Screening methods for covert bacteriuria in schoolgirls. Screening tests for bacteriuria based on two different principles were evaluated in1582 schoolgirls aged 5-11 years, and in 26 girls aged 3-16 years attending hospitalwith symptomatic urinary tract infection.  Tests for hypoglucosuria, performed by a semi-automated fluorometric method and with Uriglox strips on early-morning urine samples voided after overnight fasting, gave unacceptably high false-negative rates (16.7% and 20.8% respectively).  Oxoid and Uricult dipslides were immersed in fresh midstreamspecimens of urine obtained at school and read overnight incubation at 37 degrees C. Both gave comparable results, with low false-positive rates and no false-negative responses.  The higher cost of screening by dipslides was halved by using the "dipstream" technique, which also gave no false-negative results.  Its false-positive rate of 13.5% could be reduced to 1.8% by disregarding colony counts of 10-8 non-faecal organisms and over per litre, which appear unimportant in schoolchildren.  Bacteriuria was found in 2.3% of the schoolgirls; 39% of them had symptons, compared with 7.2% of the healthy girls, and 25% showed vesicoureteric reflux, which in 17% was associated with renalscarring.  Since the natural history of covert bacteriuria and its relationship withreflux and scarring remain undetermined further research is required.  The dipstreamtechnique offers a simple, reliable, and comparatively cheap screening method which could also be applied in general practice.


Prospective survey of availability of cadaveric kidneys for transplantation. A prospective study in Nottingham hospitals, serving 3/4 million population, identified 25 potential kidney donors in one year.  Seventeen later died in circumstances when kidney donation would have been possible.  Twelve kidneys were actually removedfor transplantation out of the possible 34.  The reasons for failure to donate kidneyswere either relatives' refusal or a failure of the doctors looking after those patientsto consider them as potential donors.  If all possible donors had their kidneys removed there would be sufficient available to approximately equal the numbers of patients likely to require renal transplatation.


Chronic renal failure in Nottingham and requirements for dialysis and transplantfacilities. A retrospective study of uraemic patients covering 12 months of 1970 and a prospective survey covering six months in 1973-4 is reported for a population of almost 3/4million.  The number of patients requiring regular dialysis treatment or transplantation or both is considered to be 45 per million of population under 65, 39 per million under 60, and 29 per million under 50 years of age.


Attempts to programme ovulation with exogenous oestrogens and LH-RH analogue. An attempt was made to programme ovulation in women on a predetermined day of the menstrual cycle by treatment used to induce ovulation in anovulatory sterility. At laparotomy for elective sterilization the ovaries were observed to assess the occurrence of ruptured follicles and ovulation. Histological analysis of ovaries and endometrium was performed, and ova were recovered from some women. Several regimens were tested but ovulation seldom occurred as planned. Clomiphene citrate, human chorionic gonadotrophin (HCG), synthetic luteinizing hormone releasing hormone (LH-RH), and ethinyloestradiol were ineffective. Human menopausal gonadotrophin followed by HCG was more effective, but multiple ovulations occurred. When one single injection of a potent long-acting LH-RH analogue was given on day 13 of the cycle to 10 women pretreated with ethinyloestradiol signs of recent ovulation were observed on day 15 in seven and on day 16 in two.


Histidine supplementation for treatment of anaemia of uraemia. The effects of supplemental histidine on the anaemia of 16 chronically uraemic patients and 26 patients undergoing maintenance dialysis were assessed. Patients were given either L-histidine 4 g/day or placebo for a mean of 17-5 weeks in a randomized double-blind controlled study. Haemoglobin and packed cell volume increased slightly and to a similar degree in the patients on dialysis receiving placebo and histidine, but this change was statistically significant only in those on placebo. Plasma histidine rose significantly in the histidine-treated patients undergoing dialysis and decreased in the uraemic patients receiving placebo. These results suggest that supplementary L-histidine in patients with uraemia or patients undergoing maintenance dialysis does not improve anaemia.


Effects of two types of dietary fibre on faecal steroid and lipid excretion. Fibre supplements from wheat bran and sugar cane residue (bagasse) were added to the normal diet of volunteers for 12-week periods in a controlled metabolic study. Stool weights and stool fat excretion increased on both dietary fibres. Bagasse increased the daily loss of acid steroids, but bran failed to affect bile acid excretion. Decreased transit time without alteration in faecal flora occurred with bagasse. The raised excretion of bile acids and fatty acids failed to lower the plasma cholesterol and triglycerides after 12 weeks. Thus different fibre sources with variable components have dissimilar metabolic effects.


Increased frequency of neonatal jaundice in a maternity hospital. The frequency of "significant" jaundice of the newborn at this hospital increased from 8-1% of all live births in 1971 to 12-1% in 1972 and 15-4% in 1973. This coincided with an increased use of oxytocic agents and epidural anaesthetics in labour, and a change in the artificial feed given to normal infants. A retrospective study of jaundiced infants born in 1972 failed to explain the increase in jaundice. Though the use of oxytocic agents was not the direct cause, since their use results in the delivery of more infants before 40 weeks of gestation it may be a contributory factor. The use of epidural anaesthetics was sastically related to the development of jaundice but the nature of the association was not clear. Mothers of infants who became jaundiced has a significantly higher frequency of poor past obstetric histories, but once again the association was not clear. The change in artificial feeds was excluded as a possible cause.


Emergence of group B streptococci in obstetric and perinatal infections. A retrospective study of obstetric and perinatal illness due to group B streptococci during 1972-4 based on bacteriological referrals from Aberdeen Maternity Hospital and Special Nursery disclosed (1) a wide spectrum of maternal morbidity, particularly associated with amniotomy and a prolonged rupture-delivery interval, and (2) the emergence of the group B streptococcus as a major cause of serious neonatal infection in infants of low birth weight, often in the absence of maternal pyrexia. The group B isolates appeared to show a previously undocumented increased resistance to the aminoglycosides gentamicin and kanamycin. A prospective study of 369 random deliveries in Aberdeen Maternity Hospital showed a group B vaginal carriage rate of 49/1000; a neonatal colonization rate of 19/1000; maternal and neonatal morbidity rates of 16 and 2-7/1000, respectively; and an overall neonatal mortality of 1/1000 live births.


Prognosis for infants with idiopathic respiratory distress syndrome. Infants with the idiopathic respiratory distress syndrome admitted to the intensive care unit during January 1972 to September 1974 were reviewed. The overall mortality rate for infants whose birth weight was 1000 g or more was under 10%, and for those who established spontaneous respiration after birth it was less than 5%. The hyperoxia test was not a useful guide to prognosis. It was possible on the basis of the infants' ability to establish spontaneous ventilation after birth to divide them into two groups. In those who established adequate ventilation the mortality rate was 4-5%; in those who did not it was 57%. This test should be generally applied, since not only does it give an immediate guide to the severity of the disease, which is better than that provided by birth weight, gestational age, or the hyperoxia test, but it may be applied to infants born in and outside a hospital providing neonatal intensive care. Improvement in the outlook for infants with a bad prognosis will be achieved only by improvements in perinatal care designed to minimize severe intrapartum asphyxia in infants of low birth weight.


Evidence of gentamicin nephrotoxicity in patients with renal allografts. Renal damage was assessed by measuring urinary enzyme excretion in 180 patients with renal allografts. Thirty-six of these patients were studied during 53 courses of treatment with antimicrobial agents which was the only antimicrobial agent which was associated with an increase in urinary enzyme activity. There was usually also evidence of reduced renal function. Renal morphological changes similar to those produced by gentamicin in rats were observed in human allograft biopsy specimens obtained during gentamicin treatment.


Cobalt iontophoresis techniques for tracing afferent and efferent connections in the vertebrate CNS. In recent years several dye and cobalt iontophoresis techniques have been successfully used by invertebrate neurophysiologists for the localization of neuron somata and their processes. The cobalt iontophoresis technique has now been extended for use in the tracing of nerve fiber pathways and the localization of neuron somata in vertebrates. The brain and spinal cord of an animal are removed following perfusion with saline, and placed in a dish of cold saline. A suction electrode, filled with 300 mM cobalt chloride, is then placed over the cut end of the nerve trunk. Cobalt ions are then iontophoresed (by means of a voltage divider) within the nerve fibers, along their course. Following iontophoresis, the brain is bathed in an ammonium sulfide solution to precipitate the cobalt as black cobalt sulfide. The brain is then processed for histological procedures. A wide variety of vertebrates has been used, including amphibians, reptiles, aves and mammals, with uniform success. The cobalt iontophoresis technique presently in use has a wide range of applicability for neuroanatomical studies.


The role of intubation macro-dacryocystography in management of problems of the lacrimal system. The Lloyd technique of dacryocystography has been described incorporating intubation, distension, macrographic and subtraction techniques. Excellent anatomic localization is possible. With this method, logical surgery may be planned.


Role of lysosomal constituents of neutrophils in corneal graft reaction. Band 2 protein exists in a firmly bound state in lysosomes, and is released when the cells concerned are specifically stimulated. The necessary stimulus can originate from different kinds of immunogenic interactions. The objective of this study was to determine whether during corneal graft reaction Band 2 protein could be detected in the host's cornea and aqueous humour. Band 2 protein was detected in the reacting host corneas (8 out of 23 eyes) and the aqueous humours (2 out of 23 eyes), mainly during the second and third postoperative weeks when parallel histological studies showed an accumulation of neutrophils in the graft bed. The severity of graft reaction appeared to run parallel to the amount of free Band 2 protein in the host cornea. After this period, in spite of the presence of a large number of neutrophils in the reacting host cornea, Band 2 protein was hardly detectable. This study indicates that the necessary stimulus for the secretion of Band 2 protein from rabbit neutrophils is present in the early stages of corneal xenograft reaction. The presence of the protein in the host cornea may be a factor in the development of the vascular response associated with the corneal graft reaction.


Migration of a wooden foreign body into the lens: report of a case. A penetrating ocular injury caused by a tree branch resulted in a small corneoscleral laceration that healed after primary repair. Post-traumatic inflammation persisted and a vitreous mass developed. The mass finally protruded through the pupil and touched the posterior cornea. Histologic examination of the enucleated eye showed that the lens had been replaced by a wooden foreign body that filled the pupillary space and was surrounded by lens capsule. No intact lens fibers remained.


