Studies on the pathogenesis of experimental anti-tubular basement membrane nephritis in the guinea pig.

Using the model of renal disease induced in guinea pigs by immunization with bovine TBM preparations in adjuvant, the following observations were made. Animals with activity induced disease show bright staining for IgG along the TBM and only faint, inconstant staining along the GBM. Following transfer of serum animals with anti-TBM disease to normal recipients, accumulation of IgG was found predominantly in glomeruli at 4 hours, but at Days 3 and 5, IgG was seen predominantly along the TBM. There was no appreciable accumulation of neutrophils in the kidneys of recipients of anti-TBM serum, even at early intervals (4 and 24 hours) after transfer. However, within 2 days, small numbers of mononuclear cells were found. By Day 3, mononuclear cells were numerous, and multinucleate giant cells and tubular cell damage were present. After that, the lesions increased in severity and by 10 days were indistinguishable from those found in actively immunized animals at 14 to 21 days. Study of frozen section of kidneys obtained from animals with active disease at 14 days, employing sheep cells coated with rabbit antibody (IgG EA) revealed rosettes around many of the mononuclear cells in the infiltrate, indicating that they are mononuclear phagocytes (monocytes or macrophages). IgM complexed with sheep cells and complement (EAC) did not react and thus failed to provide evidence for the presence of B lymphocytes. Transfer of 7 X 10(8) lymph node cells from the TBM-immunized Strain 13 donors to normal Strain 13 recipients failed to result in renal lesions. The findings are interpreted as indicating that anti-TBM antibodies mediate the renal disease without the participation of cell-mediated immunity and further that these antibodies bring about an influx of ciculating mononuclear cells, predominantly monocytes, without attracting appreciable numbers of neutrophils.


Enhancement of tissue invasion in murine aspergillosis by systemic administration of suspensions of killed Corynebacterium parvum.

The effect of killed Corynebacterium parvum vaccine on the course of murine aspergillosis is described. A grid-counting technique was employed to quantitate tissue invasion by Aspergillus nidulans in the brain, heart, and kidneys (the target organs) of normal mice and of mice treated systemically with killed C. parvum vaccine. Simultaneous treatment of mice with C. parvum and A. nidulans significantly increased the mortality rate, in contrast to treatment of mice with C. parvum prior to or following A. nidulans, which had no significant effect on mortality. Fungal invasion of the tissues of the brain and kidneys was significantly increased in mice pretreated or posttreated with C. parvum, but fungal invasion of the heart was not effected by these treatements. Simultaneous treatment of mice with C. parvum and A. nidulans significantly increased fungal invasion of the heart but did not effect tissue invasion of the brain and kidneys. It was concluded that killed C. parvum vaccine reduces host resistance to Aspergillus infection and facilitates the curse of fatal murine aspergillosis. These results suggest further caution in applying systemic C. parvum in the therapy of human neoplasia.


Immunopathology of the end-stage kidney. Immunoglobulin and complement component deposition in nonimmune disease.

Seventy nephrectomy specimens from patients with end-stage renal disease, four renal biopsies from patients with focal sclerosing glomerulonephropathy (FSGN) and normal renal function, and 17 control biopsies from normal renal allograft donors (Group I) were studied by immunofluorescence with respect to deposition of immunoglobulins and classic and alternative complement (C) pathway components. The end-stage kidneys were divided into three groups according to etiology: 16 patients with immune-mediated glomerulonephritis (Group II), 22 patients with congenital and/or familial renal disease (Group III), and 32 patients with systemic or primary renal disease in which an immune-mediated injury could not be established (Group IV). The pattern of immunoprotein deposition in glomeruli in Groups II, III, and IV, and in biopsies of patients with FSGN was similar: peripheral lobular, globular and/or granular, focal and segmental; it was limited to dying glomeruli or abnormal glomerular segments. A statistically significant correlation existed between the percent of properdin-containing glomeruli and the percent of glomeruli undergoing hyalinization in Groups II, III and IV (II, r=0.67; III, r=0.92; IV, r=0.78). No deposition was observed in normal or completely fibrotic glomeruli. In vitro heterologous complement fixation was demonstrated in 17/19 end-stage kidneys in a similar distribution. Early classic C components, C1q and C4, were detected in a somewhat higher frequency in Group II (14/16) than Group III (11/22) and Group IV (20/32) (Group II vs. III, P=.02 and II vs. IV, P=.07). C3 and properdin were detected in 77 to 100% of all 3 groups; in 18 patients, C3 and properdin were present without detectable C1q and C4. Immunoglobulins, primarily IgM, and components of the classic and alternative C pathways are regularly present in hyalinizing glomeruli irrespective of the etiology of the renal failure. These observations suggest that an immune process is operative in glomerular obsolescence regardless of the underlying etiology of the renal disease.


Function of pituitary-gonadal axis in zinc-deficient rats.

The role of zinc in gonadal function was investigated in rats. The increases in luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were assayed after intravenous administration of synthetic luteinizing-hormone-releasing hormone (LHRH) to zinc-deficient and restricted-fed control rats. Body weight gain, zinc content of testes, and weight of testes were significantly lower in the zinc-deficient rats compared with the controls. The serum LH and FSH response to LHRH administration were higher in the zinc-deficient rats but serum testosterone response was lower in comparison with the restricted-fed controls. These studies indicate a specific effect of zinc on testes and suggest that gonadal function in zinc-deficient state is affected through some alteration of testicular steroidogenesis.


Follow-up of depressed women after maintenance treatment.

The authors present follow-up results based on 150 women 1 year after maintenance treatment for depression. Maintenance treatment consisted of 8 months of amitriptyline, psychotherapy, or a combination of the two, administered by random assignment following recovery from an acute depressive episode. Approximately 30% of the patients remained in complete remission, 60% experienced recurrence of symptoms, and 12% remained mildly but chronically symptomatic. The implications of these findings for planning care for the ambulatory depressed patient on both an individual and a public health basis are discussed.


Development of different strains of Plasmodium vivax in two species of Anopheles.

Anopheles freeborni mosquitoes with oocyst infections had salivary gland infections at a higher rate of Plasmodium vivax from the New World than with strains from Asia, particularly those from South Vietnam. Anopheles maculatus mosquitoes supported development from oocysts to heavily infected salivary glands for all the strains of P. vivax tested. The results suggest that P. vivax introduced from Vietnam would be less likely to be transmitted by native A. freeborni mosiquitoes than would malaria from some other areas.


The use of serology by titering of fluorescent antibodies to evaluate levels of transmission of schistosomiasis in Rhodesia.

The prevalence of schistosomiasis has been measured by parasitological examination and by fluorescent antibody titering in a number of communities in different parts of Rhodesia. The samples were taken from areas of high, medium, and low transmission of the disease. A correlation was detected between the mean titer and prevalence of infection, particularly in the younger people (4-13 years old). It is suggested that fluorescent antibody titrating may be a useful epidemiological tool.


Spaced clofazimine therapy of lepromatous leprosy.

Patients with previously untreated borderline-lepromatous or fully lepromatous leprosy were treated with one of five clofazimine (B663) regimens: 1) 200 mg daily 6 days per week; 2) 100 mg three times weekly; 3) 300 mg weekly; 4) 600 mg every other week; and 5) 600 mg on 2 consecutive days every 4 weeks. After 24 weeks of treatment, the patients were randomly allocated to treatment either with 200 mg B663 daily 6 days per week (regimen 6) or with dapsone, beginning with a small dosage and increasing over a period of 8 weeks to 100 mg daily 6 days per week (regimen 7). Death of Mycobacterium leprae was monitored by mouse inoculation with organisms recovered from skin biopsy specimens obtained at intervals during the first 24 weeks. Killing of M. leprae proceeded most rapidly in regimen 1 and 2 patients, least rapidly in the patients of regimens 4 and 5, and at an intermediate rate in regimen 3 patients. Erythema nodosum leprosum (ENL) was no more frequent nor more severe during treatment with any one of the first-24-weeks regimen. ENL was more frequent in regimen 7 than in regimen 6 patients. Pigmentation of the skin, assessed only during the first 24 weeks, occurred in patients of all regimens, but was most marked in regimen 1 patients. No evidence of B663 toxicity was noted. Although of all of the first 24-weeks regimens were effective in terms of the rate of killing of M. lepare, greater effectiveness was associated with more frequent administration of the drug. The B663 that accumulated in the tissues did not appear to be available to exert an antimicrobial effect.


Delineation of La Crosse virus in developmental stages of transovarially infected Aedes triseriatus.

The tropisms and development of La Crosse (LAC) virus in stages of transovarially infected Aedes triseriatus were studied with fluorescent antibody (FA) stained dissected organs and titrations of individual arthropods in suckling mice. Viral antigen was detected by FA in 95 of 387 dissected larvae, pupae, and adults. In larvae highest levels of fluorescence were detected in the alimentary tract, followed by ganglia, malpighian tubule, muscle, and other tissues. No specific organs or germ layer-derived tissues appeared to be the sole source of viral replication. Most tissues and organs of A. triseriatus are capable of maintaining LAC virus. Antigen was detected in the identifiable organs immediately upon emergence from the egg. In pupae and adults antigen was detected at high levels in foregut, gonadal and associated tissues, and in salivary glands, which would indicate females could be infective upon emergence. Virus was isolated from all arthropod stages, in 32 of 130 individuals inoculated into suckling mice. Titrations ranged from less than 1.0 log10 SMICLD50 per 0.02 ml for eggs and 1st instar larvae to 3.0 log10 SMICLD50 for 4th instar larvae. Adults and pupae averaged between 2.0 and 3.0 log10 SMICLD50. Increases in titer during maturation were mainly related to increases in size of the organism rather than in titer per unit volume.


Renal transplantation in high risk patients older than sixty years.

Nine patients between the ages of sixty and seventy-one years, with end-stage renal failure, received kidney grafts during a five year period. Five received related donor kidneys and four received cadaver donor kidneys. Six of these patients are still alive--four of the five (80%) with related kidneys and two fo the four (50%) with cadaver kidneys. All six patients have normal kidney function an average of twenty-seven months after transplantation. We believe the elderly uremic patient should not be categorically excluded as kidney graft recipients on the basis of age alone. The prognosis of these patients treated by transplantation far exceeds that for uremic patients of the same age who are restricted to hemodialysis therapy.


Renal artery stenosis after renal transplantation.

