A functional classification of hypochondriasis with specific recommendations for treatment. A review of both past and present psychiatric literature reveals that the concept of hypochondriasis is inexact and confusing. In an attempt to make hypochondriasis a meaningful and useful concept for practicing clinicans, a functional classification is presented that views hypochondriasis from four aspects--(1) as a "warning signal," (2) as a symptom of psychosis, (3) as a symptom of depressive illness, and (4) as a syndrome labelled "true hypochondriasis." Each of these aspects is discussed, with emphasis placed on specific and practical recommendations for treatment.


Iatrogenic lesions of the colon and rectum. Our ability to document a number of examples of iatrogenic lesions of the colon and rectum in three general hospitals confirms the multiplicity of these lesions as presented in the literature. It appears that the careful surgeon and his associates would well heed the old admonition known as Murphy's law, that "Anything that can go wrong will go wrong." In the daily practice of the general surgeon and proctologist, it is apparent that gentleness in approaching any anal-rectal examination for either diagnostic or therapeutic purposes is mandatory. The insertion of any foreign object, be it an examining finger, a thermometer, enema tip, or proctoscope, may subject the patient to an inadvertent injury of significant proportion. The dangers inherent in the evaluation and treatment of patients with recognized disease processes is significantly greater than that associated with routine and screening examinations. Morbidity and mortality have been shown to be associated with the barium enema as well as with the barium enema as well as with some of the newer radiologic procedures such as mesenteric angiography. The use of tap water for enemas has produced morbidity both from thermal injuries and from electrolyte depletion. Antibiotics and chemotherapeutic drugs frequently result in colon and rectal disease, and therapeutic procedures directed at organs adjacent to the colon and rectum have resulted in a number of iatrogenic lesions. This reviews confirms reports of others that iatrogenic lesions of the colon and rectum are not solely due to the physician's inexperience, as significant numbers of these lesions were the result of the diagnostic or therapeutic efforts of men of considerable experience and skill. Advanced age of the patient and diseases leading to changes in the character of the bowel wall frequently were factors in the production of these lesions. A poorly prepared bowel has led to increased morbidity and mortality associated with iatrogenic perforations. The early recognition of these lesions and prompt medical and surgical management diminishes both the morbidity and mortality associated with such injuries.


Studies on multiple antibiotic resistance in obligate anaerobes. Forty-eight Gram-negative obligate anaerobic bacterial strains were isolated from faeces on selective media and their antibiotic resistance spectra were determined. R factor transfer was not detected in a series of experiments involving matings among the anaerobes, nor between the anaerobes and known donor and recipient facultative E. coli strains. Antibiotic resistance plasmids could not be demonstrated by treatment with acridine dyes and ethidium bromide in four multiply-resistant strains.


The treatment of contact burns of the palm in children. A combination of early tangenital excision and skin grafting, with early continuous splinting in an acrylic sandwich-splint, is described as a method of management of contact burns of the palm in children.


Immediate reconstruction in ablative head and neck surgery. Effective reconstructive techniques are available for immediate, primary repair of surgical defects caused by extensive ablation for malignant conditions of the head and neck. Primary repairs rely heavily on the principle of 'axial-based' skin flaps which can be transposed into the defects without delay. Three cases are presented to illustrate the method.


Antibiotic resistnace and R factors in Klebsiella pneumoniae. Strains of Klebsiella pneumoniae isolated from sewage were examined for their resistance spectra and for the presence of R factors. Infectious drug resistance was demonstrated in 104 (80%) of the 130 strains tested. Resistance to chloramphenicol, kanamycin or tetracycline was usually R factor-determined. Resistance to gentamicin was not encountered in this species.


A comparison of three benzodiazepine hypnotics as oral pre-anaesthetic medication. A comparative trial of nitrazepam, and triazolam (U-33,030) as pre-anaesthetic medicaments in patients allegedly not subject to insomnia, was undertaken the night before operation. The inclusion of placebo controls confirmed earlier findings that the majority of these patients suffer from transient insomnia. Nitrazepam and flurazepam are hypnotics, and in this study, triazolam also proved to be an hypnotic remarkably free of adverse effects.


History of mental health services in South Africa. Part X. Institutions for defectives. The first Government institution for mental defectives was opened at Maitland in the Cape, in 1921, and was named the Alexandra Institution. A second, Witrand, was opened at Potchefstroom in 1923. A third was opened at Howick in Natal, in 1949, and was called the Umgeni Waterfalls Institution. A fourth, at Westlake in the Cape, was opened in 1962 and houses Coloured patients. Over 1 000 defectives are cared for in private institutions.


Melphalan versus adriamycin in the treatment of advanced carcinoma of the ovary. The therapeutic effects of adriamycin and of melphalan in patients with advanced carcinoma of the ovary were tested in a prospective randomized study. Complete and partial remission occurred in eight of 19 patients treated with adriamycin and in four of 20 patients given melphalan. The difference, however, is not statistically significant. The median duration of complete and partial remissions was slightly longer after treatment with melphalan than with adriamycin. The number of cycles required to produce the initial regression state was less in the patients in the group given adriamycin as compared with those in the group treated with melphalan. No cross resistance was observed between the two drugs. These data indicate that, in patients with carcinoma of the ovary, the therapeutic efficacy of adriamycin is competitive with that of the most effective conventional agents, such as melphalan.


Retention suture technique using buttons. The use of buttons for retention sutures is advocated as practical, inexpensive, universally available and well tolerated bolsters over which heavy nonabsorbable sutures may be secured. We have not found any disadvantages to the described techniques in the past 12 years.


Hypothalamic dysfunction and intracranial arterial spasms. Evidence is presented that suggests that dysfunction of the hypothalamus is an important step in the development of the intracranial arterial spasm that accompanies subarachnoid hemorrhage and craniocerebral trauma. Speculation is offered as to the possible pathogenetic mechanisms involved.


Effects of methylprednisolone, glucagon, and allopurinol in the protection of pancreaticoduodenal allografts perfused for twenty-four hours. To establish a model for 24 hours of hypothermic pulsatile perfusion-preservation, methylprednisolone, glucagon, and allopurinol were added to the perfusate of five groups of canine pancreaticoduodenal segments. Results after transplantation showed that neither allopurinol nor glucagon, when used alone, had any beneficial effect on the segments. The segments perfused with the additive combination of methylprednisolone and glucagon had the best results after transplant.


Contemporary work-related environmental diseases. This paper is a general review of occupational diseases with particular emphasis on contemporary work-related diseases. Reasons for the difficulties in diagnosis and treatment of industrial disease are given. The basic principles of occupational health are reviewed. The particular occupational diseases discussed in detail are the clinical pneumoconioses, and the contemporary diseases: angiosarcoma from exposure to vinyl chloride and respiratory carcinoma from bichloromethyl ether exposure. Numerous other environmental hazards are mentioned. The role of the Occupational Safety and thealth Administration (OSHA) is discussed, as is the role of the physician from the point of view of taking an appropriate medical history from an occupational vantage and medical diagnosis of occupational disease. Attitudinal aspects are emphasized.


Ergonomics of heat and cold.

Ergonomics of heat and cold. The biophysical, physiological and some of the psychological aspects of work under unfavorable man-made ambient conditions are presented in light of the need to prevent excessive strain. Work is treated in two ways: 1) in terms of the muscles O2 demand as a fraction of maximal aerobic capacity; and 2) in terms of metabolic heat source. Since maximal aerobic capacity depends on factors such as physical fitness, age and sex, these factors require consideration in estimating strain due to work. The absolute metabolic heat (M) produced during work is needed in the consideration of the total heat balance. Radiation (r), convection (C), and, under some circumstances, evaporation (Eev) are the main avenues of heat exchange between man and his immediate environment. Eev is primarily a function of the ambient potential for evaporation (Emax). Since the relation of the sum M+R+C to Emax determines heat balance when man in under a heat load, evaluation of the avenues of heat exchange, the sources of heat load, and the stressing effect of all these on the physiological responses are treated in some detail. Psychrometrically defined limits of exposure are also discussed. Subjective sensation and mental performance are discussed in light of their correlation with physiological responses to heat. Cold is treated mainly from the point of view of safety and protective clothing.


A review of the evidence in retrospect for a rickettsial etiology in Bullis fever. The authors have presented evidence through work done 25-30 years ago for the rickettsial etiology of Bullis fever, a forgotten epidemic which occurred with over a 1,000 cases among World War II troops in training at Camp Bullis, Texas. Rickettsiae were recovered from blood and lymph nodes of patients and from ticks, Amblyomma americanum, collected in the area. All patients gave a history of tick-bites. The human and tick strains of rickettsiae, carried in chick embryo culture and in animal passage, were found to produce the characteristic syndrome of Bullis fever in human volunteers inoculated with either strain, indicating identity and specificity of infection. Wildlife in the area was found to support the stages in the life cycle of A. americanum. Deer were implicated as supporting the most abundant adult tick population, the stage which attacks man. Serologic studies eliminated othe rickettsial diseases, Colorado tick fever, dengue and many other diseases. The name Rickettsia texiana is suggested for the hitherto un-named member of the rickettsia group of organisms.


Extracorporeal model for study of factors affecting thrombus formation. Factors determining thrombus formation on a foreign surface were studied with the use of plastic flow chambers introduced into extracorporeal shunts. Silicone rubber shunts, joining the carotid artery and jugular vein, were implanted in dogs and remained patent for several weeks. The flow chamber geometry consisted of a 4.8 mm diameter straight tube having a 3.2 X 3.2 mm circumferential cavity in the wall. Chambers were introduced sequentially into the shunts for exposure times of 10 to 30 minutes and regulated blood flow rates of 100 to 400 ml/min. The dry weight of thrombus accumulated in the chamber (5 to 50 mg) was found to increase with exposure time up to 20 minutes and to decrease with increasing flow rate. Various components of the process of thrombus formation were altered by the administration of acetylsalicylic acid, heparin and lysozyme, used alone and in pairs. Heparin was found to be the most effective antithrombotic agent, dry weights of accumulated thrombus being on the order of 50 percent lower when compared to control values. The efficacy of heparin was found to be unaffected by the presence of aspirin and lysozyme, which themselves were not effective antithrombotic agents under the conditions of these experiments. The technique described here may provide a useful animal model for studying the influence of blood flow and different biomaterials on thrombus formation.