A somatomedin assay using normal rabbit cartilage in clinical studies. Somatomedin (SM) is a growth hormone (GH) dependent biological growth factor in serum. A SM assay, using mechanically sliced discs from young normal rabbit costal cartilage was developed and evaluated. This assay is as sensitive and precise, while much less laborious and costly, than the hypophysectomized rat cartilage SM assay. The elevated serum SM levels in patients with acromegaly returned to normal in two patients who were cured, and remained elevated in four incompletely treated patients. The low serum SM levels in five GH deficient patients were increased to normal after treatment with human GH. SM levels were normal in 10 patients with normal GH levels and short stature due to various causes. SM levels in serum were very low in patients with chronic renal insufficiency; the mean SM level increased significantly after renal transplantation, however, it increased only minimally after hemodialysis. SM levels were subnormal in 14 patients with sever chronic liver disease. One patient with severe acute liver disease had low serum SM levels which increased after clinical recovery. These results further suggest that the liver produces SM, while the relationship of the kidney and SM is not clear.


Effect of nitrogen source on carbon metabolism by Azotobacter vinelandii OP grown in chemostat and batch culture. Azotobacter vinelandii growing under nitrogen-fixing conditions has higher specific activities of isocitric and malic dehydrogenase than do cells growing on nitrate or ammonia. Results show that the source of nitrogen has an effect on carbon metabolism.


A new method for the isolation of methionyl transfer RNA synthetase mutants from Escherichia coli. Six methionine auxotrophs were isolated from an E. coli K-12 strain which required up to 100 times as much methionine for growth as a conventional auxotroph. In these mutants the methionyl-tRNA synthetase had an increased Km for methionine. The Km value for the mutants ranged from 0.48 to 1.63 mM, compared to 0.078 mM for the wild type. The Km (methionine) for S-adenosyl methionine synthetase was not altered.


Immunofluorescence of peritoneal phagocytes after infection of mice with L-cell-attenuated Chlamydia psittaci 6BC. Large amounts of particulate antigen of Chlamydia psittaci 6BC attenuated by growth in L cells were phagocytized by peritoneal mononuclear phagocytes during the 1st h after intraperitoneal inoculation. The phagocytes subsequently destroyed the immunofluorescent (IF) properties of the chlamydial antigens. It is suggested that the early damage of phagocytes by lysosomal enzymes activation induced by chlamydiae contributed to the relatively early disappearance of IF antigens from the peritoneal fluids.


A new method of obtaining zygotes in Saccharomyces cerevisiae. Experiments leading to a simple method of mass zygote formation in Saccharomyces cerevisiae are described. This method ordinarily requires only about 3 h of incubation, and consistently yielded 55-65% zygotes in seven different crosses among six different strains. Matings involving one strain required about 4 h of incubation but otherwise the results were comparable.


Nitrate utilization and growth in biotin-deficient Aspergillus nidulans. A marked increase in the cellular synthesis accompanied by a decrease in the total fatty acid content was observed when Aspergillus nidulans was grown on NH4NO3 as a sole nitrogen source, in the medium containing avidin. Because of the increased uptake of NH4(plus), the level of NH4(plus), was lowered in the medium; as a result there is early uptake and assimilation of nitrate by a biotin-deficient culture as compared with the normal culture of A. nidulans. At about 17mM concentration, NH4(plus) repressed the activity of nitrate reductase. The regulation of NO3(minus) uptake and its assimilation with respect to the growth of A. nidulans have been discussed.


[Physical and chemical properties of tryptophenases of five species of Enterobacteriaceae]. The molecular weight, sedimentation coefficient, and amino acids composition were determined on five tryptophanases (TPases) from Escherichia coli B and E. aurescens, Shigella alkalescens, and Proteus vulgaris and P. morganii. These TPases have identical sedimentation profile and coefficient (9.6 S), and the same molecular weight (220 000). Each enzyme is constituted of four identical subunits having a molecular weight of 55 000. The amino acids composition of these TPases is very similar, with the exception of P. morganii and P. vulgaris TPases which present significative variations in basic amino acids and tryptophan content. The species differentiation of the coli group cannot be made on their TPase characteristics only, contrary to P. morganii and P. vulgaris which can be differentiated between them and from the coli group.


[Differentiation of tryptophanases of five species of Enterobacteriaceae by sulfhydryl groups]. We have studied the sulfhydryl groups (-SH) on the tryptophanases (TPases) from Escherichia coli B. and E. aurescens, Shigella alkalescens, and Proteus vulgaris and P. morganii. The coli group and the P. morganii apo TPases have 20 -SH groups per mole of enzyme, where as P. vulgaris apoTPase has 16. In coli group TPases, there are 16 -SH groups on the mole surface and they are all implicated in the activity and the enzyme-substrate bond. Proteus morganii TPase has 8 surface -SH groups, 4 of which are implicated in the activity; the remaining 12 -SH groups are located inside the mole and take part in the activity and the enzyme-substrate bond. Proteus vulgaris TPase has 4 surface -SH groups which are constructive of the enzyme structure, whereas the 12 remaining -SH groups are located inside the mole and take part in the activity and the enzyme-substrate bond. It is concluded that Proteus TPases are molecules which have inverted quaternary structure in comparison to those of the coli group. The studied TPases have four subunits, each of them is constituted of one polypeptidic chain having a molecular weight of 55,000.


Aerobic adaptation in yeast. I. Changes in metabolic intermediates during a step-down anaerobic-aerobic transfer. Early investigation into the mechanism of mitochondriogenesis in the facultative anaerobe Saccharomyces cerevisiae used anaerobic-aerobic transitions as model systems to study the in vivo assembly of these oxidative organelles. This methodology has become entrenched in the early literature and as a result a definitive study has been undertaken utilizing this protocol (high hexose, complete medium under anaerobic growth transferred to low hexose, minimal medium with aerobic environment) to study the altered distribution of various metabolites during these transitions. Measurement of all the glycolytic, and some tricarboxylic acid intermediates during such a transition has elucidated the following points. On a qualitative basis, the metabolic controls prevalent in these growing cultures are similar to those identified in yeast under less physiological conditions. Also, the effect of anaerobic catabolism, which preconditions enzyme and pool levels in the yeast, is of paramount importance in determining the events subsequent to oxygen challenge. However, this experimental approach has severe limitations and does not lend itself to a clear-cut delineation of the events that occur during the process of mitochondriogenesis.


Aerobic adaptation in yeast. III. Changes in metabolic intermediates during anaerobic-aerobic transitions in exponentially growing cultures. The changes in mechanism of control and in the mode of metabolism which yeast cells undergo when an anaerobic-aerobic transition is imposed on them has received much attention. One experimental approach to this type of investigation has been a step-down transition. The data from our experiments (cf. papers I and II of this series) has shown that this model is too complex to arrive at meaningful interpretation. We therefore repeated these measurements of glycolytic and citric acid cycle metabolites in cells growing on either glucose or galactose media and exposed to exponential N2 yields 02 transitions. This type of experiment is designed to examine directly the effect of oxygen challenge. Interpretation of this new data shows that the major metabolic control operating in the two hexose cultures are different and suggests that adenine nucleotide controls glucose cells whereas galactose cell metabolism is controlled by the NAD/NADH balance. This concept is discussed.


Impairment of reactivity to lepromin by mycobacterial antigens related to, or identical with, Mycobacterium leprae. Three hundred and twenty young children were injected with Bacillus Calmette-Guerin (BCG) saline, or with one of the mycobacterial cytoplasmic antigens related with Mycobacterium leprae. At an appropriate time thereafter they were tested for dermal hypersensitivity to the antigens and for reactions to lepromin. Whereas all the antigens induced cell-mediated immunity, the incidence and intensity of late response to lepromin were significantly reduced in children preinjected with the cytoplasmic mycobacterial antigens, as contrasted with increased lepromin reactivity in the BCG group and with the findings in saline-injected children.


Preparation of a dane core (hepatitis B) antigen from human plasma. Hepatitis B surface antigen (HBsAg) positive plasma, obtained from blood donors, was used to prepare an antigen (HBcAg) from the inner core of the Dane particle, the larger of the two spherical particles found in the blood in hepatitis B infection. The antigen was prepared by a series of centrifugation procedures on caesium chloride and sucrose gradients. Dane particle-rich fractions obtained from these gradients and concentrated by centrifugation were treated with Tween 80 to remove the outer coats from the particles. The remaining Dane particle cores were recovered by velocity sedimentation on a sucrose gradient. Preparations containing the Dane cores were used as antigens in the immune electron microscopy and complement fixation tests to demonstrate the specificity of HBcAg and lack of fross relationship with HBsAg. HBcAg will be used for the study of hepatitis B infections in man.


Observations on the distribution and ecology of Clostridium botulinum type E in Alaska. Environmental samples collected along the coastline and from the interior of Alaska were examined for the presence of Clostridium botulinum. Clostridium botulinum type E was detected in soils from 5 of 12 beaches; in 7 of 115 non-coastal soil samples; in sediments from six of eight locales; in gills of salmon from two fishing areas; and in the feces of 1 of 44 colonic samples from marine mammals. The basic biochemical characteristics of the isolates were determined. Tube tests for demonstrating gelatin liquefaction proved insensitive with these strains, whereas a plate test detected gelatinase in all isolates. The presence of multiple nidi and the continual discharge of organic materials into the environment may contribute to the perpetuation of botulinum spores by which foods prepared form marine animals become contaminated. An emphasis should be placed upon the need for measures to reduce environmental contamination, to reduce contamination during food preparation, and to alert continually the population of the hazard wherever botulism is endemic.


Multiple-variant design for the enrichment of photosynthetic bacterial populations. A design for the simultaneous variation of acetate, sulfide, and sulfate concentrations in 11 related media is described.  Selectivity of these media by a direct enumeration technique in solid culture was compared with that for enrichment in liquid culture.  Variation of nutritional parameters resulted in the selection of Rhodospirillaceae at initial enrichment concentrations of 0.1 g or less of Na2S-9 H2O per litre and Chromatiaceae at 0.1 to 1.0 g of g of Na2S-9 H2O per litre.  The survival of sulfate-reducing and coliform bacteria indicated interdependency of photosynthetic populations with the former and  competition with the latter.  Photosynthetic bacteria selectively cultivated in liquid enrichment were tentatively identified as Rhodopseudomonas capsulata, Rhodopseudomonas speroides.  Chromatium warmingii, Chromatium okenii, Thiospirillum, and Rhabdomonas.