Renal artery stenosis occurred in eight of fifty patients who received a renal transplant during a three year period. The evaluation and management of these cases is summarized. Trauma associated with kidney procurement, preservation, or arterial anastomosis as well as the rejection process itself may contribute to the development of these lesions. Arteriography may be indicated at an earlier stage in patients who respond poorly to medical treatment of repeated episodes of "rejection."


Quantitative microbiology: its application to hand injuries.

Quantitative microbiologic analysis of civilian hand injuries has been accomplished in thirty-four patients. Most traumatic soft tissue injuries exhibited an insignificant level of contamination. The number of bacteria recovered from most of those wounds was comparable to that encountered in clean elective surgical hand cases. We now view most civilian hand wounds as clean wounds carrying a very low risk of infection. Our patients with traumatic hand injuries are considered candidates for immediate reconstruction, which includes vascular, bony, or neural repair as well as immediate implantation of Silastic rods in preparation for subsequent tendon grafting.


A critical study of Lister's work on antiseptic surgery.

The work of Pasteur on alcoholic and lactic acid fermentation demonstrated that minute organisms (germs) caused these fermentative changes. Lister applied these basic findings in the introduction of his antiseptic system. Its principles were based on the destruction of germs by antiseptics (carbolic acid) to prevent their entering the wound or spreading after surgery. Lister's work on antisepsis was therefore based on the germ theory of disease. The believers of the germ theory defended Lister's theories whereas the nonbelievers of the germ theory created an atmosphere of resistance to Listerism. The work of Koch in 1878 on the etiology of traumatic infective diseases contributed greatly to the acceptance of Lister's antiseptic principles. By the mid 1880s there was a rapid increase in the use of antiseptic technics, soon followed by the introduction of aseptic methods and rapid progress in surgery.


Surgical technic in en bloc bilateral cadaveric nephrectomy for transplantation.

En bloc bilateral cadaveric nephrectomy for transplantation has some advantages over excision of each kidney separately. There is also an advantage of single cannula perfusion through the aorta for two kidneys, especially when multiple renal arteries are present. The anatomic vascular variants are important, as are the incision and the approach to the suprarenal aorta and the lumbar venous drainage of the kidney.


Poiseuille and his law.

Comparatively little is known of the life of Jean Leonard Marie Poiseuille (1797-1869) of Paris. He made important contributions to the experimental study of circulatory dynamics but it can hardly be said that Poiseuille knowingly described the law which governs laminar flow. He did however establish, in a series of meticulously executed experiments, that at a given temperature water flow through tubes of very fine bore is inversely proportional to the length of the tube and directly proportional to the pressure gradient and to the fourth power of the tube diameter.


Tracheal dilatation.

Three cases of tracheal dilatation following prolonged ventilation through a tracheostomy tube with a conventional cuff are reported. The routine care of tracheostomies in the ITU at Northampton General Hospital is described. Possible causes for the development of dilatation are suggested and the symptoms and signs discussed.


Stenosis following tracheostomy. A quantitative study of long term results.

Seventy out of the 320 patients treated with tracheostomy and respiratory care in an intensive care unit, were included in a follow-up study. A variety of surgical (38) and medical (32) conditions had prompted IPPV for 1-59 days; 33 had had primary and 37 secondary tracheostomies. The final study included an interview, physical examination, radiographic examination and spirometry. Using radiographic measures, the area of stenosis was calculated as well as the pressure drop across the stenosis at various flow rates. The methods of calculation were tested in one patient and compared with the actual tracheal pressure and gas flow recordings. Lateral stenosis was found in 69 and frontal stenosis in 25 patients, the length being 0-2-5-0 cm. The stenosis was situated at the level of the stoma in 59, at the cuff in 6, and at both sites in 2; in 2 the level could not be determined accurately. The mean area of normal trachea was 2-8+/-0-8 cm2 in females and 3-7+/-0-7 cm2 in males, while the stenotic area ranged from 0-86 to 4-54 cm2. A stenosis of potential functional significance was found in 8 patients (area less than 1-5 cm2). The stenotic area correlated well with the pressure drop across the stenosis and better than with the stenosis percentage (1-74%). The predicted pressure falls over the stenosis at different flow rates were in excellent agreement with those measured in one patient. Spirometry was unsuitable for detecting the stenosis. Poor correlation were found between the degree of tracheal stenosis and chronic respiratory disease, smoking, age, interval between intubation and tracheostomy, or duration of IPPV. Dysponea during moderate exercise was present in all patients who had a pronounced stenosis.


Classification of peripheral nerve fibres. An historical perspective.

The historical development of the nomenclature used to describe peripheral nerve fibres is described. Some of the properties of nerve fibres and their maturation are discusses. It is suggested that when grouping fibres by their conduction velocities the original terminology introduced by Erlanger and Gasser41 (i.e. A-alpha, beta, gamma, delta, B and C) should be used for efferent nerve fibres, while the nomenclature introduced by Lloyd44 (i.e. groups I,II, III and IV) should be applied to afferent fibres. The terms B, 'gamma efferent', Ia and Ib have specific implications with regard to their source or distribution irrespective of the conduction velocities of the fibres contributing to these groups.


The development of appartus for intermittent negative pressure respiration.

The history of tank and cuirass respirators from the first known use of the intermittent negative pressure principle in 1832 to 1918, on the threshold of its extensive use in the treatment of respiratory paralysis, has been related. A second article will consider the period 1918 to the present day and suggest that negative pressure apparatus-particularly the cuirass respirator-still has its uses.


Hypglycaemia in paediatric anaesthesia: The influence of metoclopramide and oral maltose in paediatric surgical patients.

A safe and effective way to prevent the development of hypoglycaemia in young children during general anaesthesia is to give drinks sweetened with maltose 2 hours before operation. Metoclopramide (Maxolon) is injected intramuscularly to hasten absorption. The postoperative blood sugar in the maltose-treated group (28 patients) was 100+/-22-21 mg/ml (5-5+/-1-232 mmol/litre) and significantly higher ( P less than 0-0005) than in the starved group (22 patients).


A case of drowning.

A case of near drowning is described. Despite full consciousness on early admission, and apparently good immediate recovery following intensive therapy for delayed pulmonary effects, the patient died of overwhelming necrotising pneumonia on the tenth day after the accident.


Sepsis in a CPAP system.

Bacterial contamination of a continuous positive airway pressure system has been investigated and found to be virtually confined to the adjustable valve 'at the mouth'. Organisms isolated from this site are probably derived from those in the sputum. The practical implications of these findings are outlined.


The development of apparatus for intermittent negative pressure respiration.  (2) 1919-1976, with special reference to the development and uses of cuirass respirators.

This paper and the one that preceded it1 have traced the development of the design and use of negative pressure ventilators from their origins in the early nineteenth century to the present day. Their maximum use was in the nineteen-forties and the early fifties after which they were quite rapidly replaced in the treatment of acute respiratory disease by intermittent positive pressure ventilators-the turning point being the severe poliomyelitis epidemic in Copenhagen in 1952. Negative pressure ventilators, particularly cuirass ventilators, still have a place in the treatment of chronic respiratory disease.


Effect of ketamine on intracranial pressure in hydrocephalic children.

Intracranial pressure changes were observed in 10 children with hydrocephalus after ketamine administration. Three patients showed an elevation of pressure and a fall was observed in 7 patients. Two more patients who were given ketamine while under general anaesthesia and IPPV also showed a fall in pressure. No explanation is forthcoming at present for such an unusual response, but an altered cerebral vascular response in the presence of promethazine and general anaesthesia has been postulated.


Pulmonary water content in critical illness.

Pulmonary extravascular water content was measured using a double indicator technique and results compared with chest radiography. It is concluded that careful chest radiography is an effective and simple technique for assessing the pulmonary extravascular water content.


The sensitivity of the respiratory center and some circulatory and subjective responses after nalorphine and naloxone injections.

In five volunteers the sensitivity of the respiratory centre to carbon dioxide after naloxone and nalorphine injections was studied using "double blind" method and increments of doses. Alterations in the respiratory centre sensitivity were reflected by changes in respiratory minute volume, which was measured before and after drug injections, as well as after carbon dioxide stimulation. Comparison of results and their statistical verification showed that nalorphine alone causes respiratory depression and carbon dioxide stimulation is, beside the weak initial action, almost ineffective. Naloxone causes very small, if at all, respiratory depression and the respiratory centre answers efficiently to carbon dioxide stimulation.


Inhibition of gill cilial activity and of Proteus vulgaris motility as tests for aspirin idiosyncrasy.

Aspirin ingestion is likely to result in severe asthmatic attacks in patients with aspirin idiosyncrasy. There is no in vitro test for the condition. Gill cilia and Proteus vulgaris motility studies showed no differences between asthmatics with aspirin idiosyncrasy and control patients.


Opsonic activity and O-agglutinins against Escherichia coli in bovine colostrum.

Anticolibacillus antibody activity was examined in 16 samples of bovine colostrum by O-agglutination test with 6 serotypes of Escherichia coli, and its correlation with the manifestation of diarrhea was analyzed for newborn calves fed these colostrums. The 4 colostrums fed to newborn calves having diarrhea within a few days after birth had significantly lower agglutinin titers for all the serotypes tested than did the other colostrums. Other newborn calves fed on the remaining 12 colostrums did not manifest clinical signs of enteric disorders. The agglutinin spectrum against the E coli serotypes was similar between colostrum samples from the same stockfarm, but variable among the farms from which the colostrum had been collected. The agglutinin activity was sensitive to 2-mercaptoethanol and was found mainly in the macroglobulin fraction of gel filtration, indicating that the activity was due to antibodies of the immunoglobulin M type. This was evidenced directly by the agglutination test of purified immunoglobulins. Opsonic activity of colostrum and immunoglobulins purified therefrom was estimated by the rate of decrease in the number of viable E coli injected into mouse peritoneal cavity. The results indicated that the opsonic activity in colostrum was also attributed mainly to immunoglobulin M antibodies, although the contribution of immunoglobulin A and G antibodies was not ruled out. A part of the opsonic activity in colostrum seemed due to heat-labile component(s) as well.


Immune responses of the bovine fetus and neonate to Escherichia coli: quantitation and qualitation of the humoral immune response.

