[Biology of lapwing lice].

[Biology of lapwing lice]. (1) An analysis of the correlation between the number of chewing lice appearing on the nestlings of lapwing and their age is presented (fig. 2). As soon as a few hours after hatching most of the birds are parasitized by at least two species of mallophaga. Specimens of Quadraceps rapidly increase in the total during the first week of the host's life. At this time they predominantly inhabit the down on the belly. On waders this genus is abundant and generally takes the dominant position in frequency, while members of the superfamily Amblycera remain scarce components in the simple communities constituted by the parasites (fig. 3). -- (2) Nothing is known about a niche overlap of Austromenopon and Actornithophilus. Probably some competition exists between these genera on a certain host, as the mean-times of numerous occurrence and of transmigration from a parent bird to the nestlings are different in the two species considered (fig. 1). Confident generalization are not permitted, however. (3) Quadraceps junceus is an habitual blood-feeder. Most females of this species are haemophagous when invading the nestlings but males select blood only occasionally. The difference in food preference shown by the sexes proved to be highly significant and may be innate. Hence, perhaps the females have to seek a blood meal before maturation of the eggs just as mosquitoes do. Actornithophilus swarmed from the corpus of its host immediately fro considerable distance. (4) In sporadic cases overcrowding of feather-lice occurs even on birds which show no signs of weakness or injury. So far such outbursts of a population have been found only on full-grown birds, however. Here an example is given concerning a lapwing's nestlings that had hatched the same morning. In turn, attention is drawn to the factors normally regulating the variation in the order of dominance among the parasites involved and limiting their population-size. As a rule juvenile birds possess larger populations of mallophaga than adults do (fig. 4).


[Pharaoh ants in a ward for premature infants]. Pharaoh's ants (Monomorium pharaonis) appeared in a children's hospital and wounded the skin of the pre-mature births. Possibilities for control are discussed.


Insects and other pests affecting man and animals in Saudi Arabia. Survey of the insects and other pests attacking farmers and domestic animals was carried out during three successive years (1968, 1969 and 1970) in the Central province of Saudi Arabia. In this paper, the insects and other pests found were given. Also, location and time of appearance for each pest were mentioned. The pests recorded were 6 species of insects belonging to 5 families and 4 orders attacking farmers; 9 species of insects belonging to 8 families and 4 orders, and 9 species of mites and ticks belonging to 5 families attacking domestic animals.


[Parasitologic collection technic and examination methods in equatorial West Africa]. The author has been a medical doctor and parasitologist over some years in different West-African countries. Based on his personal experience he underlines the special methodological conditions as well for the diagnoser as for the collector of parasitological documenting material. In this respect, the climatological factors have to be regarded as well as sociological and religious situations.


[Genetic control of Blattella germanica]. Based on a literature survey, the possibilities of a genetic control of the German cockroach (Blattella germanica) are shown. First, an oversight is given on the cytogenetics of the German cockroach, including some important mutations. Then the control methods by genetic mechanisms are explained. This chapter begins with analysing the relevant biological pecularities. In control measures, the dominant lethal mutations (induced by rays rich with energy and by chemosterilants) have only a chance if they can be applied in the scope of autosterilization of natural populations. Reciprocal translocations may expect maximum consideration in the future of the control of the German cockroach. Some of these are already available in the heterozygote state. But the establishment of homozygous strains was not yet successful up to now. The possibilities of the application of translocation-heterozygotes are discussed. Such mutant strains of cockroaches which bear several translocations in the heterozygous state, offer the most promising way of control. This may even include the population's eradication. A long-lasting regulation of the population may be achieved with the introduction of insects mutated in this manner even in the case if a complete eradication is not attainable. It might be expected that also other genetic mechanisms may contribute, in future, to the improvement of cockroach control. Such mechanisms may be conditional lethal factors, sex distortions, and others more.


[Parasites in the GDR - introduction].

[Parasites in the GDR - introduction]. The registration of the parasitic fauna all over the world is a fundamental supposition for the strategy of antiparasitic measures. The authors make some statements about the documentation of parasite-fauna realized in some European countries and base the necessity of examinations.


[Parasites in the GDR.1. Studies on helminths occurrence in European wild pigs (Sus scrofa)]. In two different hunting-grounds in the north-eastern part of the GDR from November 1972 to March 1974 the authors tested a series of 102 killed wild boars, aged mostly from 7 month to 3 years by means of helminthological dissection and by coprological methods for helminthic stages. From more than 30 well known species of helminths the following 10 species were found: Cysticercus tenuicollis, Echinococcus hydatidosus, Ascaris suum, Ascarops strongylina, Physocephalus sexalatus, Globocephalus urosubulatus, Metastrongylus elongatus, M.pudentodectus, M.salmi and Trichuris suis. Trichinella spiralis could not be found in any case. Finally some information given of extensity and intensity of helminth-infection, parasite-host-relation with regard to the age of host and the occurrence of helminths of wild-boars in the middle-european region.


Percutaneous indirect lymphography with a new experimental contrast medium: a preliminary report. Suspension of tetraiodotheraphtalic acid-bis-oxyethylester (120-480 mg I/ml) was injected percutaneously into the testicles, mammary glands, and the cervix of the uterus in mongrel dogs. The suspension was rapidly absorbed by the lymphatics draining the injection sites and transported to the regional lymph nodes. Excellent filling of lymphatics and nodes was apparent immediately or a few minutes after injection. Because of locally produced inflammatory reaction, percutaneous indirect lymphography with tetraiodotherephtalic acid-bis-oxyethylester is now applicable only in experimental animal studies.


Silent coronary artery-left ventricular fistula: a disorder of the thebesian system? Two cases with abnormal electrocardiogram were found to have the unusual direct communication between the coronary artery and left ventricular chamber without any manifestations of the other reported coronary arterial fistula.


Nonprolapsing atrial myxoma; clinical, echocardiographic, and angiographic correlations. The auscultatory features typical of myxoma were absent in a patient with nonprolapsing left atrial myxoma. Angiocardiographic and echocardiographic findings including B-mode cross-sectional scanning are presented.


Potassium-related cardiac arrhythmias and their treatment. Severe abnormalities of potassium balance constitute medical emergencies. Symptoms of hypokalemia are vague between 3.5 and 3.0 mEq/liter. Clinical problems can occur with the plasma potassium value lower than 2.7 mEq/liter. Hypokalemia and digitalis glycosides share electrophysiologic actions. Hypokalemia is both synergistic and potentiating for digitalis. In the presence of a normal amount of digitalis, toxicity may be prompted by coexisting hypokalemia. Hyperkalemia does not threaten life until plasma potassium values are greater than 7.0 mEq/liter. The immediate suspicion and recognition of hypokalemia or hyperkalemia in various clinical situations is imperative. Once suspected, confirmation of the diagnosis should follow immediately. Probably the single most useful diagnostic aid is the electrocardiogram, especially in critical situations with hyperkalemia. Prompt intravenous infusion of a calcium preparation, sodium bicarbonate, glucose, and insulin will provide rapid relief from serious hyperkalemia. The appropriate administration of these readily available drugs may obviate an otherwise critical situation.


Theophylline half-life in infants and young children. Pharmacokinetics of theophylline elimination were studied in a 54-child population. Subjects' ages ranged from three months to six years. The mean half life was 4.92 hours, with S.D. +/- 1.88 hours. This is at variance with previous reports. Ages and half lives were compared and there were no correlations in this young age group.


Diagnosis of honey bee venom allergy.

Diagnosis of honey bee venom allergy. Studies using both an optimized RAST assay and intradermal skin testing with whole bee venom indicate that both methods should be used for diagnosis. RAST and skin test are of similar sensitivity but each misses some patients found positive by the other. Correlation between the tests was 91% with an additional 5% only RAST positive and 4% only skin test positive.


A study on the IgE levels of military recruits and association with HLA antigens. To identify antigen marker(s) on lymphocytes for the immunoregulation of IgE immunoglobulin. For this purpose, IgE determinations were performed on 58 recruits who were arbitrarily selected for HLA typing. Thirty-three recruits with IgE values ranging from 24 to 142 U/ml (71 U/ml (71 U/ml average) showed a slight increase in incidence for HLA-A23, -A33 and BW-15 when compared to a group of 25 recruits whose IgE values ranged from 153 to 2128 U/ml (615 U/ml average). Examination for C-loci specificity indicated that CW-1, CW-3 and CW-4 similar for both groups; however, the "low" IgE group had a frequency of 55.5% of recruits possessing CW-2 antigen compared with only 15% for the "high" group. The value for the "high" IgE appears to be similar to that of the normal population (10% incidence) and only slightly elevated when compared to 7% (2/29) found when the identical CW-2 antisera were tested with laboratory personnel. Thus the associations of HLA-CW2 with the recruits within the "low" IgE group suggests that this HLA marker may be an expression for a suppressed response for IgE immunoglobulin. Viral and bacterial infections, found frequently in these recruits, are discussed as a possible cause of this suppression.


Airborne fungal spores in Ahwaz, Iran.

Airborne fungal spores in Ahwaz, Iran. A one-year study of airborne fungi in Ahwaz, Iran, indicated that opportunistic fungi of clinical significance varied in response to environmental conditions. Saprophytic strains did not vary significantly. The most prevalent airbone fungi were Penicillium, Alternaria, Aspergillus and Cladosporium. This information can be useful in the study of clinically important fungal diseases in Ahwaz and other areas.


Experimentally induced feline chlamydial infection (feline pneumonitis). Cats exposed to aerosols of feline Chlamydia psittaci developed a disease characterized principally by conjunctivitis. Signs of conjunctivitis appeared between postexposure days (PED) 5 and 10, were often unilateral initially, and persisted for 22 to 45 days. Fever followed the onset of conjunctivitis (PED 11 to 15) and persisted for 3 to 8 days. Signs of mild rhinitis (occasional sneezing and mild serous nasal discharge) occurred in some cats between PED 8 and 37. Neither signs of lower respiratory tract disease nor significant pulmonary lesions were produced by the feline pneumonitis agent. Small foci of pneumonia were detected microscopically in 3 of 6 cats examined between PED 7 and 14. Chlamydiae were identified between PED 7 and 14 in the cytoplasm of epithelial cells in stained conjunctival smears. Conjunctivitis persisted for at least 18 days after chlamydiae no longer were detectable in conjunctival smears. Low levels of chlamydial infectivity, however, still were present in conjunctiva and lung on PED 45.