Comparison of several methods for the isolation of salmonellae from egg products. Lactose broth and buffered peptone water proved to be equally effective as preenrichment media in the isolation of salmonellae from egg products.  With tetrathionate bile brilliant green broth, incubated at 43 degrees C as enrichment medium, more samples were found to be positive than with selenite cystine broth incubated at 37 degrees C or 43 degreesC and selenite brilliant green broth incubated at 37 degrees C.  As selective agar, brilliant green agar proved to be more reliable than bismuth sulfite agar.  These results indicate that the ISO method for the isolation of salmonellae from meat and meat products can be successfully used for the examination of egg products.


Chromosomal location of mutations affecting the regualtion of biotin synthesis in Escherichia coli. The chromosomal locations of biotin regulatory mutations, birA, bioR, and dhbB, of Escherichia coli are determined by transduction using phage P1.  All mutant genes are mapped between bfe and supM.


Cell surface protein of Salmonella typhimurium. Lactoperoxidase-catalyzed radioiodination with Na125I was performed both on intact Salmonella typhimurium 1195 and on ghost membrane isolated from the same bacterial strain. Ghost membrane was also prepared from radioiodinated whole bacteria. The labelled proteins from both these ghost membrane preparations were compared by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate to identify the cell surface proteinmfrom the results obtained it was concluded that one major protein with an apparent molecular weight of 1200-1300 was exposed on the exterior surface of the ghost membrane.


Kinetics of yeast growth:inhibition-threshold substrate concentrations. Two Candida species and a Saccharomyces were grown on ethyl alcohol, acetic acid, ethyl acetate, and I-butanol, and their growth rates at a series of concentrations of each substrate are reported. Substrate concentrations higher than a characteristic threshold substrate concentration Stheta inhibited growth in accordance with a new relationship: mu = mumaxS/(k+S) - i(S - Stheta, where i is an inhibition constant and the other symbols have their usual meanings. Complete inhibition, that is, no growth, takes place when S = Si, the total inhibition concentration. Values of Stheta, Si, and i were calculated for the examples studied. Also discussed are the observed lag periods and also the lowered yields at high substrate concentrations.


Semiology of Tremors.

Semiology of Tremors. Since the description by Galen in the 2nd Century, A.D., clinical neurology has acknowledged the existence of two types of tremor: that which occurs at rest and that occuring during the execution of movement. With the help of refined methods of analysis, E.M.G. and cinephotography, the authors have carried out a detailed clinical assessment in more than 400 patients. The basic criterion used to define a tremor was the classical definition of Dejerine: "An involuntary, rhythmical and symmetrical movement about an axis of equilibrium." As a result of this study, the conclusion has been reached that there are two types of tremor: postural tremor and tremor of attitude. Both are present while the limb remains immobile, whether by wilful design or when at rest in a position of posture and subject only to the action of gravity. During voluntary movement, tremor is not present. Irregular, asymmetrical and non-rhythmic oscillations may appear however - as in so-called intention tremor, of cerebellar origin - but this abnormal movement can hardly be called a real tremor. It is merely a manifestation of ataxia. As a consequence of this study, it is suggested that further understanding of the basic mechanism of tremor can be reached by the investigation of the central neural structures which are involved in the physiology of posture and attitude.


Post-traumatic pulmonary insufficiency following chest trauma: identification and prophylaxis. Post-traumatic pulmonary insufficiency is a syndrome characterized by tachypnea, increasing respiratory effort, progressive pulmonary infiltrates and relentless progressive hypoxemia. Prophylaxis of this syndrome currently comprises adequate treatment and depends upon its early recognition by frequent monitoring of blood gases, chest radiograph, and determination of values of circulatory variables. Once the syndrome is recognized in its early stages, artificial ventilation, with the possible addition of positive end-expiratory pressure, meticulous fluid therapy properly monitored, and prevention of infection constitute the hallmark of treatment.


Complications of closure of loop colostomy. Among 71 patients undergoing loop colostomy closure, one complication or more developed after operation in 35. Most of the complications were not serious, but there were two anastomotic leaks and two patients died. Some of the complications may be prevented by avoiding the use of drains and by packing the skin and subcutaneous tissues open with Vaseline gauze. There does not appear to be any advantage in using antibiotics in preoperative bowel preparation. A one-layer intraperitoneal colostomy closure can be done safely but is frequently associated with minor complications.


Bacterial peritonitis and the bursting strength of intestinal anastomoses. In order to study the bursting strength of intestinal anastomoses, resection of a wedge of ileum and creation of an anastomosis were performed, and peritonitis was induced in five groups of rats. Peritonitis was induced by intraperitoneal injection of bacterial suspensions of Escherichia coli, Pseudomonas  aeruginosa, Staphylococcus aureus and Clostridium welchii, and the exteriorized ileal loop in each rat was regularly inspected for peritoneal exudation, adhesions, hyperemia, obstruction, leakage and bursting strength. All bowel anastomoses performed in the presence of peritonitis were weaker than those done in a sterile field (control group) and the type of organism influenced the strength of the anastomosis and the histopathologic changes; in this study the weakest anastomoses were associated with E. coli infection.


Computer tomography of the brain in Hamilton. Computer tomography, a new noninvasive, rapid and easily tolerated technique of brain examination, has been evaluated by analysis of 1000 examinations.  It is much more sensitive than conventional radiographic techniques and can resolve soft-tissue structures that differ only slightly in density.  It also provides direct visualization of the ventricular system.  The range of clinical applications is wide; it is especially useful in differentiating intracerebral hemorrhage from infarction, and in demonstrating many brain tumours, particularly supratentorial, though enhancement with a water-soluble contrast medium injected intravenously is often necessary.


Determination of 5-fluorouracil (NSC-19893) plasma levels in rats and man by isotope dilution-mass fragmentography. A highly sensitive and specific rapid assay for 5-fluorouracil (5-FU) in plasma samples at concentrations as low as 1 ng/ml was developed using mass fragmentography. Highly enriched C14-5-FU was empolyed as an internal standard. A two-compartmental open model for the disposition of free 5-FU in plasma is proposed. The beta-phase of 5-FU plasma elimination describes the pool size of anabolic metabolites, assuming this model is correct. Injections of 5-fu at 15, 40, and 90 mg/kg in rats resulted in an alpha-phase of elimination from plasma with a half-life of 10-18 minutes. The beta-phase could only be measured after the injection of 90 mg/kg of 5-FU and amounted to about 20 hours in two rats. Higher doses resulted in an unproportional increase in 5-FU plasma concentrations in the beta-phase, thus establishing nonlinear kinetics, presumably of the degradative metabolism. Plasma concentrations of 5-FU in man were measured after oral and intravenous administration of 15 mg/kg of 5-FU. Plasma elimination half-lives after intravenous doses were 12 minutes and dropped below measurable levels 2 hours after administration in three patients. After oral administration, peak plasma levels of 5-FU varied between 0.8 and 60 mug/ml of 5-FU in three patients after 10 minutes to 2 hours. Two of these patients showed rapid absorption and a measurable beta-phase of 5-FU plasma elimination possibly indicating a larger anabolic pool size of 5-FU-derived nucleosides and nucleotides when compared to patients receiving intravenous doses. This study may provide a pharmacokinetic rationale to monitor patients receiving 5-FU treatment.


Clinical trials with 1-acetyl-2-picolinoylhydrazine (NSC-68626) in children. Thirty-seven children with various malignant neoplasms were treated with 1-acetyl-2-picolinoylhydrazine. Complete regressions were documented in one child with embryonal rhabdomyosarcoma, in one child with generalized histiocytosis-X, and in one child with Hodgkin's disease. One patient had renal failure while receiving the drug but no conclusive cause and effect relationship could be established. Toxic effects otherwise were mild and consisted primarily of nausea and vomiting.


Adriamycin (NSC-123127) in the treatment of alkylator-resistant multiple myeloma: a pilot study. Adriamycin was given in a dose of 25-45 mg/m2 of body surface area to nine patients with multiple myeloma who had failed to respond to intermittent therapy with melphalan and prednisone. Three patients had evidence of clinical remission and in two of them there was a 60% decrease in total body myeloma cell number. However, remissions were of short duration (3 months in two patients and over 10 months in another patient) and bone marrow suppression was moderately severe. Adriamycin may prove more useful in myeloma therapy when combined with melphalan or cyclophosphamide during the initial attempt at remission induction.


Phase I. evaluation of cyclocytidine (NSC-145668). Cyclocytidine is a repository form of cytosine arabinoside and has a prolonged plasma half-life (8 hours) compared to cytosine arabinoside (12 minutes). A phase I trail was undertaken to establish the maximum tolerated dose. Nineteen patients were entered into the study (ten children, nine adults) and the dose which achieved consistent myelosuppression was established in five escalation increments as 600 mg/m for 10 days. This dose is consistent with previously reported data on the basic pharmacology of cyclocytidine and with optimum dose data in aminal tumor systems. Limiting toxicity, however, was related to the induction of postural hypotension which is not dose related. Recommendation to proceed with phase II studies of cyclocytidine must await clarification of the mechanism and prevention of the postural hypotension.


Acute monocytic leukemia in children and its response to vinblastine (NSC-49842). Seventeen children with acute monocytic leukemia were treated with (a) vinblatine (with or without prednisone), 0.2 mg/kg of body weight twice a week (13 patients); (b) 6-mercaptopurine plus prednisone patient). Four patients died within the 1st week, before having an adequate chemotherapeutic trial, and a fifth patient died of spesis at 12 days. Five patients achieved complete remissions and two achieved in this study was 41%. For the 13 patients who survived more than 1 week, the remission rate was 53.8%. Remission occurred with vinblastine inall but one patient. Of the ten patients who recieved more than one dose of vinblastine, 60% achieved a remission, indicating that vinblastine is an active agent in this rare form of leukemia.


Evaluation of daunorubicin (NSC-82151) and methotrexate (NSC-740) in combination as a remission maintenance regimen in the treatment of acute leukemia. The addition of a single monthy dose of daunorubicin (25 mg/m given intravenously) to the maximum tolerated dose of methotrexate (25 mg/m/dose given orally twice weekly) was evaluated as a maintenance regimen in 0 children with acute lymphoblastic leukemia. Seven patients who were nonevaluable were excluded from the study; 31 patients received methotrexate alone and 32 patients received a combination of methotrezate and daunorubicin. There was no significant difference between the distribution of remission times for the two maintenance  regimens (medians of 147 and 162 days, respectively). For patients with only one previous remission, the median length of remission in this study was significantly shorter than that of the original remission time. Despite the known myelosuppressive effects of both agents, daunorubicin did not cause additional toxicity nor did it interfere with the scheduled methotrexate therapy. Although the  addition of daunorubicin to methotrexate does not appear to be beneficial in the treatment of acute leukemia, this combination could be evaluated in other cancers in which both agents are known to be effective.