The humoral immune responses of fetuses and neonates of Escherichia coli O:26:K60:NM were studied in 26 Angus-Hereford crossbred calves. Bacterin (5.0 X 10(10) organism) was injected in utero directly into the amniotic fluid of seventeen 7- to 8.5-month-old fetuses (principals). Saline solution was injected in the same manner into 9 control fetuses. Colostrum-deprived neonates were allotted to 10 groups and either were euthanatized at birth or were subjected to oral revaccination, challenge inoculation with the homologous organism, or both. The resistance to challenge exposure was a function of previous in utero injection of bacterin, age when challenged, and dose of challenge organisms used. Control calves were susceptible to only a large challenge dose, whereas almost all of the prinicipal calves were resistant. Revaccination of principal calves with bacterin at birth, exposure to the large challenge dose, or both, caused a marked increase in anti-O26 passive hemagglutination titers. Results of quantitative and qualitative radioimunossay indicated that the immune response to the O26 antigen was mainly of the immunoglobulin M (IgM) class, although there were also demonstrable changes in immunoglobulins (Ig) G1 and G2. The actively acquired immune responses were serotype specific, and there was no cross reactivity with 4 other E coli serotypes. An unidentified immunoprecipitate band was observed in immunoelectrophoretograms of whole bovine serum which may represent another class of Ig or which may be a subclass of IgG1 or IgG2.


Influence of antibiotic-supplemented feed on occurrence and persistence of Salmonella typhimurium in experimentally infected swine.

The effect of chlortetracycline given at a concentration of 220.5 g/metric ton of feed and of a combination product which supplies chlortetracycline (110.2 g/metric ton), sulfamethazine (110.2 g/metric ton), and penicilin G (55.1 g/metric ton) on the occurrence and persistence of Salmonella typhimurium in experimentally infected swine was studied. Weanling pigs (av weight, 8.2 kg) were inoculated via the feed with 10(11) colony-forming units of S typhimurium 298-1NA. An equal number of nonexposed swine given identical treatment were used as controls. Infected pigs had increased temperatures (maximal av, 41 C) for the first 4 days after infection and severe diarrhea during the first 21 days. The use of chlortetracycline and a combination product at subtherapeutic concentrations in feed did not increase the Salmonella pool or prolong the carrier state in swine. A decrease in number of Salmonella shed from swine given chlortetracycline at the concentration of 220.5 g/metric ton was observed. Significant differences did not occur in Salmonella-related deaths or in emergence of multiple antibiotic-resistant Salmonella by antibiotic selection or R factor transfer. Zoonotic transmission of the infecting Salmonella to animal caretakers was not detected.


Cross reactivity between Anaplasma marginale and two Plasmodium species as demonstrated by passive hemagglutination.

Two types of antigens were prepared from each of 3 partially purified preparations of Anaplasma marginale, Plasmodium lophurae, and P berghei. Hemagglutination tests were conducted with homologous serums to detect antigenic relationships between these organisms. Serums were also absorbed with both homologous and heterologous antigen preparations. Cross reactivity between these organisms was observed.


Estimation of cardiac output in the horse by thermodilution techniques.

An evaluation and comparison of thermodilution technique with dye dilution technique was made in the computation of cardiac output in 39 conscious adult horses (av body wt, 450 kg). Estimation of cardiac output by thermodilution was found to compare favorably with values obtained from dye dilution when a volume of 30 to 40 ml at a temperature of 0 C was used. Difficulties in obtaining accurate thermodilution curves in the horse seem predominantly associated with errors in mixing and observation.


Effect of bovine neutrophil maturity on phagocytosis.

The ability of immature circulating neutrophils to phagocytose foreign particles was determined. One quarter of each of 4 cows, which were free of mastitis and pathogens and had milk somatic cell counts of less than 1 X 10(6) cells/ml, was infused with endotoxin of Escherichia coli (0.5 mg in 3 ml of saline solution) to induce a milk leukocytosis and a shift to the left in circulating leukocytes. Milk samples were taken from the infused and one uninfused quarter before and after infusion. Blood samples were collected at 9 hours after infusion, at 2-hour intervals from 13 to 21 hours, and at 36 hours after infusion. Phagocytosis was determined by incubating whole blood with yeast cells and determining the precentage of neutrophils phagocytosing and the number of yeast cells per neutrophil. Milk somatic cells increased from an average of less than 1.0 X 10(6) cells/ml before infusion to 37.0 X 10(6) cells/ml at the next milking (postinfusion hour 11). Circulating immature neutrophils increased from 7.6% before infusion to 56.6% at postinfusion hour 21. The percentage of neutrophils phagocytosing was 99 to 100 throughout the study. Number of yeast cells per neutrophil (mean phagocytosis) decreased from 6.5 before infusion was done to 5.2 after infusion. However, there was no correlation between percentage of immature neutrophils and mean phagocytosis. The decrease in yeast cells per neutrophil was attributed to the decrease in concentration of neutrophils and yeast cells in the in vitro procedure (r = 0.50). Apparently the immature neutrophils that appear after depletion of the mature form are as phagocytic as the mature neutrophils.


Clinical evaluation of commercial reagent strips for detection of significant bacteriuria in dogs and cats.

The reagent strip technique of quantitative urine culture was a satisfactory screening test for the detection of significant bacteriuria in dogs and cats. The reagent strip technique was found to be of almost equal sensitivity as the calibrated loop technique in identifying significant bacteriuria. Significant bacteriuria was detected in 38 of 148 urine samples evaluated by the calibrated loop technique. Of these 38 urine samples, significant bacteriuria was detected in 35 by the commercial test. False-negative results were obtained with reagent strips in 1 urine sample which had significant bacteriuria by the calibrated loop technique. The other 2 samples had bacterial counts of suspicious significance (10,000/ml of urine) by the reagent strip technique. False-positive results were obtained with the reagent strip technique in 3 urine samples; however, all 3 urine samples had bacterial counts (10,000/ml of urine) of suspicious significance when evaluated by the calibrated loop technique. The reagent strip technique was not satisfactory for the examination of patients with gross hematuria. The nitrite test portion of the commercial test did not detect significant bacteriuria in all samples and, therefore, was not suitable as a screening test for significant bacteriuria in dogs and cats. The nitrite test may have been inhibited by ascorbic acid, a metabolite which normally may exist in the urine of these animals.


Vaccination of cows with an Escherichia coli bacterin for the prevention of naturally occurring diarrheal disease in their calves.

A formalin-killed Escherichia coli bacterin composed of 6 enterotoxigenic strains of the organism prepared from calves with diarrheal disease with field tested for efficacy against naturally occurring diarrheal disease in young calves. The bacterin was tested in 23 privately owned beef herds in Montana involving 3,508 cows and their calves. About half the cows in each herd were given 2 subcutaneous vaccinations before calving and the other half (controls) were injected twice with a placebo. Almost all of the participating herds had a record of acute diarrheal disease. The number of calves from vaccinated dams that died of diarrheal disease was significantly less (P = 0.004) than the number of calves from control dams that died of diarrheal disease (60 vs 99 calves). There was no significant difference in the number of calves in the groups that developed mild diarrhea. There was marked interherd variation in vaccinal efficacy, possibly due in part to differences in the cause of diarrheal disease between herds. Colostral agglutinating antibody titers against formolized cells of each of the 6 vaccinal strains of E coli were markedly higher in vaccinated dams than in control dams. The agglutinating antibody titers were highest against enterotoxigenic E. coli strains 4 and 5 and lowest against strains 2 and 6. Presumably, colostral antibody passively transferred to the calf at the time of nursing was responsible for the protection observed.


Cystine aminopeptidase (oxytocinase) activity in plasma and tissues of normal and infected pregnant cattle.

Cystine aminopeptidase (CAP) activity in tissues and in plasma from pregnant cows was measured at various stages of gestation by using the substrate S-benzyl-L-cysteine-4-nitroanilide. The CAP activity was as high or higher in hepatic and renal tissues as in cotyledonary tissue. Plasma CAP activity was low and did not change with length of gestation, nor did it change when placentation was disrupted by infection with Aspergillus fumigatus.


Long-term use of intermittent positive-pressure breathing (IPPB) in chronic obstructive pulmonary disease.

The long-term use of intermittent positive-pressure breathing (IPPB) to deliver bronchodilator was compared to delivery by air compressor in 88 patients with chronic obstructive pulmonary disease who were in the home care program. There was no difference between the two groups in terms of number of hospital admissions, days spent in hospital, or mortality. The deterioration in ventilatory function was the same in both groups, althouth the patients receiving IPPB appeared to have developed greater hyperinflation. The data suggest that there is little evidence to support the long-term use of IPPB in the therapy of most patients with chronic obstructive pulmonary disease.


Indicator dilution lung water and capillary blood volume in prolonged heavy exercise in normal men.

The indicator dilution quantity of extravascular water in the lung (idQwl) increases in exercise, but whether it is a real accumulation of fluid or is due to increased distribution of blood flow to previously unperfused regions of alveolar walls is unsettled. In 9 well-trained young men, we compared idQwl and the pulmonary capillary blood volume, as measured by the carbon monoxide diffusing capacity procedure, at rest and after 10 and about 50 min of heavy work (150 watts) on a bicycle ergometer. From rest to 10-min exercise, we observed the following changes. Heart rate 72 +/- 15 beats per min (mean +/- SD) to 151 +/- 23; cardiac output 6.0 +/- 1 liter per min to 17.7 +/- 4.1; carbon monoxide diffusing capacity, 46 +/- 10 ml per min per Hg to 65 "/- 11. These all remained constant between 10- and 50-min exercise. The idQwl increased from 178 +/- 37 ml at rest to 219 +/- 46 ml at 10 min and 233 +/- 43 ml at 50 min, and pulmonary capillary blood volume increased from 140 +/- 52 ml at rest to 220 +/- 106 and 206 +/- 98 at 10 and 50 min of exercise, respectively. All of the changes from rest to early exercise were significant (P less than 0.05) by paired t test. There were no significant changes between early and late exercise. We concluded that the early exercise increase in idQwl was due to redistribution of blood flow among and within alveolar walls. The absence of any increase in idQwl between early and late exercise is evidence against accumulation of lung fluid.


Influence of bronchomotor tone on ventilation distribution and airway closure in asymptomatic asthma.

