. The major portion of the pituitary no longer had a direct communication with the hypothalamus, and the only blood supply was from short portal vessels that supply the dorsolateral part of the gland. The effectiveness of the lesion was demonstrated by very high levels of serum prolactin and very low FSH and LH. Light microscopic examination revealed a large infarct in the central region of the gland with stainable cells in the peripheral area. Fourteen days after stalk-section, the infarct had shrunken appreciably, and after 21 days it was replaced by a scar. Ultrastructural studies revealed the presence of functional mammotropes in the peripheral regions of the pituitary gland, while other cells were smaller, less active, and contained fewer secretory granules. After LHRH administration there was an increase in serum LH, thus indicating the presence of a substantial number of viable gonadotropes. This was confirmed by the ultrastructural findings which now showed the appearance of large, well-granulated gonadotropes. When LHRH was given to estradiol 17-beta primed ovariectomized stalk-sectioned rats, there was a great augmentation of LH release, and many castration cells were now apparent. Therefore, the administration of estrogen and LHRH was needed for the gonadotropes of the isolated pituitary to function optimally in the synthesis and secretion of FSH and LH. The stalk-sectioned animal model permits evaluation of pituitary function isolated from hypothalamic control while it leaves the surviving pituitary gland in its normal anatomical position.


[Critical study of the treatment of lupic nephropathies]. Therapeutic indications are not the same in the various types of lupus GN. Most cases of extra-membranous GN and focal GN require no specific treatment. In diffuse proliferative GN, the therapeutic indications depend upon the type of lesions and should always be judged in the light of renal biopsy findings. The use of cortisosteroids in high dosage, which is often followed by regression or even complete disappearence of active renal lesions, has considerably altered the prognosis in lupus nephropathy. Chronic haemodialysis and renal transplantation also make it possible to keep alive patients who have reached the stage of end stage renal failure. It nevertheless remains certain that the incidence and course of lupus nephropathy will be radically modified only when methods are available either to prevent the formation of circulating immune complexes or their deposition in the kidney.


John Hunter's alleged syphilis.

John Hunter's alleged syphilis. The allegation that John Hunter suffered from syphilis is challenged. It is suggested that he was the subject of non-luetic vascular disease, evidence for which may be found by a study of his symptoms and autopsy report. It is further suggested that John Hunter's famous inoculation experiment was performed not on himself but on another subject. It is claimed that there is in fact no scientific evidence for attributing John Hunter's illness to syphilis and it is urged that the stigma of this diagnosis should be expunged from his image.


The viability of skin flaps.

The viability of skin flaps. The historical development of skin flaps is outlined, and in particular their division into two types: random, which are supplied by small musculocutaneous vessels; and axial flaps, which are supplied by named cutaneous vessels running within the flap. Experiments are described into the viability of random skin flaps, using the pig as an experimental model. These experiments confirm that random flaps should not be designed longer than their base and probably should not exceed 12.5 cm (5 in) in length.


Lymphocyte depression by cancer.

Lymphocyte depression by cancer. We believe we have shown in the animal model that in cancer the host's lymphoreticular tissues are engaged by a systemically disseminated antilymphocytic humoral factor that destroys the T-cell-dependent pathway, allowing the dissemination of the disease that results in the death of the animal. From studies on patients with cancer there appears to be a real possibility of the presence of a similar substance in man. Such a factor may form the basis for the definiation of cancer and an explanation of cancer illness on the runt hypothesis. Moreover, if the factor could be identified and antagonized a major therapeutic advantage would be achieved.


Randomized controlled trial of early discharge for inguinal hernia and varicose veins. A randomized controlled trial has been conducted into the effects of discharging patients from hospital either at 48 h or 6-7 days after operation for inguinal hernia or varicose veins. There was no statistically significant difference in the frequency of major postoperative complications between the two lengths of stay for either of the conditions studied. Similarly there was no difference between the two groups of hernia patients in relation  to eventual recurrences.


Diagnosis of myocardial infarction by serum isoenzyme analysis. Serial monitoring of the serum isoenzyme patterns of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) in patients suspected of acute myocardial infarction has become a highly sensitive and specific diagnostic method. The predictable evolution of isoenzyme patterns following infarction permits diagnosis and recognition of early stages, recovery stages and extension of infarction in the individual. Usual therapeutic and resuscitative manipulations do not interfere with evaluation of patients with angina or following cardiopulmonary arrest without infarction. Despite significant elevations of serum enzyme levels following general and cardiac operative procedures, the occurrence of myocardial necrosis in the surgical population can be recognized by detection of the specific CPK-MB isoenzyme.


Measurement of enzymes in environmental intoxications. The paper details the enzymes which have been shown to be affected by certain zenobiotics, principally industrial pollutants, toxic metals, toxic gases and food additives. The role of mixed function oxidases is discussed and methods of assessing their activity indicated.