Isolation of feline syncytia-forming virus from oropharyngeal swab samples and buffy coat cells. Thirteen of 40 female cats were found to be chronically infected with feline syncytia-forming virus (FeSFV). Attempts to isolate the virus from these cats by conventional methods were not successful. However, virus was isolated from oropharyngeal swab samples and buffy coat cells. A new method was used involving inoculation of actively dividing Crandell feline kidney cell cultures. Cultures were trypsinized 3 days after inoculation and, as a result, cytopathic effect was amplified and ability to detect the virus was enhanced. The FeSFV was detected in 93% (92/88) of the oropharyngeal swab samples and 100% (14/14) of the buffy coat cell specimens. Feline sera were tested by immunodiffusion for precipitating antibody against FeSFV antigen. There was 100% correlation between viral infection and the presence of precipitating antibody. Virus and antibody persisted in infected cats for the duration of this study (8 months for 5 of the infected cats). Urolithiasis was observed in 15 of 28 male cats. Although a direct relationship between FeSFV infection and urolithiasis was not established, most of these male cats (20 of 21) had antibody to FeSFV.


Potency of enflurane in dogs: comparison with halothane and isoflurane. Circulatory and respiratory responses to graded increases in alveolar concentrations of enflurane were investigated in unpremedicated healthy dogs during conditions of spontaneous and controlled ventilation. The minimal alveolar concentration (MAC) of enflurane that prevented movement in response to a standard painful stimulus was determined for each dog and averaged 2.06 vol%. In these studies, enflurane produced cardiopulmonary depression in proportion to the alveolar dose. The average end-tidal enflurane concentration that produced at least 60 s of apnea was 5.29 vol% (ie, MAC 2.57). A comparison of these data with previous studies in dogs indicates that equipotent concentrations of enflurane are at least as depressant to the cardiopulmonary system as halothane and isoflurane.


Bovine dental fluorosis: histologic and physical characteristics. Incisor teeth from 5- to 6-year-old Holstein-Friesian cattle maintained on a ration averaging 40 ppm F annually from 4 months of age were analyzed by a variety of histologic techniques. These techniques included photomicroscopy, microradiography, protein staining, and microhardness testing. The features of fluorotic enamel that were noted were: hypomineralized outer enamel, coronal cementum hyperplasia, disrupted subsurface pigment band, hypoplastic pits, puckered incremental lines, periodic radiolucent regions, positive protein staining, and decreased microhardness of the outer enamel. These results were similar to the lesions of dental fluorosis observed in other species, and explain the external appearance of fluorotic bovine teeth observed under field conditions.


Cardiovascular effects of halothane in the horse. Cardiovascular effects of venous alveolar concentrations of halothane in oxygen were studied in 8 young, healthy horses under conditions of constant arterial carbon dioxide tension. The alveolar concentration of halothane was expressed as a multiple of the minimal alveolar concentration (MAC) which was known for each animal. Increasing alveolar halothane concentrations to MAC 2.0 resulted in a progressive and significant (P less than 0.05) decline in systemic arterial pressure and left ventricular work. Cardiac output decreased between MAC 1.0 and MAC 2.0 as a result of a significant (P less than 0.05) decrease in stroke volume. Heart rate, total peripheral resistance, pulmonary artery pressure, hematocrit, plasma protein concentration, arterial oxygen tension, and arterial pH remained constant over the same range of anesthetic dosages. Continuation of anesthesia, spontaneous ventilation, and the accompanying rise in arterial carbon dioxide tension and electrical stimulation of the horse's oral mucous membranes produced varying degrees of stimulation of cardiovascular function at MAC 1.5.


Survival of 59Fe-labeled erythrocytes in cross-transfused equine blood. Whole blood containing 59Fe-labeled erythrocytes (RBC) and unlabeled serum was transfused from a donor horse on 2 occasions into each of 6 recipient horses. Survival of transfused cells was monitored in the recipients as a function of time after transfusion by measuring RBC radioactivity in the recipients. After the 1st transfusion, RBC concentration of 59Fe remained at 60% to 100% of the transfused dose for 4 days, after which radioactivity values dropped to less than 10% of the dose by 6 days in 3 horses. In the 3 other horses, RBC radioactivity dropped immediately after transfusion, reaching minimal values in approximately 48 hours. After the 2nd transfusion, 1 horse retained 80% of the dose in circulating RBC for 4 days; 2 horses demonstrated a rapid loss of circulating radiolabeled RBC, reaching minimal values in 48 hours; and 2 horses demonstrated minimal radioactivity in the RBC mass even immediately after the transfusion. One horse died of anaphylactic shock during the 2nd transfusion. Erythrocyte compatibility tests, using the direct agglutination test, the antiglobulin test, and the hemolytic test, were not effective in predicting survival of transfused RBC.


Efficacy of trivalent inactivated encephalomyelitis virus vaccine in horses. Twenty-nine horses were vaccinated with a trivalent (Venezuelan, eastern, and western) inactivated equine encephalomyelitis virus vaccine. The vaccine purchased for this study was the only one licensed and commercially available in May, 1975. Plaque-neutralizing and hemagglutinin-inhibiting antibodies in response to each of the 3 equine encephalomyelitis viruses were determined after vaccination. Horses had rising levels of plaque-neutralizing and hemagglutinin-inhibiting antibodies shortly after injection with the 1st and 2nd doses of the vaccine (given 3 weeks apart) and were refractory to challenge of immunity with virulent homologous virus at 3, 8, and 12 months after vaccination. After 12 months, 8 horses were revaccinated; maximum antigenic stimulation was achieved with the 1st dose of the 2nd series of vaccinations.


Partial inhibition of the humoral immune response of pigs after early postnatal immunization. The ability of young pigs to be immunized during the postnatal period was studied. Eight groups of pigs born on the same day from 3 sows were injected with hen egg-white lysozyme in Freund's incomplete adjuvant at days 0, 1, 2, 3, 4, 5, 7, and 10 after birth. The serum antibody titers were determined each week. Results indicated that pigs injected within the first 3 days of life exhibited a delay of 10 days in the appearance of the humoral antibodies, compared with the antibody response observed in pigs injected later. Serum antibody titers were markedly lower in the early immunized pigs. The secondary immune response was similar in all pigs. This partial inhibition is not directly linked to the corticoids present in the serum at the immunization day. Possible reasons for this impairment of the humoral immune response were reviewed.


Hemostatic function in swine as influenced by warfarin and an oral antibacterial combination. Pertinent literature on naturally occurring hemorrhagic diseases in poultry and livestock were reviewed and compared with reports on recent outbreaks of a hemorrhagic syndrome in swine. Epizootiologic, clinical, and hematologic data from porcine hemorrhagic disease suggest vitamin K-responsive hypoprothrombinemia. In weanling pigs, the toxicity of warfarin was compared with that in swine given tylosin and sulfamethazine antibacterial combination versus those given warfarin only. Toxicosis was induced in weanling swine fed warfarin daily at dose level of 0.055 mg/kg of body weight. Approximately 5 days after feeding was started, signs of poisoning appeared: lameness, anorexia, subcutaneous hematomata, melena, and periarticular enlargement. Administration of warfarin at dose level of 0.017 mg/kg did not cause clinical toxicosis, and 0.028 mg/kg produced significant increases in one-stage prothrombin time (OSPT) and activated partial thromboplastin time (APTT), but no evidence of clinical bleeding. When tylosin-sulfamethazine antibacterial combination was fed at normal and high dose levels concurrently with warfarin at dose level of 0.017 mg/kg of body weight, increase of clotting time, OPST, or APTT did not occur due to antibacterial influence. The antibacterial combination fed alone did not produce changes in clotting time, OSPT, APTT, fibrinogen, total protein, differential leukocyte count, or packed cell volume.


Ontogeny of immunity and leukocytes in the ovine fetus and elevation of immunoglobulins related to congenital infection. Certain humoral and cellular aspects of the immune response were observed during gestation in the ovine fetus. Emergence and development of leukocytes in peripheral blood were observed. Morphologically mature lymphocytes were consistently present at 32 days of gestation, but mature neutrophils were not neutrophils were not consistently present until gestational day 123. Monocytes were first observed at 63 days and eosinophils at 112 days of gestational age. Numbers of each class of leukocyte increased from the time of their appearance until just prior to birth when they declined. Production of immunoglobulin G (IgG) and immunoglobulin M (IgM) was monitored from the time of their appearance at 56 and 77 days, respectively, until birth. In contrast to consistently low base-line values of IgG and IgM (below 0.22 mg/ml and 0.21 mg/ml, respectively) found in clinically normal, unstimulated fetuses, the immunoglobulin values in experimentally infected animals increased with the age of the fetus. This finding can be utilized in diagnosis of several congenital infections and anomalies.


Development of the hamster retina: a morphologic study. Hamster retinas were examined by light and electron microscopy during the first 15 postnatal days and at the adult stage. At birth, these retinas were more primitive than those of other rodents, but eventually they became very similar. Initial postnatal growth and development were more rapid than in other rodents of comparable ages. Mitotic figures were present throughout the first 9 days. The primitive inner plexiform layer formed during days 2 to 4; on day 7, several developmental changes became apparent: outer segment disks of the photoreceptor cells formed from flattened, smooth vesicles, horizontal cells became readily identifiable, the outer plexiform layer appeared, and ribbon synapses formed in the receptor cell axon terminals. By day 11, there were numerous conventional synapses in the inner plexiform layer, and ribbon synapses were beginning to appear in the terminal portions of the bipolar axons. The retinal tissue was progressively invaded by developing vasculature. The first photoreceptor outer segment disks formed from smooth membranous vesicles flattening radially around the ends of the connecting cilium. After the outer segment assumed a more mature appearance, with a stacked disk arrangement, further disk formation occurred by plasma membrane infoldings at the outer segment base. The adult hamster retinas were similar to those of other rodents.


Vaccination for fowl plague.

Vaccination for fowl plague. Influenza A/turkey/Oregon/71 virus has antigenic characteristics of fowl plague virus but is avirulent for chickens. The virus was inoculated intratracheally in chickens at several dosage levels and resulted in the formation of antibody and immunity against fowl plague. The avirulent virus replicated in chickens and was recoverable by tracheal swab specimens up to 4 days after inoculation. Although the virus was transmitted to contact controls at the time when their cagemates were inoculated, it was not transmitted to contact controls placed with chickens inoculated 24 hours earlier. After 10 passages in chickens, the virus remained avirulent for chickens and turkeys.