Simultaneous washouts of nitrogen (N2) and helium (He) boluses were performed in 9 seated symptom-free asthmatic patients. Recent work has indicated a correlation between the height of Phase IV (deltaIV) of a vital capacity washout and the end-inspiratory vertical concentration gradient of the gas in the lung. The deltaIV for both He and N2 washouts increased by a factor of 2 and 1.25, respectively, after isoproterenol inhalation. In addition, the amplitude of the cardiogenic oscillations increased from a mean of 0.32 per cent to 0.51 per cent for N2 and from 0.030 per cent to 0.051 per cent for He. Closing volume measured by the He bolus method was higher than that by the N2 method in 8 of 9 subjects, by 3.7 +/- 0.7 per cent vital capacity (mean +/- 1 SE, P less than 0.001). Similarly, He closing capacity was greater than N2 closing capacity in the same 8 subjects by 2.6 +/- 1.3 per cent total lung capacity (P less than 0.001). Despite a decrease in closing volume in 8 subjects, and in closing capacity in all 9 subjects after isoproterenol, the differences between the results obtained by the 2 methods remained unchanged. The slope of Phase III in both N2 and He washouts was influenced in an inconstant fashion, probably reflecting differing contributions from topographic and intraregional inhomogeneities of ventilation in these subjects. The results suggest that in patients with asymptomatic asthma the vertical gradient of regional residual volume as well as the pattern of airway closure is more uniformly distributed between apex and base of the lung. Furthermore, the slope of Phase III in either N2 or He bolus washouts may not reflect the degree of bronchoconstriction.


Concentration and purification of mycobacteriophages with polyethylene glycol 6000.

Experiments were performed to concentrate and purify mycobacteriophages with polyethylene glycol 6000; 6, 9, and 8 per cent polyethylene glycol 6,000 proved to be optimal concentrations for precipitating phages of Mycobacterium phlei, Mycobacterium smegmatis strain butyricum, and mycobacterium smegmatis strain Rabinowitz, respectively. Preparative polyethylene glycol reverse gradients were constructed for further concentration and purification of the precipitated phages. With the method described, large amounts of crude phage lysates can be concentrated and purified rapidly.


Inhibition of exercise-induced bronchospasm by atropine.

The ability of atropine to inhibit exercise-induced bronchospasm was evaluated in 18 children with chronic, perennial asthma. In 17 of 18 patients, exercise-induced bronchospasm was blocked by prior inhalation of 0.1 mg per kg of atropine sulfate, administered in a randomized single blind fashion. In 14 of these 17 patients, significant bronchodilatation occured after the combination of atropine and exercise. Placebo failed to inhibit exercise-induced bronchospasm in any patient. These results suggest that the parasympathetic nervous system has a role in the mediation of exercise-induced bronchospasm in children.


A surgical approach to bilateral hypernephroma using "benchwork" excision and autotransplantation.

A case of bilateral hypernephroma treated by right heminephrectomy in situ and "benchwork" excision of two tumors from the left kidney followed by autotransplantation is presented. Follow-up examination has demonstrated good renal function with no evidence of tumor recurrence or metastasis. This case illustrates the feasibility of benchwork operation and its application to renal tumors, particularly when these tumors are bilateral and preservation of renal tissue is imperative. Long-term follow-up of patients managed by this technique is mandatory.


Effect of ethanol on angina pectoris.

We evaluated the effect of ethanol on exercise performance until angina in 12 patients in a double-blind, randomized study. The mean resting heart rate times systolic blood pressure was not changed after Fresca but was increased after 2 ounces of ethanol (P less than 0.001) and after 5 ounces of ethanol (P less than 0.01). Compared to the control periods, the mean exercise time until angina was not different after Fresca but was decreased after 2 ounces of ethanol (P less than 0.001) and after 5 ounces of ethanol (P less than 0.001). Compared to the control periods, the mean maximal ischemic ST-segment depression after angina was not changed after Fresca but was increased after 2 ounces of ethanol (P less than 0.01) and after 5 ounces of ethanol (P less than 0.001). Drinking 5 ounces or 2 ounces of ethanol decreases exercise duration until angina and increases ischemic ST-segment depression after angina.


Inhibition of stimulated gastric secretion by an orally administered prostaglandin capsule. A study in normal men.

The effect of ingestion of a gelatin capsule containing 127 mug of 16,16-dimethyl prostaglandin E2 (DM-prostaglandin E2) or a liquid containing 127 mug of DM-prostaglandin E2 on stimulated gastric secretion in man was studied. DM-prostaglandin E2 significantly reduced the volume, acid concentration, and total acid output of gastric secretion. Secretory inhibition during the 3 h after treatment with the capsule was 37% (volume), 39% (acid concentration), and 60% (acid output). The DM-prostaglandin E2 capsule was nearly as effective as equivalent amount of DM-prostaglandin E2 in solution. Prostaglandin analogues, because of their oral effectiveness and duration of action, may have therapeutic value in peptic ulcer disease.


[Intermittent mandatory ventilation (author's transl)].

Intermittent mechanical ventilation is a frequent form of therapy for respiratory failure in children. Due to its difficult application in patients with high respiratory rate and difficult synchronization with the respirator, intermittent mandatory ventilation (I.M.V.) was tried on these patients, introducing a unidirectional valve, connected to a continuous flow of gases, on the inspiratory side of the respirator. With I.M.V. the patient is able to breath spontaneously the gases coming from the unidirectional valve and at the same time the respirator provides periodical insuflations at a frequency previously determined by us. The pressure generated by the respirator in the respiratory circuit, closes the unidirectional valve sending gases to patient. This technique not only reduced time of application of mechanical ventilation but made weaning shorter, easier and safer.


Paroxysmal nocturanal hemoglobinuria and marrow failure treated by infusion of marrow from an identical twin.

An 18-year-old white Canadian male patient with paroxysmal nocturnal hemoglobinuria and refractory marrow failure received a marrow infusion from his normal identical twin brother without prior ablation of the patient's marrow by drugs or irradiation. After 2 years of follow-up, the patient is well with no evidence of clinical disease or significant hematological abnormality. The results suggest that normal marrow stem cells can have a selective advantage over the abnormal paroxysmall nocturnal hemoglobinuria clone.


[Massive pulmonary hemorrhage successfully treated with mechanical respiration and CPAP (author's transl)].

A newborn baby with massive pulmonary hemorrhage at two and a half hours of life is reported. She was successfully treated with mechanical respiration and continuous positive airway pressure. The pathogenetic mechanisms and mode of action of the applied treatment is discussed.


Infections after cardiac transplantation: relation to rejection therapy.

We have analyzed the relation of the treatment of 76 acute graft rejection episodes in 45 late postoperative cardiac transplant patients to the 56 infections occurring in these patients. Intensification of immunosuppressive therapy for acute rejection greatly increased the occurrence of infection from a control incidence of 1.3 infections per 1000 patient-days to a posttreatment incidence of 3.6. Two modes of treatment, increased oral prednisone and high-dose methylprednisolone plus antithymocyte globulin, were further analyzed. Actuarial analysis of infections after these two treatment modes showed that the treatment-related increase in infection was nearly exclusively due to the latter form of therapy. Invasive cardiac procedures did not appear to be causally related to infections in these immunocompromised patients.


The management of hyperlipidemia: whether, rather than how.

The premise that measures used to lower the plasma lipids in patients with hyperlipidemia will lead to reductions in new events of coronary heart disease (the Lipid Hypothesis) should be reconsidered today as a result of several recent reports of large-scale double-blind drug trials in the United Kingdom and in the United States. To that end, the published evidence that bears on tests of the hypothesis by dietary and drug interventions is reviewed, and the conclusion reached that the hypothesis has not yet been adequately tested. A phased program is described that will prepare the ground for a fuller and more definitive trial of the premise in the future: the first steps must be to establish that a combined diet/drug regimen in large numbers of adult male hyperlipidemic patients is acceptable and essentially harmless and that during an observation period of several years a high rate of adherence to the regimen can be attained. Any advice to the general public to make large dietary changes now is considered premature.


[Emergency coronary surgery (indications and immediate results)].

Emergency surgery acute coronary insufficiency is now possible with good chances of success. The surgical risk should always be compared with the risk of purely medical treatment. In impending myocardial infarction, it seems that surgery improves the immediate prognosis. In uncomplicated infarction, the results obtained at present are too small in number and are not conclusive. In complicated infarction, the risk of conservative medical treatment is too great and thus justifies the indication for surgery. The conditions of surgery have been greatly improved by mechanical cardiac assist (intra-aortic balloon pumping). The latter permit coronary arteriography to be carried out safely and the patient is operated under the best possible conditions.


The use of clonidine and practolol in the treatment of hypertension.

The antihypertensive effects of clonidine hydrochloride and practolol were compared in 42 men, aged 45 years, who had not received any antihypertensive therapy before, except one patient. The diastolic blood pressures were at least 110 mmHg on two successive visits to the health centre before their selection to the trial. One half of them were classified into the WHO group 1 and the other half into group 2. There was no statistical difference in the systolic and diastolic blood pressures between clonidine and practolol group at the end of placebo period. The study started with a three-week placebo period. Thereafter, 20 patients were given clonidine 0.225 mg and twenty-two practolol 200 mg daily. The next control was carried out after three weeks. The dosage was kept unchanged or increased according to the antihypertensive response. After three weeks, clonidine and practolol dosages were checked again, and 25 mg of chlorothiazide were added to the treatment in 15 clonidine cases and in 18 practolol cases. After the next three-week period, the same regimen was continued on most patients for 6-9 weeks. The daily dosage of clonidine varied from 0.225 to 0.900 (mean 0.394) mg and that of practolol from 200 to 600 (mean 382) mg. Both regimens resulted, when individually adjusted, in a mean systolic blood pressure level of less than 150 mmHg and diastolic pressures less than or equal to 100 mmHg. Hydrochlorothiazide potentiated the blood pressure effect almost equally in both regimens. The blood pressure reduction was statistically significant (p less than 0.05) both in the clonidine and practolol group. There was no significant difference of the mean blood pressures after the active drug therapy between these two groups. A moderate reduction of pulse rate was observed in both main groups, but it was not related to the antihypertensive efficacy. Side-effects were mild. Dryness of the mouth and sedation were more common in patients receiving clonidine. No oculocutaneous or other "immunological" manifestation were seen during the 15-18 weeks' practolol therapy.


A comparison of debrisoquine and methyldopa in hypertension.

Debrisoquine, an antihypertensive agent, was compared with methyldopa in a double-blind trial in the treatment of hypertension in 20 patients. The cross-over method was used to treat each patient with first one and then the other drug for two periods of six weeks each. Two placebo periods of two weeks each were also included, one before the trial, and the other between the two therapy periods. The maximum daily dose was 3 X 10 mg debrisoquine compared with 3 X 250 mg methyldopa. Hydrochlorothiazide, 50 mg daily, was added in all cases for the entire trial. Both preparations lowered blood pressure statistically significantly (p less than 0.005). Tablet for tablet, debrisoquine had a slightly more pronounced effect than methyldopa, but the difference was not statistically significant. Both drugs were well tolerated and in no case had treatment to be interrupted because of side effects. Debrisoquine produced less sedation and dizziness than methyldopa. The conclusion was that both drugs were equally effective in the doses studied and well tolerated and that debrisoquine is of value in the treatment of moderate hypertension.


