Measurement of bone density by gas displacement. Small bone volumes, porous and irregular structured objects with volumes 0.05-2 cm3, were measured by differential pressure of displaced air. The differential air pressure was measured by a piezoelectric resistor pressure gauge. The gas-displacement system was used to measure the volumes of 234 bone specimens for calculation of bone density. The operation of the system, calibration, sensitivity, and errors of measurement are described.


HL-A antigens in serum from bone marrow harvested for diagnostic purposes. Tissue typing employing the lymphocytotoxicity micro-assay was performed by introducing in the system approximately 15% of autologous or homologous ultra-centrifuged blood serum, both of peripheral and bone marrow source. As a rule, the pattern of reactivity was unaffected by peripheral blood serum, whereas the cytotoxicity was nearly always inhibited by autologous bone marrow blood serum or by homologous one from donors sharing the inhibited HL-A specificities with the donors of lymphocytes. These results suggest that at least in these patients HL-A antigens are present in bone marrow blood serum at a concentration which is definitely higher than in peripheral blood.


Incorporation of radiophosphate in the inorganic and organic acid-soluble phosphate fractions of the rat sciatic nerve during Wallerian degeneration. II. After nerve crush (axonotmesis). Plasma inorganic phosphate incorporation into inorganic and organic acid soluble phosphate fractions of the rat sciatic nerve shows, for one week after the operation, parallel increases in both crushed and sectioned nerves. After two weeks the incorporation in the distal part of the crushed nerve shows a progressive return to normal values remaining however significantly increased until the 90th day. These experiments confirm the possibility of an axonal inhibitory control on the Schwann cell metabolism.


Erythrocyte sedimentation studied by an echographic method. The erythrocytes sedimentation can be monitored by an ultrasonic echographic method which is described. It is shown that this technique can give some information on the hematocrit profile in the sedimentation tube.


Urinary pseudouridine and beta-aminoisobutyric acid in patients with low grade urothelial tumours. Relations between excretion and tumour recurrence. The simultaneous 24 hours excretion of pseudouridine and beta-aminoisobutyric acid in the urine from patients treated for low grade urothelial tumours has been determined and related to tumour recurrence inside of 6 months after the determinations. The results of 53 assays in 39 patients without clinical signs of recurrence at the time of the detrmination showed a high excretion of pseudouridine in 53% and of beta-aminoisobutyric acid in 28.5% of the assays. Recurrences appeared more often after a high urinary pseudouridine (53.5%) than after a low, but the difference was not statistically significant (p more than 0.05) and more often after a low urinary beta-aminoisobutyric acid (52.5%) than after a high (p less than 0.01). The highest incidence of recurrence was in patients with a simultaneously high urinary pseudouridine and a low urinary beta-aminoisobutyric acid. Seventy per cent of these excretion patterns were from patients, who developed a recurrence before 6 months (p less than 0.002).


In vivo decomplementation of guinea pigs with cobra venom factor and anti-C3 serum: analysis of the requirement of C3 and C5 for the mediation of endotoxin-induced death. Guinea pigs were decomplemented by administration of cobra venom factor and goat anti-C3 serum in order to determine whether endotoxin-induced death could be prevented. The combined use of both reagents resulted in the complete elimination of all serum C3 and C5 hemolytic activity. This yielded, however, a shortened rather than extended longevity following endotoxin challenge. The mixing of endotoxin in vitro or in vivo with serum of animals already partially depleted of C3 resulted in no further activation of this component, further suggesting that the interaction of complement with endotoxins does not relate to mortality in animals following endotoxin challenge. Thus, although it has been demonstrated that complement components aid in the detoxification of endotoxin, the present data show that the C3 and C5 components are not mediators of endotoxin-induced death.


The ratio "circulating red cell volume/lean body mass" in normal and hypophysectomized rats on paired feeding. The ratio "circulating red cell volume/lean body mass" was calculated in normal and hypophysectomized male rats put on paired feeding for 90 days after hypophysectomy, and in control rats both at the beginning and the end of this experimental period. Control rats at the onset of the experiment, hypophysectomized rats, and rats on the sub-maintenance level of food consumption did not show a significant difference in their red cell volumes/lean body mass ratios. These values were significantly lower than those of sham hypophysectomized rats allowed to eat ad libitum. These results suggest that the reduction in the feed intake that follows pituitary ablation may play an important role in the genesis of the post-hypophysectomy anemia.


Treatment of rat fibrosarcoma by radiotherapy plus immune adjuvant. Combined radiotherapy and nonspecific adjuvant C. parvum or Piromen treatment of rat tumors show improvement over radiotherapy alone. The most effective protocol, resulting in complete remission in 6 of 6 rats was obtained with C. parvum given i.p. in three doses 1 day prior to tumor X-irradiation of three doses of 1500 R each given on days 1, 4, and 8. Animals receiving the same dose schedule without adjuvant had only partial regression of their tumor. Without adjuvant, increasing the dose to 6000 R also resulted in tumor regression, but at the expense of marked necrosis to the leg. One mechanism for the observed results may be stimulation of the reticulo-endothelial system to produce macrophages activated against the tumor. It is also possible that C. parvum causes increased rate of clearance of soluble antigens released as a result of radiation destruction of the tumor, as suggested by Proctor et al (3).


Appraisal of equations for neutral solute flux across porous sieving membranes. General transport equations, based on irreversible thermodynamics applied to membranes without regard to their structures, are compared with results based upon specific membrane models. It is pointed out that the range of validity of the general linear transport equations of irreversible thermodynamics may be extremely small, and that attempts to extend the range by thermodynamic considerations have always involved subtle assumptions of a nonthermodynamic nature. Simple membrane models are used as diagnostic tools to pinpoint such assumptions, with particular reference to the often-concealed assumption of membrane homoporosity. It is shown that it is not possible to write an exact equation for solute flux across an inert porous membrane only in terms of the three customary membrane parameters sigma (reflection coefficient), Ps (permeability coefficient), and Lp (hydraulic conductivity), unless the membrane is strictly homoporous. Even in the linear range heteroporosity imposes a hidden condition of delta p greater than delta pi for such a three-parameter description to be valid. Useful results in the nonlinear regime require more detailed information on membrane structure than is contained in just three parameters.


Effect of heteroporosity on flux equations for membranes. An investigation is made of the possible errors in simple integrated equations for solute flux across both non-sieving and sieving porous membranes that can result from variations in the membrane structure. Detailed structural models are used, beginning with a membrane consisting of a parallel array of pores and progressing to series--parallel combinations of pore segments of various lengths and cross-sectional areas, with internal cross connections among pore segments allowed. It is shown that there are both upper and lower mathematical bounds on the possible variations that can be produced in a curve of solute flux versus volume flow by arbitrary variation in the membrane structure, subject only to certain general conditions. In particular, the flux equation for a homoporous membrane is a lower bound. The maximum deviations from this lower bound for a membrane of arbitrary structure are only moderately large, and require rather extreme pore size distributions; most distributions introduce only small errors. Implications of these results in studies of real membrane structure and in the design of experiments are discussed.


The sedimentation equilibrium of heterogeneously associating systems and mixtures of non-interacting solutes: analysis without determination of molecular weight averages. Sedimentation equilibrium is first considered of a system in which a ligand of any size binds to an acceptor at p sites, the experimental result, obtained with either interference or absorption optics, being a distribution of total solute concentration as a function of radial distance. Theory illustrated by a numerical example, is presented which shows that this distribution may be analysed to give the activity of the unbound ligand as a function of total weight concentration. It is shown that this information may be used together with conservation of mass equations written in terms of the initial mixing composition to evaluate the equilibrium constant(s) relevant to the system. Correlation with composition evaluation by use of absorption optics (when possible) is also discussed. The procedure does not involve solution of simultaneous equations which are sums of exponentials nor differentiation of experimental results to obtain apparent weight-average molecular weights. It is general in that it leads to the evaluation of the activity of the species characterized by the smallest M(1-vp) product and, accordingly, is shown to be useful in the analysis of non-interacting as well as of interacting systems.


Thermal membrane potential across charged membranes in NaCl-NH4Cl and LiCl-NH4Cl solutions. Measurements of the thermal membrane potential across cation exchange membranes were carried out by using aqueous solutions containing two 1-1 electrolytes, with an anion in common. The same solution was used on both sides of the membrane. In all cases a good linear relationship was observed between the thermal membrane potential delta psi and the temperature difference delta T (in the range delta T = +/- 10 degrees C). Assuming that the activity of one cation is equal to that of another cation in the solutions and the sum of transport numbers of cations is unity, the plot of delta psi/delta T vs logarithmic activity of one cation is linear with a slope of R/F. These experimental results are in agreement with a theory presented previously. From the analysis of thermal membrane potential in mixtures of electrolytes it is obtained that the cross coefficient of cation-cation interaction in membranes is negative and about 6 to 9% of the main coefficient.


PMR studies of the self-association of DNA intercalating ellipticine derivatives in aqueous solution. In aqueous solution DNA intercalating ellipticine derivatives aggregate in n-mers. The self-association constants K are higher than those of 2-methoxy-6-chloro-9-[3-dimethylaminopropyl-amino]-acridine and ethidium bromide. They are of the same order as that of actinomycin D but inferior to that of acridine orange. The increase of the 9-hydroxy-ellipticine constant by addition of sodium chloride shows the importance of anion participation in the mechanism of stacking in accordance with the high energy of self-association. In the stacked n-mers the ellipticine rings are inverted. The geometry shows the importance of the orientation of the quadrupole axis in the intermolecular association of the intercalating drugs.


The concentration dependence of the hemoglobin mutual diffusion coefficient. Laser correlation spectroscopy was used to measure the mutual diffusion coefficient, D, of human cyanomethemoglobin (Fe+++:CN) at varying protein concentrations. These measurements were made at 20 degrees C in a 0.1 M phosphate buffer solution at pH 7.0. For low protein concentrations we find D = (6.43 +/- 0.26) X 10(-7) cm2/s and that there is a near linear decrease from this value at higher concentrations. The linear relation between the diffusion coefficient and protein concentration allows us to deduce the value of the linear frictional volume fraction coefficient, Kf=7.75, and to extrapolate to hemoglobin concentrations equivalent to that in the red blood cell where we estimate D = 4.25 X 10(-7) cm2/s. Various theoretical predictions of the dependence of the mutual diffusion coefficient on concentration are tested; we find that the generalized Stokes-Einstein relation can be made to fit our high concentration data if we assume a hard-sphere model and if we include a term involving a hydrodynamic interaction integral.


