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The contributions of radiation therapy to the management of the patient with cancer are constantly changing, both because of improving use of ionizing radiations and development of other effective treatments. Therefore, if radiation therapy is to be used to each patient's advantage, well-trained radiation oncologists must be involved in the initial and all subsequent management decisions. Such essential activity requires the immediate availability of trained physicians, who have access to adequate facilities in order to provide the best known treatment methods. This availability in turn depends on physician recruitment and training, well-considered development and maintenance of facilities and research programs which are well correlated with clinical activity.

Techniques for the growth of uniformly reacting populations of cysts of Acetabularia mediterranea and for quantitative measurement of cyst germination have been developed. Cysts of A. mediterranea can be induced to germinated by exposure to the atmosphere. Germination rates are very low in young cysts. They increased during exposure to total darkness. This "maturation of cysts" is found to be completed after a period of 12-15 weeks. Germination rates of cysts that have passed the maturation period exceed 90 percent in continuous white light and 80 percent in darkness. Cysts germinate in less than two days in darkness and less than four days in light. The influence of temperature at a range of 15 degrees C to 25 degrees C on germination kinetics is studied in light and darkness. Germination is accelerated with increasing temperature up to 21 degrees C. At higher temperature germination is delayed in light but the time of germination remains constant in darknesss. Rates of germination are not altered by the influence of temperature in light while in darkness there is a dramatic decrease at temperatures higher than 21 degrees C. From these findings it is concluded that cyst germinationA. mediteranea does not need any light but is influenced by light dependent systems. The influence of light is strongest at elevated temperatures.

In isolated perfused rabbit hearts, coronary vasodilation, produced by reduced oxygen tension seems to be independent of myocardial prostaglandin biosynthesis. a) Anoxia (N2: CO2 95: 5 %) produced coronary vasodilation without causing prostaglandin-like substance (PLS) biosynthesis and release; b) the decrease in coronary resistance during hypoxia (N2:02:CO2 - 80:15:5 %) was sustained during myocardial perfusion with the low oxygen media despite the transitory nature of its PLS release; and c) indomathacin, which abolished basal or ADP stimulated myocardial PLS release, did not abolish the coronary vasodilation produced by ischemia, hypoxia, or anoxia.

Incubation of A type prostaglandins with whole blood or washed red cells at 37 degrees C converted them to more polar products with negligible vasodepressor and smooth muscle-contracting activities. This conversion did not occur in platelet-rich plasma. Uptake of the prostaglandins by red cells was demonstrated at both 4 degrees C and 37 degrees C. The data suggest 1) that if PGA is released from tissues into the blood stream or is administered for therapeutic purposes, its biological activity would be diminished by human red cells, and 2) that development of an assay for PGA in blood should take into account its uptake and metabolism by human red cells.

[9beta- -3H]-17-Phenyl-18,19,20-trinor-PGF2alpha was injected subcutaneously into female Cynomolgus monkeys and the structures of six products appearing in the urine were determined. The main urinary metabolites were the dinor- and tetranor-derivatives of 15-keto-13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2alpha. Unchanged 17-phenyl-18,19,20-trinor-PGF2alpha was also identified among the urinary products, as well as its dinor- and tetranor-derivatives. Finally, the dinor-derivative of 13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2alpha was also found in urine. The same six products were also found in urine from human female subjects that had received 17-phenyl-18,19,20-trinor-PGF2alpha either subcutaneously or intravenously. Studies on the half-life of the compound in the circulation were also performed in human females. Two less polar metabolites in plasma were identified, viz. 13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2alpha and 15-keto-13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2alpha.

The purpose of this work was to investigate the effect of oxytocin on prostaglandin F (PGF) concentrations in uterine venous effluent. PGF was measured in utero-ovarian venous plasma from three pregnant ewes and in posterior vena caval plasma from two puerperal ewes, during oxytocin administration. Oxytocin caused 4.9 - 5.3-fold increases in PGF concentrations in the pregnant animals, the response increasing towards term. In the puerperal animals oxytocin caused 3.7 - 17.2-fold increases in PGF concentrations with a marked latency in the response. Measurement of uterine activity and progesterone and total unconjugated oestrogen concentrations indicated that neither uterine contractions nor a decreased uterine blood flow accounted for the elevated PGF levels stimulated by oxytocin.

Pregnancy had been terminated in 6 normal midtrimester pregnant patients by the extraovular injection of 10 mg prostaglandin F2alpha (PGF2alpha). In these 6 Experimental and 3 Control patients utero-placental blood flow had been measured, by changes in the density of radioactive Indium, distributed over the uterine area, as a function of time. In comparison with Controls utero-placental blood flow decreased in the Experimental patients already at 5 minutes after PG-treatment, long before advanced cyclic IUP evolved. This finding substantiates the conclusion (1-3), based on experiments in animal "models', that decrease in utero-placental blood flow is an early step in the mechanism of PG action.

A single injection of prostaglandin F1 (PGE1) of 5 mg/kg body weight on Lay 13 of pregnancy caused a consistent luteolysis and resorption of fetuses in rats by Day 20. A concomitant regimen of cortisone, a consistent blocker of nonspecific stresses or reserpine, an adrenergic nerve blocking agent as well as a specific inhibitor of GRF and PIF, concurrently with PGE1 consistently effective in preventing the deleterious efficacy of PGE1 and maintained the growth of the fetuses, placentae, ovaries and corpora lutea as healthy as recorded in the controls. On the basis of experimental documentation it is believed that the PGE1-caused fetal demise is possibly due to a break up of an appropriate hormonal synchronization rather than an over stimulation of uterine smooth musculature.

The biological activities of 8,12-diiso-PGE2 (ent-11,15-epi-PGE2), PGE2 and PGF2alpha have been compared in a series of pharmacological preparations intended to differentiate between F and E type of activity. Similar to PGF2alpha but unlike PGE2, 8,12-diiso-PGE2 increased the tone of isolated smooth muscle preparations of guinea pig trachea, guinea pig colonic circular layer, rabbit Fallopian tubes. The stimulation effect of 8,12-diiso-PGE2 and PGF2alpha on visceral smooth muscle was also shown in vivo: the two drugs were in all instances able to increase the miogenic activity and tone of rabbit uterus in situ, while these were depressed by PGE2. 8,12-diiso-PGE2 decreased pulmonary compliance and increased pulmonary vascular resistance in the anaesthetized cat; PGE2 always decreased pulmonary vascular resistance, while leaving pulmonary compliance unaltered. The possibility is suggested that 8,12-diiso-PGE2 acts on PGF receptor in different tissues.

Both sphincter and dilator muscle preparations of the cat iris contract to prostaglandins; F-2alpha and E-2 are the most potent and A-1 and B-1 the least. Ciliary muscle strips relax to PG'S provided that the strips are precontracted. E-1, E-2 and often F-2alpha are more potent relaxants than the remaining PG's. The effects of PG'S ARE NOT ALTERED BY ALPHA OR BETA BLOCKADE NOR BY ATROPINE; HOWEVER, PROPRANOLOL BLOCKS THE PG induced relaxation of the ciliary muscle. The effects of PG's on the sphincter are antagonized by catecholamines; but the latter act synergistically in contracting the dilator and in relaxing the ciliary muscle. Indomethacin markedly potentiates the effects of PG's on all three muscle preparations.