Serologic and hematologic response of rabbits to Anaplasma marginale-infected bovine erythrocytes. New Zeland White rabbits inoculated with Anaplasma marginale-infected bovine erythrocytes produced specific humoral antibodies to this parasite. Specific antibody production as measured by the card and complement-fixation (CF) tests was maximal in 7 to 21 days after inoculation; however, none of the rabbits became infected. Geometric mean CF titers of rabbits inoculated with RBC from cattle with acute anaplasmosis were significantly higher (P less than 0.001) than those of rabbits given RBC from normal cattle. Significant difference was not seen between geometric mean CF titers of rabbits given RBC from carrier cattle and those of rabbits given RBC from normal cattle. It is concluded, therefore, that rabbit inoculations cannot effectively be substituted for calf inoculations to determine the anaplasmosis status of carrier cattle.


Comparison of whole blood and purified canine lymphocytes in a lymphocyte-stimulation microassay. The optimum mitogen concentration and time required for using whole blood from dogs in a microassay were determined, and this test then was compared with a standard lymphocyte-stimulation microtest, using gradient-isolated lymphocytes, 2 different mitogens (phytohemagglutinin and concanavalin A), and 2 different culture media. Statistical analysis of the data from 10 dogs showed that whole blood was significantly more reactive than were gradient-isolated lymphocytes (P less than 0.05). Waymouth's medium was significantly better than RPMI 1640 (P less than 0.001), and concanavalin A was significantly more mitogenic than phytohemagglutinin (P less than 0.001). The interaction between lymphocyte source and mitogens was the only one of the various interactions that was significant at P less than 0.05.


Aerobic bacterial flora of the prepuce, urethra, and vagina of normal adult dogs. Staphylococcus aureus and Mycoplasma spp were the most frequently isolated aerobic microorganisms in specimens obtained from the prepuce and the urethra of 20 normal, adult male dogs. Staphylococcus aureus and Streptococcus canis were the most frequently isolated bacteria in specimens collected from the vagina (in the area of the urethral orifice) of 20 normal intact bitches and 20 spayed bitches. A significant difference was not found in the observed frequency of occurrence of any of the microorganisms isolated from the intact vs the spayed bitches.


Cone and rod photoreceptors in the white-tailed deer Odocoileus virginianus. Duplicity of the white-tailed deer (Odocoileus virginianus) retina, ie, cone and rod function, was established by histologic and electrophysiologic data. The presence of cones and rods in the deer retina was shown by light and electron microscopy. Electroretinography revealed distinct photopic (bp) and scotopic (bs) components in the b-wave of the electroretinogram that are characteristic of the cone and rod activity. These findings are in contrasts to the popular belief that deer have retina composed entirely of rods.


Echocardiography in swine.

Echocardiography in swine. Twelve clinically normal pigs were anesthetized with fentanyl citrate and sodium pentobarbital and placed in left lateral recumbency. M-mode echograms were recorded from the area of the 4th intercostal space with a 3.5 mmHz transducer. Changes in the internal minor axis diameter %deltaD were measured at 44.8 +/- 3.3 cm. An index of contractility (Vcf) was 1.12 +/- 0.16 cm/s. The caudal wall thickness dimension measured 0.61 +/- 0.04 cm and the aortic root dimension was 1.9 +/- 0.11 cm. To corroborate the echocardiographic findings, echocardiographic, cineangiographic, and postmortem studies were conducted on a 2nd group of 3 pigs. Aortic root, diastolic lumenal dimensions, and wall thickness were compared and the results never differed more than 2 mm. Echograms can conveniently be acquired from restrained, mature swine, and they provide useful, reliable structural and hemodynamic information, without the hazards or expense of invasive techniques.


Effects of feeding Oxytropis and Astragalus pollen to mice and Astragalus seeds to rats. Pollens collected from Astragalus lentiginosus and Oxytropis sericea were fed to mice. At the end of the feeding period, uterine weights were taken to determine estrogenic activity, and tissue was collected for microscopic examination. The pollen from A lentiginosus, but not from O sericea, induced lesions similar to those of locoweed poisoning. The pollen from neither plant was estrogenic. Seeds from A lentiginosus produced toxicosis when fed to rats.


Hematologic and serum protein reference values of the Octodon degus. Blood and serum from normal degus (Octodon degus) that ranged in age from 3 to 48 months were analyzed to determine reference hematologic and serum protein values. Both sexes were evaluated and were similar. The hematologic and serum protein values for males were: erythrocytes, 8.69 +/- 0.19 X 10(6) /microliter; packed cell volume, 42.1% +/- 0.59%; hemoglobin, 12.0 +/- 0.15 g/dl; leukocytes, 8.50 +/- 0.39 X 10(3)/microliter; neutrophil-to-lymphocyte ration, 40:60; and total protein, 5.70 +/- 0.20 g/dl. The hematologic and serum protein values for females were: erythrocytes, 8.94 +/- 0.16 X 10(6)/microliter; packed cell volume, 40.0% +/- 0.61%; hemoglobin, 11.7 +/- 0.17 g/dl; leukocytes, 8.20 +/- 0.36 X 10(3)/microliter; neutrophil-to-lymphocyte ratio, 40:60; and total protein, 5.62 +/- 0.18 g/dl. The hematologic and serum protein values for the degu were similar in some respects to values reported for guinea pigs and rats.


Problems in diagnosis and therapy of Mycobacterium fortuitum infections. Mycobacterium fortuitum was isolated 11 times from 8 patients during a 6-year period. Six of the isolates were from sputum; one was from aspiration of a lymph node, and 4 were from wound cultures. The isolation from sputum was believed not to be associated with pulmonary infection in all 6 instances. The difficulty in diagnosis and therapy of infections with Mycobacterium fortuitum is illustrated by these cases and by others from the literature. Amikacin and doxycycline may offer some therapeutic benefit for patients with Mycobacterium fortuitum infections.


Relationships among digital clubbing, disease severity, and serum prostaglandins F2alpha and E concentrations in cystic fibrosis patients. Nine patients with cystic fibrosis but without digital clubbing (Group A) were matched, prospectively, by sex and approximate age to 9 cystic fibrosis patients with digital clubbing (Group B) and to 9 normal persons (control subjects). Patients in Group B had significantly (P less than 0.05) lower clinical scores and forced vital capacity than did those in Group A, indicating more severe pulmonary disease in the former; however, other spirometer tests of pulmonary function revealed no differences between Groups A and B. The degree of digital clubbing had significant (P less than 0.05) linear relationships to forced vital capacity (r = -0.73) and clinical scores (r = 0.853) for Groups A and B. Plasma concentrations of prostaglandins F2alpha and E were significantly increased (P less than 0.05) in both Group A (X +/- SE, 0.48 +/- 0.03 and 0.87 +/- 0.10 ng per ml, respectively) and Group B (X +/- SE, 0.68 +/- 0.04 and 1.81 +/- 0.16 ng per ml, respectively) compared to the control group (X +/- SE, 0.14 +/- 0.01 and 0.39 +/- 0.02 ng per ml, respectively). Group B had significantly larger concentrations than did Group A; however, plasma concentrations of prostaglandin 15-keto-13, 14-dihydro metabolite were not different in Groups A and B, and were significantly smaller than in the control group. These studies suggest that the degree of digital clubbing in cystic fibrosis is related to the severity of the pulmonary involvement and that the prostaglandin system may play an important role in this disease.


Mouse model of pulmonary blastomycosis: utility, simplicity, and quantitative parameters. A murine model of pulmonary mycotic disease using Blastomyces dermatitidis is defined quantitatively. Intranasal inoculation with yeasts avoids delays in growing microconidia and can be performed with routine precautions without sophisticated biohazard facilities. The particles rapidly reach the bronchioles and alveoli, producing a progressive focal pneumonia, studied histologically. In vitro growth conditions are defined to titer inocula reproducibly with visual methods. Median survival can be titrated with the challenge inocula. Although initial postchallenge lung cultures are not always positive, replication eventually proceeds, at a rate defined for various challenge sizes, to a ceiling of 10(7) to 10(8) colony-forming units per g of tissue incompatible with life. Lung weight correlates closely with colony-forming units per g above a threshold. Lethality correlates with initial body weight and with age. During the course of infection, weight is an accurate predictor of mortality. Extrapulmonary dissemination occurs as a premortem event in protracted infections. A wide variation in fungal strain virulence is documented. Quantification of these features of the model makes it useful for study of host response or therapeutic intervention, because efficacy can be related to stage of disease and parasitic burden.


Tuberculous infection in a large urban population. A positive tuberculin reaction, which indicates tuberculous infection, is known to correlate with increased rates of tuberculous disease, but current data concerning possible relationships with factors such as ethnic group, socioeconomic status, age, and sex are unpublished or unavailable. Current background rates of tuberculous infection are also generally not available, so that expected prevalence rates of tuberculous infection in urban areas have not been confidently established. In 1973/74, the New York City Health Code presented an opportunity to study these factors in more than 50,000 employees of the Board of Education. For the first time, a specific index was used to quantitate socioeconomic status. The relative effect of each of these variables on reactor rate was measured. It was found that tuberculous infection was related to race or ethnic group, socioeconomic status, age, and sex, in that order. The over-all data presented a recent picture of the prevalence of tuberculous infection in an urban population.


The effect of Swan-Ganz catheter height on the wedge pressure-left atrial pressure relationships in edema during positive-pressure ventilation. We have studied the effect of the ventrical height of the pulmonary wedge catheter in the lung on the pulmonary wedge pressure-left atrial relationship during positive end-expiratory pressure ventilation in oleic acid-induced pulmonary edema. Pulmonary wedge catheters were placed above and below the left atrium in normal dogs and in dogs with oleic acid-induced edema. Wedge pressure and left atrial pressure were measured simultaneously during positive end-expiratory pressure ventilation (range, 0 to 30 cm H2O positive end-expiratory pressure). Pulmonary wedge catheters below the left atrium correctly recorded left atrial pressure and change in left atrial pressure at all positive end-expiratory pressures studied. Pulmonary wedge catheters above the atrium consistently recorded pressures higher than the normal left atrial pressure. They did not correctly respond to increases in left atrial pressure until it was increased to a value higher than the initial upper pulmonary wedge pressure. Pulmonary arterial catheters, when properly placed, should be reliable indicators of left atrial pressure during positive-pressure ventilation in normal and edematous lungs.