Prevalence of cholelithiasis in men and women ingesting a serum-cholesterol-lowering diet.

This study was carried out to ascertain whether, as has been suggested, the ingestion of a serum-cholesterol-lowering diet would be conducive to cholelithiasis. The prevalence of gallstones was studied in autopsied male and female patients of two mental hospitals in connection with a long-term controlled trial on prevention of coronary heart disease by means of a diet with a high polyunsaturated/saturated fatty acid ratio. The prevalence of gallstones was in men: 20/89 (equals 22.5%) on cholesterol-lowering diet and 11/44 (equals 25%) on normal diet; and in women: 151/262 (equals 42%) on cholesterol-lowering diet and 29/62 (equals 47%) on normal diet. It was concluded that in our trial the cholesterol-lowering diet was not lithogenic.


Twice-daily pindolol and alprenolol in essential hypertension of moderate severity.

A double-blind cross-over comparison of the antihypertensive actions of alprenolol and pindolol in equipotent doses was carried out in 22 patients with moderately severe essential hypertension. No other drugs were allowed. Ten patients were in WHO grade I, and 12 in grade II. The average initial pressures, similar after both the first and second 4-week placebo periods, were 175/116 mm Hg standing and 175/109 mm Hg supine. These pressures were decreased significantly by each beta-blocking drug, and about equally in both positions. An average reduction, using both 2-month treatment periods, was -13/-7 mm Hg with alprenolol, and with pindolol it was -23/-13 mm Hg. Both systolic and diastolic normotension (less than 160/100) in the supine position occurred in 45% of the patients when treated with alprenolol and in 64% with pindolol. With diastolic normotension alone the figures were 59% and 82% respectively. Rather low daily doses of 400 mg alprenolol and 20 mg pindolol were effective; increasing the doses to the average final levels of 533 mg alprenolol and 25 mg pindolol resulted in just negligible further pressure reductions. There were no serious side effects or complete resistance. Pindolol reduced the resting heart rate significantly in spite of its intrinsic sympathomimetic activity. Two aspects emerging from this study have clear practical implications. The twice-daily dosage, used here purposefully, of both alprenolol and of pindolol reduces effectively blood pressure, and increases patient convenience. Heat failure was not induced even in those 12 patients with cardiac involvement, including 5 with clear-cut radiological left ventricular enlargement.


Fate of antibodies bound to lymphocyte surface. I.--Study with complement-dependent cytotoxicity, indirect immunofluorescence and radiolabelled antibodies.

Anti-HL-A alloantiserum, heterologous antilymphocyte globulins and anti-beta2m antisera were allowed to react to human lymphocytes in vitro. The fate of the antigen-antibody complexes formed at the cell surface has been studied by means of the lymphocytoxicity test in the presence of rabbit complement, radiolabelled antibodies and the indirect immunofluorescence technique. Those techniques demonstrated that initially bound antibodies disappear from the cell surface. This disappearance requires optimal conditions; it does not result from a mere dissociation of antibodies but likely represents partial degradation, internalization and release of antigen-antibody complexes into the extracellular medium. This phenomenon can be regarded as a reflection of the dynamic state of the cell membrane, although it differs from the redistribution of antigen-antibody complexes on the lymphocyte surface (patching and capping). Possible implications of such events are discussed in relation to triggering or blocking of lymphocyte proliferation.


Mitral valve prolapse.

Mitral valve prolapse is a condition that is being recognized with increased frequency. It is not known whether its incidence is increasing, or whether we are better able to diagnose it today. In the idiopathic or familial variety, the mitral valve pathology is almost always that of myxomatous degeneration. Some authors have suggested the presence of a cardiomyopathy because of significant left ventricular dysfunction in many cases. Idiopathic prolapse occurs predominantly in females, often at a young age, and may be associated with chest pain, dyspnea, fatigue, presyncope, syncope, and/or sudden death. The clinical findings are variable and typically consist of a nonejection click and/or late systolic murmur, heard best at the cardiac apex. Diagnosis can be confirmed by echocardiography and/or ventricular cineangiography, the latter permitting accurate recognition of the anatomy of the prolapsed leaflets. The complications of infective endocarditis, severe mitral insufficiency, and life-threatening ventricular arrhythmias represent the major problems of management. It is important to distinguish the idiopathic form of mitral valve prolapse from that due to coronary artery disease and to realize that mitral valve prolapse may occur in Marfan's syndrome, Turner's syndrome, or in association with secundum atrial septal defect or ruptured chordae tendineae. Typical clicks and/or murmurs have also been described in patients with a history of rheumatic fever and in hypertrophic cardiomyopathy. Although much descriptive knowledge has accumulated over the past 15 years, many unanswered questions remain regarding the idiopathic type of prolapse. What is the nature and cause(s) of myxomatous degeneration? What is the relation of the valve pathology to the left ventricular dysfunction? What is the relation of both of these factors to disabling chest pain, electrocardiographic changes, and life-threatening arrhythmias? Hopefully, answers to these and other important questions regarding mitral valve prolapse will be forthcoming.


Vitamin K and the oral anticoagulant drugs.

The evolution of vitamin K, from a dietary deficiency in birds to a postribosomal modifier of prothrombin in man, has been a fascinating scientific saga. Its antivitamin, the oral anticoagulant drugs, has been a powerful probe both of vitamin K action and of drug interactions. These agents have emerged from a limbo of clinical therapeutics to become a light of human pharmacology.


Multiple endocrine neoplasia type II.

The clinical characteristics, methods of diagnosis, and treatment of MEN-II have been described. Attention in the future should be focused on diagnosing MCT at the earliest possible time in MEN-II family members. The development of chemotherapeutic or other antitumor agents for the treatment of metastitic MCT should prove a fertile field for investigation.


Neuroendocrine dysfunction in depressive illness.

Patients with severe depressive illnesses of the endogenomorphic type frequently manifest several hormonal abnormalities. The best documented are the hypersecretion of cortisol, particularly in the late evening and early morning, associated with relative resistance to dexamethasone suppression; diminished or absent HGH responses to insulin-induced hypoglycemia; and diminished TSH responses to TRH. There are also reports from one laboratory of relatively diminished plasma LH concentration in postmenopausal women with primary unipolar depressive illness, a finding that awaits replication by other centers. Most of these hormonal abnormalities provide further support to the concept of hypothalamic dysfunction in certain forms of depressive illness, and are consistent with current hypotheses of abnormal brain monoamine activity in these conditions. These studies suggest that analysis of neuroendocrine responses in patients with mental illnesses may be a valuable tool for the study of possible alterations in brain function. Further advances may be expected when radioimmunoassay techniques become available for the hypothalamic releasing and inhibiting factors themselves.


Neurotoxic indoleamines and monoamine neurons.

In 1968 Thoenen & Tranzer (1) discovered that the long-lasting depletion of NA in sympathetically innervated organs by 6-OH-DA is due to degeneration of NA terminals. This provided the basis for the development of a new concept in neurobiological research: the method of selective chemical neurodegeneration. The successful application of this method to produce degeneration of DA and NA neurons in brain (2,3) stimulated a search for compounds with comparable effects on central 5-HT neurons. In studies with a restricted number of 5-HT analogs, we were able to show that certain dihydroxylated tryptamines caused toxic damage to serotonin terminals. The recent findings by Björklund, Baumgarten & Rensch (4) and Gerson & Baldessarini (5) that DMI treatment prior to intraventricular 5,7-DHT injection prevents the damaging effect of the latter drug on NA but not on 5-HT neurons indicate that powerful and probably rather selective destruction of central indoleamine-containing axons and terminals can be achieved.


Cutaneous pharmacology and toxicology.

The fields of cutaneous pharmacology and toxicology existed as long as man used topical therapy; some medicaments were helpful and others harmful. This review documents recent progress in these fields in terms of the experimental method. Emphasis has been given to conceptual and methodologic progress rather than a list of new molecules. As signs of the advent of the maturity of these fields, a graduate school course has recently been completed, one text has been published (7), and at least two are in preparation. It is likely that the next review of this topic in this series will reflect this considerable progress in terms of relevance to man.


Effects of drugs on the electrical activity of the brain: anesthetics.

The major concepts presented in this review can be summarized as follows: 1. There is a multidirectional continuum of anesthetic states--some represented by CNS excitation and others by depression. 2. The reticular activating system is influenced by all anesthetics; some inhibit its action (stage III) and some hyperexcite the system resulting in a function disorganization (stage II-C). 3. Some agents traverse both excitation and depression, diethyl ether (I, II, III). 4. Others induce only stage II--catalepsia, e.g. nitrous oxide, ketamine, gamma-hydroxybutyrate, alpha-chloralose, phencyclidine, trichlorethylene, and enflurane. 5. Others induce no stage II but progress directly from stage I stage III, e.g. halothane and barbiturates. 6. Cataleptic agents may induce further CNS excitation manifested by seizures, e.g. gamma-hydroxybutyrate, phencyclidine, ketamine, alpha-chloralose, trichlorethylene, and enflurane. 7. The functional definition of surgical anesthesia is: a stage induced by a drug that makes the subject relatively unresponsive to painful stimuli and amnestic. Thus, the subject does not respond during surgery and cannot recall what happened afterwards. This state can be achieved by functional disruption of CNS systems by marked stimulation or depression.


[Possibility of the early identification of polyene antibiotic producers].

A method for identification of polyenic antibiotics at early stages of their screening was developed using the known fact of high affinity of polygens and steroids. It was found that addition of cholesterol or ergosterol to the nutrient medium in a concentration of 100 gamma/ml eliminated the inhibitory effect of the polyenic antibiotics. Screening of the antibiotic-producing actinomycetes simultaneously on 2 media, i.e. with and without cholesterol using the yeast test-organisms provided identification of actinomycetes producing polyenic antibiotics. The selective capacity of 3 yeast cultures, i.e. Sacch. cerevisiae, Cand. albicans and Tor. globosa 11-3 as test-organisms for screening polyenic antibiotics was compared. It was shown that mitochondrial mutant 11-3 of Tor. globosa was a highly sensitive model for identification of actinomycetes producing polyenic antibiotic, since 23% of the actinomycetes possessing an activity against that organism produced substances of the polyenic nature. All the strains of the actinomycetes screened with the help of Cand. albicans and Sacch. cerevisia were the same as those detected with the help of mutant 11-3 of Tor. globosa.