Distinct structural changes occur in the rabbit ciliary epithelium following intravitreal injection of prostaglandin E-1 (PGE-1). Up to four hours after PGE-1 administration, alteration of the pigmented epithelium was characterized by dilated intercellular spaces and the disruption of many intercellular junctions. The nonpigmented epithelium demonstrates a spectrum of morphologic variation from only some thinning of cytoplasmic processes to area of severe distortion. In these regions, marked thinning of the nonpigmented cells occurs in association with an absence of apical tight junctions. This alteration of the nonpigmented epithelium and its tight junctions allows for the leakage of proteins into the posterior chamber which is consistent with the breakdown in the blood-aqueous barrier. The temporal sequence of these changes would suggest a differential susceptibility of the pigmented and nonpigmented layers with the pigmented layers being affected earliest and the nonpigmented epithelium altered subsequently. The recovery of this epithelial change was rapid and complete and demonstrated the transient effects of PG on the ciliary epithelium with recovery of the blood-aqueous function by 8 hours after injection.

Topical administration of aqueous solutions of sodium arachidonate to the eyes of rabbits increases intraocular pressure, constricts the pupil and increases both the protein and prostaglandin content of aqueous humor. Arachidonic acid itself dissolved in arachis oil is less effective than sodium arachidonate, although addition of polysorbate mono-oleate greatly increases the effects produced by arachidonic acid. Pretreatment with topically applied non-steroidal anti-inflammatory agents prevents the ocular effects of sodium arachidonate, indomethacin being 2-4 times as potent as either indoxole or pirprofen. Dexamethasone was without effect in these experiments. The results suggested that nonsteroidal anti-inflammatory agents deserve serious consideration for topical use in the treatment of ocular inflammation.

Prostaglandin F2alpha concentrations were measured in human cerebrospinal fluid by the gas-chromatography-mass spectrometric technique using 2-H4-PGF2 alpha as internal standard and carrier. Normal levels of 71.6 plus or minus 34.7 pg/ml were found. Considerable increases in PGF2 alpha concentrations were found in patients with epilepsy, meningtitis or following cerebrovascular accidents or neurosurgical removals of brain tissue. The results agree in general with recent measurements using radioimmunoassay.

In isolated rabbit lung preparations perfused with tritiated PGE-1, it was found that, (1) PGE-1, is rapidly and almost completely metabolized during perfusion through rabbit lung. (2) During perfusion, there is no net uptake of PGE-1. (3) The process of metabolism of PGE-1 in the rabbit lung is inhibited by hypothermia.

The effect of locally administered prostaglandin F2alpha on the sensitivity and reactivity of the nonpregnant human uterus during the menstrual cycle was studied. An increase in uterine contractility in response to as little as 1.0 MUG PGF2alpha could be observed in all patients during both the early and late portions of the menstrual cycle, but at the time of ovulation a marked decrease in sensitivity was noted. Endogenous prostaglandin normally occurs in the secretory endometrium in levels compatible with the amount of exogenous prostaglandin which elicited increased uterine activity. These findings support the hypothesis that PGF2alpha plays an important physiological role in the cyclical regulation of uterine motility during the human menstrual cycle.

The uterotonic potency of seven prostaglandin analogues has been investigated using the single intravenous injection technique and comparison of threshold uterine contractility achieved during continuous intravenous infusion. The degree and duration of uterine stimulation in response to graded doses of some of the analogues was also evaluated following intra-amniotic, oral and vaginal administration. 17-Phenyl substituted PGE-2 and PGF-2alpha are reported upon for the first time. Among the prostaglandin compounds tested, the free acid of 16, 16-dimethyl PGE-2 not only is the most potent compound but it may also have great potential for clinical application as an easily administered vaginal abortifacient.

Induction of abortion in mid-trimester pregnancies were performed on 26 patients. The first 12 patients were treated by intra-amniotic instillation of Prostaglandin F2 alpha, with a mean dosage of 40.2 mg. and mean abortion time of 24 hours and 41 minutes (ten patients). Fourteen additional mid-trimester abortions were performed using identical protocol plus the addition of oxytocin by intravenous infusion two hours after injection of the prostaglandin. All patients aborted, with mean dosage of PGF2 alpha of 28.2 mg. and mean abortion time of 15 hours and 37 minutes.

Slices of human endometrium obtained from hysterectomy specimens were cultured for 48 hours in an organ culture medium supplemented with ethanol (control, vehicle), 17-beta-estradiol (.5 mug/ml), or progesterone (.5 mug/ml). Uncultured endometrial tissue, cultured tissues, and the media were assayed for prostaglandin F (PGF) by a radioimmunoassay technique. Hematoxylin and eosin and periodic acid-Schiff stain histologic controls were done on all tissues. The concentrations of PGF in picograms/milligram, corrected for percent recovery, in the differently treated tissues were: preculture 298; culture control 2210; estrogen-treated 2680; progesterone-treated 1260. All differences except those between estrogen and control (p greater than .10) and progesterone and control (p less than .10) are significant at the p = .02 level or better. Progesterone appears to inhibit PGF synthesis which occurs during in vitro culture of human endometrium; estrogen tended to increase PGF synthesis in this system.

The concentration of prostaglandins E and F in different parts of the male reproductive system of CD-1 and dwarf mice was measured by radioimmunoassay. In intact CD-1 mice, the vas deferens contained a significantly higher concentration of PGE and PGF than was found in the epididymis and in the seminal vesicles. All tissues studied had more PGE than PGF. Castration resulted in increased PG concentrations in both the epididymis and the seminal vesicles and decreased PG concentrations in the vas deferens. There was also a differential response of PGE and PGF in the epididymis of genetically sterile dwarf mice (dw/dw) were significantly higher than those observed in their normal littermates ((PLUS)). A reversed PGE/PGF ratio was found in the mates. The results indicate that testicular androgens affect the levels of PGE and PGF in the reproductive system of male mice. The physiological role of PGs in male reproductive functions has not been established, but there is a suggestion that PH have a role in controlling the transit of spermatozoa through the epididymis and vas deferens.

The prostaglandin synthesis inhibitors, indomethacin and eicosa-5,8,11, 14-tetraynoic acid (ETA), have been tested on the isolated lamb ductus arteriosus at low and high PO2 levels. Both compounds produced a gradual contraction of the hypoxic vessel, and at equal doses the effect of indomethacin was stronger. The maximal tension output of the hypoxic tissue under indomethacin was equal to that of the oxygen-contracted control. ETA- and indomethacin-treated preparations contracted further upon transfer from a low to a high oxygen environment, and the response under indomethacin exceeded a significantly control values. Control preparations were relaxed markedly by PGE2 in low oxygen but showed little or no response in high oxygen. In contrast, preparations pretreated with the inhibitors retained their sensitivity to PGE2 during exposure to high oxygen. The data are consistent with the idea that E-type prostaglandins play a role in the regulation of the intrinsic tone of the ductus arteriosus during foetal life. It is also suggested that the sensitivity of ductal muscle to E-type prostaglandins is controlled by the rate of endogenous prostaglandin formation.