Granulomatous biliary tract obstruction due to sarcoidosis. Report of a case and review of the literature. A 29-year-old woman with sarcoidosis developed obstructive jaundice due to granulomatous involvement of the common hepatic duct and surrounding lymph nodes. After temporary decompression by T-tube, obstruction was alleviated by corticosteroid therapy.


Mesothelioma associated with the syndrome of inappropriate secretion of antidiuretic hormone. A patient with a malignant mesothelioma developed the syndrome of inappropriate secretion of antidiuretic hormone. The electrolyte abnormalities were corrected by treatment with demethylchlortetracycline. Arginine vasopressin concentrations were increased in serum and urine. It is suggested that the syndrome might have been mediated by secretion of antidiuretic hormone from the posterior pituitary, because arginine vasopressin was not detected in the patient's tumor using a sensitive radioimmunoassay.


Superior vena cava syndrome caused by Nocardia asteroides. A patient developed the superior vena cava syndrome from Nocardia asteroides pneumonia with mediastinitis. Specific treatment was dangerously delayed because malignancy was primarily suspected, and nocardial infection was not initially considered. The correct diagnosis was eventually made by appropriate stains and culture of a lung aspirate. Specific therapy with sulfonamide resulted in a cure of the infection, disappearance of facial swelling, and a long-term state of clinical well-being. Active nocardial pneumonia with mediastinitis is a treatable cause of the superior vena cava syndrome and should be considered in the differential diagnosis.


Pulmonary tumorlets associated with Cushing's syndrome. Tumorlets of the lung generally have been considered benign nests of cells, usually found with bronchiectasis or fibrosis. We saw a patient with Cushing's syndrome whose tumorlets ultimately became roentgenographically visible as multiple small nodules throughout both lungs and metastasized to the mediastinum. The plasma corticotropin concentration was increased, as were the concentrations of corticotropin-like peptides in the tumor tissue. This experience lends support to the concept that some tumorlets arise from Kulchitsky's cells in the epithelium of peripheral bronchioles, as do carcinoid tumors, and have the same peptide-producing potential. The possibility of such tumors should be considered in patients with Cushing's syndrome who have no initial roentgenographic abnormality.


Thyroid hormones in the adult rat lung.

Thyroid hormones in the adult rat lung. Thyroid hormones have been postulated to be involved in lung development and the regulation of the surfactant system. This study was designed to determine the concentration of thyroxine and of triiodothyronine in adult rat lung. Tissue-to-plasma ratios of thyroxine and triiodothyronine were determined in adult rats by the equilibrium distribution of radiolabeled hormones. Extracellular thyroid hormone space was estimated by equilibrium distribution of radiolabeled bovine serum albumin. The mean +/- SE ratio of lung triiodothyronine to plasma triiodothyronine, corrected for extracellular space, as 2.57 +/- 0.40, indicating appreciable concentration of this hormone. In contrast, lung thyroxine ratios indicate that this hormone is virtually excluded from adult lung parenchyma. Such results support the hypothesis that thyroid hormone may have a significant role in the regulation of the surfactant system.


Microbial flora of the diseased stomach at resection. The relation of microbial flora in stomach contents and stomach wall was examined in paired specimens from 10 surgical patients and in specimens of wall from 10 additional patients. The flora of both contents and wall were similar. Paired specimens from five patients contained the same kinds of bacteria. Paired specimens from these patients were sterile. Contents from two patients contained bacteria, but the wall was sterile. Microorganisms isolated were streptococci, lactobacilli, bifidobacteria, bacteroides, staphylococci yeast, and coliforms. Bacterial counts ranged from 0 to 10(7.5) per ml or g in both contents and tissue. Survey of the literature shows that most specimens from patients with gastric ulcers or gastric malignancies are positive for bacteria, while only about 60% of specimens from patients with duodenal ulcers are positive.


Review of 555 cholecystectomies without drainage. During a 10-year period, 555 cholecystectomies were performed without drainage of the gallbladder bed or subhepatic space. Six per cent of the patients had acute cholecystitis or hydrops of the gallbaldder and 11% had common duct exploration. Only in those patients with frank infection, spillage of obviously infected bile or in whom satisfactory closure of the gallbladder bed could not be accomplished was a drain used. Meticulous closure of the gallbladder bed was performed to minimize leakage of bile. The series was critically studied to evaluate complications, morbidity, mortality and hospital stay. It was concluded that drainage following cholecystectomy or choledochotomy can safely be omitted except for the indications mentioned.


Adenoacanthoma of the pancreas: report of four cases and literature review. Cases of 20 patients with adenoacenthoma of the pancreas with clinicopathologic data, including the four added, are reviewed. The clinical manifestations, sites of metastases, survival and gross pathology appear to be similar to the usual adenocarcinoma of the pancreas. Adenoacanthoma of the pancreas most probably represents squamous metaplasia of an adenocarcinoma or arises from an undifferentiated cell in the pancreatic duct system. The metastases are typically an admixture of both elements but in four cases, pure squamous or adenocarcinoma metastases were encountered. It is suggested that the pancreas should be included as a possible source in those patients with an unknown primary who have a metastasis consisting of either an admixture of squamous and glandular elements or a pure squamous type and in those instances in which a pure squamous and a pure adenocarcinoma are encountered in different metastases.


Surveillance for postoperative wound infections: practical aspects. Intensive surveillance for postoperative wound infections was conducted for one month on three separate occasions at the Veterans Administration Hospital, West Haven, Connecticut. The mean wound infection rates for clean, clean-contaminated, contaminated, and dirty wounds were 6, 11, 17 and 18%, respectively. During the second survey, the clean-contaminated rate was 25% and was significantly higher than at other periods (p less than 0.05). Most of these infections occurred on a single surgical subspecialty service. The methods used to conduct intensive wound surveillance and the need for close liaison between the infection control team and the surgical service is emphasized. Current problems with wound surveillance are reviewed.


Staging laparotomy and splenectomy for Hodgkin's disease. The major objective of diagnostic laparotomy in Hodgkin's disease is to define the extent of involvement not detectable by nonoperative means. Fifty patients in this institution had operative staging procedures; six for recurrent disease three to 11 years after initial therapy. Twenty-four patients had nodular sclerosis, 23 mixed cellularity, and three had other types. The clinical stages were advanced in 13 patients and decreased in seven patients. Two patients (both had mixed cellularity and systemic symptoms) had positive wedge biopsy of the liver, whereas direct needle biopsy was negative. Nineteen spleens contained Hodgkin's disease but only three could be palpated on physical examination. About half the patients with abnormal lymphangiograms had positive periaortic nodes; lymphangiogram had a false negative rate of 12%. Additional procedures performed included appendectomy, oophoropexy, and resection of Meckel's diverticulum. There was no mortality and only one case had severe postoperative Salmonella septicemia. Our findings are comparable with those reported in the literature.


Use of Allen Brown shunt between profunda femoris artery and long saphenous vein for hemodialysis access. Maintaining circulatory access in some patients on chronic hemodialysis can tax the ingenuity and skill of the best of surgeons. For the last few years, we have used the Allen Brown shunt between the profunda femoris artery and the long saphenous vein in selected patients with considerable success. This procedure adds another useful weapon to the armamentarium of the surgeon who has the responsibility of maintaining circulatory access in patients on chronichemodialysis.


Hypothalamic insufficiency: the cause of hypopituitarism in sarcoidosis. Ten patients with generalized sarcoidosis and hypopituitarism were studied. Six of these 10 patients presented with sarcoid involvement of the optic nerves resulting in asymmetric visual field defects. All patients had deficiencies of two or more anterior pituitary hormones and seven had abnormalities of water metabolism. Despite hypopituitarism, nine patients had a pituitary responsive to the synthetic hypothalamic releasing factors, thyrotropin releasing hormone and gonadotropin releasing hormone, and the tenth patient had a partially responsive pituitary. The demonstration of pituitary responsiveness allows us to infer hypothalamic insufficiency as the major cause for hypopituitarism in these patients. The combination of visual field defects and hypopituitarism in sarcoidosis is a medically treatable condition that simulates the clinical presentation of a pituitary tumor.


Plasma glucose, insulin, glucagon, and growth hormone in kindreds with maturity-onset type of hyperglycemia in young people. Two kindreds affected by maturity-onset type of hyperglycemia in young people were studied. The postglucose-load hyperglycemia segregated as an autosomal dominant trait; it was always mild, never requiring insulin, and generally seemed to start in the first two decades of life. Glucose, insulin, glucagon, and growth hormone were measured during glucose-tolerance tests in patients, relatives, and control subjects. Most hyperglycemic patients were found to have insulin deficiency. There was no correlation between the age of the patients and insulin secretion. Plasma glucagon and growth hormone were normal. Maturity-onset type of hyperglycemia in young people may be a frequent type of hyperglycemia, and its identification will generally depend on the presence of a strong family history. The recognition of maturity-onset type of hyperglycemia in young people as a specific disease different from juvenile, insulin-dependent diabetes is important, especially to prevent unnecessary use of insulin in hyperglycemic children.


Non-cholera vibrio infections in the United States. Clinical, epidemiologic, and laboratory features. Non-cholera vibrios are organisms that are biochemically indistinguishable from Vibrio cholerae but do not agglutinate in vibrio 0 group 1 antiserum. Since 1972 there has been a dramatic increase in the number of these organisms referred to the Center for Disease Control for identification. Clinical, epidemiologic, and laboratory data were analyzed for 26 of 28 patients with isolates identified between January 1972 and March 1975. Thirteen (50%) of the isolates were obtained from feces of patients who had an acute diarrheal illness; no other pathogens were isolated from their feces, and all patients survived. Four (15%) patients had non-cholera vibrios isolated from other gastrointestinal or biliary tract sites; none of these patients had acute illness definitely attributable to non-cholera vibrios. Nine (35%) patients had non-cholera vibrios isolated from other tissues and body fluids; four deaths occurred in this group. Patients with acute diarrhea frequently had a history of recent shellfish ingestion or foreign travel, whereas some patients with systemic non-cholera vibrio infection had a history of recent occupational or recreational exposure to salt water.