Plasma fibrinolytic activity following oral anabolic steroid therapy. Six anabolic steroids were assessed for their ability to enhance plasma fibrinolytic activity in males with ischaemic heart disease. Five 17alpha-alkylated steroids (Ethyloestrenol, Norethandrolone, Methandienone, Methylandrostenediol and Oxymetholone) were examined and all produced a significant increase in plasma plasminogen activator as measured by the euglobulin lysis time. The only non-17alpha-alkylated steroid studied (Methenolone acetate) failed to enhance fibrinolysis. The 17alpha-alkylated steroids studied all deserve more detailed evaluation of their long term effects on plasma fibrinolytic activity.


Calcium ionophore A23187 (Eli Lilly): effect on platelet function, structure and metabolism. The addition of 0.1 muM ionophore A23187 to washed platelets incubated in citrated saline caused massive release of stored serotonin accompanied by intracellular accumulation of inosine monophosphate, but produced no detectable influx of externally added calcium or abnormal structural alterations. With increasing ionophore concentration there was a significant influx of calcium and a drastic alteration in the platelet ultrastructure. The increase in ionophore concentration was accompanied by the conversion of the major part of metabolic adenine nucleotides to inosine monophosphate and an almost complete blockage of further conversion to inosine and hypoxanthine. The metabolic changes were accentuated by the addition of calcium at concentrations less than 1/10 of the citrate concentration. In the presence of Ca++, or when citrate was omitted, there was a substantial leakage of cytoplasmic material, which at times suggested complete exchangeability between cytoplasm and extracellular medium. Our findings are consistent with the hypothesis that the platelet release reaction is triggered by intracellularly bound calcium. They also suggest that the application of high ionophore concentration has a toxicologic rather than a physiologic effect on platelets, and that a weak chelator added during incubation with the ionophore can in the absence of divalent cations prevent cell destruction, but not the toxic effect on cell metabolism.


Kidney transplantation and donor age.

Kidney transplantation and donor age. The cumulative graft survival after 355 cadaver kidney transplantations was analyzed with special reference to the age of the donors. A significant decrease in cumulative graft survival with increasing donor age was found.


Effect of phentolamine and preperfusion with glucose on insulin release from the isolated perfused pancreas from fasted and fed rats. Starvation of rats for 24 hrs resulted in decreased insulin release from the isolated rat pancreas. The effect of fasting could not be counteracted by elevation of the glucose level in the equilibration medium from 0.8 to 1.5 mg/ml. The alpha-adrenergic blocking agent phentolamine (10 mug/ml) stimulated glucose induced insulin release to approximately the same extent in fasted as in fed rats. These findings illustrate the importance of endogenous catecholamines in the regulation of insulin secretion from the isolated pancreas. Our experiments suggest that the impairment of insulin secretion on fasting is due neither to the inhibitory effect of catecholamines nor to the lack of substrate in the pancreas at the initiation of the stimulation.


Function of the pancreatic B-cell during the development of hyperglycaemia in mice homozygous for the mutations "diabetes" (db) and "misty" (m). The function of the pancreatic B-cell was studied in relation to the development of the diabetic syndrome in a new variety of the diabetic mutant mouse, which was produced at The Jackson Laboratory, Bar Harbor, Maine, U.S.A. by outcrossing of a c57bl/ksJ-db stock with C57BL/6J mice. The expression of the db-gene in the resulting strain was evaluated by measurements of the body weights and the concentrations of serum glucose and serum insulin at different ages of the animals. In the diabetic mice the body weights increased rapidly between 5 and 25 weeks of age to a weight twice that of the lean controls. During the same time hyperglycaemia and hyperinsulinaemia occurred, the maximal serum glucose and insulin values being observed between 17 and 25 weeks of age. Later on the serum glucose and serum insulin concentrations gradually decreased. Islets were isolated with collagenase from animals 5, 10 or 20 weeks old, and studied with respect to insulin content, glucose oxidation and the secretion and synthesis of insulin. The results were compared with data from control experiments with islets isolated from non-diabetic littermates. No major differences were found between islets from diabetic and control mice with regard to the glucose oxidation rate, whereas an exaggerated insulin response to glucose was observed in islets from 5 weeks old diabetic mice. In the 20 weeks old diabetic animals there was a significantly decreased islet insulin content and a considerably lowered insulin biosynthesis.


Diabetogenic effect and inhibition of insulin secretion induced in normal rats by ammonium infusions. In order to explain the abnormalities of glucose metabolism previously observed in patients with blood ammonia elevation, the effect of a transitory hyperammonemia on I.V. glucose tolerance was investigated in rats. An I.V. glucose tolerance test was performed in 3 groups of 15 rats 60 min after the beginning of a 95 min infusion of either a 2 ml isotonic NaCl solution (control group) or ammonium acetate solutions at low (0.50 mumol/kg/min. NH4+) or high doses (1.70 mumol/kg/min NH4+). The "high" NH4+ infusion produced an increase of blood ammonia to levels near 1000 mug/100 ml, a significant decrease in the K coefficient for glucose disappearance (2.53 X 10(-2) +/- 0.20 compared to 4.92 X 10(-2) +/- 0.13 in control group) and a suppression of the radioimmunological plasma insulin (I.R.I.) response to glucose. With the "low" NH4+ infusion the hyperammonemia was less pronounced (200-300) mug/100 ml), but the decrease in K(3.02 X 10(-2) +/- 0.15) and in the first phase of I.R.I. release remained significant. The decrease in glucose disappearance rate could be accounted for by the proportional decrease in insulin secretion. Thus glucose intolerance induced by ammonium acetate infusions may be due to a direct effect of NH4 + on the pancreas. These abnormalities in glucose metabolism depend on the quantity of infused ammonium.


Gastric inhibitory polypeptide: effect on glucose-induced insulin release from isolated rat pancreatic islets in vitro. Gastric Inhibitory Polypeptide (GIP; 1 or 10 mug/ml) potentiated glucose-induced (8 or 16.6 mM) insulin (IRI) release from isolated rat pancreatic islets. Basal release was unaffected. The threshold concentration of glucose necessary for GIP to modulate IRI release was between 6 and 8 mM. GIP had no effect on IRI release from islets submitted to a maximal glucose stimulus (25 mM).


Use of hot formaldehyde fixative in processing plant-parasitic nematodes for electron microscopy. A preparative technique is formulated for processing plant-parasitic nematodes of the order Tylenchida for electron microscopy. A population of Dolichodorus heterocephalus is used as test objects. One and a half grams of paraformaldehyde are dissolved in 25 ml of water at 60 C. Five drops of 1 N sodium hydroxide are added to clear the solution, which is then cooled to room temperature. Two and a half milliliters of 25% glutaraldehyde are added with 23 ml 0.1 M phosphate buffer, pH 7.3, and 0.2 M with respect to sucrose. The final solution contains 3% formaldehyde and 1% glutaraldehyde and is pH 7.2. It is heated to 70 C, poured over specimens, and allowed to cool to 4 C in 2 hr. The nematodes are then incised in a fixative containing 2% glutaraldehyde and 5% dimethyl sulfoxide at 4 C for 16-24 hr. Five milliliters of 25% glutaraldehyde and 2.5 ml of dimethyl sulfoxide are combined in 17.5 ml of water. Twenty-five milliliters of phosphate buffer (supplemented as above) are added. The final pH is 7.2. The glutaraldehyde, aided by dimethyl sulfoxide, uniformly and permanently fixes the nematode tissues. The specimens are embedded in agar. Following a 30-min buffer wash (4 C) they are postfixed in buffered 2% osmium tetroxide for 2 hr at room temperature, washed, and dehydrated through an ethanol series and two acetone baths. Dehydration includes a 2-hr stop in 75% ethanol containing 2% uranyl acetate. After embedding in Spurr's epoxy resin, specimens are sectioned and poststained in 0.5% aqueous acetate for 6 min and saturated aqueous lead citrate 3--4 min. This technique reduces killing time to less than 2 sec, straightens specimens for easier orientation, and eliminates the typically high internal pressure of nematodes which causes displacement of internal structures observed with other fixation techniques.


A blaze-dry spreading procedure for the electron microscopy of chromosomes from acid alcohol-fixed human lymphocytes. A procedure is described for the blaze-drying of human lymphocyte chromosomes on carbonized Parlodion film. Films are prepared by applying Parlodion solution to sheets of freshly cleaved mica. Damage to the film during blaze-drying is prevented by chilling the mica sheets on dry ice before flaming. After spreading, the film and metaphases are floated free from the mica and transferred to a slide of Formav-coated electron microscope grids. The resulting preparations yield complete metaphase spreads and banded chromosomes morphologically similar to those observed with the light microscope.


Modified thiocarbohydrazide procedure for scanning electron microscopy: routine use for normal, pathological, or experimental tissues. A modified thiocarbohydrazide (TCH) technique to cross-link osmium layers has resulted in a reliable method for preparing a wide variety of soft biological tissues for scanning electron microscopy without the use of evaported metal. The technique works equally well on tissues with smooth surfaces and those with abrupt changes in contour or cut surfaces, as in biopsy or autopsied material or pathologically altered tissues, and thus has wide applicability. Small surface structures and junctional areas between cells are distinct. In addition, thin cells such as alveolar endothelium in the lung exhibit a transparent property, allowing the visualization of cells within the capillary lumen while retaining adequate contrast for study of the capillary wall itself. Absence of an evaporated metal coat makes the removal of tissue from the scanning electron microscope specimen easy for embedding and examination of the same material with the transmission electron microscope.


B-lymphocyte subpopulations in the mouse. Organ distribution and ontogeny of immunoglobulin-synthesizing and of mitogen-sensitive cells. The first fetal cells synthesizing Ig can be demonstrated at day 10 of gesta tion, well before cells with detectable surface-bound Ig have been found. These early Ig-synthesizing cells are exclusively large cells. The first small cells synthesizing Ig appear at day 15-16 of gestation, a time when cells. with detectable surface-bound Ig have been found in fetal liver. Ig synthesis of liver cells declines 2 days after birth, presumably reflecting a change in cellular composition of the liver, whereas spleen cells, on a per cell basis, synthesize Ig at a constant rate from birth to adult life. At the time that the first small Ig-synthesizing cells are detected and surface-bound Ig has been found on fetal liver cells, such small fetal liver cells can be stimulated by LPS in serum-containing media to generate 19S IgM secreting PFC. Three to four days after birth, cells develop in the small fraction of spleen which can be stimulated in serum-free media by either LPS or PPD to PFC development. Thus we can distinguish three types of B-lymphocytes as they appear sequentially during ontogeny: I. Large, Ig-producing cells, not susceptible to polyclonal activation to PFC development by either LPS or PPD. II. Small, Ig-producing cells, susceptible to LPS-stimulation in serum-containing media; and III. Small, Ig-producing cells, susceptible to LPC- and PPD-stimulation in serum-free media.