[Sensitivity to doxycycline (vibramycin) of the microflora isolated from the patients in a therapeutic clinic].

Sensitivity of microflora to tetracycline, oxytetracycline, chlortetracycline and doxycicline was studied. A total of 237 pure cultures of Strep. viridans (54), beta-hemolytic streptococci (27), pathogenic staphylococci (52), non-pathogenic staphylococci (53) and Coli bacteria (51) were tested with the agar-diffusion method using standard discs. Doxycicline was most active and chortetracycline was least active. The maximum sensitivity to doxycicline was found in beta-hemolytic streptococci (85.4%) and the minimum sensitivity to that antibiotic was found in Coli bacteria (39.2%) and Strep. viridans (35.6%), which was superior to that with respect to the other tetracyclines. Coincidence of the clinical effect with the microflora sensitivity and high percentage of sensitivity to doxycicline among Staph. aureus, which is important in treatment of severe infections caused by the organism were observed.


[Intestinal yersiniasis in the Far East. The sensitivity and cross resistance to antibiotics of Yersinia enterocolitica strains isolated in the Maritime Territory].

The author studied 121 strains of Yersinia enterocolitica isolated in the Ptimorye Territory. It was found that by their sensitivity to antibiotics the strains did not differ from the analogues abroad strains: they were highly sensitive to tetracycline, streptomycin, kanamycin, neomycin and monomycin (MIC 1.25 to 0.6 gamma/ml or units/ml), less sensitive to oxytetracycline, chlortetracycline, levomycetin, oletetrine and gramicidine (MIC 10-5 gamma/ml), highly resistant to penicillin (MIC 100-50 gamma/ml), erythromycin and polymyxin (MIC 500-100 gamma/ml). No differences in the sensitivity to the above antibiotics of the Far East strains as dependent on the place period and source of isolation and inidentity of their biochemical characteristics were found. Cross resistance in Yersinia enterocolitica forms with artificially developed resistance to some antibiotics was found. No cross resistance with tetracycline was noted in the streptomycin resistant variants of the bacteria.


[State of certain indices of natural, nonspecific immunity in workers engaged in the manufacture of neomycin and monomycin].

Women occupied at various stages of neomycin and monomycin production were examined immunologically. The examination revealed insignificant changes in the phagocytic activity of the blood neutrophils, however no relation between the changes level and the level of contact with the antibiotics was observed. Changes in composition of the microflora in the deep skin layers in direction of an increase in the number of pathogenic microbes and a decrease in the bactericidal function of the skin were found in the women occupied at the final stages of the technological process, i.e. drying, packing and control.


[Practice of patenting microbiological objects in foreign countries].

Data on the main objects corresponding to the inventions in the field of microbiology and microbiological industry acceptable for patenting abroad are presented. Examples of claims for each type of the protected objects taken from patents filed in main capitalist countries are given. The examples have necessary comments.


Impregnated disk method for antifungal antibiotic testing.

Sixteen clinical fungal isolates were tested for antibiotic susceptibility by using disks impregnated with growth medium and antibiotic. The procedure was easier to perform, less time consuming, and as reliable as other currently available methods.


Inhibition of potentially pathogenic yeastlike fungi by clotrimazole in combination with 5-fluorocytosine or amphotericin B.

Clotrimazole (CTM) has a doubtful future with respect to use in treatment of the systemic mycoses. To assess the potential of CTM in combined drug regimens, antifungal effects of CTM together with 5-fluorocytosine (5-FC) or amphotericin B (AMB) were tested in a synthetic liquid medium against Candida albicans, Candida tropicalis, and Torulopsis glabrata. Viable counts were monitored over a 48-h incubation period. Weak inhibitory concentrations of CTM were tested in combination with levels of 5-FC or AMB that alone produced transient antifungal effects followed by rapid recovery of proliferative capacity. Results were similar for each of the organisms studied. Between 24 and 48 h, when cultures containing 5-FC or AMB alone were in the recovery phase, CTM plus 5-FC and CTM plus AMB continued to markedly suppress cell multiplication. It would appear that weak inhibitory concentrations of CTM can act together with 5-FC or AMB to produce antifungal effects greater than that obtained with either of the latter two drugs alone.


Antibiotic resistance among coliform and fecal coliform bacteria isolated from sewage, seawater, and marine shellfish.

Seawater and shellfish samples collected in the vicinity of a marine sewage outfall were examined for the incidence of antibiotic resistance among coliform and fecal coliform bacteria over a 2-year period. Seventy percent or more of these two groups of bacteria from both sources were resistant to one or more antibiotics. Forty-five percent of the isolates resistant to streptomycin or tetracycline were capable of transferring all or part of their resistance pattern to an antibiotic-susceptible strain of Escherichia coli K-12.


Antibiotic resistance among coliform and fecal coliform bacteria isolated from the freshwater mussel Hydridella menziesii.

Freshwater mussels (Hydridella menziesii) collected from Lakes Rotoroa, Rotoiti, and Brunner, South Island, New Zealand, contained coliform and fecal coliform bacteria. The majority of these bacteria were resistant to one or more antibiotics, but none transferred streptomycin, tetracycline, or kanamycin resistance to an antibiotic-susceptible strain of Escherichia coli K-12.


Reevaluation of kanamycin dosage in infants and children.

It was recently reported that the dosage of kanamycin formerly recommended for neonates of 7.5 mg/kg every 12 h did not produce therapeutic serum concentrations of 15 to 25 mug/ml, but a larger dosage of 10 mg/kg every 12 h was required. Reevaluation of the pharmacokinetics of kanamycin in infants and children was therefore undertaken. Sixteen time-concentration curves after a dose of 5 mg/kg were obtained from patients 2 months to 12 years of age; the mean peak serum kanamycin concentration was 10.9 (range, 3.6 to 17.9) mug/ml at 0.5 h. Ten time-concentration curves were obtained after a dose of 10 mg/kg; the mean peak serum concentration was 17.6 (range, 8.4 to 30) mug/ml. Eight patients were studied on successive days, and there was doubling of the 1-h peak serum concentration when the dose of kanamycin was increased from 5 to 10 mg/kg. Standard serum bactericidal tests were done against Escherichia coli and Enterobacter cloacae strains, each with a minimal bactericidal concentration of 5 mug of kanamycin per ml. All 3 sera containing 21 mug or more of kanamycin per ml demonstrated a bactericidal titer, whereas only 2 of 23 sera containing less than 21 mug of kanamycin per ml did so. The currently recommended dosage of kanamycin for infants and children fails to produce serum concentrations in the therapeutic range, and preliminary data suggest that the dosage should be increased to 10 mg/kg per dose every 8 h.


Microbiological quality of frozen breaded fish and shellfish products.

A survey was made of the microbiological quality of seven frozen, breaded, precooked fish and shellfish products and of frozen, breaded, uncooked shrimp at the retail level. Geometric mean aerobic plate counts per gram (and number of units examined) were as follows: fish sticks, 8,300 (1,539); fish cakes, 5,600 (1,378); crab cakes, 4,900 (1,226); scallops, 1,700 (1,392); clams, 450 (1,384); haddock, 15,000 (1,306); fish in fish and chips dinner, 7,200 (1,485); and uncooked shrimp, 220,000 (1,462). Geometric mean coliform, Escherichia coli, and Staphylococcus aureus counts for all eight products ranged from 1 to 10/g.


Inhibitory effects of H2 on growth of Clostridium cellobioparum.

Hydrogen inhibits the growth of hydrogen-producing Clostridium cellobioparum, but not of Escherichia coli or Bacteroides ruminicola. The inhibition is reversible. When hydrogen was removed either by palladium black or by gassing out the tube, glucose utilization increased as did optical density and hydrogen production of C. cellobioparum. Removal of the H2 by methanogenic bacteria favors the growth of C. cellobioparum. Grown with Methanobacterium ruminantium in various concentrations of glucose, the Clostridium reaches a higher optical density and produces more H2 and a higher viable cell count. The cell yield is also higher than in pure culture. In mixed culture, C. cellobioparum produces more acetic acid and less lactic acid, ethanol, and butyric acid than in pure culture. The significance of this metabolic shift and hydrogen utilization in methanogenesis is discussed.


Inactivation kinetics of some microorganisms subjected to a variety of stresses.

Loss of viability in aerosols of Escherichia coli B, E. coli commune, E. coli Jepp (in nitrogen atmospheres), and Semliki forest virus (in air) was determined as a function of relative humidity at 26.5 C. The decay patterns could be accounted for accurately by means of an equation derived from a postulated mechanism involving population distributions and first-order denaturation kinetics. Analyses of published curves describing loss of viability (all of which were semiexponential, ie., J-shaped) for various microorganisms stressed by different techniques showed that the proposed mechanism also provided an explanation for effects of the following factors (in the absence of open air, oxygen, or radiation): (i) influence of relative humidity upon aerosol susvival; (ii) dissemination of aerosols from the wet and dry states; (iii) protecting additives; (iv) relative humidity change before reconstitution; (v) reconstituting fluids; (vi) water content of freeze-dried product; (vii) storage gas; and (viii) storage temperature. The date indicate that low temperatures and high pressures were likely to be conducive to the preservation of viable bacteria and viruses, provided that cold shock and decompression shock were absent.


Macromolecule synthesis in Escherichia coli BB under various growth conditions.

The kinetic behavior of the macromolecule synthesis of Escherichia coli during balanced growth in various media at different temperatures as investigated. The results indicate that macromolecule contents per cell can be expressed as exponential functions of the specific growth rate at a given temperature. It was shown that the content per cell at the zero growth rate was constant in each macromolecule component, irrespective of the growth temperature. The rate of ribonucleic acid (RNA) synthesis per unit weight of deoxyribonucleic acid and that of protein synthesis per unit weight of RNA were taken as efficiencies of RNA and protein synthesis, respectively; both of them were found to be dependent on the growth rate and temperature. The efficiency of RNA synthesis was found to be very high at a high growth rate, whereas that of protein synthesis was found to decrease above certain growth rate. At the same growth rate, an increase in the growth temperature resulted in a decrease in the efficiency of RNA synthesis but an increase in that of protein synthesis.


Influence of certain indigenous gastrointestinal microorganisms on duodenal alkaline phosphatase in mice.