Water disturbances in patients treated with oral lithium carbonate. Forty-eight patients treated with oral lithium carbonate and 20 control subjects were studied to define the causes of lithium-induced water disturbances. Measurement of plasma immunoreactive arginine vasopressin, plasma osmolality, and urine osmolality after a period of dehydration separated nephrogenic diabetes insipidus, cranial diabetes insipidus, and primary polydipsia, the three postulated mechanisms of lithium-induced polyuria. Seventeen patients had a urinary concentrating defect despite serum lithium concentrations in the therapeutic range. Ten of these patients had nephrogenic diabetes insipidus, one had results suggestive of cranial diabetes insipidus, but none had evidence of primary polydipsia. Symptoms of thirst and polyuria were poor indicators of the degree of hypo-osmolar urine. No patient had electrolyte abnormalities, and none had sufficiently severe polyuria to stop lithium treatment.


Recurrent myoglobinuria due to muscle carnitine palmityl transferase deficiency. Three new cases of carnitine palmityl transferase deficiency are described. The syndrome consists of recurrent attacks of muscle cramps, weakness, malaise, and myoglobinuria. These attacks are especially likely to occur during prolonged exercise after fasting, eating a high-fat diet, or during cold weather. Occasionally after fasting alone, spontaneous muscle breakdown may occur. One patient studied in detail was excessively slow in producing ketones when he fasted. His mylagias and weakness appeared to be alleviated by beta-hydroxybutyrate. Of eight other patients thought to have idiopathic recurrent myoglobinuria, three were found to have myophosphorylase deficiency, whereas five did not have deficiency of either enzyme. Carnitine palmityl transferase deficiency may be more common than previously supposed, may be in part amenable to dietary therapy, can be easily distinguished from myophosphorylase deficiency, and may provide insight into the metabolism of fatty acids and ketone bodies as well as energy requirements of skeletal muscle.


Lymphocytic interstitial pneumonitis. Review of 13 cases. Thirteen patients with lymphocytic interstitial pneumonitis were seen at the Mayo Clinic from 1966 through 1976. The group included nine women and four men, with a mean age of 50.7 years. Their primary complaints were cough, dyspnea, and loss of weight. Chest roentgenographic features were predominantly basilar, coarse interstitial-alveolar infiltrations. Pulmonary function studies showed restrictive ventilatory impairments with a low CO diffusing capacity in all 13 patients. Lung biopsies in all cases showed diffuse interstitial infiltrations, consisting of mature lymphocytes and plasma cells. Ten of the 13 patients had an associated dysproteinemia, including two patients with hypogammaglobulinemia. Three patients had coexistent Sjögren's syndrome, including two with localized amyloidosis. Although lymphocytic interstitial pneumonitis is a histologically distinct pulmonary lesions, it occurs with a variety of immune disorders.


Serial plasma carcinoembryonic antigen measurements in the management of metastatic colorectal carcinoma. Serial carcinoembryonic antigen (CEA) measurements were evaluated in a group of 263 patients undergoing systemic chemotherapy for metastatic colorectal carcinoma. Initial CEA levels were not found to be of value in predicting the likelihood of subsequent tumor response. Although a general relation between serial CEA measurements and clinical tumor measurements was noted, these measurements were discordant in a substantial proportion of patients. Tumor measurements as an index of response to therapy were strongly correlated with survival, whereas changes in CEA values and patient survival were not correlated at a statistically significant level. Serial CEA measurements were perhaps of some value in predicting progression of malignant disease, and were roughly comparable to serum alkaline phosphatase assay in assessing response of liver metastasis to chemotherapy. Overall, serial CEA measurements added little to the standard clinical assessment of patients with advanced colorectal carcinoma receiving chemotherapy.


Carcinoembryonic antigen levels in benign and malignant pleural effusions. One hundred ninety-one unselected fluid specimens submitted routinely for cytologic examination were assayed to determine whether the measurement of carcinoembryonic antigen (CEA) levels in pleural effusions is useful in detecting malignancy. The mean +/- SD CEA level of 103 benign effusions was 4.1 +/- 2.9 ng/ml. Only one benign effusion had a level greater than 12 ng/ml (18 ng/ml). Benign inflammatory effusions (pneumonia, empyema) had a higher mean CEA activity (6.2 +/- 3.4) than effusions caused by congestive heart failure (2.9 +/- 1.5) (p less than 0.001). Twenty-four (34%) of 70 malignant effusions had a CEA level greater than 12 ng/ml, and 28 (40%) were "positive" by cytologic study. Thirty-eight (54%) were detected by one or both methods. Ten malignant effusions were positive by CEA (greater than 12 ng/ml) alone. These data suggest that the determination of CEA activity levels, when used in conjunction with other clinical findings, may be useful in detecting malignant pleural effusions.


Carcinoembryonic antigen assay of ascites and detection of malignancy. Levels of carcinoembryonic antigen (CEA) activity were measured in 105 unselected samples of ascitic fluid submitted for routine cytologic analysis to ascertain whether this assay was useful in the detection of malignancy. The highest CEA level found in the 70 specimens of "benign" ascites was 10 ng/ml. Using values greater than 10 ng/ml as indicating a cancerous effusion, CEA assay successfully detected 14 of the 29 malignant ascites studied. Cytology, on the other hand, detected only 12 of these fluids. Combining the two methods increased the yield to 20. The CEA assay alone thus detected more than one fourth of these malignant fluids. The assay was particularly useful in detecting malignant transudates, nearly half of which had elevated CEA levels despite negative cytologic findings. The CEA assay of ascites thus showed promise as an adjunct to cytology in the detection of malignant ascites when used as part of a complete clinical and laboratory assessment.


Effects of rapid smoking. Physiologic evaluation of a smoking-cessation therapy. We studied 24 healthy young male smokers to ascertain the medical safety of a highly effective smoking-abatement technique called rapid smoking. In comparison with results obtained after a 12-h cigarette fast or after normal smoking, statistically significant increases occurred after rapid smoking in heart and respiratory rates, systolic blood pressure, carboxyhemoglobin, and pH (p less than 0.05), while arterial PCO2, HCO3-, and serum [K+] fell (p less than 0.05). Rapid smoking produced alveolar hyperventilation in all subjects. In eight, arterial PO2 increased appropriately, but in 16, fell paradoxically (p less than 0.01); seven had arterial PO2 below 80 torr. Because this fall could represent ventilation/perfusion mismatch due to early bronchoconstrictive disease, in subjects with normal flow/volume loops and spirometry rapid smoking may be a simple, provocative screening test for early airway disease. Despite the changes produced there were no arrhythmias. Rapid smoking is safe for healthy subjects but should not now be used for higher-risk patients.


Ovarian (corpus luteum) hemorrhage during anticoagulation therapy. Corpus luteum hemorrhage is a complication of long-term anticoagulant therapy that has rarely been reported in the literature. Within 16 months, we saw six cases in which young women taking anticoagulants to prevent clotting of prosthetic heart valves suffered corpus luteum hemorrhages. Diagnosis was difficult and delayed. Medication stopped the bleeding in three patients; bilateral salpingo-oophorectomy was necessary in the remaining three. Our patients had great difficulty controlling their anticoagulant therapy and had histories of previous bleeding episodes. We believe corpus luteum hemorrhage may become more common as more premenopausal women undergo cardiac valvular surgery.


Nutritional vitamin-B12 deficiency. Possible contributory role of subtle vitamin-B12 malabsorption. Dietary deficiency of vitamin B-12 has been reported, yet most people ingesting vitamin-B12-deficient diets even for many years appear to achieve a balance that does not lead to overt signs and symptoms of deficiency. I present the case of a vegan of 25 years' duration who developed severe neurologic abnormalities due to vitamin-B12 deficiency. His diet provided 1.2 microgram of vitamin B12 daily at most. Despite normal Schilling test findings, he absorbed subnormal amounts of vitamin B12 given with ovalbumin. This poor absorption appeared to be related to his gastritis, achlorhydria, and subnormal intrinsic-factor secretion. Probably, vitamin-B12 deficiency in this patient resulted from both dietary restriction and the subtle malabsorption, neither of which would have sufficed alone to produce the clinical problem. Possibly such malabsorption may also be present in many of those vegans developing overt vitamin-B12 deficiency in whom Schilling test findings have been normal.


Resistant hypertension: diagnosis and management. Fortunately, hypertension resistant to a good drug regimen is rare. When hypertension fails to respond to medical treatment there is usually another explanation, such as poor patient compliance, excessive salt ingestion, drug interactions, spuriously high office readings, or an unsuspected secondary cause for the hypertension. Management of resistant hypertension can be aided by identifying the hemodynamic and humoral mechanisms responsible for its resistance and redesigning the therapeutic regimens accordingly. When they become available, two investigational drugs, minoxidil and an oral converting enzyme inhibitor, both of which lower total peripheral resistance, will offer a new approach to controlling truly resistant hypertension.


Asymptomatic hyperuricemia: the case for conservative management. The management of asymptomatic hyperuricemia is controversial. Reported benefits from treatment prevention of acute gouty arthritis, chronic tophaceous gout, urolithiasis, or gouty nephropathy. A review of experimental and clinical data suggests that the risks of asymptomatic hyperuricemia are small or unknown and the efficacy of long-term treatment in preventing gout or renal disease is unproved. The costs and risks of prolonged drug administration and practical considerations such as patient compliance mitigate against long-term therapy in asymptomatic persons. We offer some recommendations for an expectant approach to the management of asymptomatic hyperuricemia.


Plasma levels of norepinephrine.

Plasma levels of norepinephrine. Plasma norepinephrine derives from sympathetic nerves, but the proportion reaching the circulation before being metabolized varies with the type of nerve ending-effector junctions in the tissue. Plasma levels of norepinephrine also will fluctuate because of rapid metabolism rates and environmental, emotional, and endogenous stimuli provoking a sympathetic response. The responses of plasma catecholamines in spontaneously hypertensive rats and in normotensive rats of the same strain were compared after exposure to a variety of stressors. Drugs that inhibit monoamine oxidase, catechol-O-methyl transferase, or neuronal uptake were administered to show the effects of metabolic enzymes and neuronal uptake on the amounts of catecholamines reaching the circulation. Sympathetic nervous activity and the ability of the sympathetic nervous system to respond to a uniform stimulus are studied in hypertensive and normotensive subjects. A survey of the plasma levels of norepinephrine in a variety of neurologic disorders is given.


Death, dying, and the zealous phase.