Prostaglandins (PGs) F2alpha, E1 and E2 exerted a triphasic influence on the fluid transport of isolated guinea-pig gall-bladders, when applied to the serosal side. PGE1 and PGE2 produced these effects in lower concentrations than F2alpha. Directly after PG addition to the serosal side a short stimulation of fluid transport to between 200 and 400% was observed. The stimulatory effect of PGs was most distinct in gall-bladders from female guinea-pigs, less pronounced in male and nearly absent in pregnant animals. Since PGs increased intraluminal hydrostatic pressure in gall-bladders by contraction of the smooth muscle, experiments were performed in which hydrostatic pressure was increased by different procedures. These included the addition of imidazole (10- minus 2 M), raising of K+ in the bathing solution and an increase in intraluminal pressure by addition of Ringer's solution into the lumen. All three procedures stimulated fluid reabsorption temporarily in the same way as PGs, hence increase of intraluminal pressure is thought to be the reason for the observed temporary stimulation of fluid transport. Direct evidence for this thesis was obtained when the gall-bladder was mounted as a flat sheet over a chamber; in this preparation no stimulation of fluid transport was obtained. The second phase of the PG influence was characterized by a concentration-related inhibition of fluid reabsorption followed by a significant but small reverse of fluid transport (secretion of fluid). When PGs were applied to the mucosal side, only an inhibition of fluid transport was observed, which was much weaker compared to the addition to the serosal side.

Radioimmunoassay systems are described which have been developed to quantitate two principle urinary metabolites of PGF2alpha; 9alpha,11alpha-dihydroxy-15-oxo-2,3,4,5-tetranorprostanoic acid (I) and 9alpha,11alpha-dihydroxy-15-oxo-2,3,4,5-tetranorprosta-1,20-dioic acid (II). Preparation of the required metabolites was achieved by total synthesis (I) or by bioconversion (isolation from urine of animals treated with 15-keto-PGF2alpha, II). These metabolites were used to prepare conjugates for immunization. Labelled metabolites, suitable as binding markers, were prepared by metabolism of 3-H-PGF2alpha in vitro (I) or in vivo (II). Specificity of the resulting antibodies was compared to an antibody to PGF2alpha and to 13,14-dihydro-15-keto PGF2alpha. Antisera of II had little or no affinity for 20-carbon precursors (PGF2alpha or 13,14-dihydro-15-keto PGF2alpha), but had nearly equal affinity for metabolite I. Antisera of I, however, had little or no affinity for antigen of II. Therefore, analysis of samples by both assay systems enables quantitation of these excretion products of PGF2alpha. Other assay parameters (binding, affinity, recovery, precision and the repeatability of the assays) were similar to those previously described for other RIA systems, and were considered satisfactory for quantitation of compounds in biological fluids. Quantitation of 24 hour urinary excretion of di-acid metabolite in humans was in close agreement with previously published values determined by physical-chemical means. Greater quantity of di-acid metabolite was excreted by human males (42.0 mug/24 hr) than by females sampled either during the follicular (20.0) or luteal phase (21.2) of the menstrual cycle. The total quantity of C-16 metabolites (as approximated by system II) excreted/kg body weight by the rhesus monkey was similar to that excreted by the human. However, the ratio of di-acid to monoacid was much nearer unity in the monkey than the human.

A sensitive and relatively specific radioimmunoassay for 15 (S) 15 methyl prostaglandin F-2alpha has been developed to enable the measurements of the concentrations of the drug in biological fluids after its administration for therapeutic abortion. The precision, accuracy and specificity of the assay are described.

The acute and chronic effects of morphine on the turnover of norepinephrine (NE) were determined by measuring the changes in the levels of the sulfate conjugate of 3-methoxy-4-hydroxyphenylglycol (MHPG-SO4) in rat brain. Two hours after administration, morphine produced a dose-related increase in the levels of MHPG-SO4 suggesting an increase in NE turnover. The effect of morphine was evident by one hour after drug administration and was maintained for at least four hours but disappeared by eight hours. Chronic treatment with morphine resulted in lower baseline levels of MHPG-SO4 and the development of tolerance to its acute effect on NE turnover. These findings suggest that after chronic administration of morphine, the maintenance of a normal rate of norepinephrine turnover in brain is dependent upon the continued administration of maintenance doses of morphine.

Among the major metabolites of aflatoxin B1 produced by human and monkey livers in vitro is a derivative with the ketone carbonyl on the cyclopentane ring reduced to a secondary alcohol, and a hydroxyl introduced onto the carbon beta to the alcohol group. The metabolite was formed from aflatoxin B1 at a level similar to that of aflatoxin M1.Both the microsomal hydroxylase and the cytoplasmic reductase systems are required for its formation. Bioassay using chicken embryos and a mutant of Salmonella typhimurium revealed no toxicity. This newly identified metabolite was named aflatoxicol H1.

Using an empirical method, three preferred conformations for serotonin have been predicted. These three conformations corresponding to one extended form (phi equal to 80 degrees, psi equal to 180 degrees), and two folded forms (phi equals to 280 degrees, and psi equals to 100 degrees, phi equals to 100 degrees psi equals to 290 degrees). The calculated intramolecular distances in both forms agree with those obtained by the X-ray crystallography of various indoleamines. Furthermore, the dual receptor binding activity of serotonin has been explained in terms of extended and folded conformations.

Urine samples from comatose patients, identified as having taken large amounts of the drug, glutethimide, were analyzed using gas chromatography, mass spectrometry, thin layer chromatography, and nuclear magnetic resonance spectrometry in order to identify metabolites of the parent drug. The phenolic compound 2-ethyl-2-(4-hydroxphenyl)-glutarimide was fully characterized as a new metabolite in human urine. Also 2-ethyl-2-(3-methoxy-4hydroxyphenyl)-glutarimide was proposed as a new metabolite of the parent drug. Other polar metabolites of the parent drug were also detected and partially characterized.

Some sympatholytic agents have been tested for the ability to counteract either the hepatotoxic or the lethal effect of A. phalloides in rats. Propranolol displayed a marked preventive action on the liver damage induced by the poison, but only a moderate influence on the lethality. Reserpine was uneffective in terms of liver derangement, but exerted some protection against the general toxic effect of A. phalloides. Other alpha- or beta-adrenolytic compounds failed to afford any significant protection with respect to both liver injury and lethality. It is suggested that propranolol might interfere with transport or binding of phallotoxins to the liver.

Biochemical and Immunological studies have been made on streptokinase and its one to one molar complex with plasminogen. These experiments show that the complex is not recognized by antibodies to streptokinase. The potential of using this complex in vivo to avoid febrile response seen with streptokinase is considered.

An inhibitor and stimulator of in vitro hepatic fatty acid synthesis are present in renal microsomes. In addition, a stimulator of fatty acid synthesis is present in renal lysosomes. Renal microsomal inhibition of hepatic fatty acid synthesis is not due to the depletion of cofactors in the system. This inhibitor appears to be located exclusively in the kidney medullary microsomes. It is destroyed by Pronase and heat treatment suggesting it may be a protein. Its effects on fatty acid synthesis may be attributed in part to ATPase activity as well as a direct effect on the hepatic fatty acid synthesizing system. A stimulator of hepatic fatty acid synthesis is present in the buffer insoluble fraction of an acetone powder preparation of renal microsomes. This stimulator is relatively heat labile and does not appear to be a phospholipid. The lysosomal stimulator of hepatic fatty acid synthesis is associated with the contents of renal lysosomes and not with the lysosomal membranes. It acts at the acetyl-CoA carboxylase step and its activity is not affected by fasting or aminonucleoside induced nephrosis.