Alkaline phosphatase activity was assayed in duodenal homogenates or extracts from adult specific pathogen-free (SPF) and germfree mice and gnotobiotic mice monoassociated with a Lactobacillus sp., a Bacteroides sp., or a coliform strain indigenous to SPF mice. Activity levels of the enzyme were much higher in the preparations from germfree mice than in those from the SPF controls. In the gnotobiotes monoassociated either with a freshly isolated Lactobacillus sp. or a Bacteroides sp., the levels of alkaline phosphatase activity were intermediate between the values for germfree and SPF mice. By contrast, in the gnotobiotes monoassociated with a coliform strain, alkaline phosphatase activity remained at high germfree levels. Butanol extracts of duodenal tissue from SPF mice, germfree mice, and exgermfree mice associated with an indigenous microflora from SPF mice (conventionalized) were subjected to acrylamide gel electrophoresis. A stain for alkaline phosphatase activity revealed three major bands in the gels prepared with extracts from SPF and conventionalized mice, but only two in the gels prepared with extracts from germfree mice. All three bands may have been present in the latter gels. One of the bands (the middle one) may have been obscured, however, by high activity in the slowest moving band. As determined by densitometric scanning, the slowest moving band had much higher activity in the preparations from germfree animals than in those from SPF or conventionalized mice. These findings suggest that the indigenous microbial flora affects not only quantitatively, but also qualitatively, the activity of alkaline phosphatases in the mouse intestinal mucosa.


Effect of antimicrobial soap containing chlorhexidine on the microbial flora of skin.

The qualitative and semiquantitative changes in the aerobic microbial flora of normal skin with the prolonged use of a chlorhexidine scrub (6 months) were investigated. More samples in the chlorhexidine scrub group had gram-negative bacilli in their axilla (63 of 96, 66%) and groin (36 of 96, 38%) than the controls (32 of 66, 49%, for axilla and 7 of 66, 11%, for groin; P = 0.01). Klebsiella and Enterobacter were the predominant organisms in the control and chlorhexidine groups, respectively. The chlorhexidine scrub produced a reduction in the total aerobic counts in the axilla, groin, and between the toes and the fingers. Fewer samples from the chlorhexidine-treated areas revealed the presence of lipophilic diphtheroids than did the controls. Lipophilic diphteroids were also reduced quantitatively in the groin and axilla with chlorhexidine treatment. No consistent pattern for the other major groups of bacteria was noted between the treatments.


Production of a precursor to the pyrimidine moiety of thiamine.

The supernatant fluid from cultures of Escherichia coli W-11, a pur E mutant, prevented the inhibition of growth of E. coli B in a medium containing adenine or adenosine. Adenine inhibition was prevented more readily than adenosine inhibition. More than 90% of the biological activity of the supernatant fluid was recovered in the anionic fraction after treatment with Dowex-50 (NH4+). The cationic fraction, containing large amounts of 5-aminoimidazole ribonucleoside (AIRS), did not prevent adenine inhibition. The W-11 supernatant fluid was shown by bioautography to contain only one compound that prevented adenine inhibition. Proliferating and non-proliferating cultures produced only one compound that prevented adenine inhibition. The compound was shown to be an intermediate (int-1) in the biosynthesis of the pyrimidine moiety of thiamine, Int-1 was stable during sterilization at 121 C for 15 min, during concentration by either flask evaporation or lyophilization, and after storage for  several days at 4 C or at -- 20 C. Int-1 was distinguishable from other known derivatives or intermediates of the pyrimidine moiety. A scheme is presented that illustrates the proposed relationship between int-1 and the synthesis of thiamine.


Microbial transformation of 2,4,6-trinitrotoluene and other nitroaromatic compounds.

A variety of nitroaromatic compounds, including 2,4,6-trinitrotoluene (TNT), were reduced by hydrogen in the presence of enzyme preparations from Veillonella alkalescens. Consistent with the proposed reduction pathway, R-NO2 H2 leads to R-NO H2 leads to R-NHOH H2 leads to R-NH2, 3 mol of H2 was utilized per mol of nitro group. The rates of reduction of 40 mono-, di-, and trinitroaromatic compounds by V. alkalescens extract were determined. The reactivity of the nitro groups depended on other substituents and on the position of the nitro groups relative to these substituents. In the case of the nitrotoluenes, the para-nitro group was the most readily reduced, the 4-nitro position of 2,4-dinitrotulene being reduced first. The pattern of reduction of TNT (disappearance of TNT and reduction products formed) depended on the type of preparation (cell-free extract, resting cells, or growing culture), on the species, and on the atmosphere (air or H2). The "nitro-reductase" activity of V. alkalescens extracts was associated with protein fractions, one having some ferredoxin-like properties and the other possessing hydrogenase activity. Efforts to eliminate hydrogenase from the reaction have thus far been unsuccessful. The question of whether ferredoxin acts as a nonspecific reductase for nitroaromatic compounds remains unresolved.


Hot-loop test for the determination of carbon dioxide production from glucose by lactic acid bacteria.

A hot-loop test was found to be more rapid, convenient, and reliable for the detection of carbon dioxide production than were conventional methods such as displacement of agar plugs and precipitation in barium hydroxide.


Stability of Bacillus pumilus spore strips used for monitoring radiation sterilization.

Dried Bacillus pumilus spore strips had a stable D-value of 0.17 to 0.18 Mrad after 1 year at 5 or 25 C, but resistance was lost at 35 C. Refrigeration did not have an adverse effect on resistance to irradiation. The presence of water at the time of initial preparation increased this resistance to 0.23 to 0.25 Mrad. Proper drying is essential to achieve reproducible results in sterility tests using USP-type biological indicators.


Loperamide in chronic diarrhea and after ileostomy: a placebo-controlled double-blind cross-over study.

Fifteen patients (20 to 66 years) with long-standing chronic diarrhea of varying etiology were selected for an open trial of loperamide 2 mg capsules. The optimal daily dose for substantial reduction of the diarrhea ranged from two to seven capsules. Eleven patients showed a significant improvement in stool consistency and stool frequency, and a decrease of abdominal cramps. Loperamide appeared to be ineffective in two patients with cholerrheic diarrhea, and in one patient with laxative-induced diarrhea, and in one patient with diarrhea of unknown etiology. The eleven successfully treated patients then entered a double-blind placebo-controlled trial for ten days or until relapse, the daily dose being identical to the optimal one previously determined in the open phase. The investigator was able to guess the code correctly in ten out of eleven cases. Twenty ileostomy patients (ages 25 to 73 years) volunteered for the evaluation of the inhibitory activity on small intestinal peristalsis by loperamide in a double-blind placebo-controlled cross-over study. Mean daily ileostomy output decreased by 22% in the loperamide period, as compared with the drug-free study phase (P less than 0.001). Of the 20 patients, 16 were able to guess their code correctly, whereas four were uncertain, although their fecal weights were lower with loperamide. Many patients noticed an increased urinary production and experienced an improvement in their ileostomy care during loperamide treatment. Because of its effectiveness, its low side-effect liability and its lack of toxicity, loperamide is considered a promising drug in the symptomatic treatment of chronic diarrhea, and as a reliable agent in the treatment of ileostomy patients.


Tinidazole in treatment of acute amoebic dysentery in children.

The excellent results obtained in this trial indicate that tinidazole is a drug worthy of extensive evaluation in the treatment of amoebiasis, as three single daily doses is a simple form of treatment. The drug was well tolerated and free from any toxic effects.


Clinical evaluation in tinidazole in amoebiasis in children.

Forty children with symptomatic intestinal amoebiasis were treated with tinidazole in a single dose of 50 mg/kg for 3 consecutive days. A cure rate of 97% was obtained. Tinidazole was tolerated well in children and proved to be a valuable new amoebicidal drug.


Vitamin E deficiency and thrombocytosis in Caffey's disease.

An infant is described who presented with ptosis and periorbital oedema and was found to have infantile cortical hyperostosis with thrombocytosis, raised IgM, and vitamin E deficiency.


[Epidemiological and bacteriological study on the outbreak of gastroenteritis due to Escherichia coli 0111:B4 which occured in hospital environment].

The Authors report the results of the bacteriological researches carried out during an outbreak of gastroenteritis from E. coli O111:B4 having concerned, in 6 months, 40 infants of the pediatric ward at Legnano's Hospital. The researches clearly demonstrate the need for a strict control, particularly in the pediatric and neonatal wards, so as to make possible a swift identification of the gastroenteric syndromes due to E. coli strains which cause enteritis. The gravity of the symptomatology, the likelihood of the infections's spreading within the hospital and the considerable resistance to antibiotics of the strains in question are all factors which make this type of infection one particularly to be feared in hospitals.


[Comparison between fixation test with BCG and immunofluorescence in the diagnosis of leishmaniasis].

The complement fixation test with an antigen from commercially lyophilized BCG and the immunofluorescence test were carried out on serum samples from patients with visceral leishmaniasis, oriental sore and tbc. The IFT positivity was obtained only in patients with visceral leishmaniasis. The CFT with BCG showed positive results in 3 on 5 serum samples from patients with visceral leishmaniasis, in 2 with oriental sore, at low titres, and in 5 serum samples from patients with tbc. The AA. confirm the high specificity of the IFT, but suggest that the CFT with BCG can be used as a convenient screening test.


[Practical importance of quantitative bacteriology in pneumology. Preliminary studies].

Some ascertained the utility of the quantitative bacteriology in pneumology especially for the diagnosis of acute bronchopulmonary infections. Miles and Mizra technique lightly changed as analytically here described is suitable for counts of viable bacteria in sputum after liquefaction by N-acetyl-l-cisteine. Some researches prove that the technique is convenient for the control of chronic bronchopulmonary infections too with some restrictions. Quantitative tests are important to ascertain aetiological function of the bacteria in sputum and in bronchial secretions. Particularly 10(7)-10(9) coliforms per ml of sputum are likely pathogenic. The observation of the early quantitative changes of bacteria in sputum during antibiotic treatments is suitable for in vivo tests of microbial sensitivity to drugs and is preferable to the usual in vitro antibiograms.


A bacteriological study of the intestinal mucosa and luminal fluid of  adults with acute diarrhoea.

Bacteriological studies of jejunal mucosal biopsy specimens and contents were performed on 22 hospitalized adult patients with acute diarrhoea and 24 control normal subjects. None of the washed homogenates of the mucosal specimens were sterile and only one fluid specimen obtained from a control subject was sterile. A definite enteric pathogen was found in only five of the 22 diarrhoea patients. There was no qualitative difference in the bacterial profile of the jejunal mucosa and contents of the diarrhoea patients from that of the control subjects, but there were significant quantitative differences for some bacterial categories. In the control as well as diarrhoea subjects, there was no qualitative difference in the bacterial profile of the jejunal mucosa from that of the fluid, but there were significant quantitative differences for some bacterial categories. The significance of the findings is discussed.