Factors influencing augmentation and/or acceleration of lymphoreticular tumors in mice by benzo(a)pyrene treatment. The response of lymphoreticular tissues to a single i.p. injection of benzo(a)pyrene was studied in the first generation of C57BL/6J X C3HeB/FeJ F1 and C3HeB/FeJ X A/J F1 mice. Groups of 1-, 15-, and 42-day-old animals of both sexes received 75 or 150 mug of the carcinogen per g body weight. After a period of approximately 90 weeks, a high incidence (up to 43%) of reticulum cell sarcomas was observed in C57BL/6J X C3HeB/FeJ F1 mice treated with benzo(a)pyrene at 40 days of age. Animals treated with carcinogen at younger ages had a lower incidence of reticulum cell sarcomas. These sarcomas showed marked cellular pleomorphism and were classified into histiocytic, epitheloid-nodular, reticulocytic, and fibrocytic forms according to the predominant cell type. Lymphomas of thymic and extrathymic lymphoid origin and leukemia of granulocytic type were seen in a descending order of frequency. Control animals of either strain that were killed at 90 weeks of age were basically free of lymphoreticular tumors, while those kept under observation up to 170 weeks developed these tumors in 24% (C57BL X C3H F1) and 10% (C3H X A/J F1), respectively. Studies revealed that the augmentation and/or acceleration of development of the lymphoreticular neoplasms and specifically reticulum cell sarcomas by benzo(a)pyrene was dependent upon the strain and sex of mice used and the age at which the animals were exposed to carcinogen.


Hepatic arterial infusion for liver metastases from colon cancer: comparison of mitomycin C(NSC-26980) and 5-fluorouracil (NSC-19893). This study compares the effectiveness of hepatic arterial infusion of mitomycin C with that of 5-fluorouracil in the management of carcinoma of the colon metastatic to the liver. A higher tumor response rate was obtained with 5-FU (ten of 12 patients) than with mitomycin C (six of 13 patients). The patients treated with mitomycin C had a median survival time of 9.5 months compared to 12 months for those receiving 5-FU, but this survival is not much different from that of the untreated historical controls. Femoral artery thrombosis requiring surgical thrombectomy developed in five of the 30 catheterized patients.


Adriamycin (NSC-123127) therapy for advanced gastrointestinal cancer. Sixty-nine patients with advanced gastrointestinal carcinomas were given adriamycin intravenously at a dose level of 40-75 mg/m once every 3 weeks. Toxic effects included nausea, vomiting, diarrhea, stomatitis, alopecia, leukopenia, thrombocytopenia, and minor ECG changes. There was a slight trend toward move severe leukopenia in patients with markedly abnormal liver function test (serum glutamic oxaloacteic transaminase and alkaline phosphatase). Of the 57 pateints with colorectal cancer treated with adriamycin, four (7%) showed partial objective responses. In a controlled comparison of adriamycin versus 5-fluorouracil (5-FU) in patients with previously untreated large bowel carcinoma, three of 23 patients (13%) receiving adriamycin showed partial objective responses as compared with six of 25 patients (24%) receiving 5-FU. The median duration of response with adriamycin was 3 months com pared to over 6 months with 5-FU. Four of eight patients with gastric carcinoma showed partial objective responses. No responses were noted in a small number of patients with pancreatic and gallbladder carcinomas. Adriamycin would not seem to have any role in the treatment of advanced colorectal carcinoma. Our results, however, would justify further evaluation of this agent in gastric carcinoma.


Adenocarcinoma of the pancreas in azaserine-treated rats. Development of a model of carcinoma of the pancreas in rats was approached by attempting to identify chemicals that (a) behave as mutagens and (b) localize in the pancreas following systemic administration; and then to study the effects of long-term administration. Azaserine was selected because it behaves as a direct-acting mutagen in two bacterial test systems and because tissue distribution studies showed concentration especially in kidney and pancreas. Groups of rats have been given i.p. injections once or twice weekly for 6 months, and rats have been autopsied after 6 to 18 months. During the first year pancreases developed (a) nodules of atypical exocrine cells which seem to represent hyperplastic foci and (b) encapsulated adenomas. After 1 year most pancreases from treated rats are diffusely abnormal and contain many hyperplastic nodules and adenomas, while more than one-quarter have had pancreatic adenocarcimona. Metastases have been observed in lymph nodes, liver, and lung. No carcinomas or adenomas have been observed in control rats. No other organ shows as high an incidence of involvement as pancreas, but renal neoplasms were frequent. Studies with another chemical O-(N-methyl-N-nitroso-beta-alanyl)-L-serine, are at an earlier stage. The tissue distribution of radioactivity following injection of a 14C-labeled sample is similar to that of azaserine; however, this compound is not a direct-acting bacterial mutagen. Rats treated for 6 months twice weekly i.p. have a higher incidence of nodules of atypical acinar cells than did controls, although the number of nodules per rat is few. No adenomas or carcinomas have been found during 13 months of the study. We conclude that azaserine is a carcinogen in rats and causes major abnormalities of growth and differentiation of the exocrine pancreas, including adenocarcinoma in some rats. O-(N-Methyl-N-mitroso-beta-alanyl)-L-serine had less effect than azaserine on pancreatic growth and differentiation.


Factors affecting metabolism and mutagenicity of dimethylnitrosamine and diethylnitrosamine. For exploration of the factors affecting dimethylnitrosamine (DMN) mutagenicity, for gathering of information on the metabolism of DMN, a frequently used and relatively well-understood carcinogen, and for explanation of metabolic variations in DMN carcinogenicity, parallel in vitro assays of the microsomal activation of  DMN to a mutagen and of DMN demethylation were performed. Salmonella typhimurium G46 reversions to histidine independence increase linearly with time of incubation for 30 min. At low concentrations of microsomal protein, increases in protein yield a more than proportional increase in mutations. Increasing DMN concentration saturates the enzyme, yielding less demethylation and fewer mutations proportionately. Mutagenesis is completely inhibited by 1 mM 2-diethyl-aminoethyl-2,2-diphenylvalerate. When both DMN and microsomal protein are varied at high concentrations, there is a simple linear relationship between mutagenicity and DMN demethylase activity. Thus DMN demethylase activity may be the primary controlling factor in the metabolism of DMN to a mutagen, and probably to a carcinogen; other simultaneous pathways of DMN metabolism proportional to demethylation have not been ruled out. Induction with both phenobarbital and 3-methylcholanthrene (3-MC) increased rat and mouse liver DMN demethylase activity. Mouse liver microsomes from the C57BL/6 strain demethylate DMN at a markedly lower rate than do microsomes from the C3H strain, but after 3-MC induction the relationship is reversed. Strain differences in activation of DMN were not found in the activation of diethylnitrosamine to a mutagen. Hepatic dealkylation of DMN and diethylnitrosamine to active mutagenic metabolites is increased in both rats and mice by both 3-MC and phenobarbital induction, which is in contrast to the findings of others that 3-MC and phenobarbital induction, which is in contrast to the findings of others that 3-MC decreases the incidence of DMN-induced hepatic tumors in rats, and phenobarbital decreases the incidence of diethylnitrosamine-induced hepatic tumors in mice.


Intensive cyclophosphamide (NSC-26271) therapy for solid tumors. Cyclophospamide was given in two dose schedules to 25 patients with a variety of nonlymphoid solid tumors. Eleven patients were given 18 courses of cyclophosphamide at a total dose of 60 mg/kg. Sixteen  patients received 26 courses at a total dose of 100 mg/kg. Two patients were treated with both regimens. Partial responses were achieved in two patients treated with 60-mg/kg dose of cyclophosphamide. One of these patients had osteogenic sarcoma and the other had renal carcinoma. The higher dose also produced two partial responses, one in a patient with anaplastic carcinom a of the lung and the other in a patient with anaplastic carcinoma of the lung and the other in a patient with embryonal testicular carcinoma. Mean leukocyte counts fell to a nadir of 1400 cells/mm after 60 mg/kg while they dropped to below 1000 cells/mm for 5 days after 100 mg/kg of cyclophosphamide. Mean platelet counts remained above 150,000 platelets/mm after both cyclophosphamide schedules. In fective complications were documented aftter three of the 18 courses at 60 mg/kg and after ten of the 26 courses at 100 mg5kg. In the latter group, there were three episodes of bacteremia, including one death from pseudomonas sepsis. Nonhematologic toxicity noted with the 100-mg/kg dose of cyclophosphamide included rare instances of electrocardiogram changes and serum enzyme alterations compatible with myocardial toxicity. The intensive cyclophosphamide therapy did not appear to result in an increased antitumor response in malignancies usually considered to be refractory to alkylating agents.


Metabolism of cigarette smoke condensates by human and rat homogenates to form mutagens detectable by Salmonella typhimurium TA1538. Nineteen fractions of whole condensate of smoke from the University of Kentucky Reference Cigarette IRI were tested for mutagenicity in vitro using a bacterial indicator system. As little as 25 mug of the active fractions were mutagenic toward histidine-requiring Salmonella typhimurium TA1538, if the condensates were incubated in the presence of rat or human liver homogenates of lung were relatively inactive. Homogenates from livers of rats that had been treated with 3-methylcholanthrene converted condensates to mutagens more efficiently than did liver homogenates from man or from normal or phenobarbital-treated rats. Use of homogenates from animals treated with 3-methylcholanthrene gave much more reproducible results in smoke fraction assays because larger numbers of revertants were obtained, and dose-response curves were linear over the range 25 to 250 mug condensate. The linear dose-response curves permitted quantitative comparison of the various fractions. The mutagenicity per mg of basic fractions of whole smoke condensate is very high and that of neutral polycyclic hydrocarbons is very low. Because of the exquisite preferential sensitivity of the TA1538 test system to polycyclic amines and insensitively to alkyl polycyclics, there is a poor quantitative correlation between mutagenicity and carcinogenicity, as measured by skin painting or in vitro cell transformation. There is substantial evidence that many carcinogens are mutagens but that most of these compounds require metabolism before they are biologically active. If further development improves the sensitivity of the bacterial testing system to mutagenic derivatives of alkyl polycyclic and heteropolycyclic hydrocarbons, it may provide a convenient, rapid, quantitative, and inexpensive bioassay for the detection of potentially carcinogenic substances in tobacco smoke condensates.