The effects of chronic clofibrate administration were studied in long-term ethanol-fed an control mice. Long-term administration of ethanol to adult-mice resulted in an increase in liver and plasma total triglycerides and hepatic cholesterol levels as compared to the corresponding controls. Cloribrate feeding resulted in about 15-25% decrease in hepatic and plasma cholesterol levels in the ethanol-fed group. The administration of ethanol led to a rise in levels of hepatic triglycerides, plasma triglycerides, plasma free fatty acids and hepatic alpha-glycerophosphate. Treatment with clofibrate partially prevented the changes in the concentration of these metabolites and resulted in a significant increase in the activity of hepatic alpha-glycerophosphate dehydrogenase. Clofibrate administration resulted in about 20% increase in the rate of 14-C-cholesterol oxidation to 14-CO2. It is concluded that while clofibrate is able to retard ethanol-induced lipid accumulation in the liver, it is unable to completely prevent hepatic lipid accumulation.

Jejunal and ileal intestinal segments were obtained from patients undergoing laparotomy, from peroral jejunal biopsies, and from fresh cadavers. The excised mucosa was weighed and assayed for total lipids, neutral and polar lipids. The lipid families were separated and identified, and their individual fatty acid composition determined. In addition, DNA, RNA, collagen and total protein were measured.

Delta-9-Tetrahydrocannabinol (0.31 mg - 1.25 mg per kg body weight) given to immunized rats by intraperitoneal injection depresses the activity of macrophage migration inhibition factor. The lowest levels of activity in peritoneal exudates were observed 15 hours after the injection of cannabinoid. This decreased activity may be related to the impaired cellular immunity observed in regular users of cannabis.

The effect of 1-epinephrine administered I. P. to pregnant rats during sodium pentobarbital anesthesia on fetal liver glycogen levels has been investigated. Sodium pentobarbital (22 mg./kg. maternal body weight) was administered I. P. to all pregnant rats in the control group and each 1-epinephrine dosage group twenty minutes prior to the surgical removal of the fetuses. L-epinephrine (10, 20 or 30 micrograms/kg. maternal body weight) given ten minutes after the administration of the barbiturate reduced the fetal liver glycogen levels significantly. The glycogen-depleting effect of 1-epinephrine on the fetal liver in the rat was found to be dosage-dependent.

Serum samples from 449 swine in 78 herds distributed in 28 counties in Illinois were tested for HI antibodies against A/Swine/Ill/63 and A/Swine/Taiwan/7310/70 (H3N2) from 1971 to 1973. No antibodies to the Taiwan strain were detected. A herd reactor rate of 42.3% and a prevalence rate of 25.4% against A/Swine/Ill/63 was detected. Age specific reactor rates were 6% for animals 12 months of age or under and 33% for swine 13 to 18 months of age.

Toxicity investigations were conducted with 4 chemicals: hydrazine, 1,2-dimethylhydrazine di HCl, phenylhydrazine HCl and Beta-N-(gamma-L(+)-glutamyl)-4-hydroxymethylphenylhydrazine in Swiss mice. Hydrazine and phenylhydrazine HCl were administered daily in drinking water, the former at 0.01% and the latter at 0.001% concentrations. The 1,2-dimethylhydrazine di HCl and Beta-N-(gamma-L(+)-glutamyl)-4-hydroxymethylphenylhydrazine were given as a single subcutaneous injection at 45 mug and 100 mug/gr. body weight basis, respectively. The findings clearly showed that all four chemicals exerted a stronger toxic effect in male than in female mice. It is, therefore, recommended in similar situations to use different doses of chemicals for each sex in the long-term tumorigenesis studies.

Plasma renin activity (PRA) was measured in 3 subjects during control period, after 3 days of oral furosemide (40 mg B.I.D.) and on the 2nd, 3rd and 5th days post diuresis. PRA, ng of angiotensin per ml plasma per 3-hour incubation was 8, 0.4 ng during the control period and rose to 51, 6 and 16 respectively. During the post diuretic phase, PRA rose to 99 in the first and 49 in the second subject. Urinary sodium was drastically reduced during this period. By 5th post diuretic day PRA returned to normal values. Striking elevations of PRA during intense sodium conservation are in accord with a concept of reduced Na load to macula densa stimulating renin release.

Samples of rabbit kidney histidine decarboxylase were incubated with substrate, L-histidine, either in the presence or absence of one drop of benzene. The extent of histamine formation was then assessed in vitro on the isolated ileum of the guinea-pig. Benzene potentiated the activity of histidine decarboxylase by a factor of approximately five. This activating effect occurred only during the summer months. No potentiation of histidine decarboxylase was recorded during the winter in either control rabbits or in animals receiving ascorbic acid in their drinking water. It was concluded that this vitamin is probably not involved in the mediation of the benzene effect.

Administration of 1-methyl-4-piperidyl-bis(p-chlorophenoxy) acetate (SaH 42-348) at a dietary concentration of 0.15% for 3 weeks, increased the activity of catalase in both liver and kidney of male wild type (Cs-a strain) mice. A marked increase in the activity of short chain carnitine acyltransferase in the liver was also noted. By electron microscopy, a remarkable increase in the number of peroxisomes (microbodies) was noted in the liver cells. A mild to moderate increase in number of peroxisomes in proximal convoluted tubular epithelium of the kidney was also seen. These studies demonstrate that SaH 42-348 is a potent hepatic peroxisome proliferator.

Sodium cyanate has been proposed as a therapy for sickle cell anemia. Histologic studies have suggested abnormal accumulation of glycogen in livers of rats. Quantitative liver glycogen determinations reported here showed a significant increase (P smaller than 0.05), which, however, was mobilized normally during fasting and after glucagon injections.

Female rats were treated with L-phenylalanine-14C or L-histidine-14C, 20 mug/kg i.p. one hour before receiving pentagastrin 250 mug/kg s.c. Sixty minutes after injection of pentagastrin the incorporation of L-phenylalanine-14C into the proteins of the squamous and fundic portions of the stomach was significantly increased respectively by 18 and 17.5%. On the contrary, the uptake of Lhistidine-14C into the proteins of the squamous (-24%), fundic (-18% and duodenal (-16%) regions was significantly decreased. Incorporation of histidine and phenylalanine into the proteins of the pylorus was not significantly affected by pentagastrin.

Immune responsiveness to the streptococcal group polysaccharides at the clonal level can conveniently be monitored by analytical isoelectric focusing combined with autoradiography. The parameters investigated in this paper can be summarized as follows: [1] Within the first week after injection antistreptococcal p0lysaccharide responses are characterized by IgM antibodies, followed by subclass restriction in Balb/c mice to IgG2a antibodies. [2] The clonal pattern of specific IgG2a antibodies established in the second week after immunization does not change within the following 6 weeks. [3] Persistence of a specific response pattern established within a primary immunization course holds for Balb/c mice and rabbits for as long as 12 to 13 months. [4] Repeated immunization courses in mice and rabbits maintain established clonal antibody patterns in toto. Temporal variations of clonal expression are generally quantitative rather than qualitative. B-cell memory within this system is therefore stable and long-lived.