Death, dying, and the zealous phase. During the past decade an unprecedented public and professional interest has developed around issues involving death and dying. Persons of differing backgrounds and with different objectives are rushing onto this scene in rapidly increasing numbers. Some of these persons have little understanding of the medical complexities of dying and no clinical experience with dying patients. In this essay I attempt to identify a number of ways in which well-intentioned persons engage dying patients or influence public opinion on death and dying, ways that might prove less than salutary for all concerned.


Eustachian tube function assessed with tympanometry. On 15 normal ears and 14 pathological ears of adults with intact tympanic membranes, Eustachian tube function was measured by using tympanometry in an effort to reproduce the results published by Holmquist. His method appeared to be a promising tool for clinical determination of Eustachian tube function. However, our results on normal ears were not significantly different from our results on pathological ears and were inconsistent with Holmquist's results. In contrast to Holmquist, 60% of our normal ears were unable to attain achieved negative middle ear pressures of -100 mm to -250 mm H2O. Our normal ears, as well as our pathological ears, required repeated swallows to normalize negative pressure. Tests in both our groups were not always repeatable even though recorded applied nasopharyngeal pressure was identical. Therefore, our findings do not substantiate this procedure as a useful, reliable clinical tool for measuring Eustachian tube function on ears with intact tympanic membranes.


Melanocyte system of the endolymphatic duct and sac. One hundred fourteen human temporal bones from 64 individuals were studied for the presence of melanized melanocytes about the endolymphatic duct and sac. Specimens were from Caucasians (104), Orientals (6) and Negroes (4). Of the specimens from people above nine years of age 79% demonstrated melanized melanocytes about the endolymphatic duct and sac, as well as occasionally about blood vessels in the adjacent bone. These represented 74% of the Caucasian and 75% of the Negro and Oriental individuals. Pigment granules were noted in occasional epithelial lining cells and in macrophage-type cells within the lumen. Heavily melanized melanocytes were noted in five of six specimens of Ménière's disease (all from Caucasian individuals), five of five specimens with previous labyrinthitis (two of which were from a Negro woman), and in occasional specimens from patients with presbycusis, metastatic carcinoma (three of the four adult Oriental patients), chronic otitis media, otosclerosis and lymphoma, as well as in several apparently normal specimens. No clear cut correlation of degree of melanization with specific disease processes can be discerned.


Neoglottic reconstruction after total laryngectomy: a preliminary report. This paper is a preliminary report on neoglottic reconstruction of the larynx after total laryngectomy following the techniques described by Staffieri. Also included are general observations on the criteria for selecting candidates for this procedure. At the University of Texas Medical Branch in Galveston, this procedure has been attempted on eight candidates. Reconstruction was accomplished in six, of whom five achieved satisfactory speech, providing an 80% success rate. One of the five did not like the quality of his voice and refused to use it. The sixth produced speech with difficulty and is still undergoing speech therapy. One patient died from recurrence before a second stage could be carried out, and another patient did not have sufficient tissue for neoglottic reconstruction after total laryngectomy. Three patients developed salivary fistulas at the drain site, but all closed spontaneously with the application of pressure. From this data, one may conclude that this technique offers much potential and warrants further study.


Otitis media with effusion: a steroid and antibiotic therapeutic trial before surgery. Eustachian tube dysfunction has been considered the main factor in the etiology of otitis media with effusion (OME). A short-term systemic steroid therapy, with combined chemotherapeutics, yielded 53.1% cure in 160 children in which OME had been diagnosed, whereas only 12.5% of similar 116 children were cured by chemotherapeutic treatment alone. It is postulated that steroids, acting by a mechanism much similar to the one in the newborn lung, increase the level of a tubal surface active agent, thus enhancing Eustachian tube refunctioning. This combined treatment, we believe, deserves its place as a routine conservative trial before surgery.


Air calorics: a technique and results.

Air calorics: a technique and results. A major problem with air calorics appears to be one of technique. A pilot study led to the design of irrigating tips which allow consistant air presentation and simultaneous measurements of irrigating temperature at the delivery orifice (adding a second sensor). Preset temperatures of 24 C and 50 C in our system yielded air equilibration mean temperatures of 27.4 C and 45 C at the delivery orifice during testing. A normal study was carried out at these temperatures with an air flow of six liters per minute for 60 seconds. The range of caloric responses, mean maximum speed, and standard deviation are comparable to values previously reported with water stimulations. Statistical testing indicated no difference between ears for either warm or cold. Also, there was no significant difference for warm versus cold responses. We have performed over 2000 clinical examinations that incorporate this technique with satisfactory results and remarkable acceptance by the patients. The normal or "standard" probe size has been found to be adequate for the majority of the clinic population.


Immunoglobulin E in chronic middle ear effusions: conmparison of RIST, PRIST, and RIA techniques. To investigate the possible role of allergy in otitis media with effusion (OME), the immunoglobulin E (IgE) content of 138 middle ear effusions (MEE) and paired serum samples from patients with chronic otitis media with effusion was determined. The initial 62 paired specimens were assayed for IgE by the radioimmunosorbent test (RIST), while the later 76 paired specimens were assayed for IgE by the paper radioimmunosorbent test (PRIST). When the results obtained by these two techniques were compared, it was noted that the PRIST procedure gave significantly lower IgE values for effusions than the RIST method. When the effusion-to-serum ratios (E/S ratios) were computed from the PRIST data, the E/S ratio was less than one, while RIST data gave an E/S ratio greater than one. The results obtained with the PRIST procedure were confirmed by double antibody radioimmunoassay for IgE. Thus, the PRIST procedure appears to measure the IgE content of MEE more accurately, and the results obtained by this procedure fail to support the concept of allergy as a major causative factor in OME.


Morphology of tensor veli palatini, tensor tympani, and dilatator tubae muscles. The relationships among the paratubal muscles were studied in human fetal and adult Eustachian tubes. That which has, in recent years, been labeled the tensor veli palatini muscle actually consists of two distinct groups of muscle fibers: a medial group, henceforth termed dilatator tubae, and a lateral group, called tensor veli palatini. The latter was found to have no Eustachian tube origin, but was continuous superiorly with the tensor tympani muscle. The dilatator tubae muscle was found to have a tubal attachment. The participation of this muscle system in the normal functioning of the Eustachian tube-middle ear system in man, and the problems inherent in the development of animal models simulating the physiology of the physiology of the human system, are discussed.


Neomycin ototoxicity.

Neomycin ototoxicity. A case of oral neomycin ototoxicity is presented, followed by a summary of known cases in the English literature. While it is known that neomycin is concentrated in the inner ear fluids, at the present time the biochemical basis of its ototoxic effect has not been definitively elucidated. High frequency audiometry can aid in the early detection of the onset of neomycin-induced deafness. Dialysis has a limited but useful role in preventing neomycin ototoxicity.


Actinomycosis: masquerader in the head and neck. The diagnosis of cervicofacial actinomycosis is usually not simple, but may be essential for adequate treatment. Cases seen in a Head and Neck Service illustrate some of the many guises under which actinomycosis may be concealed, and a review of recent literature confirms its propensity to be a masquerader. A combination of techniques is necessary to diagnose, and both surgical and medical approaches are needed to treat this often distressingly persistent affliction.


Clinical significance of rebound nystagmus in neuro-otological diagnosis. The present study is concerned with a clinical analysis of 17 patients with "rebound nystagmus" examined over a period of three years. All of them have shown a short duration second degree nystagmus evoked by changes in the direction of fixation, from the lateral to straight ahead gaze. This nystagmus was a fixation nystagmus, that is to say, it was enhanced in the presence of active optic fixation and inhibited in its absence. Almost all the patients (16 out of 17) had cerebellar signs on neurological examination (in one subject rebound nystagmus was the first sign suggesting cerebellar involvement and appeared several months before any other cerebellar sign was present). Rebound nystagmus was far more common than the other neuro-otological signs suggesting cerebellar dysfunction (vestibular hyperexcitability, dysrhythmia in postcaloric nystagmus and ocular dysmetria). In three out of four patients with unilateral lesions rebound nystagmus was ipsilateral with respect to the side of the lesion. Postmortem studies were carried out upon five cases and showed either pathological changes in the cerebellum or a lesion involving the cerebellar peduncles in the brain stem.


Fine-needle biopsy of the thyroid gland: a cytohistological comparison in cases of goiter. At the ENT Clinic of the Regional Hospital in Orebro, cytological investigation of fine-needle biopsy specimens has been carried out to a steadily increasing extent for more than ten years as a complement to clinical methods in investigation and laboratory tests in cases of goiter. Evaluated here are the method's diagnostic accuracy and its value in investigatory work. The material consists of 303 patients with goiter who were operated from 1964 to 1971 following fine-needle biopsy. Cases where biopsy only was undertaken are not included. Assessable cytological material was obtained in 284 cases (94%). Although not less than 15 doctors carried out the fine-needle biopsies there was approximately a 93% agreement between the cytological and histological diagnoses. In 15 of 28 cases of thyroid carcinoma it was possible to make a definite diagnosis preoperatively, while in 12 of the remaining cases atypia suspected of malignancy was found. The possibility of being able to demonstrate or suspect a carcinoma preoperatively is of greate importance for the surgeon, as a more extensive intervention can be planned in advance and the patient informed before the operation.


Results of new air caloric testing method among normal subjects. I. Biphasic testing. A new air caloric testing method is described in which the temperature of a continuous aural irrigation is switched hot and cold values at times calculated to control the intensity of the resulting vestibular stimulation. Applications of low or high caloric stimulus intensities to normal subjects were well tolerated and reliably produced appropriate low or high intensity nystagmic responses. Nystagmus intensity values obtained from this study were compared with predicted intensity values from a computerized simulation of the actual test conditions, and also with values obtained when using biphasic water irrigations. As a result, further improvements in our methodology have been effected.


Use of heart rate response for the assessment of hearing in infants. The clinical utility of the heart rate (HR) response as an index of hearing in infant children under 12 months of age was investigated. The most prominent component of the averaged HR response elicited with a short tone burst of 100 msec duration was a brief HR deceleration which mostly occurred between the first and second beats after stimulation. The mean response detectability for tones of 250 Hz and 1 kHz were 50, 82 and 100%, with stimulations of 40, 60 and 80 dB above subjective threshold of normal adults, respectively. The detectability decreased a little at 4 kHz stimulation. Though there was an individual variability in the appearance of the response, the method was considered to be useful as a supplementary tool for evaluating hearing in infant children.