Decreased nucleotide and serotonin storage associated with defective function in Chediak-Higashi syndrome cattle and human platelets. Prolonged mean template bleeding time of 14 min observed in seven cattle with the Chediak-Higashi syndrome (CHS) prompted the examination of platelet function in these animals. There was no distinguishable difference in concentration of circulating platelets between CHS and control cattle. CHS bovine platelets failed to aggregate in vitro in response to concentrations of acid-soluble collagen which induced aggregation in all normal samples. The primary platelet response to 5 muM ADP was normal in CHS cattle. A markedly decreased amount of serotonin (1.2% of normal) was detected in CHS bovine platelets. Bovine CHS platelet ATP and ADP contents were significantly less than normal, and the ATP/ADP ratios were 5.04 in normal and 29.38 in CHS platelets. Results of these animal investigations prompted a similar study of two patients with CHS. In humans, an increased bleeding time greater than 15 min and an in vitro impaired aggregation response to acid-soluble collagen and 5 muM adrenaline were discovered. Both ATP and ADP were reduced in CHS human platelets, and the ATP/ADP ratio was 3.96, compared to a ratio of 1.52 for platelets of two normal subjects. These findings suggested the presence of a "storage pool disease" of CHS platelets.


Potassium uptake and release by human blood platelets. Thrombin is known to reduce the K+ content of human platelets, but the subcellular origin of the lost K+ is not known. The effect of aggregating agents on K+ release was studied in platelets labeled in plasma by preincubation with 42KCI. Platelets were separated from plasma by gel filtration through Sepharose 2B equilibrated with K+ -free Tyrode's buffer. Platelet K+ was 116nEq/10(8) platelets, of which 23% was found to be extracellular immediately after gel filtration. K+ influx was 65 nEq/10(8) platelets/hr at pH 7.5 and was more rapid at pH 7.9. About 70% of cell K+ exchanged with plasma in 4 hr with first-order kinetics, while a minor fraction of about 30% exchanged with a slower time course. This slowly exchanging fraction of platelet K+ was thought to arise from heterogeneity in the platelet population. Epinephrine and ADP aggregated gel-filtered platelets and released serotonin, but with loss of only 5%-10% of cell K+ and no beta-glucuronidase. In contrast, thrombin released up to 30% of platelet K+, whether aggregation occurred or was prevented by not stirring the cells. The specific activity of K+ released by all aggregating agents was identical to the specific activity of total platelet K+. Thrombin (0.01-0.2 NIH U/ml) released serotonin and also beta-glucuronidase (an enzyme of the alpha-granule), and there was a linear relation between release of K+ and this enzyme (r = 0.88). No lysis of platelets occurred, since lactic dehydrogenase was not detected. Pretreatment of platelets with aspirin in vitro inhibited thrombin-induced release of serotonin but had no effect on the loss of K+ or beta-glucuronidase. In contrast, the ingestion of aspirin by mouth inhibited the release of serotonin, beta-glucuronidase, and K+ by thrombin. The data suggested that the K+ loss induced by thrombin was primarily derived from release of alpha-granules and that these organelles contained about 20% of the total platelet K+ in a freely exchangeable and nonsequestered state.


Phospholipid transfer between plasma and platelets in vitro. Washed rabbit platelets were resuspended in plasma in which all of the major phospholipids had been isotopically labeled by injection of 32PO4 into rabbits. At certain time intervals during a 6-hr incubation at 37 degrees C, aliquots were removed from the incubation mixture and the platelets were isolated and subjected to lipid extraction and phospholipid analysis. A continuous rise in platelet non-lipid-bound and lipid-bound radioactivity was observed through-out the incubation period. Two platelet phospholipids, lecithin and lysolecithin, were significantly labeled, whereas little or no labeling of the other phospholipids was found. There was no detectable change in total or individual platelet phospholipid content. At 6 hr, 4% of total platelet phospholipid, 43% of platelet lysolecithin, and 7% of platelet lecithin were labeled. Platelets incubated in plasma from rabbits with diet-induced hyperlipidemia took up and incorporated significantly more label into their phospholipids than did platelets in normal plasma. Labeling of both platelet lysolecithin and lecithin could be due to uptake and metabolism of plasma lysolecithin by platelets. However, labeling of platelet lecithin could at least in part be the result of direct exchange of this phospholipid with the plasma. Uptake and incorporation of endogenous plasma lysolecithin by platelets and, possibly, direct exchanged of platelet lecithin may be important mechanisms in the modification by plasma lipids of platelet membrane phospholipid fatty acid composition and platelet function.


Spinal cord disease in hereditary spherocytosis: report of two cases with a hypothesized common mechanism for neurologic and red cell abnormalities. Two unrelated patients with hereditary spherocytosis developed idiopathic spinal cord dysfunction. This coincidence, combined with similar individual case reports in the older European literature, suggests that abnormalities may exist in constituents common to red cell membranes and nerve tissue. A similar conclusion has been proposed to explain red cell membrane abnormalities in some of the muscular dystrophies.


The conformational requirements for the mechanical precipitation of hemoglobin S and other mutants. The mechanical stability of human hemoglobin mutants was studied for the specific effects of single and double amino acid substitutions, the ligand state of each chain, and the effect of hybrids between oxy and cyanmet partners on precipitability. It was found that the beta6Glu leads to Val and the beta73 Asp leads to Asn mutations increased the degree of mechanical precipitation in the liganded but not in the deoxy form. When these mutations occurred on the same chain, the effects were approximately additive. Heat labile mutants such as Hb Gun Hill and Hb Leiden exhibited mechanical instability, but probably through a different mechanism, as very little dependence on ligand state was apparent. Studies with valency hybrids of HbS(alpha2 betas2-and-alpha2 betas2 where = cyanmet) revealed that instability was primarily determined by the state of the betas chain, which must be liganded to confer instability on the tetramer. A good agreement between surface activity and mechanical precipitability of these mutants has been found.


Molecular and cellular effects of antisickling concentrations of alkylureas. Alkylureas are capable of inhibiting sickling in vitro and the gelation of solutions of hemoglobin S at concentrations between 0.05 and 0.1 M with increasing effectiveness that is directly proportional to the length of the alkyl chain (butyl greater than propyl greater than ethyl greater than methyl). 6The inhibitory effect is independent of pH between 6.5 and 7.5 and is a process driven by entropy. The alkylureas at concentrations of 0.1 M have minimal effects on several erythrocyte functions. Oxygen equilibria, osmotic fragility, reduced glutathione content, and glutathione reductase activity are totally unaffected, while pyruvic kinase activity is decreased only by butylurea by about 20%, and glucose-6-phosphate dehydrogenase activity is decreased progressively to a maximum of 30% in direct proportion to the length of the alkyl chain. Alkylureas not only inhibit sickling but are also capable of desickling erythrocytes that have been maintained in the deoxygenated state. They have little effect on several erythrocyte functions at antisickling concentrations, but their toxicity must be evaluated before they can be examined as potential therapeutic agents for the treatment or prevention of acute episodes in sickle cell anemia.


A diffusible stimulator of eosinophilopoiesis produced by lymphoid cells as demonstrated with diffusion chambers. Previous experiments have indicated that eosinophilopoiesis is stimulated in lymphoid cell-dependent eosinophil responses to certain antigens. In order to study if the potential for this stimulation of eosinophilopoiesis is a function of lymphoid cells and can be expressed on challenge with the eosinophilia-inducing antigen, the diffusion chamber technique for the culture in vivo of murine hemopoietic cells has been modified. A quadrachamber diffusion assembly allows for the simultaneous maintenance in the same host of four cell populations, pairs of which are separated by a cell-impermeable Millipore diffusion membrane of defined porosity. Spleen cells for chambers were from normal mice and mice primed with tetanus toxoid; secondary challenge induces eosinophilia. These spleen cells were placed transfilter from isogeneic bone marrow cells and cultured in vivo for 6 days in normal mice that received tetanus toxoidintraperitoneally following chamber-assembly implant. The marrow cell transfilter from spleen cells of primed-donor origin exhibited significantly greater eosinophilopoiesis than contiguous-chamber marrow transfilter from normal spleen cells. Such stimulated eosinophilopoiesis was independent of total chamber marrow cellularity. The data indicated that antigen-stimulated lymphoid cells may be the source of an eosinophilopoietic factor.


Evidence for early recruitment of granulocyte precursors during high-dose methotrexate infusions in mice. The effects of constant exposure to high concentrations of methotrexate in vivo on the committed stem cell (CFU-C) were studied by in vitro culture of mouse bone marrow. Bone marrow samples were obstained from animals receiving a continuous infusion, and were cultured in a methotrexate-free semisolid gel system. The effects of methotrexate infusion on the pluripotent stem cell population (CFU-S) were studied as well. Constant exposure to 10(-5) M methotrexate produced a rapid decrease in total nucleated cells per femur, reaching 35% of control at 12 hr and remaining at approximately this level throughout 48 hr of drug infusion. A decrease in the number of both CFU-C and CFU-S per femur was observed, which paralleled the drop in nucleated cells during the first 24 hr. However, in contrast to an additional drop in the number of CFU-S, an increase of CFU-C number per femur was observed from 24 to 48 hr. These data indicated a self-limited cell kill of nucleated bone marrow cells, and suggested recruitment of CFU-C from the CFU-S pool between 24 and 48 hr of infusion despite continued methotrexate infusion.


The biochemical basis of nitroblue tetrazolium reduction in normal human and chronic granulomatous disease polymorphonuclear leukocytes. Normal human polymorphonuclear leukocytes (PMN) placed in anaerobic chambers reaching pO2's of less than 5 mm Hg fail to generate O2-, iodinate ingested particles, and stimulate glucose-1-14C oxidation through the hexose monophosphate shunt. The observation that anaerobic cells are incapable of generating O2- or reducing nitroblue tetrazolium (NBT) to formazan supports the idea that NBT reduction in phagocytizing PMN is due exclusively to oxygen-dependent O2- generating oxidase which is deficient in chronic granulomatous disease leukocytes, despite their hyperphagocytic capacity.