Lymphocyte subpopulations in the thymus. The thymus of mice and chickens contains at least four discrete populations of lymphoid cells: Two distinct cortical populations of small lymphocytes (early and late population), a hydrocortisone resistant and presumably medullary population of small lymphocytes, and a population of medium sized lymphocytes (prolymphocytes) (see Table I and Figure 3). These four cell types were identified with preparative cell separation techniques (e.g. cell electrophoresis, BSA-density gradient centrifugation, and velocity sedimentation) in combination with size distribution analysis. The combination of these techniques provides two-dimensional distribution patterns ('fingerprints') with high power of resolution. At present the two cortical populations of small lymphocytes cannot be identified as distinct populations by any other method. The physical parameters also provide useful markers for the identification and comparison of cellular subpopulations in animals of different ages, different strains, and to a certain degree even of different species. It is believed that each of these subpopulations is in itself heterogeneous in respect to antigen specificity, and it is proposed to call lymphocytes with different antigen specificity but identical physical characteristics 'isotypic lymphocytes'. The medium and large thymocytes serve as progenitors of the small thymic lymphocytes, as shown by different investigators. Small and larger lymphocytes are thus believed to represent different stages on developmental pathways (vertical heterogeneity). The different populations of small thymocytes, on the other hand, are believed to represent different independent pathways (horizontal heterogeneity). There is clearly the possibility that functionally distinct sublines of peripheral T-cells are generated by separate developmental pathways in the thymus, and the functional properties of single thymic cell types (e.g. of the thymic suppressor cells) may accordingly correspond to the functional properties of their peripheral progeny.


Separation and functional analysis of subpopulations of lymphocytes bearing complement and Fc receptors. A highly versatile procedure is described in this review which can be used to separate and obtain in pure form subpopulations of lymphoid cells which express different cell surface structures. The method is based on the observation that when rosetting and non-rosetting leukocytes are centrifuged on a cushion of Isopaque/Ficoll, the rosetting leukocytes and red cells sink whereas the non-rosetting leukocytes float. Thus, any subpopulation of leukocytes can be separated providing they can be identified by rosetting. The earlier sections of this review describe the method, its efficiency of separation and its advantages compared with other fractionation procedures. Subsequent sections describe experiments in which the procedure was specifically applied to separating Fc receptor (Fc+) and complement receptor (CR+) lymphocytes. On the basis of these two receptors it was possible to subdivide T and B lymphocytes into distinct subpopulations. Four subclasses of B lymphocytes were identified in mouse spleen (Fc+CR+,Fc+CR-,Fc-CR+ and Fc-CR-) and two subclasses of T cells were also detected (Fc+ and Fc-). The functional relevance of these subpopulations of lymphocytes was examined. It was found that in all cases examined, antigens could successfully activate CR+ B cells to produce antibody. However, only polymeric antigens, whether T-dependent or T-independent, were capable of triggering CR- B cells to synthesize antibody. Furthermore, preliminary experiments suggest that Fc receptors are present on functional B cells and helper T cells but are not expressed on cytotoxic T cells. On the basis of these results it is proposed that complement receptors on B lymphocytes provide an additional binding site which stabilizes the union between the antigen-specific receptors and soluble antigen. In contrast, due to their multi-determinant nature, polymeric antigens can avidly bind to B cells without involvement of the complement receptors. The possibility of Fc receptors playing a similar role in stabilizing the interaction of antigen with specific receptors on lymphocytes, particularly on T helper cells, is also discussed.


Millipede burns in man.

Millipede burns in man. A review is made of the clinical features and treatment of the lesions caused by the secretions of millipedes. The toxicology of these secretions is discussed. The geographical distribution is reviewed. The species identified as inflicting injury to man are enumerated. Lesions of soft parts of the skin can be moderately severe. Eye injuries may be serious and must receive effective treatment rapidly to prevent residual damage.


[Course of Trypanosoma musculi infections in Plasmodium berghi-infected mice (author's transl)]. Trypanosoma musculi brought into Plasmodium berghei-infected mice in the later stages of the malaria infection shows rapid, approximately logarithmic multiplication in the peripheral blood. The trypanosome number increases by a factor of 2-9 per day, multiplication of the parasites kills most mice in a few days. Many multiplicative forms of the trypanosomes and a few trypanosomes without nuclei are seen in blood smears. Histologically and in touch preparations, masses of multiplicative forms of the trypanosomes are seen in the sinusoids of the liver. Aggregates of trypanosomes are found, too, in the kidney medulla and, inconstantly, in venous sinuses of the spleen and postcapillary venules of lymph nodes. Occasionally, trypanosomes may be found extravascularly in the interstitial connective tissue especially of the pancreas, in lymph vessels and lymph node sinuses. - Mice infected in earlier stages of the Plasmodium berghei infection achieve stabilization of trypanosome numbers.


[Altered reproductive behaviour of Trypanosoma musculi after several years of passage in mice (author's transl)]. The modified strain multiplied less in pregnant and in Plasmodium berghei-infected mice, more in heavily infected normal mice, and more or less in weakly infected normal mice. The discordant behaviour in weakly infected mice was due to the occurrence in some animals of a second phase of more rapid increase of the parasitemia. This behaviour could be seen occasionally in the original strain, too. In inbred mice (BALB/cHan) the length of parasitemia clearly depended on inoculum size and height of the developing parasitemia.


[On the migration of the third stage larvae of Wuchereria bancrofti in Anopheles gambiae (author's tranls)]. The migratory pattern of the third stage larvae of Wuchereria bancrofti from the thorax into the head of Anopheles gambiae has been studied. A total of 1269 infected mosquitoes were dissected and examined from the 7th through the 19th day after the blood meal. The filarial worms migrated from the thorax through the abdomen before they reached the head of the mosquito. Third stage larvae first appeared in the abdomen on the 9th day after infection, where their number increased progressively up to the 13th day and then decreased steadily thereafter. In contrast, mature larvae were first found in the head on the 11th day, and a concentration of larvae could be observed in this region only from the 14th day onwards.


[Acinar epithelium as a source for the formation of the human pancreatic islets in embryogeny]. By electron microscopy in the islets of Largenhans and acini of the pancreas of the human fetuses 4-7 months old acinar-islet (transitional) cells were revealed. The cytoplasm of some transitional elements contained zymogen and endocrine A-granules, while in others zymogen and endocrine B-granules were found. Acinar-islet cells differed by the structure of organelles and by the quantity of endocrine granules, which can be regarded as transformation of acinar cells into endocrine cells. A conclusion was drawn that during human pancreas embryogenesis the acinar epithelium is one of the sources of islet tissue formation.


[Comparison of the parts in relation to some problems of the statistical processing and planning of cytological experiments]. A possibility is studied of using phi-transformation for comparison of portions in homogenous totalities with intra-group variability. The phi value distribution is approximated satisfactorily by normal distribution, beginning from a certain amount of observation (n) depending on P, P being a portion of cells (individuals) with the character under study. On this basis, a method of statistical treatment and experiment planning is proposed.


[Studies in the automation of human chromosomal analysis. II. The development and testing of a system for the semiautomatic measurement of chromosomes]. The elaboration and testing the "PAUK" system intended for human chromosome measurement is described. The system is based on the semi-automatic measurement projector and computer "Minsk-22". Chromosomes of 83 cells were measured. The system allows to make measurements of chromosomes in the large scale with high precision. The measurement installation can be used for measuring any macro- and micro-objects on photographic film and photographic plate.


Controlled trial of 6- and 9-month regimens of daily and intermittent streptomycin plus isoniazid plus pyrazinamide for pulmonary tuberculosis in Hong Kong. A comparison has been made between 6- and 9-month regimens of streptomycin, isoniazid and pyrazinamide given daily, 3 times a week or twice a week from the start of chemotherapy, in the treatment of newly-diagnosed, smear-positive, pulmonary tuberculosis in Chinese patients. At 6 months the twice-weekly regimen was marginally inferior in that 5 (4 per cent) of 126 patients with drug-sensitive strains pretreatment had an unfavourable bacteriological status compared with only 2 (1 per cent) of 141 on the 3 times weekly and none of 137 of the daily regimen. Of a total of 211 patients treated for 9 months, only 1 of 74 on the twice-weekly regimen relapsed bacteriologically between 6 and 9 months. The bacteriological relapse rates in the first 6 months of follow-up after 6 months' chemotherapy were 13 per cent on the daily, 16 per cent on the 3 times weekly, and 18 per cent on the twice-weekly regimen, and after 9 months' chemotherapy they were 3 per cent, 4 per cent and 4 per cent respectively. All 33 relapses were with strains sensitive to isoniazid and streptomycin, and 76 per cent of them occurred in the first 3 months after the end of chemotherapy. Although patients with drug-resistant strains pretreatment fared less well, about two-thirds had a favourable bacteriological status at 6 months, and all 3 regimens given for 9 months had low relapse rates. The implications of these findings are discussed.


Magnesium deficit after renal transplantation with secondary posttransplantation hypocalcemia and hypophosphatemia. Hypomagnesemia, hypocalcemia and hypophosphatemia after renal transplantation in an 18-year-old patient is described. Serum magnesium decreased in consequence of increased renal transplant function with high urinary magnesium excretion. At the time of serum magnesium depletion, pretransplantation hypocalcemia persisted and severe hypophosphatemia developed. Magnesium oxide treatment was followed by the increment not only in serum magnesium but also in serum calcium and phosphate to normal level. Causal relationship between magnesium deficit and impaired renal transplant tubular reabsorption of magnesium and between magnesium deficit and serum calcium and phosphate depletion in the patient is suggested.


Vesicoureteral reflux in patients in end-stage chronic renal failure. Vesicoureteral reflux was observed in 19 of 180 patients (10.5%) with end-stage chronic renal failure. The underlying disease in the patients with reflux was chronic glomerulonephritis in 8.3%, chronic pyelonephritis in 28.5% and renal hypoplasia in 40%. Reflux was bilateral in 13 patients and unilateral in six. Most likely bladder dysfunction due to uremia may have been the cause of the reflux.