Effectiveness of single doses of Fenbendazole Hoe 88I against Ascaris, hookworm and Trichuris in man.

Fenbendazole (Hoe 881) 5-(phenylthio)-2-benzimidazolecarbaminicacidmethylester in doses of 1-0 g and 1-5 g per person were effective against Ascaris and gave substantial egg count reductions against hookworm (mainly Necator americanus). The 1-5 g dose gave good results against Trichuris. In a trial with a suspension of Hoe 881 with a high specific surface of 25 m2/g there was no advantage over tablets with a specific surface of approximately 8 m2/g. Two doses of 500 mg given with an interval of 24 hours were no more effective than one dose of 1-0 g. In a comparative trial using Hoe 881 1-5 g, Pyrantel 10 mg/kg and placebo respectively Hoe 881 showed equal potency against hookworms and Acsaris as Pyrantel and good effectiveness against Trichuris. Pyrantel showed only moderate activity against Trichuris in this trial.


Diagnosis of Wuchereria bancrofti filariasis by immunofluorescence using microfilariae as antigen.

A new technique for the diagnosis of wuchereriasis is described. Microfilariae treated with proteolytic enzyme were used as antigen for the immunofluorescent reaction. The specificity of the reaction is demonstrated in sera from persons who have a microfilariaemia, individuals with clinical symptoms of the disease but no microfilariaemia, those who have no clinical symptoms, but harbour other parasites, and in persons living in France, where the Wuchereria bancrofti filariasis is absent.


The passage of serum immunoglobulins through the gut of Sarcophaga falculata, Pand.

Rabbits were immunized with brain, muscle or haemolymph of adult Sarcophaga falculata, and groups of Sarcophaga were then fed on serum collected from the immune rabbits. Rabbit serum immunoglobulins on the tissues of the fed flies were demonstrated by the indirect fluorescent antibody method, using fluorescent goat-anti-rabbit IgG. The antibodies were specifically demonstrated in the tissues that had been used as immunizing antigen. It was also shown that antibodies unrelated to fly antigens pass through the fly gut and react with the specific antigens.


[Presence of salmonellae, E. coli and their homologous phages in the seawater].

Comparative experiments were carried out on samples of sea water at different degrees of natural pollution. The aim of such experiments was the quantitative estimation of coliforms and salmonellae and their respective phages. The results obtained show that it is thus possible to get better informations regarding the nature and degree of water pollution, than these obtained by the E. coli count alone.


[Urinary infections due to Serratia marcescens: clinico-statistical pictures of patients hospitalized in the S. Maria della Scala Hospital in Siena during 1971, 1972, and 1973].

The Authors have carried out a clinical-statistical research into cases of urinary tract infection by Serratia marcescens isolated in 42 of 2500 urine-cultures effected during the period 1971-1973 by patients hospitalized in "S. Maria della Scala" Hospital of Siena. The Authors point out the high incidence of isolation of Serratia marcescens in urological patients and show some control measures to prevent the diffusion of such infections in hospital.


Technique for the coronary snake graft operation.

The use of one end-to-side anastomosis with side-to-side technique for all additional vein-coronary anastomoses has given continually good results and has been used in 227 of 411 patients undergoing vein graft operations, including all multiple graftings done since April, 1972. The operative mortality was 4.6%. Arteriography by the end of the third postoperative month has been obtained in 98.4% of the 377 eligible patients. It showed that 98% of the 304 side-to-side anastomoses were patent, with 289 (95%) having unrestricted communication with the aorta. The proximal segment was widely patent in 193 (97%) of the 200 patients with snake grafts having postoperative arteriography. The distal end-to-side anastomosis was patent in 176 (88%) of these 200 patients. The average was 2.3 unrestricted grafts per patient. These results are better than the patency rates of 89 and 87% obtained previously with single and Y-grafts, respectively. Technical details have been worked out for construction of suture lines, choosing the correct length for segments, obtaining a reliable proximal segment, routing grafts to multiple coronary branches, and removing air from the grafts.


Management of tracheobronchial disruption secondary to nonpenetrating trauma.

The pathogenesis, pathology, clinical presentation, diagnosis and management of tracheo-bronchial injuries secondary to nonpenetrating thoracic trauma are discussed.


[The antigenic structure of vibrions studied by means of agglutination and fluorescent antibodies].

Cross immunofluorescent and serological studies were made of strains of Vibrio coli of different forms-a short, commashaped strain and other long, spiral-shaped and serpent-like strains isolated from swine. Some standard strains of Vibrio foetus were also included for comparison. An antigenic difference was established between vibrions of long and short forms, as well as the known difference between strains isolated from swine and those from cattle which can be established by means of immunofluorescent techniques. Combined studies using immunofluorescence and serological methods give the possibility for rapid group and species typing of different strains of vibrions.


[Preventive disopyramide in patients with ventricular arrhythmias detected by exercise].

Twenty patients with coronary heart disease subjected to exercise testing presented ventricular arrhythmias. In a "double blind" design, oral disopyramide was administered during 7 days, after which the test was repeated. In 16 patients disopyramide prevented the appearance of arrhythmia or decreased their severity. Basal heart rate increased. Significant toxic or colateral effects were not observed. In 6 cases, placebo also hindered exercise arrhythmias. It is suggested that disopyramide may be useful in the prevention of sudden death from ventricular arrhythmias.


[Carpentier's ring in mitral surgery. Surgical technic].

The technic used to insert Carpentier's ring in the mitral position, in 128 patients, is described.


[Isolated premature breast development in young girls. Results of the LH-RH test].

Thirty-six cases of premature thelarche in girls 9 months to 7 years old have been studied. In most cases, breast development began before 3 years and came to regression. Onset after 3 years was less common and led usually to breast persistance. Height was lightly but significantly advanced. Plasma levels of estrone, estradiol (in 21 cases) and gonadotropins (FSH and LH, in 12 cases) were not significantly increased. However, LH-RH test (in 12 cases) suggested prolongation and/or increase of the physiologic gonadotropic hyperactivity of normal female infants.


[Laryngo-pharyngeal paralysis. Complications during the course of myelomeningoceles].

Report of 5 cases in babies with myèlomeningocele and hydrocephalus stridor and troubles in swallowing appeared after a free interval. These facts were already reported in literature. They represent an impairment of cranial nerves (IX,X and XI). The lesion may be located at the level of the nerves themselves or at the level of the origin nucleus in the brain stem. The mechanism of the lesion is not well known. The role of intracranial hypertension and of Arnold-Chiari malformation seem to be prominent.


Potentiation by metyrosine of thioridazine effects in chronic schizophrenics. A long-term trial using double-blind crossover technique.

Four patients with chronic schizophrenia of stationary character were studied in order to titrate the lowest dose of thioridazine necessary for symptomatic control when the drug is given in combination with the inhibitor of catecholamine synthesis, metyrosine. The study showed 15% to 50% of the pretrial dose level of thioridazine hydrochloride was effective. In the present trial, the 779704 combination was maintained without any alterations in dosage for six months, and the therapeutic effect persisted unchanged. This treatment period was terminated by a double-blind crossover design, and the activity of metyrosine was corroborated in all cases. Plasma drug concentrations and cerebrospinal fluid amine metabolites were measured. The data indicate that schizophrenic symptoms can be profoundly influenced by changes in catecholamine synthesis. Catecholamine-carrying neurons thus seem to be fundamentally involved in those brain functions that are disturbed in schizophrenia. The clinical usefulness of metyrosine in combination with neuroleptic agents deserves more extensive investigation.


Methadyl acetate and methadone as maintenance treatments for heroin addicts. A veterans administration cooperative study.

This was a double-blind comparison of methadyl acetate and two dose levels of methadone hydrochloride in the maintenance of 430 street heroin addicts from 12 Veterans Administration hospitals. The starting sample consisted of 146 patients receiving low-dose methadone, 142 patients receiving methadyl acetate. Patients were first given 30 mg of both drugs, and doses were incremented by 10 mg/week until they stabilized at methadyl acetate, 80 mg three times a week, and methadone hydrochloride, 50 mg daily or 100 mg daily. Dosage was fixed for the balance of the 40-week treatment period. Safety was evaluated by clinical and laboratory observations conducted at frequent intervals throughout the study. Relative efficacy was evaluated by illicit drug use, program retention and attendance, and global staff judgments. It is concluded that methadyl acetate is as safe a drug as methadone and that it compares favorably with highdose methoadone in terms of efficacy. Both methyadyl acetate and high-dose methadone appear to be better maintenance regimens than low-dose methadone under the conditions of this study.


Hypertrophy and hyperplasia in the endocrine and exocrine pancreas of rats fed soybean trypsin inhibitor or repeatedly injected with pancreozymin.

Rats were 1) fed raw soybeans for 30 days, 2) given trypsin inhibitor as drinking water for 7 days, or 3) repeatedly injected with cholecystokinin-pancreozymin (CCK-PZ) for 7 days. After all these treatments the pancreas of the animals was markedly enlarged. Microscopic examination revealed, besides hypertrophy of acinar cells, increased mitotic figures in the acinar, centro-acinar, intercalated portion and excretory duct cells. The islets of Langerhans were found conspicuously enlarged due to mitotic proliferation of B cells. The endogenous CCK-PZ released by the intraluminal trypsin inhibitor and the exogenous CCK-PZ given by injections thus exerts not only secretagogous, but also trophic effects upon the endocrine and exocrine pancreas. The exocrine pancreas likely is affected also by the increased release of insulin from the B cells stimulated by CCK-PZ.


Comparison of a new antidepressive, lofepramine, with imipramine in a double-blind multicentre trial.

Lofepramine, an imipramine derivative, shows lower acute toxicity in animals when compared with desipramine and imipramine. Its anticholinergic effect is less pronounced than that of desipramine. In an open clinical trial lofepramine showed a marked antidepressive action. A double-blind multicenter trial of lofepramine v. imipramine, evaluated by means of the AMP system, showed a remarkable degree of concurrence with regards to the effects of those two products.


Early severe renal allograft rejection.

An early, severe form of renal allograft rejection, occuring after an initial day or more of good function and within the first week after transplantation, is an increasingly recognized phenomenon. This type of rejection occurred in 17 of 187 (9%) postmortem-donor renal transplants. It could only be reversed in four grafts, and two of these failed because of recurrent rejection within four months. No clinical observations were helpful in determining which cases were likely to respond to antirejection therapy. Of the 17 patients, four died. Because of the poor graft survival and the high mortality, attempts to treat early severe rejection may not be warranted.