[Metabolism of o,p'-DDD (mitotane) in human and animals. Actual notions and practical deductions (author's transl)]. The metabolism of o,p'-DDD (mitotane), a well-known inhibitor of adrenal steroidogenesis in man and animal, is reviewed. Following oral administration, about 65% of the ingested drug were found to pass in the stool. The drug appeared in the urine in metabolized forms: o,p'-DDA and mono-and dihydroxylated derivatives of o.p'-DDA. These latters were found as well in the stools. An unsaturated metabolite, o,p'-DDE was described in plasma and tissues in man. Serum specimens of treated patients were analyzed for o,p'-DDD during various phases of therapy: the levels and the rate of rise during treatment were very variable (5 to 90 microng/ml). Tissue levels were obtained from animals (rats, dogs) or men (biopsy as well as autopsy): o,p'-DDD was primarily found stored in adipose tissue and fat-containing tissues, essentially adrenals. Practical conclusions can be drawn from these results: there is no correlation between the dose of o,p'-DDD administered and its blood level; there is no correlation between blood levels and the patient's responsiveness to the drug; there is a possibility that the molecule transformed in an active metabolite through its metabolism.


Intestinal mucosal enzymes in the diagnosis of gastrointestinal metabolic disease. The small intestinal mucosa is an actively metabolizing, rapidly proliferating, absorptive epithelium with nutritional and homeostatic functions. A metabolic dysfunction of this organ might, therefore, be expected to cause not only gastrointestinal dysfunction, but also systemic symptoms. Several diseases characterized by primary or secondary gastrointestinal metabolic alterations are discussed.


Ionic basis of myocardial contractility. Knowledge about the basic physiology of mammalian cardiac muscle has lagged behind that of skeletal muscle because the tissue is more difficult to deal with experimentally. The cells are much smaller, they do not tolerate anaerobic conditions very well, and they cannot be tentanized. Therefore as knowledge has developed about skeletal muscle, there has been a tendency to extrapolate to the myocardium. In many instances such extrapolation has been misleading especially in the area of ionic control of contractility. The mammalian heart, with its "all or none" contraction, must have an intrinsic mode of modulating its force development. There is no mechanism as in skeletal muscle for recruitment of more or less motor units as force or work required varies. The heart cell uses two basic mechanisms in the regulation of its contraction--the variation of force with initial cellular length (the classic Frank-Starling mechanism) and the variation of the amount of Ca that reaches the myofilaments. This brief review has focused on the second mechanism. I have emphasized the following points: 1. The source of contractile-dependent Ca in the heart is at the cell surface in rapid equilibrium with the extracellular space. 2. It is likely that a large portion of this surface Ca is bound to negatively charged molecules located in the surface coat/external lamina complex. Sialic acid is a major constituent of the surface complex and recent studies indicate that it is important in the control of Ca permeability in the myocardial cell. 3. The Ca derived from the surface complex crosses the sarcolemmal unit membrane by two routes: (a) a "pore" system: passage through this system is electrogenic and measurable by voltage-clamp technique; (b) a "carrier system": passage through this system is coupled to the outward movement of another cation--most likely Na--such that it is electroneutral and therfore, the inward Ca movements are not detectable by voltage-clamp technique. 4. The primary action of the digitalis glycosides is to inhibit the Na-K pump. This increases Na intracellularly, which in turn increases the Na-Ca carrier activity with the result that more Ca is delivered to the myofilaments. This produces the well-known positive inotropic effect. 5. Finally, there remains considerable controversy with respect to the foregoing points. At this time, they should be viewed as components of a working model that awaits the development of experimental tools to test further its validity.


Enzymatic screening of genetic diseases. (Including hyperammonemia). The application of the techniques of clinical enzymology to the study of human biochemical genetics has laid the foundations for the practice of clinical genetics. In the study of inborn errors of metabolism of the urea cycle, these investigations have resulted in an understanding of the pathophysiology of hyperammonemia as well as delineating additional information on the molecular mechanisms of ammonia detosification. Insight has been obtained through recent investigations of another group of genetic disorders, hypercholesterolemia, which has resulted in opening new horizons relating to metabolic regulation of enzyme action through effector-receptor interactions at cell surfaces.


Modification of functional serum antithrombin III assay for fibrometer. Results of examination of 50 patients. The functional antithrombin III assay of von Kaulla is described and modified for the fibrometer with substitution of readily available Owren's buffer for previously described buffers. The assay is compared with immunological techniques on 50 hospital patients and comparable discrimination of normals and patients with thrombotic disease are shown. Normal values are 51.1+/-13.9 secs. Results in patients with thrombotic diseases are 16.7+/-1.8 secs.