[Significance of LDH determination in renal perfusions as criterion of vitality in kidney transplantations (author's transl)]. The activity of LDH in perfusate on human kidney and in experiments on dog kidney was investigated during the preservation by the Gambro perfusion apparatus. The enzyme activity of perfusate was characterized by a quotient of volume activity in relation to the perfusion flow rate. With this method we are able to distinguish the values of damaged and normal kidneys. A correlation was established between this quotient and the function resumption day in human kidney transplantation.


Angiographic evaluation of machine perfused kidneys. An intact and patent renal vascular system is a prerequisite for even and complete perfusion during machine preservation and the reestablishment of renal blood flow after transplantation. Most of the so called "viability tests" for machine perfused kidneys refer to the cellular viability, not taking into account possible lesions of the vascular system. Angiography during machine preservation is a simple, safe and reliable means of examining alterations of the renal vascular system and detecting occult vascular pathology. The degree and reversibility of vasoconstriction can easily be demonstrated, as well as normal and pathologic perfusion patterns. Angiographic examination during preservation may be useful in addition to the tests of cellular viability in order to evaluate borderline kidneys prior to transplantation.


Replacement of urinary bladder wall in the cat by autologous x-ray treated full thickness skin graft. A partial urinary bladder resection was performed in 25 female cats. The defect was replaced with an X-ray treated autologous full thickness skin graft. This graft was shown to be an appropriate foundation for the rapid regeneration of transitional cell epithelium which was proven to be present after 4 weeks. Smooth muscle fibres were present in all cases after 12 weeks. Postoperatively, bladder capacity was adequate without evidence of incrustation or ossification. No changes were seen in the upper urinary tract. Compared to other types of autologous bladder wall replacement this method is simple and warrants clinical investigation.


Free autogenous grafts into the penile cavernous tissue. An experimental study in dogs. The behaviour of free autogenous fat, dermofat, and dermo grafts in the penile cavernous tissue was studied experimentally in dogs. Dermo-fat grafts were those most easily maipulated during surgery and allowed perfect haemostasis. All the grafts were gradually replaced by fibrous tissue causing subsequent scarring and contraction. This reaction was least noticeable with dermis grafts. Cavernous transformation of the adipose tissue was not observed. For the surgical correction of Peyronie's disease the use of a dermo-fat graft is suggested. The grafts should be slightly larger than necessary to allow for the subsequent fibrosis, and the layer of fat should be kept very thin.


Factors that influence surgical wound infections. Role of prophylactic antibiotic therapy. A comprehensive review of the factors responsible for postoperative wound sepsis is discussed, along with the experimental basis for the use of prophylatic antibiotics and a review of the results of the use of systemic and topical antibiotics on the incidence of surgical wound infections. Based on the data presented, suggestions are made which should minimize the development of postoperative wound infections.


Evaluation of Sacks solution for hypothermic preservation of kidneys. The efficacy of Sacks solution for hypothermic preservation of dog kidneys was determined. Complete ischemia was produced in one kidney for thirty minutes by clamping the renal pedicle in situ, followed by excision and immediate washout with the cold preservation fluid. Kidneys were stored in Sacks solution at 2 degree C. for forty-eight hours, reimplanted in the donor, and the normal, contralateral kidney was removed. Complete reversal of renal impairment with long-term survival was observed in 2 of 9 animals. Of 7 animals with graft failure, 2 showed the beginning of a tendency to reverse a rising serum creatinine at the time of death or sacrifice. In the remaining 5, creatinine rose unrelentingly until death or sacrifice occurred. The observed 22 per cent survival rate was significantly (p less than 0.05) less than the 83 per cent survival reported by Sacks, Petritsch, and Kaufman. Evidence suggestive of intrarenal deposits of MgHPO4-3H2O was found in 2 of 4 dogs sacrificed for graft failure. This raises questions of the solution's safety as well as its efficacy. We are unable to confirm the success of the original investigators with this new preservation solution.


Study of local and systemic effects of intravesical BCG. Defects in cell-mediated immunity have been implicated as one of the underlying causes for the appearance and progression of neoplasms. One approach toward correcting these defects employs immune potentiators for the purpose of stimulating cell-mediated immunity. BCG is the immune potentiator which has been used most frequently in the experimental and clinical situation. A preliminary study directed toward ascertaining the local histologic changes and systemic serum response to BCG injection in the dog bladder was undertaken in anticipation of its possible application in the treatment of bladder neoplasm. Local response was predictable and was associated with low morbidity. The appearance of serum precipitin bands to culture filtrates of Mycobacteria tuberculosis strains strongly suggests systemic absorption and reaction to BCG administered intravesically.


Retrieval of indwelling ureteral stent utilizing Fogarty catheter. The efficacy of silicone rubber ureteral stents for long-term urinary diversion has been demonstrated to be of value in certain cases. However, complications, including migration of the stent, do occur.  A method for retrieval of the ureteral stent utilizing a Fogarty arterial embolectomy catheter is described.


Surgical repair of congenital colobomas. Congenital colobomas usually occur as full-thickness defects of the medial third of the upper lid and are commonly associated with a benign dermoid at the apex. Exposure keratopathy and corneal trauma are rare; however, it can be prevented with the Expo Bandage--Bubble (Fig 18). Periodic examinations should also be performed. Surgical resonstruction should be performed at approximately 3 to 6 months of age and primary closure should be attempted initially. Lateral cantholysis, lid-sharing surgery, and external levator resection may be required to correct the residual deformity.


[Ways of mortality reduction after operations on the extrahepatic bile ducts]. Based on the analysis of the immediate results of 231 operations on extrahepatic bile ducts, 174 primary interventions and 57 reoperations, it is concluded that the operation at the height of the attack of acute cholecystitis or in total obturation of bile passages yields considerable mortality (1/3 and 1/5 of observations, accordingly). The best results of surgery were obtained in attenuation of acute inflammatory phenomena in the gallbladder under conditions of liquidation of obturation of extrahepatic bile ducts (1/7 of observations). However, bile peritonitis and progression of destructive acute cholecystitis would necessitate an urgent operation. According to the authors' data well-grounded indications to surgery, a selection of optimum terms and extent of its accomplishment could contribute to favourable immediate results of surgical therapy for diseases of extrahepatic ducts.


[Clinical problems of vascular surgery during transplantation of the kidney]. In transplantation of 245 kidneys in patients with chronic renal insufficiency in the right (75% of all grafting procedures) and in the left iliac region several variants of vascular anastomoses were elaborated and employed. Technical details are described, and some valuable recommendations are given.


[Bone homoplasty in treatment of chronic hematogenic osteomyelitis in children]. The authors report their experience with 44 homoplasties in chronic hematogenous osteomyelitis in 42 patients on definite indications. Positive results were obtained in 28 operations. In 15 patients homografts were removed, but in 7 cases they showed an adequate functioning ultimately. In 3 observations there was a recurrence of the pathological process. Thirteen patients are still under treatment. It is believed that osteohomoplasty used on proper indications for chronic hematogenous osteomyelitis is a largely warranted and perspective measure.


[Significance of some coefficients resulting from dye photometry in the functional characterization of mitral defects]. One hundred and eighty six patients with mitral defects were examined and subdivided into four groups according to the basic clinical and instrumental tests: 59 with pure, 46 with prevailing mitral stenosis, 37 with prevailing and 44 with pure mitral insufficiency. The patients, within the pointed group were subdivided into subgroups, depending on the character of the auricular rhythm, the presence of accompanying tricuspid insufficiency with hemodynamic significance and cardiac decompensation. The circilatory times, TA, TD and TC were calculated for all the patients and especially the coefficients (see article) from the dye dilution curves. The analysis covers only patients from the different groups without other defects and cardiac decompensation. Fluctuations of the minimal and maximal values of TA, K1, K2, and K3 are presented. Their average values are calculated as well as the square deviations. In sinus rhythm and compensated heart, the combination of the values for K1 over 1,80 and K2 over 1,50 in prevailing and for K1 over 1,90 and K2 over 1,60 in pure mitral insufficiency might be used as a criterion for differentiation of pure and prevailing mitral stenosis. The close values in pure and prevailing mitral stenosis, as well as in pure and prevailing mitral insufficiency do not present a possibility to be used in the differentiation of the groups with hemodynamic significance of stenosis and insufficiency. In arrhythmia absoluta, accompanying tricuspid insufficiency and cardiac decompensation, the coefficient K1 and K2 have no value in mitral defect characterization. The close average values of TA and K3 for all patient groups devaluate their importance as functional indices of mitral defects.


[The importance of the eyelids for ophthalmodynamographic recordings-- an oscillographic study before and after total plastic reconstruction of the eyelids (authors transl)]. Ophthalmodynamography (ODG) of an empty orbit apart from a covering of atrophic skin 1mm thick revealed only one twentieth of the pluse amplitude of the contralateral normal orbital oscillographic waves. After total plastic surgical reconstruction of the lids, isolated oscillographiy of the eyelids was performed for the first time. The pulse amplitude now reached about 1/4 of that of the contralateral side. It is concluded that these reconstituted eyelids contribute at least 25% towards the volume and 25% towards the oscillographic pulse wave amplitude on performing ODG in the usual manner. These values could well be exceeded in normal lids on account of their better blood supply.


Reduction of azo food dyes in cultures of Proteus vulgaris. 1. Rates of reduction of a number of azo food dyes were measured in anaerobic cultures of Proteus vulgaris. The rates of colour loss were found to be zero order under conditions in which the concentration of viable cells remained constant. 2. A significant increase in the rate of reduction followed the onset of cell mortality. 3. The zero-order rates correlate with the redox potentials of the dyes. A mechanism consistent with these observations involes an extracellular non-enzymic reducing agent which acts as an electron shuttle between dye and cellular reducing enzymes.