Free, total, and peptide hydroxyproline levels were determined in synovial fluid obtained from the knee joints of 60 patients with theumatoid arthritis (RA), and 26 patients with degenerative joint disease. In addition, in 160 synovial fluid samples obtained from 121 patients including 50 with degenerative joint disease, 60 with RA, 3 with Reiter's syndrome, 3 with hydarthrosis intermittens and 5 with ankylosing spondylitis, the collagenolytic activity was determined. The mean values of free and peptide hydroxyproline in the inflammatory and degenerative fluids were the same, but slight differences were found in the mean values of total hydroxyproline. No effect on the level of free and bound hydroxyproline was observed after treatment with intra-articular hydrocortisone and gold salts. The collagenolytic activity of synovial fluid was registered in 38% of cases of RA and in some cases of Reiter's syndrome and hydrarthrosis intermittens, but it was not found in 50 cases of degenerative joint disease or in cases of ankylosing spondylitis. During a longer observation of patients with inflammatory forms of RA a variability in the collagenolytic activity was observed in repeated examinations of the fluid obtained from the same patient; this activity appeared and disappeared. The incidence of collagenolytic activity and its values were higher in patients with active rheumatoid process and this activity was present more frequently in patients with a short history of the disease (up to 3 years). The collagenolytic activity of rheumatoid fluids was, to a high degree, inhibited by normal human serum. The problem of presence or lack of collagenolytic activity in rheumatoid fluids is discussed.

Both male and female patients with rheumatoid arthritis show a significant bone loss in the femur, compared with the loss of bone seen in normal subjects with increasing age. A very similar pattern is seen in corticosteroid treated patients with rheumatoid arthritis. There is no evidence to suggest that the corticosteroid therapy has caused a greater loss of bone from the femur than would have occurred as a result of the rheumatoid arthritis alone. There was a statistically significant relation between the duration of the rheumatoid arthritis and femoral bone lo-s in women over the age of 45 years, whether or not they had been given steroid therapy in both male and female patients over 45 years of age, but again it appears unlikely that corticosteroid therapy had contributed significantly to the femoral bone loss. The Metacarpal and Femoral Indices of the patients were significantly related in both male and female groups.

Thirty-four patients with rheumatoid arthritis, aged 38 to 63 years (mean age 56 years), were studied before and after a 6-week stay in hospital. Twenty-three of these patients underwent special physical training twice a day during this period. Physical performance, cardio-respiratory fitness and muscle strength improved significantly in the training group. In the control group there were no major changes in these measurements during this period except for an increase in muscle strength. Perceived exertion during submaximal exercise was much lower in the training group following the conditioning. Joint status was virtually unchanged over the experimental period in both groups. It is postulated that the low physical performance seen in these types of RA patients may, to a large extent, be attributed to lack of physical activity.

Twenty-three patients with rheumatoid arthritis were retested about 6 months after 5 weeks' physical conditioning and 7 patients from a former control group were also retested. Former training group patients, who had continued to train about 4 times or more per week, had maintained the improved physical status obtained during the initial conditioning, while those patients who had trained less than that or discontinued training, had lost some or most of their improvement. The physical status in the former control group was virtually remained unchanged. Joint status in the former training group was no different at re-test than at post-training or pre-training examinations. A questionnaire, given to the training group patients. Four patients from this group returned to work had positively affected the daily physical activity of these patients. Four patients from this group returned to work after the hospital training program.

Eighty-two patients subjected to late synovectomy of the hand were followed up. Late synovectomy was defined as an operation performed after at least 3 years' duration of local synovitis in the type of joint operated on. The minimum follow-up period was 24 months for the fingers joints (IP + PIP and MCP) and 18 months for the dorsal aspect of the wrist (W). The multifocal swelling of joints, preoperatively, was symmetrical in 89% of the patients. The X-ray changes, however, were symmetrical in only 22%, 27%, and 68% for IP + PIP, MCP, and W, respectively. These findings may preclude the use of controlled studies on early synovectomy using the non-operated hand as a control in a long-term assessment of X-ray progression. The rate of X-ray progression during the observation period was 60% for IP + PIP joints. The corresponding figures for MCP and W were 64% and 39%, respectively. Absence of bony lesions prior to synovectomy was favourable sign.

This study examined the vocational and social adjustment of 62 persons with cancer of the larynx. Predisability data were obtained by interview on 14 measures which assessed the vocational, social, and home adjustment prior to cancer. Post-disability data were obtained after laryngectomy by interview on 21 measures of adjustment. Additional measures include severity of laryngeal cancer classified by clinival stages, total or partial laryngectomy, presence of radiation therapy, presence of speech, months since surgery, age, sex, education, and marital status. The best predictors of vocational and social adjustment after laryngectomy were: removation, realism, rehabiltation outlook, previous vocational plans, highest educational grade, educational plans, and acquisition of speech. There were no significant differences in adjustment among patients in different clinical stages.

A system for evaluation of motor function, balance, some sensation qualities and joint function in hemiplegic patients is described in detail. The system applies a cumulative numerical score. A series of hemiplegic patients has been followed from within one week post-stroke and throughout one year. When initially nearly flaccid hemiparalysis prevails, the motor recovery, if any occur, follows a definable course. The findings in this study substantiate the validity of ontogenetic principles as applicable to the assessment of motor behaviour in hemiplegic patients, and foocus the importance of early therapeutic measures against contractures.

An assessment has been made of the linearity of the relationship between oxygen uptake and cardio-respiratory parameters measured during pedalling with one leg on an upright bicycle ergometer. Four young male subjects pedalled at four submaximal grades. Individual regression lines of heart rate on oxygen uptake; minute ventilation on oxygen uptake; and carbon dioxide on oxygen uptake were found to have significantly high correlation coefficients. A comparison was made in 21 healthy males, of mean age 34 years (range 20-61 years), between the effects of pedaliling with one leg or two legs on the heart rate, minute ventilation and carbon dioxide production were significantly higher during work with one leg then with two legs, but there was no significant difference in the heart rates. The oxygen cost of pedalling with one leg instead of two was also higher. The comparisons were made at a standard oxygen uptake of 1.0 1 min minus 1.

A taxonomy of error--regarding the visual, grapheme-phoneme, and semantic aspects of reading--is proposed; and it is related to data from developmental studies. A preliminary analysis of recovery curves, based on the performance of two patients in tests of word-reading and object-naming, is also presented. Finally, the problem of extrapolating from test data to functional efficiency is briefly discussed.