Quantitative immunofluorescence studies of the tumor antigen-bearing cell in giant cell tumor of bone and osteogenic sarcoma. Tumor-associated antigen was found by reacting sera from two patients with giant cell tumor of bone with cells derived from their tumors, using autologous serum as intermediate reactant and fluorescein-conjugated goat anti-human IgG as final reactant. Approximately 40% of the plump, spindle-shaped cells that formed the background stroma of these tumors possessed the antigen; however, it was not present on giant cells. Fluorescence was much greater than that on similarly stained cells from 4 osteogenic sarcomas, suggesting that the antigenic density on cells from giant cell tumor was greater than that on cells from osteogenic sarcoma. Antibodies in sera from giant cell tumor patients and osteogenic sarcoma patients showed specific cross-reactivity. Stromal cells of giant cell tumors were established in culture and retained tumor-associated antigen, whereas giant cells failed to divide and detached from the flask within two weeks. Intensity of fluorescence (antigenic density) decreased with progressive passage levels, but a larger percentage of cells showed fluorescence. At the tenth passage, all cells bore tumor-associated antigen. Cultured cells that were injected s.c. into mice formed progressively growing nodules, the cells of which were morphologically indistinguishable from stromal cells of the original tumor; all cells retained tumor-associated antigen, but antigenic density had decreased to about one-seventh of the value found originally. No giant cells were present in the nodules.


Cell-mediated antitumor immunity in breast cancer patients evaluated by antigen-induced  leukocyte adherence inhibition in test tubes. Tumor antigen-induced inhibition of leukocyte adherence was adapted and modified for use in glass test tubes for the study of cell-mediated antitumor immunity to human adenocarcinoma of the breast. Peripheral blood leukocytes from 40 to 47 patients with proven breast cancer responded to an antigenic extract of breast cancer with significant leukocyte adherence inhibition, whereas only 2 of 32 controls showed a response. Further, 7 patients with histologically proven benign breast disease did not react to the breast adenocarcinoma extract, indicating that only breast cancer patients have leukocytes sensitized  to the breast cancer antigen. The cell-mediated antitumor response of the breast cancer patient was dependent on the stage of the cancer, and patients with disseminated cancer had decreased responsiveness. In fact, 4 of 7 breast cancer patients who had no response in the assay had disseminated breast cancer. Also, surgery and irradiation depressed leukocyte adherence inhibition responsiveness. Chromatographic fractionation on Sepharose 4B of the breast cancer extract showed that the antigenic component was greater than 10(6) daltons. The responsive cell in the assay interacts directly with the tumor antigen, and as a result subsequent adherence to glass is inhibited. The assay described is a comparatively simple and sensitive technique for demonstrating cell-mediated antitumor immunity and appears to be immunologically specific.


Selective cleavage of glycosidic linkages: studies with the O-specific polysaccharide from Shigella dysenteriae type 3. Treatment of the O-specific polysaccharide from Shigella dysenteriae Type 3 with hydrazine in the presence of hydrazine sulphate resulted in quantitative N-deacetylation with the formation of a modified polysaccharide containing free amino groups.  Oxidation of the modified polysaccharide with periodate did not destroy the 2-amino-2-deoxygalactose residues, thus indicating that they were substituted at position 3.  Acid hydrolysis of the modified polysaccharide afforded 3-O-(2-amino-2-deoxy-beta-D-galactopyranosyl)-D-galactose, which was identified as the N-acetyl derivative.  Deamination of the modified polysaccharide with nitrous acid cleaved the 2-amino-2-deoxy-D-galactopyranosyl linkages to give a pentasaccharide as the major product, which appeared to be the modified chemical repeating unit of the O-specific polysaccharide.


The relationship of hypertension to coronary, aortic, and iliofemoral atherosclerosis. Evidence from actuarial statistics, epidemiologic studies, and laboratory experiments clearly indicates that hypertension has an accelerating effect on atherogenesis, and this atherogenesis appears to be a graded function of elevated intra-arterial pressure. The fact that atherosclerosis occurs preferentially in the abdominal aorta and iliofemoral arteries seems likely to result from the pressure augmentation by reflected pulse waves that is intensified by vasoconstriction and also by the increase in hydrostatis pressure that results from gravitational stress during standing. Vasoconstriction is a characteristic of hypertension and occurs also with upright posture. The predilection of the coronary epicardial vessels for atherosclerosis seems likely to relate to subtle pressure-volume changes in these arteries as a result of this vascular bed being in the highest pressure area of the arterial system and because intramyocardial arterial branches are completely occluded during systole. The possibility is presented that hypertension accelerates atherosclerosis because it is a metabolic determinant of the multifunctional arterial smooth muscle cells which have the potential for forming collagen and mucopolysaccharides as well as phospholipid.


Metallic copper-induced granulocyte exudation in the study of granulocytopoiesis. C3H/HeHa mice implanted with rods of metallic copper (CR) or glass (GR) exudate neutrophil granulocytes and mononuclear cells into the site of rod implant (peritoneal cavity). Exudation in CR mice is substantially greater than in GR animals. In CR mice there is an impressive stimulation of myelopoiesis measured in the femoral marrow subsequent to the initial accumulation in the peritoneal cavity. Serum levels of colony stimulating activity (CSA), an in vitro myeloproliferative stimulating activity, are elevated in such animals, as are femoral marrow agarcolony forming cells (CFC). The procedures is useful to the study of myelopoiesis and myelopoietic regulatory mechanisms.


A non-destructive method for measuring intestinal cell transit time. Villous exfoliation of intestinal epithelial cells, which had been previously labeled in the crypt with 125I-iododeoxy-uridine, can be detected by thyroidal accumulation of the liberated 125I-. The latter can be monitored externally. The interval between labeled precursor injection and the steep portion of the thyroid activity accumulation curve corresponds to the intestinal cell transit time, as measured by destructive techniques, in three animal species. The technique allows estimations of intestinal cell transit time to be made on an individual basis, and can be expeditiously applied to large animals. Very small tracer doses are required for detection.


Influence of castration on incorporation of exogenous peroxidase into "synaptic" vesicles of the median eminence. II. The perivascular part of the palisade zone in male rats. In the median eminence of male rats, nerve profiles in the immediate vicinity of portal capillaries have been divided into 4 categories on the basis of their vesicular content: profiles a with agranular "synaptic" vesicles of about 50 nm, b with similar agranular vesicles and also with granular vesicles of mainly 60-140 nm, c with granular vesicles alone and d without vesicles. Twenty-four hours after castration, the percentage of profiles of category a was significantly increased when compared with sham-operated animals, whereas the percentage of profiles of category b was significantly decreased. After intravenous injection of exogenous peroxidase, especially the nerve profiles located in direct contact with the outer basement membrane of the portal capillaries contained peroxidase positive "synaptic" vesicles. Injection off peroxidase after castration resulted in a significant increase in the percentage of nerve profiles containing both peroxidase positive and peroxidase negative "synaptic" vesicles (category a). It is suggested that, in certain nerve terminals, castration may lead to release off the content of granular vesicles, which may contain gonadotropin releasing factor. This release then may cause that nerve terminals with agranular vesicles and granular vesicles (category b) change in their vesicular content and are therefore classified as terminals with only agranular vesicles (category a). An increased turnover rate in the ultrastructurally affected terminals may be reflected in increased uptake of exogenous peroxidase. The observations imply that certain neurones projecting to portal capillaries in the median eminence are, directly or indirectly, sensitive to changes in the level of gonadal steroids.


Brain tissue transplanted to the anterior chamber of the eye: 3. Substitution of lacking central noradrenaline input by host iris sympathetic fibers in the isolated cerebral cortex developed in oculo. Fetal parietal cerebral cortex was homologously transplanted to the anterior chambers of the eyes of adult rats. The transplants got vascularized, proliferated, as measured by in vivo stereoscopic inspections, and differentiated into brain tissue similar to cortex cerebri in situ and survived for long times, greater than 41/2 months. Fibers from the intact sympathetic adrenergic ground plexus of the iris were able to innervate the transplants in an organotypic way regarding fluorescence morphology, pattern of distribution of the nerve terminals and, to a certain extent, density of innervation, the only variable parameter being density of innervation. Thus, in unpretreated or MAO inhibited transplants only rather few to scattered terminals could be found, while after preincubation in 10(-5)M alpha-methyl-noradrenaline the number of visible terminals was normal or slightly less than normal, as compared to cortex cerebri in situ. When superior cervical ganglia (SCG) were transplanted together with fetal cortex tissue to sympathetically denervated eyes the ingrowth in the cortex tissue was similar to that after single cortex transplantation combined with 5 day old SCG, while a marked hyperinnervation was encountered when combined with adult SCG. It is concluded that the developing cortex cerebri, deprived of its normal CNS source of adrenergic nerves, is able to receive sympathetic adrenergic nerves from the iris in an organotypic way upon transplantation to the anterior chamber of the eye.


Encapsulation of implanted foreign bodies by hemocytes in Locusta migratoria and Melolontha melolontha. Sterile fragments of cellophane, cat-gut, cotton, or beef muscle implanted into the body cavity of Locusta migratoria and Melolontha melolontha are immediately surrounded by granular hemocytes which form a multi-layered capsule around each foreign body. The cytoplasm of the granular hemocytes of the outer zone of the capsule in both species shows an accumulation of fibrous material (microtubules and microfilaments). None of the implanted material appeared to be degraded.


Changes in glia-neuron relationships in cell cultures of spinal ganglia caused by puromycin. Dorsal root ganglia of chick embryos were cultured for one to four weeks on Maximow-slides. Puromycin was added to cultures for a pulse of 30' in a dose of 100 mug/ml medium. Particular interest was given to the ultrastructural features of the glia-neuron relations. Puromycin caused a shrinkage of the glial processes and consequently the continous glial envelope of the spinal ganglion neurons disappeared. These changes of glia-neuron contacts were reversible after a few days when puromycin was withdrawn from the medium. The newly formed glial sheaths around the neurons were comparable to those in untreated cultures and to those in vivo. The effects of an inhibition of protein synthesis caused by puromycin are discussed in relation to the effects on the cell motility, on the renewal of cell membranes and on the formation of cell contacts in nervous tissue.