[Dependence of various antigen formation of Proteus mirabilis strain 1095/67 growing on minimal nutrient media]. Proteus mirabilis strain 1095/67 has been cultivated in surface culture on different minimal media, which were composed either of single amino acids or combinations of several amino acids without or with stepwise addition of other C-sources up to the complete medium. We found a direct dependence of the formation of the various antigens (moving to the cathode, to the anode, or not moving) on the composition of the medium. Certain amino acids (Ala, Glu, Asp. Ser) elicit only parts of the antigenic spectrum formed in complete medium, but enrich special antigens. With only 2 amino acids (Ala and Glu) and the vitamins thiamine, pyridoxal, and niacine in the anorganic basic medium the complete antigenic spectrum can be formed. We have shown that the composition of the cell wall varies with the composition of the culture medium. In shaked cultures we found serine to be essential for the production of the antigen moving to the cathode and the thermolabile antigene moving to the anode (ATA), niacine to be of fundamental importance in the biosynthesis of all antigens. Already under very limited supply of nutrients ATA, common to all gram-negative bacteria, is formed and, therefore, it seems to be a very basic cell wall component.


[Some endocrinological and therapeutic problems from the geriatric aspect]. Age-specific criteria must be taken into consideration in the treatment of hormonal dysregulations during senescence and senium. A general transmission of the endocrine conditions of younger periods of life to the senium is not possible and induces the possibilities of complications which are demonstrated at the example of the thyroidal and parathyroidal metabolism. The course of endocrine crises is the severer the older the patients concerned are. Dealing with the pathophysiological findings, the author demonstrates and explains therapeutic standards according to own experiences.


Trypanosoma lewisi, Trypanosoma rhodesiense: mitotic activity in normal and folic acid deficient rats. Ten experiments were performed to compare mitotic activity in livers of rats infected with Trypanosoma rhodesiense and Trypanosoma lewisi. The host dietary groups were: (1) complete of full complement; (2) folic acid deficient, and (3) pair-fed or calorically restricted. Liver mitotic counts of T. lewisi-infected rats fed complete and pair-fed control diets showed a high degree of significance over that of control rats. From days 35 to 55, liver mitotic counts of T. lewisi-infected rats deficient in folic acid showed an average of 16 +/- 2 mitotic phases as compared to 9 +/- 2 for livers of uninfected animals. Liver mitotic counts of T. rhodesiense-infected and non-infected rats fed complete and pair-fed control diets showed that there were essentially no differences in the mitotic counts from that seen in liver from control, uninfected animals. On day 25 (day 5 of infection), folic acid-deficient infected rats showed a significantly higher number of dividing cells than the controls. Folate was measured in isolated, washed T. lewisi and T. rhodesiense cells. T. lewisi and T. rhodesiense contained 9.6 ng folate per 10(8) cells and 6.2 ng of folate per 10(8) cells respectively. Metabolic products of T. lewisi contained an average of 0.51 ng of folate per 10(8) trypanosomes. T. rhodesiense metabolic products contained 0.3 ng of folate per 10(8) trypanosomes.


Immunologic heterogeneity of the lymphocyte surface in various diseases. Employing the surface immunofluorescence technique and rosette test, surface receptors of lymphocytes from 83 healthy subjects (57 adult donors and 2l infants), 3 mature fetuses, and 110 patients, including 23 infants with acute repiratory infections, 22 patients with multiple sclerosis (MS), 20 patients with viral hepatitis (VH), 22 patients with chronic brucellosis, and 1 patient with ataxia-telangiectasia lacking serum IgA were studied. Surface immunoglobulins complement-receptor lymphocyte (B lymphocytes), rosette formation with uncoated sheep erythrocytes (T lymphocytes), and receptor for Fc IgG, characteristic mainly of B lymphocytes, were determined. Percentages of B lymphocytes in peripheral blood of adults (21%) and infants (about 24%), T lymphocytes in adults (about 70%) and infants (about 52%) were determined. On the surface of lymphocytes from adults, IgM predominated, followed by IgG, and IgA was least frequent. In acute upper respiratory tract infections in infants percentages of B lymphocytes in peripheral blood were markedly increased. Glucocorticoids used in treatment exerted a distinctly suppressive effect on these cells. In multiple sclerosis the number of cells with receptors for complement and density of receptors for Fc IgG on the surface of lymphocytes were decreased. In acute viral hepatitis, no significant changes in the contents of B and T lymphocytes in peripheral blood were noted. In chronic brucellosis, the numbers of T lymphocytes were decreased, and atypical mononuclear cells with partial lack of receptors typical of B lymphocytes were observed. The findings indicate that in diseases based on bacterial or viral infections and in multiple sclerosis, B and T lymphocytes play an essential role, which is reflected by the percentages of B and T lymphocytes in peripheral blood.


[Malignant tumor (sarcoma) on a fetal neck, diagnosed during pregnancy by means of ultrasonics]. Authors present a case of congenital sarcoma discovered by ultrasound at 30 weeks of pregnancy. The tumour was shown projecting from the anterior neck, well limited and measured 12 X 12 X 8 cm associated with maternal hydramnios. Pregnancy was terminated. Patho-histological finding was a spindle cell sarcoma of the neck and mandibular region. Discussion is about clinical, ultrasound-diagnostic and morphological aspect of this rare entity.


[Developmental trends in obstetrics at the Leipzig University-Gynecological Hospital since the existence of the German Democratic Republic]. An analysis of development in the obstetrics allows following comments: Peripartal and perinatal mortality shows a significant positive development. Maternal mortality has become very rare. The high percentage of approximately 10% of premature birth has a bad influence on the perinatal mortality. The intranatal mortality compared to ante- and post-natal could be sunk to a great extent. The eclampsia is observed very rarely. The reasons for the good results are to be seen not only in widening of indications of obstetrical operations but also in improvement of solicitude, prophylactical, diagnostical and conservative therapeutic measures.


[Comparative investigation on recovering bacteria from the artificially contaminated hand (author's tranls)]. A modification of the basin-procedure (PRICE), the plastic-bag-(GASCHEN), the fingertip-(SCHUMBURG) and the glass-cup-method (STORY) were compared in order to evaluate their efficiency to recover bacteria from the artificially contaminated hand. With all 4 methods there was a linear relation between the bacterial content of the contamination and the rinsing fluid in which the germs were collected from the hands (FIG. 1, Tab. 9). The number of recovered bacteria per ml, however, differed greatly with the method used. Without regard to the volumes of rinsing fluid and the size of the offered skin area, both differing with the metheod, the finger-tip-procedure yieleded the highest counts followed by the plastic-bag-, basin- and glass-cup-method (Fig. 1). Compensating the influence of the volume the three procedures first mentioned appeared equally effective (Fig. 2 and Tab. 11). It, however, has to be noticed that the finger-tip-method uses a skin area considerably smaller than the other two methods. The glass-cup-method was the least effective but used on the palm the recovery was still 10 times that of the yield of the back (Fig. 2). Because of its high efficacy, the better exploitation of the subungual spaces and because of its simplicity, the finger-tip-method seems to be the procedure best suited for recovering bacteria from the artificially contaminated hand.


[Microbial contamination of air by activated sludge units (author's transl)]. Measurements of the germ emissions in various activated sludge units with different ventilations systems have shown that the lowest density occurs with small bubble ventilation; with medium bubble and brush ventilation rather high values were measured; the spray devices used for foam elimination had a particularly unfavorable influence. In great germ densities above the pools (50-100 000 germs/m3) - depending on the weather - between 500 and 1500 germs/m3 were measured at a distance of 50 and 100 meters. At distances of 200 and 400 m the number of germs was about the same as normally measured in the outside air (100-500 germs/m3). In a closed pool altogether considerably higher values were measured: In the immediate neighbourhood of the activated sludge unit they amounted to abt. 10 000-25 000 germs/m3; in the hall 3000-4000 germs/m3 were measured, whereby the part of coliform bacteria amounted to 1-2% and that of enterococci to 2-4%. It has to be taken into account that besides the measured intestinal flora further pathogenous agents are present in the aerosols. In closed units, therefore, a greater risk of aerogenous infections exists, whereas in open-air pools this danger can be judged as very small.


Light sensitive chloramphenicol analogues. Some chloramphenicol analogues have been prepared in order to find reagents which could be used in a photoaffinity labelling study of the peptidayl transferase center of the E. coli ribosome. The compounds were tested for antibiotic activity in vitro in the "fragment reaction" assay, and for their ability to generate very reactive species upon irradiation.


Binding of a nitroxyl to radiation-induced DNA transients in repair and repair deficient of E. coli K-12. Binding of tritiated 2,2,6,6-tetramethyl-4-piperidone-N-oxyl (3H-TAN) to radiation-induced DNA-transients in E. coli K-12 strains AB 1157 and JO 307 rec A uvr A has been studied under in vivo conditions. After irradiation the cells were washed and resuspended in growth medium and left overnight at 37 degrees C. Within an uncertainty of about 10%, no effect of repair could be detected on the yield of TAN bound to DNA for any of the strains. During the period after resuspension. TAN or fragments of TAN leaked out of the irradiated cell samples. This leakage may be attributed to semi-permanant association between TAN and radiation-induced radicals within the cell. The relevance of different interactions between TAN and transients in DNA is discussed.


Endocrine function of the canine pancreas. The effect of duct ligation and transplantation of the total duct ligated pancreas. Pancreas transplantation was studied in the dog using a total duct ligated pancreas as allograft. In a group of 10 mongrel dogs the effects of long-term (6-36 months) total duct ligation on the endocrine pancreas function were studied by means of repeated intravenous glucose tolerance tests (iv-GTT). One year after total duct ligation the mean glucose assimilation coefficient (k-value) was 75%, the median insulin peak value (IPV) 63% and "total" insulin secretion in the first thirty minutes (TIS) 58% of the pre-operative values. These levels were maintained up to three years after duct ligation. The total duct ligated pancreas was then used as an allograft in 28 beagles in order to study the influence of DL-A (dog leucocyte-antigens) matching on the survival time of the graft. DL-A identity compared to one or two haplotype difference gave a fourfold increase in median survival time from 9 to 40 days. In a second group of 14 beagles with one haplotype difference the effect of immunosuppressive therapy was studied. The methods used (antilymphocyte serum and a combination of prednisone and azathioprine) increased the median survival time to the level seen in DL-A identity. In conclusion the total duct ligated pancreas can be used as an insulin secreting allograft, providing rejection can be suppressed adequately.