In vitro function and post-transfusion survival of granulocytes collected by continuous-flow centrifugation and by filtration leukapheresis. The function of granulocytes collected by continuous-flow centrifugation (CFC) and by filtration leukapheresis (FL) was studied in vitro, and the post-transfusion recovery and intravascular survival of these cells was studied by autologous transfusion in normal donors. Granulocytes collected by both FL and CFC leukapheresis (CFCL) functioned normally in the quantitative nitroblue tetrazolium, oxygen consumption, and chemotaxis assays. Bacterial killing was slightly but consistently decreased in FL but not CFCL granulocytes. The post-transfusion recovery of control granulocytes collected by ordinary phlebotomy averaged 52% in eight transfusions, compared with 34% for six CFCL granulocyte concentrates and 16% for six FL concentrates. The intravascular half-times were 3.8 hr for phlebotomy and 3.0 hr for CFCL granulocytes. FL granulocytes had survival curves which were nonlinear and a single half-life could not be calculated. The average half-time 30 min after transfusion was 1.3 hr, and 3 hr after transfusion it was 2.6 hr. Granulocytes collected by FL had a mild impairment of bacterial killing, decreased post-transfusion recovery, and altered intravascular kinetics. None of these abnormalities was found in granulocytes collected by CFCL.


Management of health services in the Commonwealth Caribbean. Putting aside the very substantial gains made in recent years by health services of the Commonwealth Caribbean, this article reviews the administrative problems faced by those services at the present time. For the most part, these problems appear to have two main sources: weakness of the colonial heritage, and greatly increased popular demands following the attainment of associated or independent status. In general terms, there are a great many current needs. In many cases, for example, it would help to give more attention to identification and delineation of specific health problems, to make more extensive use of planning, to update existing legislation, to establish a better information system, to revise the budget classification system and loosen budgetary controls, to improve supply management, to more thoroughly define areas of official responsibility, to reassert individual responsibility for decision-making, and to streamline administrative channels. All in all, the problems faced by the health services make it imperative to reexamine the possibilities for implementing administrative reforms. It is felt, however, that besides being addressed to current problems, such reforms should be designed to help the health service cope with any new situations that may arise - before such situations can threaten its vital contribution to social and economic well-being.


Study of the area affected by onchocerciasis in Brazil: survey of local residents. An epidemiologic survey encompassing most of Brazil's Federal Territory of Roraima and the northern tip of Amazonas State has been carried out in an effort to define the boundaries and the epidemiologic characteristics of onchocerciasis in Brazil. This article describes results relating to human infections--including discovery of a new focus at Auaris in northern Roraima and analysis of data from tests conducted there and at various other locations. These findings lead the authors to conclude that the three known Brazilian foci represent independent influxes of the disease from neighboring Venezuela, that groups of both Yanomama and Makiritare Indians have been infected, and that various factors (including proximity of these foci and the route for Brazil's Northern Perimeter Highway) indicate the disease could pose a potential danger for other areas of Brazil.


Clinical aspects of human Venezuelan equine encephalitis in Texas. The Venezuelan equine encephalitis epidemic which occurred in Texas in 1971 produced a wide range of predominantly mild clinical symptoms. This epidemic, which peaked on 13-14 July, was most intensely felt in the far-south counties of Cameron and Hidalgo. In all, 88 laboratory-confirmed human cases were reported to the U.S. Center for Disease Control by the Texas State Department of Health. The ratio of male to female cases was about two to one. An attack of 20.8 cases per 100,000, observed in both the 20-29 and 30-39 age groups, was higher than attack rates experienced by other age groups and by the population at large. Together, Cameron and Hidalgo counties experienced a much higher overall attack rate (21.7 cases por 100,000) than did affected counties in the Corpus Christi area (4.9 cases per 100,000). Knowledge about when various patients were first exposed points to an incubation period ranging from 27.5 hours to four days. In those 79 cases for which clinical data were available, the most common clinical manifestations were found to be fever, severe headache, myalgia, and chills. Evidence of mild to moderate central nervous system involvement was found in 10 out of 25 children and young people under 17 years of age, and in six out of 54 adults. Two children still had residual paralysis six weeks after onset of illness, but by 10 months these sequelae had disappeared. Seven of the 54 adults, however, still complained of tiring easily a year after onset of illness. Leukopenia, as demonstrated by a count of less rhan 4,500 white blood cells per cubic millimeter, was observed in 75 per cent of the patients examined.


Policies of the Office of Population Censuses and Surveys. Philosophy and constraints. The Medical Division of the Office of Population Censuses and Surveys (OPCS) organizes and indexes general systems of records for medical research and administration. The main sources of records are the census, registrations of births and of deaths, hospital discharge records, registered cases of cancer and of congenital malformations, surveys by the Social Surveys Division, and samples of records in general practice. Results take the form of regularly published series of statistics and commentaries and of studies in depth, often by scientists in the National Health Service (NHS), and research institutions which are encouraged to use the systems for prospective and retrospective surveys. The surveys are facilitated by the central registry where a note of every death in the country is attached to the relevant record (and the causes of death are available). Recent developments include studies of records of general practitioners; the causes of deaths among immigrants in England and Wales; the fertility, migration, and mortality of a cohort of about 1 percent of the population. The publication policy of OPCS is described.


Malignancy in relatives of patients with coeliac disease. A survey of 1329 relatives of 139 patients with coeliac disease demonstrated an overall increase of cancer deaths particularly in women, but this did not quite reach 5 percent significance in men. Evidence is insufficient to determine whether this was due to the occurrence of cancer in relatives with undetected coeliac disease or to the operation of independent factors.


Seasonal distribution of Henoch-Schönlein purpura. A review of 76 Southampton children with Henoch-Schönlein purpura has confirmed that there is no evidence of a streptococcal aetiology in the majority of cases of this disease. Among these patients the frequency of preceding respiratory infection of all kinds was only 7 percent greater than that in controls. Data on month of admission in four areas of England and Scotland show that the incidence of the disease is lowest in the June-August period. Contrary to previous findings there is no marked peak of incidence in any single month.


Twinning and anencephalus occurrence in relation to fetus-fetus interaction. The hypothesis proposed by Knox (1970) that an anencephalic fetus arises from a fetus-fetus interaction between two dizygous twins predicts that the twinning rate, the population incidence of anencephalus, and the female proportion of anencephalics in a population should be positively interrelated. These associations were tested using Canadian data during a long period of time and over a large geographical area. The results did not support the hypothesis.


Trace elements in water and congenital malformations of the central nervous system in South Wales. The concentrations of 20 trace elements were determined by atomic absorption spectrophotometry on representative samples of tap-water collected from 48 local authority areas in South Wales. The associations between twelve trace elements and central nervous system (CNS) malformation rates for the 48 areas were examined. Significant correlations for four trace elements were observed. Of these, Al was positively correlated while for the remaining three-Ca, Ba, and Cu-negative associations were found. Regression analysis of the data suggested that the relationships between Ba and Cu with CNS malformation rates were improtant than those of Al and Ca.


Maintenance of weight loss in obese subjects. The records of a selected group of 215 subjects who had successfully lost surplus weight were followed-up for periods of one to six years. Mean initial weight was 131% of standard (19.5 kg surplus) and the mean time taken to achieve 'goal weight' was 7.05 months (range two to 20 months) at a mean rate of 2.9 kg per month (range 1.85 to 5 kg). Altogether 121 subjects (56.3%) maintained goal weights within plus or minus 2.3 kg of goal; 79 subjects (36.7%) maintained within plus or minus 4.5 kg. At time of examination of the records, 39 subjects (18.8%) had maintained constant weight for more than four years, 22 subjects (10.6%) for three to four years, 65 subjects (31.4%) for two to three years, 58 subjects (28.5%) for one to two years, and 23 subjects (11.1%) for periods of up to one year.


Incidence and variables contributing to onset of cigarette smoking among secondary school children and medical students in Lagos, Nigeria. This paper reports the findings of a survey of smoking habits among secondary schoolchildren and medical students in Lagos, Nigeria. Altogether 40% of boys and 8.4% of girls at secondary school, and 72.4% of men and 22.2% of women at medical school were found to smoke. While the smoking habit of the secondary schoolboys was influenced by the smoking habits of their parents and friends, the smoking habit of the secondary schoolgirls and female medical students was mainly influenced by that of their friends. This study provides a baseline against which future studies on smoking habits in developing African countries may be measured, and the results show that health education on cigarette smoking must start in primary and secondary schools.


Radiology of acalculous gall-bladder disease - a new sign. Radiography of excised gall-bladders, immersed in water, has shown that chronically infected gall-bladders frequently contain fat. This fat can be seen in vivo, and the frequency of the finding was assessed by reviewing 43 patients with acalculous gall-bladder disease. Other radiological signs in the cholecystograms were looked for retrospectively, and their incidence assessed. In 20 cases out of 40, no radiological abnormality was found.


Ultrasonic diagnosis of choledochal cyst in pregnancy. Two patients are reported with obstructive jaundice in pregnancy. In one of these ultrasonic scanning confirmed a diagnosis of choledochal cyst, and in the other made this diagnosis. Ultrasonic scanning is suggested as the preliminary radiological examination for obstructive jaundice in pregnancy. Any patient with a clinical diagnosis of choledochal cysts should have an ultrasonic scan.


Analysis of dose, dose-rate and treatment time in the production of injuries by radium treatment for cancer of the uterine cervix. A retrospective study has been made of 15 patients who had developed severe complications to the bladder, rectum and ureters after radiation therapy for carcinoma of the cervix. Comprehensive dose distribution in the pelvis were calculated with computer assistance to visualize how the normal organs had been irradiated. The risk of normal tissue injury was analysed graphically with respect to the maximum radium dose, dose-rate and irradiation time. The two groups of data representing the injured and non-injured organs separate much better in a dose-rate versus dose plot than in a conventional Strandqvist type dose-time plot. This implies that in radium therapy, the dose-rate rather than the treatment time, is the important parameter in modifying the risk of normal tissue injury. Our results show a good separation of injured from non-injured cases only when the maximum values of dose and dose-rate were used. This suggests that clinically significant injury may develop from relatively small regions of high dose and dose-rate. Since the dose-rate varies from point to point in the pelvis (unlike treatment time), comprehensive determinations of dose-rate distributions are required in order to locate the sites of potential injuries.