Earmold configuration: relation to speech discrimination scores. Choice of the earmold for a particular individual is perhaps the most subjective of all decisions made by clinicians in hearing aid fitting. The four earmold designs used in this study were standard-long, standard-short, belled-vented, and cavernous. Conslusions were: 1) performance differences in earmolds of contrasting design can be assessed by discrimination scores with monosyllabic word lists of equal difficulty; 2) among the physical measures taken of the earmold-receiver systems, frequency-response overall range (HAIC) ranked the devices in agreement with group responses to a word identification task; and 3) these data offer a basis for endorsement of the standard-long and cavernous-short earmold types over the other two with their superiority evident in each of the discrimination categories of excellent, good, and poor.


Masticator space abscess complicating removal of suspension wires: case report. Masticator space abscesses have been reported more frequently in recent years. They are usually secondary to extractions of the first and second mandibular molar teeth. The use of antibiotics has changed the presentation and clinical course of these abscesses, masking the symptoms and resulting in secondary infection by resistant organisms. Therefore, selection of appropriate antibiotics is important, but surgical intervention remains the cornerstone of treatment. Suspension wires are being used widely in the treatment of midface fractures. These wires may extend from the zygomatic arch or frontal bone through the masticator space into the oral cavity to attach to arch bars. A case of masticator space abscess resulting from the removal of suspension wires is reported, and the relevant literature is reviewed. Suggestions are made for preventing and treating this complication.


[The tricho-rhino-phalangeal syndrome (Giedion) (author's transl)]. We describe here six members of a family with Giedion's syndrome: sparse, fine, slow-growing hair, pear-shaped nose, cone-shaped epiphyses of the middle phalanges and variable growth retardation. There are other signs: elongated philtrum, thin upper lip, big and low set ears, medially broad eyebrows but narrow at the tip, clinobrachydactyly and marked dental caries, are as well observed in those patients. Differential diagnosis with other dysplasias is pointed out and both histological and trichological data are being valued.


Effects of adenoidectomy: a controlled two-year follow-up. A prospective controlled study was made on the effect of adenoidectomy performed on 105 children. For various reasons, mainly severe long-standing nasal obstruction, 29 children were omitted from the study. The remaining 76 children were randomly divided into two groups, one adenoidectomy, and one control. Both groups were slightly reduced in number due to drop out. Thus 36 adenoidectomized children were followed during one year and 35 children during two years. The corresponding numbers for the children in the control group were 37 and 33. The incidence of common cold, purulent and serous otitis media and moderate nasal obstruction was compared in the two groups. A considerable reduction in the incidence of these variables was observed in both groups. The occurrence of moderate nasal obstruction was reduced more among the operated than among the unoperated children. The difference was only slightly significant during the first and not at all during the second year. Regarding the other variables, the differences were not significant, implying that adenoidectomy seems to have no effect on the incidence of common cold, serous and purulent otitis media.


Dermoid of the nasopharynx.

Dermoid of the nasopharynx. A case of a cystic polyp of the nasopharynx in a three-year-old Caucasian female is presented. Although cases of teratomas of the nasopharynx have been reported, our literature search revealed only one prior report of a hamartoma. To our knowledge, a lesion with these histological features occurring in the nasopharynx has not been previously reported.


[Contribution to the etiologic diagnosis of hypertrichosis and hirsutism of functional origin in women during active genital life by statistical study of observations (author's transl)]. After a recall of the etiologies of hypertrichosis and hirsutism, a method of diagnosis limited to functional pathological cases, was established. Having 31 complete case reports of functional hirsutism or hypertrichosis in women whose diagnosis--ovarian dystrophy or corticosuprarenal hyperplasia--was confirmed, the authors established a decision procedure based on the confrontation of two criteria obtained with a discriminant analysis program. These criteria included a clinical examination (intensity and localization of pilosity) and the effect of dexamethasone blockade on two plasmatic steroids, i. e., 17-hydroxyprogesterone and testosterone. The proposed diagnosis was furnished with a confidence index. 43 new cases confirmed the consistency between the clinical diagnosis and the automatic diagnosis.


[Anetodermic cutaneous changes above Malherbe's tumors (author's transl)]. Clinical and histological anetoderma-like changes of the skin above Malherbe's tumor (pilomatricoma) may be of diagnostic value since they have been observed 5 times in a series of 22 consecutive cases. The histological study of 46 cases of Malherbe's tumor shows a high incidence of dermal atrophy and decrease of elastic fibers in reticular dermis above the tumor, a possible consequence of cellular infiltrates surrounding the tumor and seen in half our cases.


[Piebaldism. Clinical, pathological and ultrastructural study of three cases (author's transl)]. Comparative study of achromic and normally pigmented skin of three piebald patients from two families is reported here. DOPA-positive cells were not seen in the achromic areas, but the number of ATPase sites appeared to be normal; therefore the assumption of the replacement of the melanocytes by Langerhans cells cannot be supported. Through electron microscope, Langerhans cells looked strictly normal. Melanosomes appeared reduced in size and some alterations were noticed in their shape and contents. Ultrastructurally, a more prominent change consisted in increased undefined clear cells in the achromic skin. These dendritic suprabasal cells were devoid of melanosomes or Langerhans granules and might represent undifferentiated melanocytes. These features were discussed according to previous literature.


[Dermatosis caused by bone graft material (author's transl)]. Cases of dermatosis caused by surgical implants are not infrequently observed. They are represented by many clinical forms. The pathology slides most often reveal a more or less dense dermal infiltration associated with signs of allergic angeitis. The pathophysiology is described as an intermediate or retarded hypersensibility or continuous non-specific antigen stimulation. The diagnosis is confirmed by the cure following removal of the surgical implants since the epicutaneous tests are not always fiable. We noted two patients whose clinical profile ressembled that of hematodermie.


A new family of mathematical models describing the human growth curve. A new family of mathematical functions to fit longitudinal growth data is described. All members derive from the differential equation dh/dt = s(t). (h1-h) where h1 is adult size and s(t) is a function of time. The form of s(t) is given by one of many functions, all solutions of differential equations, thus generating a family of different models. Three versions were compared. All were superior to previously described models. Model 1, in which s(t) was defined by ds/dt = (s1 - s)(s - s0) was especially accurate and robust, containing only five parameters to describe growth in stature from age two to maturity. Derived "biological" parameters such as Peak Height Velocity were very consistent between these three members of the family but, in some cases, differed signficantly from previous estimates.


A method for studying shape change in children. A method is given measuring shape change with age, utilizing two dimensional body outlines. Problems of standardization for overall size are discussed and it is shown how the method can be used to draw D'Arcy Thompson-type transformation grids. The method is applied to serial measurements on a girl from 31/2 to 19 years of age.


Tooth emergence in Australian Aboriginals. Patterns of dental development in 125 Australian Aboriginal boys and girls, in a growth study at Yuendumu in the Northern Territory of Australia, were compared with Australians of European origin using mean tooth emergence curves constructed from the emergence times of right and left side permanent teeth. There were two active phases of tooth emergence separated by a quiescent period of 1.4 years in boys and 1.0 years in girls. Phase one included emergence of the first 12 teeth, that is the first permanent molars and all incisors; phase two included emergence of the canines, premolars and second molars. In Aboriginal girls most teeth emerged earlier than in boys. Compared with the European-descended, the Aboriginal children displayed earlier emergence of most teeth during phase two and a shorter quiescent period between the two phases, an emergence pattern similar to that reported in other non-European populations. In Aboriginals the process tooth emergence and subsequent alignment is aided by adequate space and compensatory bone growth growth in the alveolar regions. These factors, as well as the genetic differences between groups, contribute to the earlier emergence of teeth during phase two in the Aboriginal children.


A step function model using tooth counts to assess the developmental timing of the dentition. Step functions representing median attainment ages of successive counts on numbers of permanent teeth present in the mouth were obtained separately for 12 early-emerging teeth (I1, I2 and M1) and for 16 late-emerging teeth (C, Pm1, Pm2, and M2). Displacement of each step function to best fit of individual tooth counts defined the variation in dental maturation for early teeth and for late teeth. Moreover, differences in the displacements of the two-step functions defined individual variations in the duration of the emergence process.


Size and shape differences among six South American Indian tribes. Measurements of height, face height, nose height, nose breadth, head length and head breadth from individuals living in 17 villages of six South American Indian tribes were compared using Mahalanobis's morphological distances and their partition into size and shape components. Total D2 values correlate well with estimates of linguistic differentiation, but not with geographic distances between tribes. Three of the six tribes were also studied for blood polymorphisms, and again measures of distances based on these haematological traits did not correlate well with the morphological ones. The shape component was about three times as important as size in contributing to the intertribal variation.


Combinations of cytotoxic agents that have less than expected toxicity on normal tissues in mice. A pretreatment dose of cyclophosphamide reduced lethality caused by high doses of busulphan or cyclophosphamide. In the case of cyclophosphamide given prior to busulphan, increased survival could be attributed to greater regeneration of haemopoietic stem cells in animals that received the combined dose compared with those that received busulphan alone. The mechanism by which cyclophosphamide pretreatment increased the animals' tolerance to a large dose of cyclophosphamide has not yet been elucidated. However, the urothelium in mice given the combined treatment was much less damaged than the urothelium in mice given the large dose alone, and its a known that bladder damage is a major feature of toxicity in patients given high-dose cyclophosphamide. This sparing combination exerted its expected toxicity on Lewis lung tumours, however, and so provided a useful differential effect against tumour tissue.


[Admixture in commercial tetracycline preparations]. The content of admixtures in tetracycline stored under different conditions was determined with chromatographic and spectrophotometric methods. Biological activity, toxicity and colour of the drugs was tested. The changes in teh colour of tetracycline most pronounced on its storage at a temperature of 37 degrees C and elevated humidity were not accompanied by an increase in the content of anhydrotetracyclines. In parallel with the changes in the colour of tetracycline, the loss of its biological activity up to 30 per cent and increased toxicity were registered. The LD50 decreased by 40 per cent as compared to the initial level. Simultaneously an additional spot with high chromatographic mobility (Rf 0.98--1.0) was detected on thin-layer chromatograms. It was shown that the processes of tetracycline degradation resulting in marked darkening of the drug colour were not accompanied by an increase in the content of anhydro admixtures. They were probably the result of accumulation of other products which are as highly toxic and low active as the anhydroderivatives of tetracycline.