Ependymal absorption of luteinizing hormone-releasing hormone injected into the third ventricle of the rat. LRH injected into the third ventricle induced increases of serum LH and FSH in the rat. Following injection of LRH-125I into the third ventricle, autoradiographic grains were concentrated in the ependymal cell bodies and ependymal processes in the median eminence. Aggregations of grains were also found in the capillaries of the portal vessels, and in both sinusoids and parenchymal cells of the adenohypophysis. These findings show that the ependymal cells represent a link between the cerebrospinal fluid and the portal blood.


Extra-adrenal chromaffin cells grown in tissue culture. 1. Extra-adrenal chromaffin cells from adult frogs were grown in tissue culture and their morphology and behaviour observed with both light and electron microscopy. 2. Two types of chromaffin cells were distinguished: Type A cells contain large, electron dense vesicles (2000-6000 A) and are equated to Type I chromaffin cells seen in vivo, i.e. they contain noradrenaline; Type B cells contain smaller vesicles (700-2000 A) which are incompletely filled with an electron dense material and are equated to Type III chromaffin cells seen in vivo, i.e. cells depleted of their catecholamines by stimulation. No cells comparable to Types II and IV cells in vivo were seen. 3. Close associations between the cultured chromaffin cells and sympathetic neurons were observed with the light microscope, but no examples of synaptic structures were seen in the material examined with electron microscopy in this study.


Temporal order in yeast chromosome replication. Previous work with bacteria has shown that a gene is maximally sensitive to mutagenesis by N-methyl-N'-nitro-N-nitrosoguanidine (NG) at the time it is being replicated. NG was used to test for temporal order in the replication of the genome of the unicellular eucaryote, Saccaromyces cerevisiae. Yeast cells growing exponentially were more sensitive to mutagenesis by NG than cells in which DNA synthesis had been inhibited. Further, in a synchronized population of cells, individual genetic markers exhibited maximum sensitivity to muta-genesis at distinct limited intervals within the DNA synthesis period. The peaks of sensitivity are interpreted as reflecting the times of replication of different genes. Since markers for five genes on four different chromosomes showed discrete periods of maximum sensitivity, it is likely that temporal ordering of replication exists for most genes in the yeast genome. These results imply that sites for initiation of DNA replication occur at fairly specific regions along yeast chromosomal DNA moleucles, and are activated at predetermined times in the DNA synthesis period.


[How can forensic medicine assist historical findings]. The authors wanted to demonstrate in their present paper that forensic medicine and its modern methods can help to elucidate some historical findings not only as regards mechanisms of injury but in the first member's of the dynasty of Premysl also by evidence of group appurtenance using the two-phase and two-circle system.


Effect of norepinephrine and fluid administration on pulmonary extravascular water volume in dogs. The effects of norepinephrine-induced vasoconstriction on pulmonary extravascular water volume (PEWV) and central volume were studied before and after intravenous volume expansion with 5% dextrose and water (20 ml/kg body weight). PEWV was measured by double isotope dilution and gravimetric analysis and assessed by electron photomicrography. Comparisons were made with saline-treated control dogs. Thirty-six dogs were studied after they had been anesthetized with sodium pentobarbital. PEWV determined by indicator dilution increased during norepinephrine infusion, especially after volume expansion; in contrast, PEWV in control dogs was constant despite similar increases in pulmonary arterial and left atrial pressures. However, measurements of PEWV by gravimetric analysis and inspection of electron photomicrographs failed to reveal extravascular accumulation of water in vasoconstricted dogs. Thus, it was concluded that the increased PEWV measured by indicator dilution in norepinephrine-treated dogs compared with that in saline-treated dogs reflects more complete perfusion of pulmonary capillaries and access of the diffusible indicator to additional lung tissues and spaces. Improved capillary filling presumably is attributable to peripheral vasoconstriction and redistribution of blood into the thorax. PEWV determined by gravimetric analysis in dogs that had had open-chest procedures for lung biopsy and electron photomicrography was significantly less than that in dogs with their chests closed throughout the experiments. Although the mechanism for the water loss in unknown, the difference must be recognized when the results from various types of experiments are compared.


Right ventricular dysfunction detected by gated scintiphotography in patients with acute inferior myocardial infarction. Twenty-seven patients with acute myocardial infarction not complicated by cardiogenic shock and ten normal volunteers were studied with gated cardiac blood pool scans. The ratio right vetricular area/left ventricular area (RVA/LVA) determined from the left anterior oblique end-diastolic scans was examined. The ratio was 1.11 +/- .06 in the normal volunteers. In patients with anterior infarction the ratio fell to 0.75 +/- .12 (P less than .05) due to left ventricular enlargement. In those with inferior infarction the ratio was 1.12 +/- .23 which was greater than in those with anterior infarction (P less than .05) due to enlargement of both the left and right ventricles. Six patients with cardiogenic shock, three with inferior and three with anterior infarction were studied. The three with anterior infarction had left ventricular enlargement and a decrease in the ratio of RVA/LVA to 0.62 while the three with inferior infarction had an increase in the ratio to 2.05 suggesting right ventricular dilatation and dysfunction. These studies suggest a high incidence of right ventricular dysfunction in patients with inferior myocardial infarction.


An analytical system for rapid separation of tissue nucleotides at low pressures on conventional anion exchangers. An analytical anion-exchange procedure has been developed for the rapid separation of acid-soluble nucleotides (the so-called "free" or tissue nucleotides). It permits assay at low pressures (275-415 kPa; 40-60 psi) in less than 1 h on 10-cm columns of Aminex resins (conventional styrene-type anion exchangers) with alkaline citrate solutions as the eluent. Separation variables have been investigated, to determine optimum conditions for the routine analysis of samples containing tissue nucleotides. Also described here is a simple solvent-extraction procedure for removing HCIO4 or CCI3CO2H quantitatively from cell extracts that contain acid-soluble nucleotides: they are removed from aqueous acid solutions with a water-insoluble amine dissolved in a water-immiscible solvent.


Determination of hydroxyproline polypeptides in urine and blood serum by gel filtration. Hydroxyproline-containing polypeptides were isolated from urine by filtration on polyacrylamide gel Bio-Gel P-2. This fraction was quantitatively and qualitatively similar to the nondialysable hydroxyproline in urines of normal adult subjects, patients with chronic uremia, and with primary or secondary hyperparathyroidism. Hydroxyproline polypeptides isolated from urines of patients with extensive Paget's disease or from normal growing subjects contained a group of smaller polypeptides slightly retarded on Bio-Gel P-2 which were not retained by the dialysis membrane Spectrapor-TM. In these two groups of subjects the values of hydroxyproline polypeptides were 35-45 percent higher than those of dialysable hydroxyproline. Increased excretion of hydroxyproline polypeptides was found in chronic uremia, primary and secondary hyperparathyroidism, Paget's bone disease and in normal growing subjects. With the notable exception of chronic uremia the excretion of hydroxyproline polypeptides paralleled that of total and oligopeptidic hydroxyproline. In some cases of chronic uremia the polypeptidic hydroxyproline represented the predominant fraction. On long columns of Bio-Gel P-6 hydroxyproline polypeptides separated into several peaks. The chromatographic pattern was rather characteristic for chronic uremia, secondary hyperparathyroidism, Paget's bone disease and physiological growth. Ahydroxyproline fraction of similar chromatographic properties was isolated from blood serum after deproteinisation with heat or ethanol at pH 4.8. High serum levels of this hydroxyproline fraction were observed in pathological conditions with increased urinary excretion of polypeptidic and nondialysable hydroxyproline.


Automated assay of N-acetyl-beta-glucosaminidase in normal and pathological human urine. An automated method for the assay of N-acetyl-beta-glucosaminidase in human urine is described and a normal range of urinary N-acetyl-beta-glucosaminidase activity is reported. The automated method has been used routinely over a twelve month period in two London hospitals for monitoring the excretion of N-acetyl-beta-glucosaminidase in renal transplant patients. The abnormal elevation of urinary N-acetyl-beta-glucosaminidase provides an early warning of rejection by indicating the presence of renal parenchymal damage. The automated assay of urinary N-acetyl-beta-glucosaminidase may also be used in screening for the presence of renal disease.


Sex hormone levels and gonadotrophin release in the polycystic ovary syndrome. The response to synthetic luteinizing hormone-releasing hormone was studied in eighteen patients with the polycystic ovary syndrome. The release of follicle-stimulating hormone was similar to that found in normal women. The mean response of luteinizing hormone was similar to that found in the luteal phase, but significantly greater (P less than 0-02) than that found in the early follicular phase of the normal menstrual cycle. Basal serum levels of FSH and LH, estimated in twenty-five patients, were similar to those found in normal subjects. The sex hormone binding globulin capacity was reduced in twenty-four of them. Basal serum testosterone levels were elevated in twelve of twenty-two patients and the mean level was significantly greater (P less than 0-01) than the mean level of normal women. Basal serum androstenecione levels were elevated in nine of twenty-two patients and the mean level was also significantly greater (P leess than 0-001) between basal testosterone and LH levels. These data suggest the pituitary gland of patients with the polycystic ovary syndrome contains adequate amounts of LH but that the ovulatory surge of LH which occurs in normal women is inhibited by testosterone acting on either the pituitary or, more probably, on the hypothalamus.


The effect of oestrogen pretreatment on subsequent response to luteinizing hormone releasing hormone in normal women. Twenty-two normal, regularly menstruating female subjects had an LHRH test performed before and after pretreatment with 0.5 mg, 1 mg. or 2.5 mg of oestradiol benzoate during the follicular phase of their menstrual cyclees (days 4-8). Two further women acted as controls and received no oestrogen; they showed identical responses for both LH and FSH release when LHRH tests were performed at intervals of 48 h. Oestrogen pretreatment induced a biphasic effect upon subsequent LHRH response. Four subjects retested 20 h after 0.5 mg oestradiol benzoate showed either no change or a slight suppression of LH and FSH release. Fifteen of the eighteen women pretreated with oestradiol benzoate and retested 44 h later showed significantly increased LH release and fourteen significantly increased FSH release when compared to their control responses. The responses appeared to be dose related with a positive correlation between sum of LH increments and basal oestradiol levels (R = 0.61; P less than 0.001) and a similar correlation (r = 0.67; P less than 0.001) between sum of FSH increments and basal oestradiol levels. The physiological significance of this biphasic action of oestrogen upon pituitary sensitivity is discussed in relation to the control of the menstrual cycle.