Mathematical derivation of optimal treatment schedules for the radiotherapy of human tumours. Fractionated irradiation of exponentially growing tumours. A mathematical model is developed to allow derivation of optimal treatment schedules for the radiotherapy of exponentially-growing tumours. Preliminary calculations based on available data suggest that optimal schedules would (in general) be more protracted than conventional schedules and might achieve a significantly better tumour cell kill without causing excessive damage to normal connective tissue. The model is too simple, and the data inadequate, for the conclusions reached to be used as a guide to clinical practice at present. However, the analysis can be extended to more realistic models which may be of clinical benefit when the appropriate data can be obtained.


Pseudo optimization of radiotherapy treatment planning. A chain consisting of three computer programs has been developed for treatment planning of external beam radiotherapy without manual intervention. Apart from the data necessary to identify the patient, the institute, etc., the input consists only of the anatomical information indicated on an outline sheet. Firstly, combinations of incidence directions for a two or three-beam set-up are judged by the first program. Then a limited number of these combinations is selected by this program. For every beam of each selected combination a set of wedges and weights is calculated. Next the dose distributions belonging to each combination with wedges and weights are judged by the second program. Finally, the isodose pattern of the dose distribution judged the best is determined by the third program. The judgement of incidence directions is done by coarse score functions corresponding to a set of criteria. The judgement of dose distribution is done by detailed score functions corresponding to another set of criteria. These criteria with their score functions are treated in some detail. The use of the programs in the clinic is discusses and results are shown.


Change in oxygen enhancement ratio with depth in tissue-equivalent material for a collimated beam of fast neutrons. Survival of reproductive capacity of murine leukaemia P-388 cells was assayed in vivo after the cells had been irradiated in vitro under aerobic or hypoxic conditions with collimated beams of X rays or 16 MeV D-Be fast neutrons at various depths in tissue-equivalent phantom material. The response to X-irradiation was the same in the absence of the phantom and at 8-7 cm depth. The response to fast neutrons under aerobic conditions was unchanged from 0 to 23 cm depth within the phantom. However, under hypoxic conditions, the dose-response curve for fast neutrons became significantly steeper with increasing depth in the phantom. The OER decreased from 2-0 in the absence of the phantom to 1-5 at 15 cm deep.


Role of neocortex in binaural hearing in the cat. II. The 'precedence effect' in sound localization. The 'precedence effect' in sound localization refers to the situation in which two speakers, separated in space, emit identical sounds but one speaker leads by a few milliseconds. Normal observers perceive all the sound as originating from the leading speaker. In the present experiment cats were tested before and after unilateral ablation of auditory cortex on how well they could transfer a learned sound loclization response from situations involving unpaired sound sources to those with paired sources. Cats were tested with tone pairs separated by 5 msec and with clicks separated by delays of 3, 5, 7, 9, 12 and 16 msec. Preoperatively, the cats averaged 98% correct at a delay of 3 msec and 58% correct at 16 msec. Before surgery the probability of an error was independent of which speaker was leading; after surgery cats made significantly more errors when the leading speaker was located opposite the side of the lesion. Considerable individual variability was found with the 3 and 5 msec delay tests; some cats showed no evidence of a cortical deficit while others exhibited initial severe deficits which disappeared with training. At delays of 7-16 msec all cats showed severe directional deficits which were still present after 9 months of retraining. Results are interpreted as supporting the hypothesis that unilateral lesions disrupt binaural loudness rather than temporal relations.


Respiratory frequency as a function of preoptic temperature during sleep. The effects on respiratory frequency of preoptic heating during slow-and fast-wave sleep were studied in freely moving cats. During slow-wave sleep, at neutral ambient temperature, the subliminal range of preoptic temperature for thermal polypnea extends to 0.2-0.4 degrees C above control preoptic temperature. During fast-wave sleep, at neutral ambient temperature, the subliminal range of preoptic temperature for thermal polypnea increases beyond 0.9-1.0 degrees C above control preoptic temperature. Moreover, the polypneic response is weak and unstable. The results show the suspension of a precise thermoregulatory control during fast-wave sleep in a homoiothermic species.


Early and permanent effects of monocular deprivation on pattern discrimination and visuomotor behavior in cats. Visuomotor behavior and pattern discrimination were studied in a group of cats raised with one eye closed by eyelid suturing 7-10 days after birth. At the age of 8-10 months the animals were forced to use their deprived eye by reversal of eye closure (closing the normal eye and opening the deprived one). Visuomotor behavior and pattern discrimination were tested before as well as after reverse closure, to compare performances of the deprived eye with those of the non-deprived eye. In order to get optimal visuomotor experience, the animals were kept in large playrooms for at least 4h each day. Except for normal tactile placing responses, visually triggered extension responses and uncertain jumping, 2 years after reverse closure all other tests (visually guided reaching, visual cliff behavior, obstacle avoidance, tracking, jumping, and visual blink responses) still showed impairments; the optokinetic nystagmus was asymmetric. In contrast with this partial behavioral recovery, pattern discrimination in a simple nose-push training box requiring no complicated visuomotor coordination was found to be positive. Discriminations of gratings of different orientations, starting 4 weeks after reverse closure, appeared to be normal, in comparison with performance using the non-deprived eye of the same cats tested before reverse closure. Form discrimination was also found to be positive; some monocularly deprived cats required more trails than normal cats in upright vs. reversed solid triangles discrimination, but succeeding form problems were mastered within the same range as found in normal cats. Apparently behavioral defects after monocular deprivation are due to deficiencies in visuomotor control rather than in pattern identification.


On the structure and function of a neurohemal organ in the eye cavity of Eledone cirrosa (Cephalopoda). The subpeduncualte lobe of the octopod brain produces a hormone that is released into the orbit. The hormone was extracted from Eledone cirrosa and assayed on the isolated perfused heart of the same species. It has a remarkable effect on amplitude, beat frequency and blood pressure; compared to equivalent extracts of posterior salivary gland it is about 70 times more effective. The substance is not a biogenic amine.


Polypeptide secretion from the eye of Aplysia californica. The possibility of neurosecretory activity by the eye of Aplysia californica has been suggested by morphological findings. An investigation was conducted to determine if evidence for the release of macromolecular material labeled with radioactive amino acids could be obtained. Depolarization of the eye by superfusion with medium containing an elevated potassium concentration resulted in a significant increase of labeled macromolecular material in the superfusate. This potassium-induced release could be blocked by reduction of the calcium concentration in the superfusing medium. The locus of release appears to be the eye proper and not to involve the optic nerve.


Quantitative data on serotonin nerve terminals in adult rat neocortex. Serotonin (5-HT) nerve terminals, specifically labeled with [3H]5-HT have been counted in light microscope radioautographs from the fronto-parietal neocortex of adult rats, following prolonged superfusions with relatively high concentrations of tracer (10(-5) M or 10(-4) M), and after 15 or 30 days of radioautographic exposure. Comparative analysis of the results indicated that all 5-HT varicosities did not possess the same capacity to accumulate the exogenous amine. Nevertheless, superfusions with 10(-4) M[3H]5-HT provided a sufficient loading of 5-HT boutons to allow their complete detection within any given layer of the neocortex. The labeled varicosities were found to be present within all cortical layers, except layer VI. Their total number was extrapolated to be approximately 1 X 10(6)/cu.mm of cortex. This figure represented a mean incidence of one 5-HT nerve terminal/850-1400 cortical synapses (0.07-0.12%). The intralaminar density of 5-HT innervation increased progressively from layer V to layer I, in a distribution pattern suggestive of unspecific afferents. Based on endogenous 5-HT levels of 346 +/- 32 ng/g for the fronto-parietal neocortex, the mean 5-HT content per varicosity could be estimated to be 0.35 X 10(-3) pg, and the concentration 1900 ng/g wet weight of terminal or 0.2%. In view of their particular ultrastructural features7, ubiquitous repartition and endogenous amine content, 5-HT nerve endings may be considered as capable of exerting a rather widespread influence in the neocortex.


Selective cell association of catecholamine neurons in brain aggregates in vitro. Brain tissues (aggregates) were reconstructed in vitro from dissociated single cell suspensions derived from 12- to 18-day embryonic mouse midbrain containing the substantia nigra. The application of the Falck-Hillarp histofluorescence method to these cell systems allows the visualization and identification of this specific population of developing catecholamine (CA) neurons during their reassembly, differentiation and histogenetic patterning in vitro. CA neurons are unselectively distributed in the initial dissociated cell suspension and in the reaggregating tissue up to 24 h. By 48 h the CA neurons have selectively associated into small clusters which further coalesce into a thick and elongated band along one margin of the aggregate by 96 h. This structure is similar in organization to the morphology exhibited by substantia nigra neurons in situ during their migratory phase in normal development. In addition, the differentiated neurons observed in the later aggregates appear to produce normal processes. Catecholamine analyses show a significant increase in dopamine and noradrenaline levels during the process of differentiation and histogenetic organization in vitro.


Interactive effects of brain catecholamines and variations in sexual and non-sexual arousal on copulatory behavior of male rats. In pargyline pretreated male rats, an intraventricular 6-hydroxydopamine procedure which resulted in subtotal brain catecholamine (CA) depletion produced a mild defict in copulatory behavior followed by rapid recovery. Challenges employed to study the behavioral capacities of these 'recovered' animals revealed: (1) a heightened sensitivity to acute treatment with the CA synthesis inhibitor alpha-methyl tyrosine (AMT) as reflected in a reinstatement and exaggeration of the original copulation deficit; (2) a greater dependence on the sexual eliciting properties of the female, since abolishing her soliciting behavior also reinstated and exaggerated the sexual dysfunction; and (3) a pattern of behavioral impairment indicating increased difficulty in both initiating sexual activity and maintaining copulatory performance. Furthermore, in males not copulating after 6-OHDA/AMT treatment, copulation could easily be induced by the simple application of a non-specific activating stimulus. On the basis of these data and parallel findings reported for other behaviors, we have concluded that: (1) both the initiation and maintenance of copulatory behavior in the male rat is the part dependent on normal functioning in one or more of the brain CA-containing systems; and (2) this copulatory deficit is symptomatic of a broader functional impairment reflecting reduced behavioral responsiveness to stimuli that normally elict appetitive or approach responses but not to stimuli requiring more automatic, inhibitory responses.