[Experimental studies to set hygienic standards for benzylpenicillin in the air of a work area]. The character and level of benzylpenicillin toxic effect was studied in accordance with the methodic instruction for performance of the experiments on toxicological estimation and hygienic norms of antibiotics in the air of working areas in production premises. It was shown that the antibiotic was of low toxicity under conditions of a single exposure, did not cumulate and had no local irritating and resorbing effect. It was shown to be an allergen. Prolonged inhalation of benzylpenicillin in a concentration of 14 mg/m3 resulted in reversible changes in the function of the kidneys and liver of the animals, their sensitization and development of pronounced dysbacteriosis of the mouth and intestine mucosa. In a concentration of 1 mg/m3 benzylpenicillin had no general toxic and sensitizing effect but induced reversible changes in the normal autoflora. This allowed the authors to consider the above concentration to be maximum with respect to the antibacterial effect. On the basis of the experiments the maximum permissible norm (MPN) of the aerosol of benzylpenicillin disintegration was recommended at the level of 0.1 mg/m3.


[Effect of industrial contact with grizin on nonspecific immunity factors]. Data on the dynamic examination of persons being in professional contact with grizin, an antibiotic used as a food additive are presented. It was shown that contact with grizin resulted in changes in the humoral, cell and barrier factors of the non-specific immunity. The trends of the changes and their manifestations were different depending on the age, period and contact level. The levels of lysozyme, absorption and digestion activity of the neutrophils provided differentiation of the adaptive reactions and phenomena of frustation in the compensatory mechanism. The methods used in the study allowed the authors to detect changes in the state of the nonspecific immunological reactivity of the persons being in contact with grizin before the appearance of the clinicaly pronounced forms of the pathology.


[Combined action of aminoglycoside group antibiotics and bile acids on staphylococci]. The results of in vitro studies on the potentiating effect of cholic, taurocholic, glycocholic and desoxicholic acids on the bacteriostatic and bactericidal activity of aminoglycoside antibiotics are presented. Ten fresh isolates of staphylococci were used in the experiments. Sensitivity of the isolates to the antibiotics and bile acids and their combinations was determined by the method of serial dilutions. Investigation of the combined effect of gentamicin, monomycin, kanamycin and neomycin with the bile acids showed that all of them had potentiating effect on the antimicrobial activity of the antibiotics. The potentiating effect of different acids and antibiotics was not the same. The highest potentiating activity was observed with the use of gentamicin or neomycin in combination with desoxycholic and cholic bile acids. Desoxycholic acid increased the bacteriostatic activity of gentamicin and neomycin by 781.3 and 2083.3 times respectively and cholic acid increased it by 382.7 and 2083.3 times. Cholic and desoxycholic acids potentiated also the bactericidal effect of gentamicin and neomycin. Taurocholic and glycocholic acids produced potentiation of various antibiotics by 8 to 60 times.


[Action of lincomycin, chymotrypsin and their combinations on the course of experimental staphylococcal infection]. The culture of Staphylococcus aureus was administered intraperitoneally in a dose of LD30 to albino mice. The animals of the 1st, 2nd and 3rd groups were treated with lincomycin, chymotripsin and combination of lincomycin with chymotripsin respectively. The animals of the 4th group were used as control and were not subjected to the treatment with the drugs. A part of the animals from every group was killed on the 3rd, 7th, 14th, 21st and subsequent days and their organs were investigated microscopically and bacteriologically. It was found that staphylococci was isolated from the control mice during a 50-day period after inoculation. Complete liberation of the organs from the causative agent within 25 days from the beginning of the experiment was registered in the animals treated with lincomycin. Isolation of the staphylococci was over by the 27th day in the animals treated with chymotrypsin. Liberation of the organs from the causative agent by the 17th day was observed in the albino mice treated with the combination of lincomycin with chymotrypsin. The combined use of lincomycin with chymotrypsin proved to be most effective: no death was registered among the albino mice, the levels of the pathogenicity and antibiotic resistance in the pathogenic staphylococci decreased.


[Experimental study of the organotropic properties of dactinomycin]. Dactinomycin was studied pharmacologically on experimental animals. When dactinomycin was administered to the test-animals in doses close to the therapeutic ones for humans, suppression of the bone marrow blood formation was registered in spite of some increase in the number of the reticulocytes and thrombocytes in the peripheral blood and acceleration of the process of blood coagulation. In addition, the urea nitrogen blood levels increased. When the drug was administered in higher doses, suppression of the bone marrow blood formation was pronounced and the number of the leucocytes, reticulocytes and thrombocytes in the peripheral blood decreased. The rate of the blood coagulation decreased, while the biochemical values of the blood were indicative of impairement of the liver and kidney functions.


[Role of the adrenal glands in the cytostatic action mechanism of antitumor antibiotics]. The state of the steroidogenic function of the adrenal glands, lipid spectrum of the adrenal gland tissue and metabolism rate of 11-oxycorticosteroids (11-OCS) in the liver tissue and their levels in the blood plasma were studied on rats after a single administration of karminomycin in a dose of LD50 (1.55 mg/kg). The hormones of the adrenal cortex were shown to play a definite role in the mechanism of the karminomycin damaging effect. Dependence of the changes on the time of the drug effect was noted. The shifts were of a reversible character. No direct toxic damages in the tissue of the adrenal glands were observed. Only an increase in the 11-OCS blood levels and a decrease in the steroid metabolism in the liver tissue were shown. The latter must be due to the direct cytotoxic effect of karminomycin on the tissue of this organ.


Reversible inhibition of cellular metabolism by ribavirin. The broad spectrum antiviral drug ribavirin (Virazole, 1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) inhibits cellular macromolecular synthesis as well as cell division in eucaryotic cells. The concentration and time dependence have been studied. One-hour treatment with 25 muM ribavirin or 18 h with 2 muM inhibited the deoxyribonucleic acid synthesis to 50%. Higher concentrations of ribavirin were required to obtain a similar inhibition of ribonucleic acid and protein synthesis. This effect on cell metabolism and cell division can be reversed by removing the drug from the cells.


Clinical pharmacology of mezlocillin.

Clinical pharmacology of mezlocillin. Mezlocillin is a new broad-spectrum semisynthetic penicillin that has shown encouraging in vitro activity against the infecting organisms most likely to cause mortality and morbidity in cancer patients receiving chemotherapy. The serum clearances and urine recoveries of mezlocillin, ampicillin, and carbenicillin were compared after the intravenous administration of single 3-g doses. The peak mean serum concentrations of mezlocillin and carbenicillin were 269 and 278 mug/ml, respectively, whereas the peak ampicillin level was lower at 167 mug/ml. The terminal half-life of mezlocillin, 66 min, was not significantly different from those of ampicillin and carbencillin (63 and 77 min, respectively). Recoveries of mezlocillin, ampicillin, and carbenicillin from urine over 6-h periods after drug dosage were 45, 61, and 80%, respectively. A further study in 11 cancer patients examined serum maintenance levels of mezlocillin when 3-g doses were given intravenously every 4 h for at least 7 consecutive days. After 3 days of therapy, the mean serum concentrations were maintained above 50 mug/ml. Although therapeutic efficacy was not an objective of this study, all of three documented bacterial infections were cured, and no serious toxicity was encountered.


Synthesis and antibiotic properties of chloramphenicol reduction products. Analogs of chloramphenicol were prepared for the first time in which the nitro group was replaced by hydroxylamine, nitroso, hydroxamic acid, methyl hydroxamate, and O-acetyl hydroxamate functional groups. These compounds were tested for antibiotic activity in order to determine whether the antibiotic activity of chloramphenicol is mediated by one or more of these potential metabolites of chloramphenicol. None of these analogs was as active as chloramphenicol against the four test organisms, and two of the compounds were essentially devoid of activity. The significance of these findings with regard to the importance of the nitro group to the biological activity of chloramphenicol is discussed.


Use of high-pressure liquid chromatography to determine plasma levels of metronidazole and metabolites after intravenous administration. A rapid and sensitive high-pressure liquid chromatography assay for metronidazole and its two principle metabolites, 1-(2-hydroxyethyl-2-hydroxymethyl)-5-nitro-imidazole [hydroxy metabolite] and 1-acetic acid-2-methyl-5-metronidazole [acid metabolite], was developed. The retention times observed were 5.7, 3.3, and 4.5 min, respectively. A reverse-phase muC(18) Bondapak column using a solvent system of methanol, acetonitrile, and 0.005 M pH 4 potassium dihydrogen phosphate (4:3:93, vol/vol) was used to achieve separation of the three compounds. Patients receiving metronidazole therapy were given a loading dose of 13.6 mg of drug per kg intravenously over 1 h, followed by a maintenance dose of 1.43 mg/kg per h. The range of metronidazole concentrations observed was 6.8 to 47.5 mug/ml. These levels are well above the minimal inhibitory concentrations of most clinically significant anaerobic bacteria including Bacteroides fragilis. Little of the acid metabolite was observed in the plasma. The concentration of hydroxy metabolite ranged from 1.6 to 16 mug/ml. The latter may represent an additional source of antimicrobial activity since the hydroxy metabolite has approximately 30% the biological activity of metronidazole.


In vitro activity of cefaclor against aerobic and anaerobic bacteria. Cefaclor (CCL), a new cephalosporin, was tested in vitro against 602 (271 anaerobic and 331 aerobic) clinical isolates in comparison with cephalothin, cefazolin, cephradine, and cefamandole. Sixteen micrograms of CCL per ml inhibited 68% of all aerobes tested and 80% of the 211 enteropathogenic organisms (Escherichia coli, Salmonella, and Shigella) isolated from cases of infantile diarrhoea. CCL inhibited 88% of gram-positive anaerobic cocci and 72% of Bacteroides other than B. fragilis at a concentration of 16 mug/ml. B. fragilis and Clostridia were resistant to CCL. Increased inoculum of E. coli from 10(5) to 10(9) increased the minimal inhibitory concentration of CCL and cefamandole by fourfold against 7 of the 64 strains tested. All seven were beta-lactamase negative. No antimicrobial synergism was noted between CCL and penicillin. The in vitro efficacy of CCL, an oral cephalosporin, against enteropathogenic E. coli, if proven safe, may be tested in vivo against such infections.