The LH response to LH releasing hormone in children with true isosexual precocious puberty treated with cyproterone acetate. Fourteen girls and one boy with isosexual precocious puberty were submitted to LHRH stimulation tests, during and without therapy with cyproterone acetate. In addition, fourteen girls with isosexual precocious puberty not receiving any therapy were tested and served as controls. It was found that cyproterone acetate induces suppression of the responsiveness of the pituitary gland to secrete LH on LHRH stimulation. Daily oral therapy was found to be more effective than the regimen of intramuscular depot injections. These findings demonstrate that cyproterone acetate has an antigonadotrophic effect.


Allergic interstitial nephritis: report of a case with activation of complement by the alternate pathway. An eighteen year old woman developed a streptococcal pharyngitis documented by throat culture. After two days of treatment with penicillin she developed arthritis and abdominal pain and within a week became anuric. Her renal biopsy revealed extensive interstitial nephritis without proliferative glomerular changes. Serum properdin levels were significantly reduced and immunofluorescence studies demonstrated properdin deposition within the glomeruli, C1, C4 and C2 were not depressed nor were they demonstrable within the glomeruli. These results support activation of complement apparently only by the alternate pathway, a finding heretofore noted only in membranoproliferative glomerulonephritis.


A simple combinatorial method for calculating genetic risks. A method is presented whereby genetic counsellors can calculate genetic risks in a wide variety of circumstances using only arithmetics. The method is general in that it can handle such information as gene frequency, mutation rate, mode of inheritance, penetrance, pedigree to which the consultand belongs, phenotype of the consultand and his relatives, biochemical findings, etc. Each of the possible combinations of genotypes which may be present in the pedigree is listed and considered in turn. The method consists of a series of simple steps leading mechanically to the right answer.


Interactions in man of delta-9-tetrahydrocannabinol. II. Cannabinol and cannabidiol. Oral doses of delta-9-tetrahydrocannabinol (THC) 20 mg, combined with placebo or with 40 mg dses of cannabinol (CBN) and cannabidiol (CBD), were given to volunteers. The combination of THC with CBN produced no detectable changes in the quality, intensity, or duration of the effects of THC alone. The THC-CBD combination tended to delay onset and prolong effects of THC, while making them somewhat more intense. Even this interactive effect was slight, providing no reason to abandon the current practice of basing doses of marihuana for clinical studies solely on THC content.


Potassium-sparing effect of amiloride in a diuretic factorial study in man. 1. The effects of amiloride (M, 20 mg/day), chlorothiazide (C, 1000 mg/day), ethacrynic acid (E, 100 MG/day) and frusemide (F, furosemide 80 mg/day, given alone and in combination, were investigated in eight patients in a 2(4) factorial study. Effects between blocks of four treatments in each sixteen-treatment replicate were confounded with higher interactions to allow for differences between early and late diuresis. 2. All patients exhibited marked diuresis, with significant mean increases in daily urinary sodium excretion (P smaller than 0.05) and urinary volume (P smaller than 0.01) induced by chlorothiazide, frusemide and ethacrynic acid (68, 69 and 38%; and 35, 40 and 34%, respectively). Amiloride appeared to be half to one-third as potent as the other diuretics. 3. Amiloride produced a significant potassium-sparing effect (P smaller than 0.01), reducing urinary potassium excretion by 30%, compared to significant urinary potassium wasting with frusemide (increase of 33%, P smaller than 0.01) and chlorothiazide (increase of 31%, P smaller than 0.05). 4. No adverse reactions occurred, but serum potassium levels twice rose to 6 mmol/l and subsided without additional therapy, and on one occasion fell to 2.5 mmol/l, requiring a potassium supplement for 4 days. 5. It was concluded from these factorial studies that amiloride is a mild diuretic and potent potassium-sparing agent acting independently and additively in combination with chlorothiazide, ethacrynic acid or frusemide. For the three latter diuretics, all two-drug interactions were simply additive also, without evidence of synergism or antagonism between drugs.


Antihypertensive effect of a dopamine beta hydroxylase inhibitor, bupicomide: a comparison with hydralazine. The cardiovascular effects of a new antihypertensive drug, bupicomide, were compared with those of hydralazine in 6 patients with mild to moderate hypertension. The mean supine arterial pressure of patients was reduced 15.2 mm Hg by bupicomide (900 to 2,000 mg/day) and 15.7 mm Hg by hydralazine (300 to 600 mg/day). Heart rate increased an average of 11.3 bpm during bupicomide and 14.5 bpm by hydralazine. Neither drug was associated with a postural decrease in mean arterial pressure. The heart rate response during maximum tolerated treadmill exercise was not diminished by either drug. Cardiac index was increased during administration of both drugs. Bupicomide and hydralazine reduced forearm vascular resistance, while renal blood flow and renal vascular resistance were not significantly modified. Evidence of equivalent augmentation of sympathetic nervous activity during administration of both drugs consisted of equal and significant increases in heart rate and urinary norepinephrine excretion, and decreases in duration of the pre-ejection period. The absolute values of these parameters were correlated with mean arterial pressure, which may indicate that the increase in sympathetic nervous activity was mediated by baroreceptor reflexes. Although bupicomide inhibits dopamine beta-hydroxylase, our results suggest that it is acting as a direct vasodilator.


Nonemergency use of slow infusions of diazoxide. Slow infusions of diazoxide were administered to 10 hypertensive patients who had stable, nonaccelerated hypertension. The 10-min diazoxide infusion was associated with a 16% average reduction in arterial pressure, a 21% average increase in heart rate, a 16% average increase in cardiac output, and a 36% reduction in total peripheral resistance. These changes in hemodynamic parameters lasted for an average of 70 min. It was concluded that slow infusions of diazoxide produce a consistent and predictable antihypertensive effect in patients with stable, nonaccelerated hypertension. Slow infusions of diazoxide may have a limited use in nonemergency situations where an abrupt change in arterial pressure is to be avoided and a parenteral antihypertensive agent is needed.


Effect of dosage regimen on natriuretic response to furosemide. We have examined the differences in urinary excretion of water, sodium, potassium, chloride, urea, and creatinine produced by different dosage regimens offurosemide in normal volunteers. Three oral dosage regimens were compared: 20 mg daily, 20 mg twice daily, and 40 mg daily. Furosemide, 20 mg, did not produce a significant weight loss, diuresis, or natriuresis in 12 normal subjects. With 40 there was a significant weight loss, diuresis, natriuresis, and chloruresis over 24 hr. Comparison of the divided regimen with 40 mg daily revealed significantly greater sodium excretion, and chloride excretion with 20 mg twice daily. The divided dosage regimen produced a different pattern of diuresis with most of the sodium and water excretion occurring after the second dose. These differences in response to different regimens are predictable from pharmacokinetic considerations and may have clinical significance.


Respiratory effects of nefopam.

Respiratory effects of nefopam. A respiratory study has been done to compare the respiratory effects of a potent new analgesic, nefopam, to morphine.  Morphine was a potent respiratory depressant at therapeutic dosage while nefopam was not.


Bioavailability of oral dexamethasone.

Bioavailability of oral dexamethasone. Bioavailabilities of dexamethasone tablets and elixir in man were evaluated by each of 3 model-independent methods of pharmacokinetic analysis employing plasma and urinary values as determined by radioimmune assay. There were no significant differences among the results determined by the 3 methods nor between the respective availabilities of the two formulations; the latter averaged 82.6 +/- 17.7% for the elixir formulation and 78.0 +/- 12.1% for tablets.


Normal velopharyngeal function in speech. What has been presented in the foregoing pages is the broad outline of a theory of velopharyngeal function in normal speech production. It is suggested that the velopharyngeal musculature functions in a predictably variable manner to provide predictably variable structural movements and positioning. The variability is predictable, based on the phenomenon of coarticulation, given knowledge of where the structures are, where they must go to produce a perceptually acceptable phonime, and where they must subsequently be for later phonemes. The theory is not complete, as will be discussed below. Nevertheless, it demonstrates the complexity of velopharyngeal function. Many variables are involved simultaneously in the movements of this mechanism, and it is not enough to consider a muscle, a structure, or a phoneme. The action of any muscle is influenced by the action of others in the system, the movements of any structure are influenced by movements of other structures, and any phoneme is influenced-sometimes heavily so-by phonemes around it. Thus, the central nervous system programming of oralization and nasalization gestures must be a complicated process. Certainly, the results of that programming are complicated.


A 10-year experience with subcutaneous mastectomy. Subcutaneous mastectomy appears to remain a procedure of promise.  This 10-year experience indicated that it is feasible in at least 80 per cent of selected patients to successfully remove the breast parenchyma and subsequently reconstruct the breast without serious complications.  It is resonable to assume that as surgical technique and experience improve, the complication rate will diminish.  Furthermore, it is essential that better breast implants be devised and developed in the future.  This would clearly enhance all forms of cosmetic breast surgery.  The use of subcutaneous mastectomy as a prophylactic cancer procedure will parellel the improvement of implant breast reconstruction.  Whether subcutaneous mastectomy will measurably reduce the mortality rate of carcinoma of the breast will, of course, take a generation to determine.  However, I have no doubts that is it as justifiable and valuable surgical tool in the treatment of breast disease.  The concept of almost total breast biopsy has great merit in the discovery of occult carcinoma.  Clearly, caution should be exercised in the selection of cases for this modality, and further study must be devoted to develop diagnostic guidelines of ever-increasing precision to determine which breasts are potentially malignant and should be afforded the procedure.


Ultrasound in the diagnosis of fluid collections following renal transplantation. Ultrasound examinations of the pelvis and kidney have been carried out following 68 renal transplants. In 16 patients moderate sized or large perirenal or pelvic fluid collections were demonstrated. The composition of the fluid was lymph in seven cases, pus in four, blood in three and urine in two. Ten of these 16 patients had clinical features compatible with a pelvic fulid collection while six had no such localising features. We have found ultrasound to be extremely valuable in the diagnosis and precise localisation of pelvic fulid collections following transplantation, often at a stage before pressure effects and symptoms have appeared. It also provides a rapid and reliable means of excluding a pelvic or perirenal abscess in the pyrexial patient.