Effects of GABA, glycine, picrotoxin and bicuculline methochloride on rubrospinal neurones in cats. A microelectrophoretic study was performed of the actions of GABA and glycine, and of their antagonists on rubrospinal neurones. GABA and glycine depressed antidromic and synaptic potentials, hyperpolarized the cell membrane and increased the membrane conductance. GABA was more effective than glycine. Corticorubral IPSPs and the GABA-induced membrane hyperpolarization could be reversed by intracellular application of hyperpolarizing currents. Picrotoxin and bicuculline methochloride antagonized inhibitory GABA actions and the corticorubral IPSP or the corresponding extracellular positive field potential. The results support the hypothesis that GABA is the transmitter of the corticorubral inhibition in the cat.


Brain metabolism and the acquisition of new behaviors. I. Evidence for specific changes in the pattern of protein synthesis. The pattern of incorporation of labeled valine into goldfish brain proteins was compared for animals trained in a new swimming skill with controls. Double labeling studies followed by electrophoretic separation of the proteins on SDS-polyacrylamide gels, showed that there was a consistent increase of valine incorporation for the trained animals at 3 band positions on the gels. These alpha, beta, andnu bands correspond to molecular weights of 37,000, 32,000 and 26,000 daltons. The protein changes were confined to the brain cytoplasmic fraction, in that they were absent from the brain nuclear, brain synaptosomal, and kidney cytoplasmic proteins. Such protein changes were not obtained for a variety of control behavioral situations. The results suggest that there is higher rate of synthesis of specific proteins in goldfish brain following the acquisition of a new pattern of behavior.


Adenosine triphosphate in cholinergic vesicles isolated from the electric organ of Electrophorus electricus. Synaptic vesicles have been isolated from the electirc organ of the bony fish Electrophorus electricus using sucrose step gradients and zonal centrifugation. Although the acetylcholine (ACh) content of the Electrophorus electric organ is only 2% of that of Torpedo, ACh and ATP can readily be measured in the peak fractions using the leech microassay and the firefly luciferin luciferase assay respectively. The protein content of the vesicle fraction in experiments with Electrophorus was much higher than with Torpedo, but a possible contamination of this fraction with mitochondrial or cytoplasmic particles could be excluded. The ACh to ATP ratio of 10.8 is close to that found for cholinergic vesicles isolated from Torpedo and also to that of other amine storing granules.


Release of amino acids from the maturing cobalt-induced epileptic focus. A study was made of the release of excitatory, inhibitory and other amino acids from epileptic foci induced in the sensorimotor cortex of rats by cobalt implantation. A new in vivo superfusion method was employed which gives free movement to the animals and allows study over periods of days and weeks. Most amino acids showed maximum release rates during the first 2 or 3 days after surgery. Glutamate showed maximum release rates during days 3-6 when epileptic limb jerks were at a maximum. This pattern was not seen for other physiologically active amino acids.


Clinico-pathological study of an organized plaque in exudative diabetic maculopathy. A clinical and histopathological study of an organized macular plaque in a diabetic with hard exudate plaques showed diabetic microangiopathy, degeneration, proliferation and serious separation of the pigment epithelium, but no evidence of disease of Bruch's membrane or the choriocapillaris. The possible absence of choroidal neovascularization suggests that the fibrous scar originated in the retina and pigment epithelium. This lesion may be a specific response to the development of a plaque of hard exudate at the macula.


Results of the carotid and the differential jugular compression tests in normal and glaucomatous patients. A carotid compression tonographic test was performed in 53 normal persons and 40 patients with primary open-angle glaucoma. Fifty normal and 58 glaucomatous patients were investigated by a differential jugular compression test. In the glaucomatous eyes as compared to the normal eyes the volume changes in the eyeball were found to be significantly greater during compression of the common carotid artery and significantly less under the influence of the jugular compression test.


Malignant melanoma of the choroid with balloon cells a clinicopathologic study of three cases. We report the findings on clinicopathologic examination of three patients with balloon cell melanoma of the choroid. Ophthalmoscopically, all three had small, slowly progressive tumors at the posterior pole, with an encircling yellow halo. With fluorescein angiography, the yellow halo showed fluorescence similar to the remainder of the tumor, thus differentiating this substance from lipofuscin pigment, drusen and exudates. Light microscopy demonstrated prominent balloon cells which were most numerous at the tumor margins. These cells showed variable melanin pigmentation and were negative for lipid, acid mucopolysaccharide, and glycogen. Special enzyme studies (lactic dehydrogenase, succinic dehydrogenase, acid phosphatase, beta glucoronidase and aminopeptidase) demonstrated some similarity to melanocytic cells. Electron microscopy revealed premelanosomes and complex melanosomes in the cytoplasm of balloon cells without evidence of significant lipid.


[Zona ophthalmica and dendritic keratitis]. Two cases of herpes zoster ophthalmicus with dendritic keratitis are reported. Virological studies confirmed the double infection with herpes simplex type 1 virus in the corneal lesions and herpes zoster virus in the cutaneous lesions. We suggest the use of the immunoperoxidase test to identify the viral agent mainly because of its rapid and specific results. We are against the use of local steroids in dendritic keratitis unless the etiological agent is proved to be herpes zoster virus and not herpes simplex virus.


An assessment of the generation times of neuronal precursors in the sensory retina and subventricular zone of the newborn rat. Generation times and the times for their respective phases were determined for neuronal precursors in the sensory retina and subventricular zone of the brain of newborn CD rats. These regions can be induced to form retinoblastoma and medulloepitheliomas, respectively, following injection of adenovirus-12. Through use of autoradiographic techniques, it was shown that the cell cycle duration in the subventricular zone was almost twice as long as in the sensory retinal layer. The G1 phase durations were found to account for the majority of the time difference.


Survival of two trematode parasites (Diplostomum spp.) in mammalian eyes and associated pathology. Cercariae of Diplostomum spathaceum dropped onto the eyes of small unanaesthetized rabbits penetrated through the cornea, crossed the anterior chamber, and entered the lens. After 2-3 weeks they died and became semi-permanent amorphous cataracts. Cercariae remaining in the cornea became the centres of stromal nebulae 0.1-0.2 mm across which remained visible for at least 3 months. Re-exposure produced marked conjunctival inflammation. Parasites applied to the eyes of large adult rabbits or cold-stored enucleated eyes of man entered the cornea but failed to penetrate as far as the anterior chamber. It is suggested that cercariae are unlikely to reach the lens of bathers because of the thickness of the human cornea. However, exposure to infection may result in temporary conjunctival inflammation and more persistant stromal nebulae. Cercariae of the closely related D. adamsi, did not penetrate or develop in the eyes of mammals.


Chemotactic migration of leucocytes through corneal layers: an in vitro study. The ability of polymorphonuclear leucocytes (PMNs) to migrate into the different corneal layers in the presence or absence of a chemotactic stimulus was investigated in rabbits. The epithelial and/or endothelial surfaces were damaged in some corneas and in others they were intact. One side of the cornea was kept in contact with a viable population of rabbit PMNs and the other side with a chemotactic agent (zymosan activated human serum). The migration of PMNs into the cornea was traced histologically. The PMNs could not penetrate intact epithelium and Descemet's membrane even under the influence of a chemotactic stimulus. The stroma allowed PMN migration only when the chemotactic agent was present. The endothelium offered no resistance to PMN invasion whether the chemotactic stimulus was present or not.


Causes of initial visual loss following blunt ocular injuries: an experimental study. We have investigated in anaesthetised pigs the electrical responses of the retina to light after blunt injuries to the eye. Retinograms, cortical visual evoked responses and intraocular pressures were recorded before and after non-perforating mechanical trauma of sufficient severity to produce traumatic retinal opacification. After injury, applanation pressures rose up to 34 mm. Hg above normal, reaching peak values 4 to 12 minutes after trauma and returning to pre-trauma levels after about 45 minutes. These pressure changes were not responsible for the immediate abolition of the B wave of the retinogram or of the cortical visual evoked responses which occurred after trauma, but increases of intraocular pressure modified the recovery pattern of the visual evoked response.


Traumatic macular hole.

Traumatic macular hole. A traumatic macular hole has never been seen immediately after the causal accident. We examined a case of macular hole within half an hour of the injury and photographed it within three hours. We comment on the genesis of traumatic macular edema.


Orbital amyloidosis.

Orbital amyloidosis. A 51-year-old male presented with a chronic asymmetrical ptosis which was variable. Repeated anticholinesterase testing gave equivocal responses. The patient was treated for myasthenia gravis until a mass was detected in the orbit. Although rare, localized orbital amyloidosis should be considered in the diagnosis of patients with ptosis, particularly when the results of anticholinesterase testing are equivocal.


Amyloidosis of the iris.

Amyloidosis of the iris. A case of ocular lepromatous leprosy with secondary amyloidosis of the iris is reported.


Presumed glial retinal hamartomas in Usher's syndrome. The presence of glial hamartomas of the retina and the optic disc in retinitis pigmentosa is discussed. This association is described in a 26 year old white male with Usher's syndrome who had at the posterior pole of each eye a mass which closely resembled the mulberry-like lesions of tuberose sclerosis. Several fine blood vessels were seen on the surface of these masses. The significance of the association of these presumed hamartomas with retinitis pigmentosa is not clear. They might be the result of a focal reactive hyperplasia of the glial cells of the retina.


Internal ophthalmoplegia following chickenpox. A six year old girl with a six day history of varicella presented with a fixed dilated pupil, paralysis of accomodation and an anterior uveitis in the left eye. The anterior uveitis rapidly resolved but the internal ophthalmoplegia has persisted for fifteen months. Four similar cases are reviewed.