An evaluation of the diagnostic value of synthetic luteinizing hormone releasing hormone. The potential use of LH-RH as a test of pituitary function in women has been investigated. In this study the synthetic material was administered intravenously, and samples of peripheral blood were removed at defined times. The levels of plasma oestradiol, LH and FSH were determined by radioimmunoassay. The administration of incremental doses of LH-RH (from 1.56 to 450 mug) demonstrated that a maximal response was obtained with 100 mug in the majority of apparently healthy subjects. Accordingly, this amount was selected as the standard dose for use in a test of pituitary function. The application of this test to 96 patients with secondary amenorrhea showed that the release of LH and FSH (as assessed by the maximum value, and the area under the response curve) was within the normal range in 82, high in 4 and low in 10. There was no correlation between the cause of the amenorrhea, the results of the LH-RH test, and the endogenous levels of oestradiol, LH and FSH. In addition 5 patients with primary amenorrhea and 8 patients with pituitary disorders were tested with LH-RH. In primary amenorrhea low basal levels of LH were found, but all subjects had a normal response to LH-RH. In 3 patients with clinical hypopituitarism the basal levels of gonadotrophins were in the normal range, but there was an impaired response to LH-RH. It is concluded that 100 mug of LH-RH administered intravenously may be used to test the ability of the pituitary to release LH and FSH, but the magnitude and duration of the response is not of additional diagnostic value.


The effect of maintenance haemodialysis and renal transplantation on the plasma testosterone levels of male patients in chronic renal failure. Plasma testosterone levels were measured at the beginning of a 14 h period of haemodialysis, one hour later, midway through the period and at the end, in 18 male patients in chronic renal failure. The level fell from 8.70 +/- 2.63 nmol/l at the start to 8.08 +/- 3.33 nmol/l at the midpoint, and rose again to 10.12 +/- 3.9 nmol/l at the end of a dialysis. All seven of the patients tested on a non-dialysis day showed similar levels at the same time. At the beginning of a 10 h dialysis period 19 other male patients showed a plasma testosterone level of 10.12 +/- 3.99 nmol/l and, at the end, of 8.98 +/- 4.54 nmol/l. Over the same period the plasma corticosteroids rose from 301 +/- 101 nmol/l to 483 +/- 199 nmol/l. Eight male patients who had had successful renal transplantation had plasma testosterone levels of 15.08 +/- 7.49 nmol/l. It is concluded that the plasma testosterone is low in chronic renal failure, but the circadian rhythm is preserved. Treatment with maintenance haemodialysis does not itself affect the plasma testosterone level, or alter the circadian rhythm despite the procedure's being a stress. Successful renal transplantation restores the plasma testosterone to normal in most cases.


Quantitative analysis of pancreatic islet development and insulin storage in the foetal and newborn rat. Pancreatic islet development and insulin storage were studied in foetal rats during the last 4 days of gestation (day 19 to 22 post-coitum (p.c.)) and in 1 and 5 days old neonatal rats. Adult female virgin rats were also studied. The percentage of granulated B-cells per islet, the degree of B-cell granulation and the islet insulin concentration rose from low levels on day 19 to adult levels on day 22 and remained stable after birth. This indicates that the qualitative maturation of the pancreatic islets as insulin producing units is completed on the last day of gestation. The percentage of islet tissue slowly rose from 0.7% at day 19 to 1.5% on day 22. A further and much more rapid rise occurred during the first day of birth. At the 5th postnatal day the islets comprised 3.6% of the pancreas versus 1.1% in adult rats. Likewise, the neonatal pancreatic insulin concentration was about 3 times higher than in the adult pancreas. The foetal pancreas as a whole showed rapid exponential growth between day 18 and 21 p.c., but a sudden decline in growth rate occurred from day 21 onward. The total mass of islet tissue, on the other hand, continued to expand at its high initial rate up to the first day after birth, whereafter this high rate also declined. The high concentration of insulin in the neonatal rat pancreas therefore appears to be due to differential growth rates of the endocrine and exocrine tissue during the last day of pregnancy and the first day after birth.


Plasma testosterone levels in C57BL/6J male mice: effects of age and disease. Plasma testosterone (T) was measured by radioimmunoassay in both healthy and diseased, mature (8-11 months) and senescent (29-31 months) C57BL/6J male mice. Pathological lesions in diseased mice included reticulum cell sarcoma and enlarged mesenteric lymph nodes. In healthy mice neither plasma T nor testicular weight differed between age groups. Median levels and 95 percentiles of plasma T in ng/ml were 1.12 (0.19-12.18) in mature mice and 1.17 (0-7.31) in senescent mice. In diseased mice testicular weight and the range of values of plasma T were significantly reduced. The marked decreased in plasma T and testicular weight in diseased senescent mice illustrates the importance of distinguishing between disease-related changes and effects of aging, per se.


The pituitary reserve in FSH and LH in amenorrheic and anovulatory women. The pituitary gonadotropic response of FSH and LH "reserve" was studied in ten normal women, twelve amenorrheic and two impuberal patients, as compared with six sterile women with anovulatory cycles. The method as the intravenous injection of 100 microgrs. of synthetic porcine LH-RH followed by the radioimmunologic estimation of FSH and LH in plasms, before and after 15, 30, 45, 60, 90 and 120 minutes. This method allows an accurate estimation of the capacity of the adenohypophysis to release gonadotropins, the so called gonadotropic reserve. There are observed four types fo gonadotropic response to the LH-RH injection. Anovulatory sterile women and prepuberal girls have a very similar pattern with normal or very decreased FSH reserve and marked diminution in LH levels. Primary amenorrhea due to ovarian failure presents basal high values of both gonadotropins and increased response to the LH-RH stimulation. In primary amenorrhea without ovarian failure and in secondary amenorrhea, the LH patterns were normal, but in some cases a slight decrease in the FSH curve was observed. The method is regarded as very useful in the diagnosipothalumus-Pituitary-Ovary) Axis.


Cardiorespiratory function during thoracic anaesthesia: a comparison of two-lung ventilation and one-lung ventilation with and without PEEP5. Previous studies have shown that, in patients undergoing thoracic surgery, a relatively high positive end-expiratory pressure (PEEP of 10 cmH2O = PEEP10) has no beneficial effect on oxygenation during one-lung ventilation (OLV). In the present investigation, cardiorespiratory function was examined in 11 patients intubated endobronchially and undergoing thoracotomy. Comparison was made between two-lung ventilation (TLV) and OLV and between zero end-expiratory pressure and PEEP5 during OLV. Cardiac output was determined to obtain information of the total oxygen delivery (cardiac output times arterial O2 content. The change from TLV to OLV was accompanied by a marked fall in PaO2 and a marked rise in shunt, whereas no significant change was observed in mean cardiac output. Oxygen delivery also remained unchanged due to relatively small decrease in SaO2 (arterial oxygen saturation) and maintenance of cardiac output. The application of PEEP5 during OLV produced no significant changes in these parameters. The findings in individual patients demonstrated the relative importance of cardiac output in determining oxygen delivery during OLV. A significant negative correlation was found between inspiratory airway pressure and cardiac index during OLV.


Electron microscopy of the endocrine pancreas of cattle (Bos taurus L.). The electron-microscopic structure of the islets of Langerhans in cattle is studied. Four cell types are described: A, B, C and D, differing mainly in the structure of specific granules. In the A cells half-moon- or ring-shaped mitochondria are observed. Two modes of islet cell secretion are observed: by means of 'active-releasing sector's and emiocytosis.


Carbamazepine (Tegretol) as an anticonvulsant. A controlled double-blind comparison with diphenylhydantoin (Dilantin). A large double blind crossover study of carbamazepine (CBZ) in comparison to diphenylhydantoin (DPH) is underway, and the results are presented for the first 20 patients to complete the protocol. The importance of preparatory steps is outlined-beginning with the gathering of preliminary kinetic data about half-life and peak-time in epileptic patients. A detailed pilot study was performed with open administration of the agents and hospitalization during the crossover. Detailed blood level monitoring and dose-equivalence calculations lead to the design of blind crossover protocol from the pilot study. Of the 20 patients reported on at this point, 12 had fewer seizures on CBZ, but 4 of these preferred DPH because of the CBZ side effects. Of the 8 having fewer seizures on DPH, 3 preferred CBZ - leading to a final disposition of 11 on CBZ and 9 on DPH. Mean serum levels were 34.1 mug/ml for DPH and 10.6 mug/ml for CBZ. The patients having fewer seizures on DPH had higher serum DPH levels than those doing better on CBZ, but the opposite was found for the CBZ levels. The implications of this difference are discussed. Over all, DPH and CBZ are effective anticonvulsants of the same general magnitude, but individual patient responses to effects and side-effects will influence their usefulness in any given case.


A double blind study of carbamazepine and diphenylhydantoin in temporal lobe epilepsy. In a double 0lind study no difference was found between carbamazepine and diphenylhydantoin with regard to efficacy in preventing temporal lobe seizures, i.e. partial seizures with complex symptomatology, when the drugs were given without other medication for periods of 16 weeks, and when the serum concentrations were within selected therapeutic levels corresponding to usual therapeutic dosage. Some patients, however, had considerably fewer seizures on carbamazepine, some on diphenylhydantoin. It therefore seems advisable to try both drugs separately, before using a combined medication.


A double blind study of the influence of dipropylacetate on behaviour. The influence of dipropylacetate (D.P.A.) on behaviour was studied in 20 patients using a double blind cross over trial. 5 patients were rated as improved on D.P.A., 6 on placebo, 3 as deteriorated on D.P.A., 3 on placebo, 12 as unchanged on D.P.A. and 11 on placebo. This study gives us no reason to believe that D.P.A. exerts a psychotropic action within 3 weeks which is better than a placebo effect.


Continuous phrophylcatic anticonvulsants in selected childrens with febrile convulsions. The recurrence rate of febrile convulsions is assessed in 108 children who had had either prolonged or repeated initial fits or had both a positive family history and persisting neurological disorder. Only 7 of 40 (17%) who received continuous prophylactic phenobarbitone or primidone for at minimum of 18 months had another fit compared with 40 of 68 (59%) children who were untreated (p less than 0.0005). Indications for continuous therapy are discussed.