The activity of compensatory muscles during walking was analysed in three paraplegics. The purpose of this study was to find out how the loss of motion of the lower extermities can be compensated and which muscles compensate most efficiently. This activity was assessed by clinical and EMG studies of thoracic and dorsal muscle contraction during swing-through gait. The study started with the first walking trial for each paraplegic, using a treadmill. At that time, all the thoracic and dorsal muscles (which were normal: 5 at the manual testing) showed a full contraction which gave an interferential pattern at the EMG. After 10 weeks, the activity of some muscles was already well rationalised (latissimus dorsi, rhomboids) in such a way that these muscles adapted themselves: contraction was followed by a period of rest which was observed clinically and recorded at the EMG. On the other hand, some muscles presented an irregular activity or even lack of activity (abdominal muscles). After 3 months there was no further modification of these patterns. In fact, thoracic muscles exhibited an excellent compensation by adaptation and rationalisation of their activity. The latissimus dorsi seemed to compensate most efficiently of all.

A model for control of the desynchronized phase of the sleep cycle postulates reciprocal interaction between cells in the pontine gigantocellular tegmental field (FTG cells) and cells in the nucleus locus coeruleus and nucleus subcoeruleus (LC cells). This physiological model leads to equations of the Lotka-Volterra type; the time course of activity predicted by the model is in good agreement with actual long-term recordings of FTG cells and single-cycle data for LC cells.

Nervous impulses causing lophophore retraction over large areas of Membranipora membranacea and Electra pilosa were recorded with external electrodes. The response propagates at about 100 centimeters per second, presumably through the colonial nerve plexus of Hiller and Lutaud. Impulses are rapid up to 200 per second. A second impulse was recorded from individual zooids, probably generated by the polypide's nervous system. The retractor muscle shortens at more than 20 times its own length per second and is apparently the most rapidly contracting muscle known.

Hyperuricemia and gout has been recognized among the Filipinos in Hawaii, Alaska, and mainland United States for almost two decades. Several studies bearing out this impression have been reviewed. The awareness of these observation prompted an extension to the Filipino in his natural environment. These studies showed a lower mean of serum uric acid values in healthy subjects when using comparative enzymatic spectrophotometric determinations. Aside from genetic factors, Filipino hyperuricemia may become manifest because of environmental stress, including dietary stress, and investigators postulate that some Filipinos possess a renal defect that may lead to hyperuricemia due to renal inability to compensate for an increased purine intake which may occur in the shift from a low-purine Filipino diet to a high-purine Western diet in his new environment, as in the case of the Filipino immigrant. The clinical profile of gout as it exists in the Philippines has been compared and found to be similar generally to that of other series. The control of the hyperuricemia and gout has been satisfactorily accomplished in the Filipino patients with the long-term use of allopurinol, sometimes complemented with colchicine taken daily.

The distribution of gold Au 198 after intraperitoneal administration in dogs and rats was determined by scans and tissue radioassays obtained 24 hours after injection. Relative activity and percent of injected radioisotope contained in different organs were calculated. The radioisotope was found to be heavily concentrated in mediastinal lymph nodes and liver, with liver uptake averaging 36.5% of the injected isotope 24 hours after injection. The use of therapeutic intracavitary radiocolloids should be reevaluated in light of possible excessive irradiation of the liver.

This paper presents some preliminary data on physician suicides from the American Psychiatric Association Task Force on Suicide Prevention as well as pertinent items from the literature. Data are presented according to age, gender, method, and health status. Signs and symptoms that physicians should recognize in their peers and approaches that may be used to identify a physician at risk are described.

With the popularity of the augmentation mamaplasty has come a variety of approaches, prostheses, and results. In reviewing my own cases and experience, I have attempted to: (1) establish the criteria of the ideal breast contour and (2) point out a few of the pitfalls to be avoided when attempting to create surgically the ideal breast contour.

Two recent patients presenting with anuria due to abdominal aortic aneurysm and metastatic retroperitoneal tumor and illustrating this dramatic aspect of obstructive uropathy, provide the basis for this paper. Other reported causes of ureteral compression resulting in anuria are mentioned; these include billharzial strictures, iatrogenic ligatures, idiopathic retroperitoneal fibrosis, primary retroperitoneal tumors, and perirenal lymphocele.

Fiberoptic colonoscopy has seen its early development in the past five years and in the last two to three years a rapidly expanding experience has developed. The use of this instrument has been documented abundantly both as a diagnostic tool and as a therapeutic tool, and its effectiveness in both areas is well established. The chief therapeutic use of the colonoscope is in the removal of polyps, and in this area the experience has been most gratifying in regard to the ability to remove most polyps and the low incidencs of complications.

At the Medical University of South Carolina during the past five years, 62 patients have had intracranial aneurysm surgery, with an overall mortality of 4.8%. Anesthesia was given by me to 14 of these patients. Preoperatively these patients were placed on bedrest, steroid prophylaxis, and sedative and antihypertensive medication to reduce th possibility of recurrent subarrachnoid hemorrhage. Halothane-nitrous oxide-oxygen endotracheal anesthesia with controlled ventilation was used, with careful monitoring of EKG, direct arterial pressure, arterial blood gases, body temperature, and urinary output. Adjuncts for control of bleeding and intracranial pressure were osmotic diuresis, cerebrospinal fluid drainage, minimal head-up tilt, and controlled hypotension using trimethaphan (Arfonad). There were no operative deaths, although one patient died postoperatively. Three patients had neurologic deficitys. These data indicate that controlled hypotension is a safe technic which, when properly used, can reduce the risk of anesthesia for intracranial aneurysm surgery.

The medical work-ups received by hypertensive patients at Charity Hospital, New Orleans, during a three-month period in 1972 were evaluated. One hundred charts were reviewed using a questionnaire which covered aspects of history, physical examination, and laboratory tests important to the clinical evaluation of hypertension. The frequency with which these ideal parameters appeared in the charts reviewed is given in percentage form.

Frequently surgical amputation of a lower extremity is required when gangrene develops as a result of peripheral vascular disease. This is particularly true in geriatric patients. A below-knee amputation, with refinements in the surgical procedure, and immediate rigid-cast prosthetic fitting are strongly advocated by our group. The progress of two patients treated in this manner is described. Preservation of the knee joint improves the amputee's prognosis for ambulation with a below-knee prosthesis. The rigid-cast dressing on the below-knee amputation reduces edema and postoperative pain, is of psychologic value to the patient, and permits him to stand at from one to two days postoperatively.

Fever is usually thought to accompany tuberculosis. However, a review of 103 cases of tuberculosis presenting to a general hospital showed that 53% of the patients did not have fever when they first came to the outpatient clinic, and 10% did not have fever at any time while under observation. Absence of fever in a patient with pulmonary disease should not be used as evidence against the presence of tuberculosis.

A case of xanthomatous inflammatory pseudotumor of the lung is reported. Large lipid-laden macrophages were the most prominent microscopic feature of thelesion. Within the lung parenchyma three possible sources of alveolar lipids are serum lipids that pass into the alveolar spaces after injury to alveolar capillary walls, lipoproteins secreted by type 2 alveolar epithelial cells, and lipoproteins formed within alveolar macrophages. Phagocytosis and retention of such lipids by alveolar macrophages are proposed as important factors in the pathogenesis of the xanthomatous inflammatory pseudotumor of the lung.