The Stryker turning frame in surgery of posterior displacement of the lens. A Stryker turning frame was used during surgical removal of a posterior displaced lens. Its use had the following advantages over other methods: simplified management of the patient under general anaesthesia; constant stability of the eye and transfixing needle during the procedure and the maintenance of sterility in the operating area.


Gastrointestinal hormones.

Gastrointestinal hormones. The availability of pure intestinal hormones and the development of radioimmunoassays for their measurement has expedited research into many aspects of gastrointestinal endocrinology. A complex balance evidently exists between the different intestinal hormones and also the rest of the endocrine system. Polyendocrinopathies have been described, and, so far, two diseases due to intestinal hormone excess (Zollinger-Ellison syndrome and the syndrome of watery diarrhea, hypokalemia and achlorhydria) elucidated. It seems likely that many more gastrointestinal endocrine diseases await discovery.


Effects of ambient and stagnant hypoxia on the mechanical and electrical activity of the canine upper jejunum. The effects of ambient and stagnant hypoxia on the mechanical and electrical activity of the upper jejunum were studied in 32 anesthetized dogs. A 50 or 75% reduction in oxygen content of inhaled air produced ambient hypoxia; superior mesenteric artery (SMA) occlusion or thrombin-induced mesenteric thrombosis resulted in stagnant hypoxia. Induction of hypoxia was immediately followed by a transient increase in mechanical activity. A 50% reduction in oxygen content had no other effect. A 75% reduction in oxygen content resulted in a gradual decrease in electrical control activity (ECA) frequency and in the disappearance of electrical response activity (ERA), and in jejunal contractions; however, ECA persisted until cardiac arrest occurred after 30 to 45 minutes of hypoxia. Occlusion of the SMA resulted in a significant decrease in contractile activity but ECA was not affected. Thrombin-induced mesenteric thrombosis produced rapid and irreversible disappearance of both electrical and mechanical activities. Jejunal contractions and ERA are dependent upon an adequate oxygenated blood supply. ECA however, is highly resistant to reduction in oxygen content of perfused blood and continues until perfusion stops.


Dexon versus conventional sutures in hernia repair. An unselected study of 87 inguinal herniorrhapies was carried out over a 2-year period using polyglycolic acid (Dexon) sutures in 46 procedures and conventional sutures in the remaining 41. Tissue reaction was the same with both types of suture; however, the incidence of recurrence was lower with the use of conventional sutures. This study has not confirmed the superiority of Dexon sutures reported in other studies.


Use of the thermography for the early diagnosis of deep vein thrombosis following hip operations. Up to 50% of patients suffer from deep vein thrombosis (DVT) after major hip surgery. Frequently DVT cannot be diagnosed clinically. To the present, venography alone has been used in these patients, but it is time consuming, necessitates an intravenous dye injection and is not without complications. Now, however, the technique of thermography is available as an additional diagnostic aid. The results of thermography were assessed in 24 patients who had recently undergone major hip operations and compared with those obtained by venography. Thermography did identify DVT in the lower leg veins of patients with no clinical symptoms, but higher obstructions were only diagnosed by venography. Thermography gave one false-positive result later disproven by venography. Thermography has the advantage of being noninvasive and economical; it will become more useful when smaller portable systems are developed.


Diffuse cavernous hemangioma of the spleen. Diffuse hemangioma of the spleen occurred in a 59-year-old man. The presenting features were a dull ache and heaviness in the left upper quadrant for 3 weeks, severe left-sided pain and fever immediately before hospitalization, and a tender mass in the left upper quadrant. The condition was diagnosed at laparotomy; splenectomy was performed. In this case intrahemangiomatous hemorrhage had occurred, but not rupture of the spleen, which is a potentially lethal complication. Other complications of diffuse splenic hemangioma are thrombosis, infarction, infection with abscess formation, and partial calcification of the vascular spaces. The condition is rare; only 56 cases have been reported.


Conservative management of extrauterine pregnancy. An abdominal pregnancy in a 28-year-old nulliparous woman with a fertility problem was treated conservatively. The clinical antenatal course was unremarkable. A healthy 2000-g infant was delivered at term by laparotomy. The placenta was removed at the same time. Three years later the patient had a ruptured tubal pregnancy which was treated by salpingectomy. The literature on extrauterine pregnancy is reviewed briefly.


Radiation therapy and Corynebacterium parvum in the treatment of murine tumors. The relative effectiveness of local irradiation alone or combined with Corynebacterium parvum (C parvum) treatment has been investigated employing four tumors: a mammary carcinoma (MCa) (nonimmunogenic), a fibrosarcoma (moderately strongly immunogenic), and two squamous cell carcinomas (SCC-2 being weakly and SCC-4 being very weakly or nonimmunogenic). C parvum treatment was started when the isotransplanted tumor growing in the mouse leg was 5 mm in diameter and the local irradiation was administered to 8-mm diameter tumor. Effect of the combined treatment was barely evident with the MCa but strongly present in FSa; up to 60% of mice were cured of FSa by C parvum alone and the response to low radiation dose, e.g., 200 rads, was highly increased. For SCC-2 the TCD50 was approximately 7000 rads and 3000 rads in control and test mice, respectively. Comparable values for SCC-4 were 7700 and approximately 5500 rads. Importantly, for SCC-4 there was a large and highly significant reduction in the proportion of mice that died of metastases to lung but were free of evident tumor at the primary site.


The treatment of radiation necrosis with hyperbaric oxygen (OHP). Sixty-nine patients with radiation necrosis were received by the authors from January 1, 1969 through August 1, 1975. The patients were categorized according to site of injury. Full treatment protocol is discussed including local wound care, antibiotic coverage, surgical procedures, and the administration of hyperbaric oxygen. Results indicate that the combination of hyperbaric oxygen, properly timed surgery, and antibiotic therapy has resulted in improvement in all cases of radiation necrosis and full healing in most.


Results in irradiation of the in situ carcinomas of the vocal cords. From 1952 through 1973, 79 patients with the diagnosis of in situ carcinoma and seven with the diagnosis of leukoplakia and/or atypical hyperplasia were treated with irradiation. The staging system was the same as for the invasive squamous carcinomas. The irradiation techniques were also identical to those used for invasive squamous cell carcinomas. The failure rate for the T1 lesions was 11% and 26% for the T2 lesions--in the same range as the failure rates observed for the invasive squamous carcinomas. Only two of the 12 failures were on the initially involved cord. These two facts suggest that most of the failures were not recurrences but were new disease developing on the dysplastic epithelium. There was a delay in the appearance of failure for the in situ carcinomas as compared with that for the invasive squamous cell carcinomas of the supraglottic larynx. Seventy-six percent of the patients have a normal voice.


Recurrences from malignant parotid salivary gland tumors. The clinical course of 130 patients treated for malignant parotid tumors at the three institutions have been reviewed. Fifty-six of these 130 patients developed recurrences following their primary treatment by a surgical procedure. There were a total of 109 recurrences among these 56 patients. The average number of recurrences was two per patient. The average survival from first recurrence was 3.7 years, with the median survival 2 years. The range of survival was 0.5 to 17 years. Once recurrence developed, treatment was by surgery, radiation therapy, chemotherapy, or a combination. Of 56 patients with recurrence, 33 are dead and 9 patients are alive with disease. Fourteen patients are alive and well with no evidence of disease. These NED patients had an average number of 1.6 recurrences and a median survival to date of only 3 years. Our study indicates that for the majority of patients who develop recurrence, survival is relatively short and treatment is usually ineffective in three of four patients. The authors conclude that after a surgical procedure for malignant salivary gland tumors, a trial of wide field postoperative radiation therapy to high dose should be considered as part of the initial treatment.


Preliminary results of fast neutron teletherapy of metastatic cervical adenopathy. Between September 21, 1973 and May 9, 1975, 36 patients with metastatic cervical adenopathy from cancers primarily arising in the pharynx or oral cavity, including six with bilateral cervical involvement, received fast neutron teletherapy at the University of Washington. At the conclusion of treatment, the masses were no longer palpable in nine of 42 (21%) heminecks and were reduced more than 50% in 23 (55%). In 12 patients with partial regression, the masses eventually disappeared, so that in all, 21 heminecks (50%) or 20 patients (56%) were controlled for periods up to 66 weeks. Fixed cervical masses were controlled in 11 of 23 (48%) patients. These results, which must be sustained for longer observation periods, are comparable to results reported in the literature. Treatment was well tolerated; therefore, doses can be raised to study the influence on tumor control.


Fast neutron radiotherapy for locally advanced pelvic cancer. Between March 1973 and May 1975, 82 patients with locally advanced pelvic tumors were treated with 50 MeVdleads to Be neutrons. Seventy-nine have been included for analysis. The clinical material included 51 patients with gynecologic cancers, 15 with colorectal adenocarcinomas, and 13 with prostatic adenocarcinomas. Three treatment approaches have been used: 1) neutrons only--160 rad mu gamma twice weekly, 2) neutron boost following 25 MV photon irradiation--160 rad mu gamma twice weekly, and 3) mixed beam--photons (200 rads) three times weekly and neutrons (65 rad mu gamma) twice weekly. The preliminary results with the mixed beam are superior to those obtained with neutrons only or a neutron boost. However, the cancer and have been treated to slightly higher equivalent doses than those treated with neutrons only. The superior results with the mixed beam may be related to a better volume distribution and/or five-times weekly fractionation.


Radical irradiation with the split-course technique in carcinoma of the lung. The possible advantages of a split-course of irradiation in the treatment of patients with locally advanced and/or inoperable carcinoma of the lung were explored in over 200 cases. The patients were separated into two groups with different prognostic factors: Group A, patients with well-differentiated tumors confined to the lung and mediastinum; and Group B, cases with anaplastic tumors and/or supraclavicular metastases, bone erosion, or superior venal caval syndrome. The treatment consisted of 5500-6000 rads tumor dose in 20 to 24 fractions over a period of 7 to 8 weeks with a rest interval of 2 to 4 weeks in the middle. The 3- and 5-year survival figures, 19% and 16%, respectively, in Group A cases, along with the excellent tolerance, suggest that the split-course approach has definite advantages.