Effect of proper oral hygiene on gingivitis and dental caries in Swedish schoolchildren. The present paper reports the effect of a 3-year study of regularly repeated professional toothcleaning on oral hygiene status, gingivitis, and dental caries. At the initiation of the study in 1971, the children were 7-8 years old (Group 1), 10-11 (Group 2) or 13-14 (Group 3). The children were divided into test and control groups. Before the study all the children were examined regarding oral hygiene, state of the gingiva and dental caries. Throughout the 3-year period the controls brushed their teeth with a 0.2% sodium fluoride solution once a month under supervision. During the first 2 years of the trial all the children of the test groups were given professional oral prophylaxis once every second week during the school terms. During the third year the interval between consecutive prophylactic sessions was prolonged to 4 weeks in Groups 1 and 2 and to 8 weeks in Group 3. The results demonstrated that regularly repeated professional cleaning of the teeth combined with fluoride applications and toothbrushing instructions, over a 3-year period in schoolchildren resulted in the establishment and maintenance of excellent oral hygiene standards. Inflammation of the marginal gingiva almost entirely disappeared, and practically no new carious lesions developed.


The psychiatric halfway house: how is it measuring up? To obtain data on the effectiveness of the psychiatric halfway house and to update information about such facilities, 26 recent statistical reports were examined. Only two studies include control group comparisons. In addition to descriptive information, data are reported in terms of employment or school attendance and independent living as contrasted with rehospitalization. Results indicate that a median of approximately 80 per cent of halfway house residents adjusts to community living. Despite differences among halfway houses in resident selection, length of stay, rehabilitative criteria, and nature of follow-up, data suggest that rehospitalization rates are lower after residence in a halfway house. Some cautions are drawn regarding evaluative studies and potential attenuation of halfway house facilities to low-quality custodial care.


The relationship between patient demographic characteristics and psychiatric rehabilitation outcome. Professionals engaged in psychiatric rehabilitation need to know what specific factors contribute to the success or failure of attempts to reintegrate the psychiatric patient back into the community. A review of the research literature succeeded in identifying various demographic charcteristics of expsychiatric patients that are related to recidivism and posthospital employment. A composite picture of patients who are more likely to be recidivists or unemployed (or both) was advanced. The factors that appear to be related to posthospital employment are not consistently the same factors that are related to recidivism.


Stereotactic treatment of action myoclonus in a case of combined status marmoratus and multiple sclerosis. A contribution to the pathophysiology of basal ganglia with multiple lesions in both the striatum and the substantia nigra. A patent, who suffered from nonprogressive athetotic-myoclonic hyperkinesia of the left arm and spastic paresis of the underdeveloped left leg since early childhood, experienced a febrile episode at the age of 23, after which a weakness and ataxia of the right limbs with frequent falling persisted; at the age of 28, he developed a right-sided rigidity, tremor at rest and mask-like face as sequelae of encephalitis disseminata exacerbations. The violent intention myoclonus of the left side of the body could be abolished by stereotactic coagulation in the V.o.p and V.o.a and zona incerta until death 11 days later. The athetotic myoclonic hyperkinesia is the consequence of a left-sided severe status marmoratus of the right putamen with extensive loss of nerve cells and shrinkage. The additional nerve cell loss in the right substantia nigra due to demyelinating encephalitic foci did not produce Parkinson symptoms, because these require a normal striatum. This loss did, however, exaggerate the original hyperkinesia to a violent intention myoclonus, which was abolished by interruption of denatatothalamic afferents to the V.o.p nucleus and of pallidothalamic afferents to the V.o.a nucleus. The Parkinson syndrome of the right side is due to demyelinating foci of different ages. The Parkinson symptoms were manifest on the right side, because the left status marmoratus did not severely reduce the striatal nerve cells. In this case, there is no indication that the introduction of the stereotactic electrode has precipitated new demyelinating foci.


Nuclear placentography.

Nuclear placentography. Localization of the placenta by radionuclide imaging techniques is useful in assessing the cause of vaginal bleeding late in pregnancy. Placenta previa is the most threatening cause of late gestational bleeding, and the acceptably high accuracy of nuclear placentography in detecting this condition is well-established. Nevertheless, B-mode ultrasonography is a preferable method because it delivers no ionizing radiation and is capable of identifying the cervix in virtually all patients. The latter method will eventually replace nuclear placentography.


Evaluation of intracardiac shunts.

Evaluation of intracardiac shunts. This article will review the qualitative and quantitative methods of radionuclide evaluation of intracardiac shunts. Radionuclide angiocardiography of the cardiopulmonary system has proven adequate, with few exceptions, for qualitative detection of left-to-right and right-to-left intracardiac shunts. Numerous authors have reported on the detection of intracardiac shunts using qualitative methods such as rapid sequential visualization of nuclide angiocardiography using the scintillation camera with Polaroid, 35mm or 70mm film. Recent development of videotape storage systems and computers offers a quantitative technique of permanently recording the nuclide angiocardiogram and thus the capability for replay and analysis of the study. Quantitative analysis of the nuclide angiogram in the form of heart chamber dilution curves or pulmonary dilution curves permits 1) determination of the presence or absence of left-to-right, right-to-left, or bi-directional intracardiac shunts, including shunts which might go undetected using the qualitative techniques, 2) shunt location at the atrial or ventricular level, 3) determination of the functional status of a corrective left-to-right shunt, and 4) shunt quantitation. By quantitative analysis of the isotope dilution curves, it is possible to calculate the size of left-to-right or right-to-left intracardiac shunts (Qp/Qs ratio) to within 10% of the values obtained at cardiac catheterization.


The significance of soft tissue injury in the roentgen diagnosis of trauma. Soft tissue damage is an integral part of trauma. This basic fact is commonly ignored in the evaluation of roentgenograms obtained because of trauma. The soft tissue component of the traumatic lesion may produce the most obvious roentgen sing of injury and is, in these instances, fundamental to the correct roentgen diagnosis. In many instances, the soft tissue lesion is frequently of greater clinical significance that the more obvious skeletal injury. An awareness of the roentgen signs that signal soft tissue injury, and of those skeletal lesions that are commonly associated with radiographically silent, but clinically more significant, soft tissue damage, leads to prompt institution of appropriate additional diagnostic studies or therapeutic measures. Thus, the soft tissue injury in the roentgen diagnosis of trauma has both diagnostic and therapeutic significance. Each will be discussed in this article.


Peripheral arteriography an overview of its origins and present status. Within a month after Roentgen's discovery of the X-ray, the first cadaveric peripheral arteriogram was performed. It was not until 28 years later that the initial in vivo femoral arteriogram was reported. Arteriographic growth and development since that time have been punctuated with such names as Seldinger, Steinberg, Viamonte, Abrams, Sones, and many more. Keeping pace with their technical and diagnostic achievements has been the cause for a whole new industrial field - that of angiographic equipment and technology. New X-ray tubes, generators, film, etc. have been developed. Angiographic tables are available which have been designed to do highly subspecialized studies. The spectrum of catheter curves and materials available allows visualization of vessels down to the order of 0.1 mm when combined with magnification. Chemoangiography for treatment and subselective venous sampling for hormonal assays are commonplace. Although "the beginnings" for all angiography lie in the evaluation of peripheral vasculature, equipment sophistication for this basic study has often lagged behind that of the more glamorous organal examinations. The development of the biphasic ijection technique hopefully represents an anwer to both multiple injections and X-ray exposures. It allows single injection and single exposure visualization of the vascular tree from distal aorta to the pedal vessels.


A survey of the benefits and risks in the practice of radiology. The findings from both animal and human studies on the radiation risk at low doses and low dose rates are far from conclusive, primarily due to statistical limitations. However, to arrive at some estimate of radiation risk, a conservative approach has been taken, and a linear extrapolation of radiation effects from high doses to low doses has been made. Thus, it is assumed that any exposure to radiation carries some risk of somatic or genetic damage and that there is no threshold or safe dose. In medical practice, diagnostic radiological procedures should be performed only if useful clinical information will be derived. In addition, this information should be obtained at the least possible risk to the patient. For mass chest X-rays, mammography, and lung scans, a quantitative determination of benefit to risk is developed. This approach, though possible desirable, is exceedingly difficult to establish for most diagnostic radiological procedures. Thus, good clinical judgement should be employed in radiological practice, just as it should be employed in all aspects of medical practice.


A comparative study of the activity of a new agent, indapamide, in essential arterial hypertension. A single-blind crossover trial was carried out in 38 elderly, hospitalised patients with essential hypertension to compare the hypotensive activity of 5 mg. indapamide daily with 100 mg. chlorthalidone daily. After initial treatment for 10 days with placebo, patients received treatment for 45 days with either indapamide or chlorthalidone and were then crossed over to the alternative drug for a similar period. Potassium supplementation was necessary in 25 of the patients receiving chlorthalidone, but was precribed as a precautionary measure in only 1 patients whilst on indapamide. Results showed that there were significant drops in blood pressure following both active medications, but that the percentage reduction in diastolic pressure was greater after indapamide. Indapamide also proved more effective than chlorthalidone in controlling the patients' subjective and functional symptoms of their hypertension. In an overall assessment of the effectiveness of both drugs, indapamide was judged to be better tolerated as well as more effective than chlorthalidone in 18 of the 38 patients, whilst chlorthalidone was preferred in only 7 instances.


Preliminary clinical experience with meptazinol, a new analgesic. The analgesic effect of intravenous meptazinol at various dosage levels was studied in 30 patients suffering from acute renal colic. Out of a total of 41 injections (dose range: 20 to 120 mg.) a favourable analgesic response was recorded on 39 occasions. The onset of action was rapid with the minimun duration of action of 1 hour. Higher doses increased the drug's action but were accompanied by nausea and dizziness. There was no overall effect on blood pressure or heart rate.


Cephradine in urinary tract infections: a double-blind comparison with ampicillin. A double-blind trial was carried out comparing cephradine and ampicillin in the treatment of urinary tract infections in 42 females attending a hospital Department of Obstetrics and Gynaecology. Results showed that patients did better in the cephradine group than the ampicillin group, both bacteriologically and clinically. The numbers in each group were small, however, and did not reach statistical significance.


Cyclamates: a review of the current position. Cyclamates were prohibited for use as food additives in the U.S.A. and other parts of the world during 1970 because of the fears of carcinogenicity. The author reviews the evidence leading to this ban and discusses the appeal made against the decision which led to the lifting of the cyclamate restrictions in Australia in November 1974.