In virtually all populations, the prevalence of dental caries is increasing. To elucidate the local situation, especially as regards the influence of sugar intake, appropriate studies, In association with dental research workers, were made on 16-17-year-old pupils in four South African ethnic groups-Back, Coloured, Indian and White. As expected, the caries situation in Whites was poor, and in rural Blacks, excellent; data on Coloureds and Indians were intermediate. The most outstanding finding was that urban Blacks still have very good teeth despite relatively high sugar intake and an increasing consumption of refined cereal products. Discussion of these results, as well as those reported in numerous similar investigations, leads to the view that sugar is neither the sole nor the principal cariogenic component of modern dietaries.

A case is described of a 30-year-old White male who drank 120 ml carbon tetrachloride (CCI4). The patient suffered severe liver damage and oliguria, he developed atrial fibrillation and become confused and irritable. During recovery, his bone marrow became depressed. He was discharged 29 days after admission.

The tyramine content of certain South African cheeses has been determined by gas chromatographic analysis. Aged (mature) cheese such as cheddar and Roquefort contain relatively large concentrations of tyramine as compared with other cheese, especially cottage cheese. Foods containing pressor amines must be avoided by certain patients.

Lynestrenol 0,5 mg was administered daily for a total of 1 082 cycles to 143 women of proven fertility and natural sexual activity. Twenty-three women withdrew from the trial for various reasons, the commonest of which were menstrual distrubances. No unplanned or accidental pregnancies occured. The menstrual disturbances tended to become less troublesome with continuation of treatment, and this was noted in relation to other side-effects, of which headache and loss of libido were initially the most troublesome.

Malignant melanoma of the skin in Blacks in formidable and sinister tumour. This study is concerned with the epidemiology of malignant melanoma, as seen in both urban and rural Black Africans. A smaller series in which follow-up on the patients was available is included. To our knowledge, this is the first study of its kind in which follow-up, and hence survival figures, can be quoted. Although the numbers are relatively small, they provide a valuable indication of the behaviour of melanomas in this group. The difficulties of follow-up cannot be overemphasised, and follow-up on 79 cases out of 100 could be obtained only by the employment of an able and enthusiastic Black social worker for 3 years. The first recorded survival figures in a Black population show a 3-year survival rate of only 28,4%. Prognosis is related to the size and extent of the tumour with larger and more widespread tumours faring worse than others. The incidence of malignant melanoma in Johannesburg Black was 1,2 per 100 000 and accounted for 2% of all cancers. The largest number of cases occurred in the 50- 70-year age group and there was a female preponderance. As in previous studies, the sites predominantly affected were the foot and the hand, mainly on the plantar and palmar surfaces.

Plasma renin was measured by immunoassay in 10 normal Zulu controls and 72 hypertensive Zulu patients. Plasma renin values were similar in controls and patients with benign essential hypertension (1,6 plus or minus 0,83 and 1,7 plus or minus 0,21 ng/ml).

In the period 1970-1974, 45 patients with Crohn's disease were seen. The incidence of the disease seems to be increasing. Twenty-nine of the patients were White, and 16 Coloured. The disease involved the small bowel alone in 9 patients, the ileocaecal region in 17, the large bowel alone in 4 and both the small and the large bowel in 15. Alone or in combination, abdominal cramps and diarrhoea were the commonest modes of presentation. The type of therapy used is discussed. Only 10 patients in this study have not as yet required surgery. Salazopyrin, steroids, antibiotics and azathioprine have been used with varying success in the treatment of most of the patients. Crohn's disease has a high degree of morbidity, but a low mortality rate.

The precision, accuracy, sensitivity and clinical results of a radio-immunological method for the determination of total serum thyroxine are compared with similar criteria of a competitive protein-binding assay. Application of both methods in the assay of thyroxine in 150 serum samples gave good agreement between the two techniques. The radio-immunoassay offers certain methodological advantages and is considerably less costly than thyroxine determinations in which commercially available kits are used.

An analysis of 50 children suffering from severe dogbites showed that the face was the anatomical site of predilection (75%(, and that the breed of dog most commonly involved was the Alsatian (German Shepherd). Primary debridement and suture under general anaesthesia is the treatment of choice. Ampicillin has been shown to be the antibiotic giving the widest over-all prophylactic chemotherapeutic cover.

The autosomal dominant variety of craniometaphyseal dysplasia was diagnosed in 8 members of three generations of a White family living in the Cape Province and in Natal. Radiographic investigations of these individuals permitted assessment of the spectrum of involvement and of the age relationship of the abnormalities. Characteristic radiographic features included cranial hyperostosis and sclerosis, in association with metaphyseal splaying. Diagnostic precision in this order permits accurate prognostication and rational genetic counseling.

Leiomyosarcomas comprise only 1-3 percent of malignant growths of the stomach. In the case presented, the correct diagnosis was not made pre-operatively. This article emphasises that, although they are rare, these tumours have certain characteristics which make possible a correct pre-operative diagnosis. Only 1 Black African patient has hitherto been described.

Prevention of the development of dependence on drugs and tranquillizers in hospital is a task which requires constant vigilance on the part of the hospital authorities as well as the right attitude on the part of prescribing doctors, administrating nurses and receiving public.

Air transport of patients by light aircraft and air ambulance is safe, fast and comfortable, and it is becoming increasingly popular. There are, however, specific problems, shortcomings and other details which must be dealt with effectively at various levels to ensure the best service for the patient.

Stools from Black and White children with gastroenteritis and from controls were investigated for potentially pathogenic agents by conventional virological and bacteriological methods and by electron microscopy. Isolations were obtained in 30 percent of cases but electron microscopy more than doubled the number of agents found. Orbiviruses were present in 40 percent of all cases, often in combination with other organisms. There was no difference between the Black and White groups.

Cancer mortality rates for Whites, Coloureds and Asians for the period of 1949 - 1969 have been analysed, and a changing pattern has been found. Some comparisons with other countries have been made, and the risk for each race group has been delineated for cancers at the commonest sites.

A prospective clinical study of 114 Malawian patients with cardiac disease seen at Queen Elizabeth Central Hospital, Blantyre, is presented. Rheumatic and hypertensive heart disease, cardiorenal failure and severe anaemia were the most common causes. Pericardial disease, mainly due to tuberculosis, was an important treatable cause of cardiac disease. Endomyocardial fibrosis was not diagnosed with certainty and cardiomyopathy was relatively uncommon. Ischaemic heart disease was not seen.

A group of 26 haemophilic patients was successfully managed on a home infusion programme over a one-year period. Single donor units of dried fresh plasma, the coagulant activity of which was adequate to ensure haemostasis of most of the haemorrhagic episodes treated, were used. The transmission of hepatitis was kept to a minimum by careful selection of regular, known donors and by the utilisation of single donor units of plasma in preference to plasma pools. Although the programme was costly, it was less expensive than it would have been had alternate antihaemophilic products been used. The advantages and disadvantages of self-administration are discussed. No serious mishaps occurred, and the programme was considered an outstanding success by both laymen and medical personnel. Minor alterations in liver function tests were demonstrated in several of the recipients. No factor VIII inhibitors were detected.

In summary, balloon flotation catheterization of the central circulation provides data in patient management which are meaningful and important. It has allowed the application of sound physiologic principles to the understanding of the circulatory abnormalities characterizing an illness in an individual patient, and provides a rational basis for selection of therapy with objective, quantitative assessment of patient response. The procedures are simple, the complication rate is low, and the information highly relevant to clinical care.