Small cell anaplastic carcinoma of lung. Reappraisal of current management. The relative roles of radiotherapy, intensive chemotherapy, and a combination of both were evaluated by an analysis of 157 of 188 patients who were registered at Tumor Registry and the Department of Radiation Medicine at Massachusetts General Hospital with a diagnosis of small cell anaplastic carcinoma of the lung between 1968 and 1974. Stage of the tumor was the single most important prognostic factor. Bone marrow involvement was found in 29% of patients studied. For extensive tumor, better survival was obtained by a combination of intensive chemotherapy and radiotherapy than with radiotherapy alone. However, no improvement of survival was noted with combination of concomitant or sequential intensive COPP or COP chemotherapy and radiotherapy over that obtained with radiotherapy followed by subsequent chemotherapy for progressive disease in patients with localized tumor. For localized tumor, primary radiotherapy should be given with an intention of local control or cure. Conclusions regarding the proper timing of chemotherapy and radiotherapy in apparently localized small cell anaplastic carcinoma require further prospective evaluation.


Irradiation for bronchial carcinoma: reasons for failure. I. Analysis of local control as a function of dose, time, and fractionation. Radiation therapy is the only potentially curative form of therapy for patients with carcinoma of the lung who are not surgical candidates. Previous studies have evaluated response by evaluating survival. Evaluation of local control of disease is essential if one is to understand and modify therapeutic approaches in an effort to increase survival. Clinical data are presented on 197 patients with primary epithelial tumors of the lung. An analysis of local control data is presented using the concept of nomial standard dose (NSD). If local failure is to occur, it is manifest by 15 months. Survival is affected by the ability or inability to achieve local control. Above a dose of 1450 ret, no correlation between increasing ret dose and increasing local control is observed.


Locally recurrent carcinoma of the breast. Results of radiation therapy. Local and regional recurrences are frequent problems in breast cancer management. Radiation therapy is effective in producing long term remission. This study evaluates the results of radiation therapy of 215 patients with recurrent disease limited to the chest wall and/or regional lymph node areas. The local results showed complete control in 67% of cases (mean and median durations 32 months and 22 months, respectively), partial control in 24% of cases (mean and median 11 and 8 months, respectively) and no control in the remaining 9%. The radiation dose recommended for the treatment of recurrent mammary carcinoma is 5000 rads in 5 weeks for relatively small lesions. Supplementary local doses of 500-1000 rads in 1 week may be given to bulky lesions as necessary for residual disease. Although local relapse indicates a poor prognosis, it is by no means totally hopeless. Of 215 patients treated 44 (21%) survived 5 years and 10 (5%) survived 10 years following radiation therapy of recurrent disease. There were seven patients, or 3%, who were free of cancer at 5 to 15 years. Radiation therapy was valuable in controlling local lesions, and thus, in improving quality of survival, even in those patients who eventually died of metastatic disease.


The role of postoperative irradiation in carcinoma of the breast. Chest wall and regional nodal recurrences, and survival following postmastectomy radiation therapy, were analyzed in 352 patients. Patients with T1 and T2 central and medial breast lesions, negative axillary nodal findings, and no evidence of skin or chest wall extension received irradiation to the peripheral lymphatics alone. There were no chest wall recurrences among these patients. The remainder of the patients, including those with axillary nodal involvement, regardless of the site of the primary breast lesion received irradiation by a three-field technique directed to both chest wall and regional nodes. The chest wall recurrence rate was 1.9% when axillary nodes were negative for metastatic disease, 1.3% when the axillary nodes showed less than 50% positivity, and 14.2% when axillary nodes showed greater than 50% involvement. The overall chest wall recurrence rate was 5.1%. A possible mechanism of chest wall recurrence is discussed. Cumulative 5-year survival for stage I is 76%, for stage II, 79%, and for stage III, 57%. If chemotherapy proves to be effective in controlling distant microscopic disease local control may become an equally critical issue in long-term survival of patients with breast carcinoma.


Total body irradiation of chronic lymphocytic leukemia. Relationship between therapeutic response and prognosis. There is lack of evidence to date that treatment of chronic lymphocytic leukemia (CLL) alters the natural history of disease or influences survival. In the present series, total body irradiation (TBI) produced a range of therapeutic responses among patients with active, progressive CLL. One-third of patients experienced virtually complete clinical and hematologic remissions with the initial course of TBI. These patients did not differ from the less complete responders with respect to age or sex, degree of lymphocytosis in the peripheral blood, incidence of anemia and/or thrombocytopenia, or the frequency of constitutional symptoms. However, the patients with complete remissions noted a return to normal performance status, had fewer serious infections, demonstrated recovery from depressed immunoglobulin levels, and had significantly longer survival. These data indicate that TBI is capable of inducing remissions which modify the course of disease in patients with CLL and that prognosis has a direct correlation with the response to therapy.


Adjuvant methotrexate in the radiotherapeutic management of advanced tumors of the head and neck. Oral methotrexate (MTX) was administered to a group of 48 patients with advanced head and neck tumors prior to radiation therapy in a nonrandomized manner. A second group of 75 similar patients were randomized to intravenous (i.v.) MTX plus radiation or radiation alone. Three-year survival rates by life table analysis show no significant statistical difference between i.v. MTX plus radiation or radiation alone. Those treated with oral MTX plus radiation have a statistically significant improved survival. The degree of tumor regression in the oral MTX group was correlated with survival. No similar correlation could be found in the intravenous MTX group. The use of either form of MTX correlated with a lower rate of distant metastasis.


The treatment of meningiomas in childhood. Thirteen cases of meningiomas in the pediatric age group seen at the University of California are reviewed. Four of these patients are alive; one had complete surgical resection of tumor and three had subtotal resection followed by irradiation, with total tumor doses of 4500 to 5500 rads. On the basis of these data, together with our total experience in the treatment of 188 patients with meningiomas, we conclude that patients who have complete surgical resection need no further treatment but patients who have subtotal removal may have recurrences delayed or prevented by the addition of postoperative irradiation to their therapeutic regimens.


Pinealoma. A report of twelve irradiated cases. The records of 12 patients with a diagnosis of pinealoma or ectopic pinealoma irradiated at Montefiore Hospital and Medical Center between 1961 and 1971 were reviewed. Diagnosis was made clinically and radiographically. Histology is available in three cases. Eight cases were treated with small fields (4 X 4 to 6 X 8 cm), two cases with intermediate, and two with whole brain fields. Doses between 5000 and 6000 rads were given by Cobalt-60 or 33 MeV x-rays. Eight patients (66%) showed no evidence of active disease from 4 to 14 years after irradiation. Of eight patients treated with small fields, seven are free of disease (88%). Of the remainder, 50% are free of disease. One patient subsequently developed cerebrospinal spread. The challenge to the radiotherapist is to identify the more aggressive or extensive lesion with the ultimate aim of achieving cure with the most limited treatment.


Computerized (axial) tomography in the serial study of cerebral tumors treated by radiation. A preliminary report. The difficulty in evaluating the effectiveness of radiation therapy of primary cerebral tumors is well appreciated. Changes in the tumor size and the presence or absence of edema or necrosis during or following treatment cannot be readily evaluated by present noninterventive roentgenographic methods. At New York University Medical Center, computerized (axial) tomography (CT) has been routinely used both before and after radiation therapy with the aim of assessing, by noninterventive means, tumor response, presence or absence of edema, or necrosis. A selected series of patients is presented with correlation of the clinical findings and CT-scan results both before and after therapy. The significance of these findings and their implications in the management of cerebral tumors are discussed.


Computerized radiation therapy data.

Computerized radiation therapy data. A computer data system by which data from radiation therapy records are stored, corrected, and up-dated continuously as information becomes available is described. Two main programs are involved. A data storage and retrieval system called TAXIR uses a high-level language similar to English and allows display of information in alphabetic or numerical fashion. The other program, MIDAS, is a statistical package designed to perform multiple statistical analyses on the data accumulated on the former program. Both of these programs utilize a logical syntax permitting easy identification and partition of a data set. In addition, several smaller program have been developed to advance survival information in a rapid and reliable way and to obtain information directly from computerized data available at the University of Michigan Cancer Follow-Up Unit. Programs to obtain life tables or graphs on survival or reactivation of neoplasms have been developed. Stress is placed on the development of a strategy to obtain the maximum accurate information with a minimum input. The development of suitable coding sheets including appropriate diagnoses and tumor classifications is discussed. The importance of keeping a continuous up-to-date flow of information is stressed.


Intensive radiotherapy of locally advanced bladder cancer. Over a 10-year period, 82 patients with locally advanced bladder cancer were treated by one of two intensive radiotherapy routines. They received either 320 rads/day for 11 consecutive treatment days; or two sets of 320 rads/day for six consecutive treatment days each, with a three-week rest interposed between sets. Side effects were briefly annoying, but quite tolerable. Good quality palliation was obtained. Uncorrected survival rates for the entire series were 48% at 1 year, 20% at 3 years, and 13% at 5 years.


Carcinoma of the prostate. Its treatment by a combination of radioactive gold-grain implant and external irradiation. Out of 67 patients treated with radiotherapy from 1967 to August 1972, a small group of 17 patients were treated by a combination of radioactive gold grain implant plus external Cobalt-60 teletherapy. The average dose from the implant was 4000 rads, which was supplemented with external irradiation to a total dose of 8000 rads TD. Because of the small number of patients and the short follow-up, no definite conclusions can be drawn at this time. The technique used permits the delivery of a higher total tumor dose of about 8000 rads with relatively low complication rate.


The value of frequent treatment verification films in reducing localization error in the irradiation of complex fields. Using treatment verification film to detect geometric miss or localization error (LE), a follow-up analysis of LE for patients treated with extended mantle fields was made for the period 1973-1974. There were 451 treatment verification films for 19 patients reviewed and 67 errors were detected for an error rate of 15%. This rate represented a continued decrease compared to the previous rate of 35% (330 errors for 902 films) during 1969-73. There was a continued reciprocal increase in number of films per patient per course of treatment which was thought, in part, to account for the improvement in technical precision. Reanalysis of localization error by site within the field showed a decrease in rate of error for the axillae from 1969-73 to 1973-1974 and a relative increase in rate of error for the upper abdominal nodes. The decrease in error rate for the axillae was ascribed to increased attention to leaving adequate margin between pulmonary shield and axilla and the increase in error rate for upper abdominal nodes was ascribed to inadequate margin between shield and spine. The relative increase in errors for the upper abdominal nodes correlated with the physicians who made the original decision about margin between spine and shield. Propagation of LE by site has been noted and can be prevented by monitoring treatment fields with verification film and correcting errors as they are noted.