Factors in the pathomechanism of chronic lymphocytic leukemia. It has been shown that CLL is characterized by a piling up of highly differentiated lymphocytic cells. These cells have the structural and metabolic characteristics of a neoplastic cell line of B lymphocytes (except in cases of "T-cell CLL"). However, they lack the immunoglobulin-secreting ability of normal B cells, and are immunologically incompetent and inert. Next to this population, there is a normal but reduced population of B cells and a periodically slightly increased T-cell population. The accumulation of pathological cells is based on a 10-fold increase in proliferation of cells that have a 5-fold increase in their life span. In addition, there is a disturbance of exchange of cells between the intra- and extravascular pools. These characteristics clarify the development of the clinical picture: through packing of the bone marrow with pathological cells on the one hand, and the spleen on the other, anemia, thrombocytopenia, and finally granulocytopenia develop. The gradual displacement of normal B cells often leads to extreme hypogammaglobulinemia as the main component of a multifactorial syndrome of immune deficiency.


Malignant hyperpyrexia.

Malignant hyperpyrexia. Malignant hyperpyrexia is a genetically related syndrome that cannot be predicted reliably in advance of administration of anesthesia except by a strong family history. The definitive etiology is unknown, although triggering agents that release calcium from the calcium-storing sarcoplasmic membrane of the muscle cell are highly suspect. As soon as the syndrome is diagnosed, therapy must be prompt, vigorous, and carried out with the same urgency as a cardiac arrest. Specific therapy with dantrolene sodium may prove to be an answer to this serious problem in anesthetic practice.


Paroxysmal nocturnal hemoglobinuria (PNH) as a clonal disorder. 1. Clonal theories of disease, particularly progressive clonal growth and selection in tumorogenesis, were briefly cited. 2. Evidence for the clonal nature of PNH was presented. Correlation of red cell hemolysis with (a) G-6-PD type in two female G-6-PD mosaics with PNH and with (b) erythrocyte acetylcholinesterase deficiency, provides strong evidence for the clonal theory of PNH. 3. Possible pitfalls in defining "hidden PNH clones" in other diseases by the use of PNH hemolytic tests were discussed. 4. The potential of PNH as a study model for clonal evolution in human disease was emphasized.


Pulmonary complications of general surgery. 1. Patients should be divided preoperatively into low- or high-risk categories, depending on their probability of developing postoperative pulmonary complications. The evaluation should include spirometry as well as an assessment of the previously defined risk factors. 2. Patients in a low-risk category need only instruction in deep breathing pre- and postoperatively. Routine use of supplemented oxygen postoperatively is reasonable until it can be demonstrated whether such is necessary. 3. High-risk patients should be as free as possible of respiratory secretions at the time of surgery. A regimen for this purpose includes cessation of smoking, and administration of inhaled bronchodilators followed by chest percussion and postural drainage. 4. High-risk patients should be carefully instructed in deep breathing and coughing preoperatively. A mechanical device such as an incentive spirometer may be beneficial in this regard. If it is not possible to achieve spontaneous deep breathing, an attempt to accomplish this by IPPB may be undertaken. The tidal volume desired should be ordered. If IPPB does not result in large tidal volumes, it should be discontinued. 5. The deep breathing procedure found to be most successful preoperativelly should be continued postoperatively. 6. The patient should be as mobile as possible while in bed and ambulated as soon as is feasible. 7. Patients with preoperative expiratory flows of less than 20% of predicted values or with chronic hypercapnia should be carefully observed for postoperative ventilatory failure.


Critique of coronary artery bypass surgery. Patients with single-vessel disease, with normal or mildly abnormal ventricular function (EF greater than 40%), have a good prognosis both for natural survival and long-range symptomatic improvement; therefore medical therapy is strongly recommended. Surgery is considered only if symptoms persist after aggressive medical therapy. It is possible that single-vessel left anterior descending disease is a special variant of this group, and surgery may, with further reports, show an increased survival. However, no adequately designed study has yet suggested this, and it is currently our opinion that patients with single-vessel disease do not have an improved survival following surgery. It is not clear whether surgery improves survival in patients with multivessel disease and normal or mildly abnormal ventricular function (EF greater than 40%). Consequently, cardiologists are divided as to whether to advise surgery in these patients solely for survival. Currently, it is our opinion that these patients should have surgery only for improvement of symptoms after failure of medical therapy. In left main coronary disease the evidence favoring improved survival after surgery has convinced most cardiologists, including ourselves, to recommend surgery. Patients with poor ventricular function (EF less than 30%) secondary to coronary artery disease often have congestive heart failure and not angina as their chief symptom. Surgery is usually not advisable for these patients, because of the increased operative mortality and lack of improvement in ventricular function. Patients with poor ventricular function with angina are not usually significantly improved by surgery. In patients with moderately abnormal ventricular function (EF = 30-40%), relief of angina is frequently obtained, but with some added surgical risk. We recommend surgery in these patients after aggressive medical therapy has failed. Patients with unstable angina are initially medically stabilized, after which they are generally managed as stable angina. Patients with persistence of pain at rest in spite of vigorous medical therapy are usually managed by early catheterization and surgery.