Bacterial flora in relation to cataract extraction. III. Postoperative flora. The conjunctival flora of 499 patients operated for cataract was studied on the 4th and 7th postoperative days and compared with the flora examined previously on admission to the hospital and at the time of surgery (Fahmy et al. 1975b, c). Antibiotics had been administered approximately 18 hours before operation, at the conclusion of surgery, and then on the 4th postoperative day after the cultures had been taken. After a significant fall in incidence, including all kinds of bacteria at the time of surgery (Fahmy et al. 1975c), Staphylococcus albus showed an increase in incidence on the 4th postoperative day to the level found on admission. Corynebacteria and gram-negative bacilli likewise showed increasing incidence but not to the level of admission. The incidence of Staphylococcus aureus and streptococci remained unchanged. On the 7th postoperative day, S. aureus showed a fall in incidence while other bacteria had largely the same incidence as that of the 4th postoperative day. The origin of S. aureus isolated postoperatively from the conjunctiva was studied, and showed that the great majority of strains were similar to those found on the patient's own conjunctiva preoperatively. In a few instances, S. aureus could be traced to the patient's own nose or to the noses of some of the nurses. The air of the wards, eye drops or ophthalmic ointments used in the treatment of the patients apparently did not play any role as a source of S. aureus infection. Cultures obtained on the 4th postoperative day showed only a minor relationship to the flora of the wound site observed at the conclusion of surgery.


Menière's disease and diphenidol. A critical analysis of symptoms and equilibrium function tests. In 24 patients with Ménière's disease, chemotherapy using Diphenidol (1,1-diphenyl-4-piperidino-l-butanol hydrochloride), a non-phenothiazinic antiemetic agent, was carried out using the double-blind technique in the cross-over design. The prevalence and intensity of symptoms at the three stages were recorded every three weeks according to fixed scales which were graded: vertigo, unsteadiness, tinnitus, nausea, headache, and shoulder stiffness. The hearing was measured by tone audiometry. Equilibrium function tests were also performed every three weeks and these included the electronystagmographical procedure to determine caloric response and the ARG-Tilt tests. Both symptoms and the results of equilibrium function tests, showed a higher incidence of improvement during the period of Diphenidol administration than during that of placebo. The difference was statistically significant with respect to vertigo, dizziness or unsteadiness, and general condition subjectively, as well as caloric response and ARG-Tilt tests. The Diphenidol effect consisted of an improvement of imbalance, both in the peripheral and in the central vestibular system through its neural and circulatory action. Only 8% of the patients dropped out and no side effects were observed in this series. Both the feasibility of the graded symptom scales and the utility of each parameter obtained from the equilibrium function tests are discussed in connection with testing of the drug in various stages of the disease.


Fanconi's anemia. II. Are multiple endocrine insufficiencies a substantial part of the disease? Three children with Fanconi's anemia belonging to a family where 6 children had the disease were investigated. One child had growth hormone deficiency, a second child showed subnormal response of testosterone to gonadotropin stimulation and the third child had a missing insulin release following arginine. This report shows that growth hormone deficiency is not necessarily liniked with Fanconi's anemia when it occurs in a family. Multiple endocrine insufficiencies do no appear to be part of the disease.


Breast feeding and biological properties of faecal E. coli strains. Human milk may contribute to protection against gram-negative infection by promoting intraluminal agglutination or killing of bacteria or by preventing bacterial attachment to epithelial surfaces. This paper explores the effect of human milk on the sensitivity of faecal E. coli to serum bactericidal activity and agglutination specificity, factors which have been regarded as related to virulence. Faecal E. coli isolated from breast-fed infants differed from those from formula-fed infants in two respects: They were more sensitive to the bactericidal effect of human serum and more often spontaneously agglutinating. E. coli strains isolated from sources outside the gastro-intestinal tract, that is the prepuce and female peri-urethral region, were in breast-fed babies less sensitive than faecal strains. The findings are compatible with the hypothesis that a breast-milk factor favours the proliferation of mutant strains. The observed effects of breast-milk might be associated with decreased bacterial virulence, and be one of the ways in which breast-feeding protects against infection.


Respiratory insufficiency syndrome (RIS) in preterm infants with gestational age of 32 weeks and less. Neonatal management and follow-up study. The clinical entity of respiratory insufficiency syndrome (RIS), i.e. irregular breathing leading to recurrent apnea and bradycardia in an otherwise healthy preterm infant, has been studied in respect of symptomathology and management with intensive case including ventilatory support. During a 4-year period 26 of 103 infants with gestational age less than or equal to 32 weeks and mean weight 1304 g (range 710 to 1830 g) developed RIS. In most infants the initial apnea occurred after 2 and before 72 hours post delivery but in some infants later. Because of progressive hypoxemia and acidosis 15 of the 26 RIS infants required IPPV treatment. The 76% survival rate of RIS infants seems to justify intensive care with ventilatory support even in the smallest preterm infants with RIS, especially as the follow-up study performed at 15 months to 3-1/2 years of age showed neurological sequelae in only 3 of 20 surviving babies, i.e. 15% sequelae rate.


Experimental murine leprosy. 6. Cellular reactions in the draining lymph node after injection of Mycobacterium lepraemurium into the foot-pads of mice. The reaction patterns of the draining lymph nodes were studied in C3H and C57/BL mice after foot-pad inoculation of Mycobacterium lepraemurium (MLM). Bacilli were found in the lymph nodes of both strains already a few days after inoculation, but any marked reaction did not occur until approximately 3 weeks later and then only in the lymph nodes of C57/BL mice. The reaction involved enlargement, epithelioid cell granuloma formation and proliferation of pyroninophilic blast cells in the T-cell area. The lymph nodes in these animals remained large and showed a reactive pattern for up to 230 days. At this stage, bacilli were relatively few. In C3H mice, no reactive changes developed and it was not until much later that they became significantly enlarged. In the advanced stage, normal lymph node structures were replaced completely by giant macrophages loaded with acid-fast bacilli. C3H and C57/BL mice are polar as regards the lymph node reaction against MLM; in C3H mice it resembles the advances stages of human leprosy while it in C57/BL mice mimics the situation in the BT-TT region. Immunofluorescence studies did not reveal any early proliferation of Ig-containing cells and the lack of cellular immune reaction against MLM in C3H mice cannot be explained as an early B-cell reaction to interfere with the development of cell mediated immunity.


Experimental murine leprosy. 8. Ultrastructural features of the inflammatory exudate and bacterial morphology in C3H and C57BL mice after foot-pad inoculation with Mycobacterium lepraemurium. Mice of the inbred strains C57BL and C3H were inoculated in the foot-pads with Mycobacterium lepraemurium (MLM) and the inflammatory reaction was studied using light and electron microscopy. In C57BL mice a granulomatous reaction developed 3-4 weeks after inoculation. The inflammatory exudate at this stage showed numerous lymphocytes, monocytes and macrophages. The latter cell type often contained many lysosomes and appeared activated. The bacilli which were all within phagosomes showed extensive electron dense aggregates of the cytoplasm suggesting severe damage. Lymphocytes and macrophages in close contact with each other were often observed. In macrophages which contained damaged bacilli, spherical lipid-like bodies surrounded by granular endoplasmic reticulum were observed. It is suggested that this cell product could be of some significance for the bactericidal function of the macrophage. Contrary to these findings, the cellular infiltrate developing in C3H mice showed no lymphocytes and consisted exclusively of macrophages. These were all heavily loaded with bacilli. The vast majority of bacilli encountered in this strain was morphologically intact and presumably viable. Lipid-like bodies similar to those observed in infected C57BL macrophages were not encountered in C3H mice. It is concluded that unless the infected macrophages become immunologically activited they are unable to cause bacterial damage or to inhibit the growth of MLM.


The basement membrane of the uterine cervix in dysplasia and squamous carcinoma: an immunofluorescent study with antibodies to basement membrane antigen. Histological preparations with normal epithelium, dysplasia, carcinoma in situ and squamous invasive carcinoma of human cervix were studied by immunofluorescence using human sera containing antibodies against basement membrane material, against intercellular substance of squamous epithelium (ISSE) and against reticulin. A continuous basement membrane was observed in normal epithelium dysplasia and carcinoma in situ, but was faintly stained, discontinuous or even absent in specimens with invasive squamous carcinoma. Staining with anti-reticulin did not reveal any condensation in the basement membrane areas in any of the preparations examined. ISSE was demonstrated in the normal epithelium, dysplasia and carcinoma in situ as well as in invasive carcinoma.


Cardiopulmonary blood volumes at rest and during muscular exercise measured by 113mIn radiocardiography. Cardiac output, stroke volume, right heart and left heart blood volume, pulmonary blood volume and pulmonary mean time were measured at rest and during muscular exercise in 14 healthy subjects in the supine position. The method used was 113mIn radiocardiography measured precordially with a single detector. The results were analyzed with a minicomputer by a modified gamma function fitting method. The increase in cardiac output during exercise was 140 per cent (p is less than 0.001). The stroke volume increased 15 per cent (p is less than 0.05) in subjects with heart rates less than 160 beats/min, and decreased in subjects with heart rates greater than or equal to 160 beats/min. The right heart blood volume decreased from 115 ml/m2 to 105 ml/m2 to 215 ml/m2 (5 per cent; p is less than 0.1) and the left heart blood volume decreased from 120 ml/m2 to 110 ml/m2 (5 per cent; p is less than 0.01). The total heart blood volume thus decreased from 235 ml/m2 (5 per cent; p is less than 0.05). The pulmonary blood volume showed a corresponding increase from 250 ml/m2 to 280 ml/m2 (12 per cent; p is less than 0.005), and the cardiopulmonary blood volume did not markedly change (485 ml/m2 and 495 ml/m2). Pulmonary mean time decreased from 5.0 s to 2.4 s (52 per cent; p is less than 0.001).


A double-blind trial of maprotiline (Ludiomil) and amitriptyline in depressed outpatients. The results of a double-blind trial of a tetracyclic antidepressant, maprotiline (Ludiomil) and a conventional tricyclic, amitriptyline (Elavil), in 67 ambulatory depressives are reported. Hamilton's Rating Scale for Depression was the main outcome criterion. No statistically significant differences were found between the drugs in onset of action, efficacy, side effects or predictors of response. Patients on either drug showed a significant reduction in symptoms after 1 week of treatment and at the end of the trial. Both drugs were tolerated well. A review of double-blind comparisons of maprotiline and tricyclic antidepressants, spanning 13 countries, and including over 900 patients, both ambulatory and inpatient, shows essentially similar results. The main outcome criterion in all these studies was manifest psychopathology assessed on the Hamilton Rating Scale for Depression by the treating physician. The absence of additional types of outcome criteria or assessment techniques, which may have detected differences in motor activity or drive as originally postulated, may have obscured results which were expected to be subtle.