Radiation reaction of rat skin. The role of the number of fractions and the overall treatment time. Acute skin reactions resulting from orthovoltage x-irradiation were measured in the WAG/Rij rat. A wide range of combination of fraction number and overall time were used in an attempt to determine their relative importance. There appeared to be little effect of prolongation of overall treatment time until periods of over 2 weeks were reached. In treatment periods of 3 weeks and over the stimulation of extensive time-dependent recovery was seen. A model based on cell kill with provision for the stimulation of accelerated proliferation at about 17 days adequately describes the experimental results.


Embryonal rhabdomyosarcoma of head and neck in children. Correlation of stage, radiation dose, local control, and survival. Nineteen consecutive children are analyzed according to clinical stay, radiation dose (NSD), local control, and survival. The majority received 1600 to 1750 rets and courses of actinomycin during their radiation treatments. The favorable sites were the orbit, facial soft tissue, and the larynx. The primary site control rate was 89%, and the metastatic neck control rate was 80%. The 2-year survival was 70%, and the 5-year survival was 67%. Five children are alive and well 12 to 15 years after irradiation. Late sequelae are hypoplasia of the orbit and maxillary sinus.


Nasopharyngeal carcinoma in children.

Nasopharyngeal carcinoma in children. Ten children with lymphoepithelioma of the nasopharynx were reviewed. Six had regional spread at presentation and four developed distant metastases. Seven patients are alive, six free of disease. The 5-year survival rate was 62.5% of this series. Five patients presented later with endocrine abnormalities probably related to the radiotherapy; these endocrine problems were minimal and responded to therapy.


Abdominal irradiation in non-Hodgkin's lymphomas. The incidence of subdiaphragmatic relapses in a group of 170 patients with non-Hodgkin's lymphomas treated with radiation to lymph-node bearing areas above and below the diaphragm is described. In patients treated with the standard inverted "Y" abdominal radiation portals, subdiaphragmatic relapses occurred in 29% of 132 patients. This high local failure rate may be attributed to the exclusion of many of the mesenteric lymph nodes and most of the liver and intestines from the irradiated fields. A safe and apparently effective radiation technique which treats the whole abdomen, used at Stanford in 38 patients since 1973, is described. Full thickness lead blocks protect the right hepatic lobe during the initial 1500-rad whole abdominal treatment (through anterior-posterior opposed fields). Horizontal decubitus (cross-table) lateral fields are then used to bring the para-aortic and mesenteric lymph node radiation doses to 3000 rads, followed by an additional 1400 rads through wide anterior-posterior ports, for a total central abdominal dose of 4400 rads. Dosimetric considerations, anatomic descriptions of subdiaphragmatic lymphatic drainage, complications of treatment, and the initial results of whole abdominal radiation therapy are also presented.


Non-Hodgkin's lymphomas of stage III extent. Is total lymphoid irradiation appropriate treatment? Many investigators have regarded Stage III lymphomas as a generalized form of disease and have accordingly recommended systemic treatment programs. Between 1961 and 1973, 68 patients with clinical or pathologic Stage III non-Hodgkin's lymphomas were seen in the Division of Radiation Therapy at Stanford University Medical Center and were treated by high dose (3500 rads or more) total lymphoid radiation therapy only. Of the 17 patients who had a diffuse histologic pattern, the actuarial survival at 5 years was 39%, but only three patients have remained free of disease. In contrast, for the 51 patients who had a nodular histologic pattern, the actuarial survivals at 5 and 10 years were 75% and 65%, respectively. Corresponding relapse-free survivals for patients with nodular lymphomas were 43% and 33%, respectively. Of 28 patients who relapsed with nodular lymphomas, 18 (64%) had relapses confined to lymph nodes; six of these were extensions to previously unirradiated epitrochlear-brachial nodes. Seven of the 18 patients were treated only with further conventional external radiation therapy at the time of their relapses and remain free of disease for additional periods of 2 to 5 years. Hence, 30 of 51 (59%) patients with nodular lymphomas have thus far been controlled by high dose total lymphoid irradiation only. Over 90% of relapses among patients with nodular lymphomas were seen within the first 5 years. The data suggest that high dose conventional radiation therapy to incorporate not only the routine total lymphoid fields but also the epitrochlear, mesenteric, and Waldeyer's ring region has curative potential even in Stage III non-Hodgkin's lymphomas, especially in the nodular group.


Mantle irradiation in Hodgkin's disease. An analysis of technique, tumor eradication, and complications. Analysis of the treatment and follow-up records of 377 Hodgkin's disease patients who received mantle irradiation but no planned chemotherapy reveals an overall supradiaphragmatic relapse rate of 21%. Complications of treatment included symptomatic pulmonary radiation reaction (20%), pericarditis (13%), Lhermitte's sign (15%), and thyroid dysfunction (13%). The addition of a subcarinal block after 2500 to 3500 rads and the use of the thin lung block technique in selected patients have reduced the incidence of pulmonary and pericardial complications to less than 5% without sacrificing local control. Further modifications in technique and treatment policy are discussed in terms of improving the therapeutic ratio.


Long term remissions with combined modality therapy for advanced Hodgkin's disease. A new treatment program for advanced Hodgkin's disease employing five-drug combination chemotherapy and low dose radiation to the sites of bulk disease (nodal or parenchymal) was designed in 1969. Eighty patients have now been treated, 60 of whom have achieved a complete remission. More significantly, only 5 of the 60 completed responders have relapsed with follow-up from 1-6 years. The cumulative survival at 5 years of patients entering complete remission is 92%. For those patients not sustaining a complete remission, it is 19% at 2 years. This program has resulted in substantially lower relapse rates than previously reported by other investigators, probably because of the administration of radiotherapy in the manner described. Hopefully, a significant number of these patients may be cured of their disease.


Can pelvic irradiation be omitted in patients with pathologic stages IA and IIA Hodgkin's disease? From April 1969 to December 1973, 81 unselected laparotomy-staged IA and IIA patients with supradiaphragmatic Hodgkin's disease were treated at the Joint Center for Radiation Therapy. Mantle and para-aortic fields alone were treated to 3600-4000 rads. Median follow-up was 31 months. There were six relapses including three true recurrences, two extensions, and one extra-nodal dissemination. Relapses were not related to histologic type. There were no pelvic or inguinal extensions. Disease-free survival was 95% in stage IA patients and 86% in stage IIA patients. Only one patient died of disease, with an overall survival of 96%. These results indicate that mantle and para-aortic irradiation is sufficient treatment for pathologic stage I and IIA supradiaphragmatic Hodgkin's disease. Such treatment obviates the need for pelvic irradiation or combination chemotherapy without compromising the success of treatment.


Initial relapses in previously treated Hodgkin's disease. I. Results of second treatment. Two hundred forty-three consecutive patients with Hodgkin's disease who relapsed after an initial course of treatment at the Stanford University Division of Radiation Therapy underwent subsequent systematic evaluation and retreatment. An analysis of the influence of numerous parameters, including sex, histopathology, original stage, relapse site, and original and second therapy, on actuarial survival and on relapse-free survival was undertaken. Most relapses (87%) occurred within 3 years of the initial treatment course. The 5-year relapse-free survival measured from the time of second treatment increased from 14% before to 39% after the introduction of multiple agent chemotherapy (MOPP) for relapsing disease. Patients treated with MOPP chemotherapy for nodal relapses showed increased subsequent relapse-free survival (61%) when compared with patients treated only with radiotherapy for nodal relapses. Based on the combined findings of this analysis, recommendations are made regarding the management of patients with Hodgkin's disease who have suffered a relapse.


A preloaded radium needle implant device for maintenance of needle spacing. A small stainless steel bar was machined to accept radium needles. The stainless steel bar will hold a rack of two, three, four, or five radium needles in a single plane. The crossing needle may be affixed to the bar so that textbook-like geometry is possible. The stainless steel bar remains in place during the entire implant. Spacing between needles is close to perfect. The time required to insers the implant is reduced compared to free-hand insertions, and less variation in dose is seen on computer-assisted calculations. Two years' experience in the use and development of the radium needle holder will be reviewed.


Patterns of recurrence following surgery alone for adenocarcinoma of the colon and rectum. Two hundred and eighty patients with previously untreated large bowel adenocarcinoma were retrospectively evaluated following complete primary resection to determine patterns of recurrence. One hundred and five patients (37%) subsequently developed recurrent disease. Sixty percent (63/105) presented with local recurrence alone, 14% (15/105) with concomitant local recurrence and distant metastases, and 26% (27/105) with distant metastases alone. Ninety-two percent of local recurrences developed in structures contiguous to the operative area of the incision. The degree of tumor anaplasia and depth of tumor penetration into the bowel wall influenced the rate of local recurrence. Through 5 years, local recurrence without clinical evidence of distant metastases was the most common cause of death. Plans for adjuvant radiation therapy are discussed.


Preoperative radiotherapy for adenocarcinoma of the rectosigmoid. Ninety-seven patients with adenocarcinoma of the rectosigmoid have been treated with high dose (5000-6000 rad) preoperative irradiation from 1960 through 1972 at the University of Oregon Health Sciences Center. Fifty-seven were initially clinically resectable and 40 were initially inoperable. Forty of the 57 initially clinically resectable patients had "curative" resections and are at risk for more than 5 years. An increase in 5-year survival (from 38% to 53%) and an absence of pelvic recurrence have occurred in those patients receiving preoperative irradiation and "curative" resection. Four of the 40 initially inoperable patients are alive without tumor. Three of the four survivors had irradiation and surgery; one had irradiation only. An additional four patients had no evidence of tumor at death. Tumor was totally sterilized by irradiation and nine patients and reduced to microfocal extent in an additional three of the 97 patients. Incidence of complications was no greater than has been reported in a surgical series from the same institution.