Pipamperone (Dipiperon, R3345) in troublesome mental retardates: a double-blind placebo controlled cross-over study with long-term follow-up. A 6-week double-blind cross-over study comparing pipamperone with placebo was conducted in 20 female mental retardates with behavioural disorders. The ages of the patients ranged between 22 and 42 years. After a 2-week washout period, patients were randomly allocated to either pipamperone or placebo treatment. The initial dosage of pipamperone was 40 mg b.i.d., which was gradually increased to 80 mg b.i.d. within 5 days. Patients were assessed using a ten-item rating scale before and after each week of treatment. For six of the ten items, patients showed a better response during the pipamperone than during the placebo period. When pre-trial scores were compared with those at the end of the trial, seven items had significantly improved with pipamperone. The nursing staff considered the patients more alert and amenable during pipamperone treatment.


Clonidine in alcohol withdrawal.

Clonidine in alcohol withdrawal. In a doubl-blind study, patients receiving a rapidly falling dosage of clonidine recovered about 1 day faster from the symptoms of moderately severe alcohol withdrawal than patients receiving placebo. The effects of clonidine were especially noticeable with respect to tremor, sweating, elevated systolic blood pressure, tension, anxiety, depression, and general condition. Clonidine had no effect on the sleep disturbances. No significant side effects were seen. It is suggested that clonidine is a useful aid in the treatment of alcohol withdrawal, especially when it is desirable to minimise the use of tranquillisers.


A two-gene model for schizophrenia with the possibility to detect carriers of the modifier gene. A two-gene model for the hereditary transmission of schizophrenia is presented involving two pairs of autosomal alleles Ss and Pp. It is hypothesized that the recessive gene can produce schizophrenia in homozygous state with a penetrance of .40. In the presence of the gene P schizophrenia can occur in the heterozygote Ss, resulting in a more serious form of the disease and having a manifestation rate of .70. The population frequencies best fitting the available data are estimated to be approximately .03 for P and .07 or .08 for s. It is also hypothesized that the reproductive fitness is .80 in manifest schizophrenics with genotype ss pp and .50 in overt schizophrenics carrying the modifier gene P. The model is proposed to cover only the so-called "process" or "nuclear" type of schizophrenia. The remaining schizophrenics of "reactive" and other types may belong to different genotypes or consist in phenocopies. The model is discussed in relation to literature observations and our own previous studies. The possibilities for increased fitness of non-schizophrenic carriers of P and s are also discussed.


Myelography in metastatic lesions.

Myelography in metastatic lesions. The radiologic appearances at gas myelography were analysed in 57 metastatic lesions, all histologically verified, or having known primary tumours. Five of these cases were also examined with a water-soluble contrast medium, metrizamide. The results were correlated to the findings at surgery and to tumour pathology. It is concluded that myelographic findings simulating juxtamedullary growth are usually due to local indentation of the dura by the extradural tumour, and not to intradural extension.


Arterial calcification and progressive peripheral gangrene after renal transplantation. Report of two cases treated with parathyroidectomy. Two cases of progressive arterial calcification and peripheral gangrene after successful renal transplantation are presented. Parathyroidectomy was performed and was followed in one case by healing of the peripheral necroses. It is suggested that parathyroidectomy should be considered in similar cases even in the absence of hypercalcemia.


Resistance to beta-lactam antibiotics Proteus strains. A total of 218 Proteus strains isolated from clinical sources were tested for their susceptibility to three penicillins and two cephalosporins. The ability to beta-lactamase production was examined in 36 of these strains. Proteus mirabilis strains were generally more susceptible to cephalosporins than to penicillins, whereas indole-positive Protei were almost uniformely resistant to cephalosporins as well as to ampicillin and benzylpenicillin but susceptible to carbenicillin. Fairly good correlation was found between the amount and hydrolytic soectryn if beta-lactamase activity and the pattern of resistance to penicillins and cephalosporins in the strains examined. Some observations indicate, however, that the resistance of Proteus bacilli to this group of antibiotics is partly related to permeability barriers in bacterial cell. About 37% of Proteus strains transferred their ampicillin resistance to E. coli K12. Beta-lactamase activities mediated by R plasmids in E. coli cultures were 1.5 to 5 times higher than in respective Proteus donors.


Ultrastructural changes in zygote formation and autoradiographic study of DNA replication during conjugation in Saccharomyces cerevisiae. The following stages of mating reaction were analysed in electron micrographs: initial contact of the conjugating cells, formation of a tube-like structure between the mating partners, nuclear fusion and formation of first diploid bud. Nuclear fusion was observed to take place within the conjugation tube, the fusion nucleus, however, was often localised in one of the initial conjugants. The stage of fusion nucleus, preceding the first diploid bud formation, is of longest duration in the mating process. The second longest stage is the formation of a tube-like structure. The whole conjugation process lasts at 25 degrees approximately 60 min. According to the autoradiographic data, DNA synthesis begins after nucelar fusion and proceeds during formation of the first diploid bud.


Cancer of the colon and rectum: a review of the newer technics in diagnosis and treatment. The greatest improvements in the survival rates of patients with carcinoma of the colon and rectum have come with the application of sound principles of cancer surgery. This, coupled with the decrease in operative mortality that accompanied the wide use of thorough bowel preparation and improved postoperative care, has brought surgery to its present plateau. Further improvements have come with difficulty. Wider application of adequate resection and the use of preoperative irradiation may improve survival somewhat. However, the maximal benefits probably have already been derived from operative therapy. Early and more thorough diagnostic technics might result in increased survival through earlier diagnosis. Development of a simple and highly accurate method for the detection of blood in the stool that could be applied widely probably would be the best screening procedure. Greater may come in the field of immunotherapy, along with a beter understanding of the body's immunologic mechanisms. At the present time, the surgeon must content himself with the application of thorough operative procedures.


Inflammatory diseases of the pancreas.

Inflammatory diseases of the pancreas. The first attack of acute pancreatitis is best treated medically, by fasting and general supportive measures unless complications ensue or the patient does not get better. There is no specific therapy for this disease at the present time (while trypsin inhibitors have not proved to be effective, there is some question as to whenter the newer version will be valuable). Since, at least in private hospitals, the majority of patients with acute pancreatitis have gallstones, surgery in these individuals is directed primarily toward removal of the gallbladder and/or common bile duct stones, or to the drainage of cysts. Most acute cysts are small and can be treated medically. Otherwise they shouldbe drained 8-10 weeks later into the adjacent stomach...


Ischemic heart disease: an overview.

Ischemic heart disease: an overview. The studies on natural history of ischemic heart disease are reviewed and the major predictors of mortality identified. The severity of the coronary atherosclerosis and the status of ventricular function are found to be more important predictors of survival than the clinical presentation. The objectives of therapy in patients with ischemic heart disease are (1) to improve the quality of life by reducing symptoms, (2) to improve ventricular function, and (3) to increase survival time. The results of surgical therapy are examined in relation to these three objectives. Symptomatic improvement is present in 85 to 95 percent of patients after surgery, but convincing evidence for improved ventricular function is lacking and controlled studies of natural history have failed to show that surgery increases survival time. Analysis of the mechanism of symptomatic improvement after surgery suggests that increased blood flow to the ischemic area as well as infarction of ischemic myocardium and the nonspecific effects of surgery may account for the improvement. The prevention of coronary atherosclerosis is viewed as an attainable long-term solution to the problem of ischemic heart disease.


Pharmacologic therapy of ventricular arrhythmias. To treat patients with ventricular arrhythmias properly, one must characterize the arrhythmia, define the underlying heart disease and look for and treat reversible causes. When arrhythmias are suitable for pharmacologic suppression, it is necessary to predefine therapeutic goals, then carefully document that the drug accomplishes these goals. Knowledge of a drug's metabolism, excretion, active metabolites and plasma protein binding is often required for full understanding of its clinical effect. Pharmacokinetic principles require that antiarrhythmic drugs be given on a rigid schedule and that plasma drug levels be frequently determined. Use of compartment models and the principle of superposition can enable one to achieve and maintain therapeutic drug concentrations while avoiding toxic side effects. The drugs commonly used to treat arrhythmias, lidocaine, propranolol, procainamide, diphenylhydantoin and quinidine, as well as some newer agents, have specific pharmacokinetics and toxic effects that must be understood.


Intrapatient comparison of treatment with chlorthalidone, spironolactone and propranolol in normoreninemic essential hypertension. The effects of chlorthalidone, spironolactone and propranolol in reducing blood pressure were compared in the same 11 normoreninemic hypertensive patients. All three drugs decreased the blood pressure significantly and no agent had a superior blood pressure-lowering effect. The blood pressure did not normalize. The data suggest that no one variable--volume factors, relative hyperactivity of the renin-aldosterone system or beta-adrenergic hyperactivity--is the prime mover in normoreninemic hypertension. Long-term treatment with chlorthalidone resulted in slight hyperreninism (26.3 +/- 4.9 ng-ml-1-3 hours-1) (mean +/- standard error) with concomitant changes in plasma aldosterone (23.0 +/- 3.2 ng-100 ml-1). The body weight decreased significantly (--1.8 kg, P less than 0.005). Plasma potassium concentrations were low (3.2 +/- 0.1 mEq-liter -1). Creatinine clearance was unimpaired (117 +/- 6 ml-min-1). Treatment with spironolactone resulted in more marked hyperreninism (47.0 +/- 14.3 ng-ml-1-3 hours-1) and hyperaldosteronism (61.9 +/-11.8 ng-100 ml-1). The body weight decreased significantly (--1.9 kg, P less than 0.004). Significant hyperkalemia occurred (4.4 +/- 0.1 mEq-liter-1). The glomerular filtration rate decreased significantly to 93 +/- 3 ml-min-1 (P less than 0.004). Treatment with propranolol resulted in marked suppression of the plasma renin activity (1.8 +/- 0.2 ng-ml-1-3 hours-1) and plasma aldosterone levels (8.9 +/- 1.3 ng-100 ml-1). A significant increase in body weight occurred (+2.3 kg, P less than 0.013). The plasma potassium concentration increased to a level not significantly different from the value found after treatment with spironolactone (4.2 +/- 0.1 mEq-liter-1). The creatinine clearance decreased significantly to 99 +/- 5 ml-min-1 (P less than 0.008). Hyperreninemia (by spironolactone and chlorthalidone), effective hyperaldosteronism (by chlorthalidone) and volume retention (by propranolol) are considered to represent expressions of mechanisms counteracting the depressor effects of these different pharmacologic maneuvers, leading to the maintenance of supranormal blood pressure.