External counterpulsation represents a rational extension of the basic principles of counterpulsation as developed over the past 20 years. Its unique properties of being totally noninvasive, free of significant morbidity, and easily and quickly instituted clinically suggest that it may have a significant therapeutic role in the prevention and treatment of cardiogenic shock following acute myocardial infarction as well as being helpful in other cardiac disorders. Continuing evaluation is necessary, and it should be thought of as one of several useful mechanical circulatory assist devices now available to the internist, cardiologist, and surgeon caring for the critically ill patient.

Cardiac tamponade is an insidious and often fatal complication which can occur on any service, in many diseases, and at any age. The increasing pressure within the pericardium prevents ventricular filling and depresses cardiac output, coronary and systemic perfusion, and venous return. Compensatory mechanisms may protect the patient for some time, but prompt diagnosis and rapid decompression are usually required and must be followed by meticulous evaluation and treatment of the underlying disease.

The dilution of whole blood leads to a significant improvement of its rheologic properties based on a decrease in hematocrit and, hence, blood viscosity. Under conditions of normovolemia and an adequate response of the cardiorespiratory system, the acute dilution of blood will enhance the venous return to the heart and thereby improve total and capillary blood flow significantly. In the hematocrit range of 25 to 30 per cent (limited hemodilution), this increase in flow rate is able to compensate fully for the diminished oxygen content of the blood. Changes in oxygen extraction or in oxygenhemoglobin affinity are only encountered at hematocrits below 20 per cent or if hemodilution is associated with hypovolemia. Since normovolemia is the condition sine qua non for the heart to increase its output compensatorily, intentional hemodilution should preferably be performed with colloid solutions which are capable of maintaining the colloid osmotic pressure of plasma and the circulating volume in normal limits. Limited normovolemic hemodilution with its beneficial effects on microcirculatory flow and tissue nutrition is emphasized for the treatment of impaired microcirculation as occurring in shock and low flow states, polycythemia, and high viscosity syndromes. Acute preoperative hemodilution is a means of reducing the use of bank blood and of avoiding the risks of blld transfusions in patients undergoing major elective surgery. Extreme hemodilution and total body washout in hypothermia appear to be effective clinical tools.

In critically ill patients there is frequently more than one problem, which may not be obvious, contributing to the shock state. The history, physical exam, and monitoring devices may not be reliable individually, but must be considered together and interpreted in the light of the pathophysiologic mechanisms involved. A plan for monitoring and treating critically ill patients is outlined. The advantages and limitations of various monitoring techniques are discussed.

The effective use of vasoactive drugs in shock requires an understanding of the pathophysiologic mechanisms involved in the various types and stages of shock and knowledge of the specific pharmacologic effects of each drug in the abnormal state. Vasoactive drugs should be used after the primary and secondary causes of shock have been corrected. Specific vasoactive drugs should be selected on the basis of measured hemodynamic abnormalities.

A semi-micro method for the mixed lymphocyte culture (MLC) test in dogs is described. Optimization of various factors influencing the test were invistigated. Discrimination between allogeneic and isogeneic cell mixtures was possible after 90 h or culture but a culture period of 144 h was found to be optimal. The method measures MLC identity or non-identity and can be used as a tool for histocompatibility testing of lymphocyte defined (LD) Antigens.

The correlation between MLC reactivity (LD) and serological leukocyte typing (SD) was studied in a beagle colony. Disparity for a serologically defined non-DL-A lymphocyte antigen did not correlate with MLC reactivity. Lymphocytes of colony members with common ancestors and SD identical DL-A haplotypes did not stimulate each other in the MLC. This implies that LD typing in the beagle coolony can be generally predicted by DL-A SD typing. Consequently, lymphocytes of sibs homozygous for a given DL-A SD haplotype could be shown, with few exceptions, to be also homozygous for MLC determinants. Cells of these homozygous sibs can be used in MLC typing as reference cells for DL-A LD specificities. Two exceptions to the expected linkage between DL-A SD typing and MLC reactivity were found. These findings could not be explained by recombination with the DL-A region assuming a single major LD locus coding for MLC. Thus, suggestive evidence for more than one single LD locus has been obtained.

Serum from a grand multiparous Inuit (Eskimo) woman, who is HL-A identical but stimulatory in MLC with cells of her husband, contains strong ABCIL reactivity. This serum is operationally monospecific against a cell membrane determinant on lymphocytes, but not platelets, of some unrelated persons. Cells of those who are ABCIL positive with this serum always give a lower MLC stimulation index compared with their MLC responsiveness to cells that are ABCIL negative. This serum also contains good MLC inhibitory activity but only in those one way MLC reactions in which it reacts, by ABCIL, with the stimulating cells. It is postulated that the ABCIL activity is directed against a common MLC factor on lymphocytes.

Certain otherwise well-definedHL-Atyping sera contain extra antibodies which do not appear to be closely related to known HL-A specificites and which react in the cytotoxic test with chronic lymphaticleukemia lymphocytes but not with normal lymphocytes. Despite nonreactivity in thecytotoxic test, absorption studies show that the antigenic factors are well represented onnormal lymphocytes. Based on cross-absorption experiments using both normal andleukemic cells, followed by back-testing with the cytotoxic test against a leukemiccell panel, evidence is presented suggesting the existence of a complex, probablymultiple allelic system on human lymphoid cells which appears distinct from the, HL-Asystem, and is definable by serologic techniques.

In a kindred of 66 members spanning four generations, seven cases of ankylosing spondylitis (AS) HAVE BEEN FOUND. Four of these were in a single sibship of 13. AS was associated with HL-A27 in three of the four involved siblings, but close linkage was shown to be unlikely. Knowledge of HL-A genotype has made possible informed counseling for younger members of the sibship of 13, some of whom, as teenagers, already have back pain.

Dose distributions as well as mean doses to cylindrical cavities of bone marrow on X-ray irradiation have been calculated using (a) Monte Carlo method and (b) a simplified straight line approximation method. The results are compared with earlier published ones. Point doses differ appreciably from the earlier results by as much as 40 percent at some points, whereas mean doses agree to within 10 percent for all the three methods.

Author demonstrated subsequent to high-dose grid irradiation in Guérin-tumours of the rat the histological grid pattern corresponding to inhomogeneous dose distribution. Two to four days after irradiation through the grid of narrow openings in some sites certain phenomena could be observed, which seem to refer to the severe damage acquiring a diffuse character, but after 7 days the histological grid pattern has been clearly defined and the severely damaged stripes were about 50 percent narrower than the relatively intact ones. On the basis of the results on the actual tumour and among the applied experimental conditions the existence of a specific grid-tumour effect could not be justified by histological methods.

Thiourea in three different concentrations ranging from 10-4-M to 10-2-M was employed in pre- and post-treatments to test whether it decreases the chromosomal fragment frequency induced by 1000 R of X-rays in the growing root tips of Hordeum vulgare. In pre-treatment experiments thiourea in 10-2-M concentration yielded the maximal protection of 28.9 percent against radiation- induced chromosomal fragments. In post-treatment approximately a similar rate of protection is secured. It is discussed that the test-chemical protected the chromosomes against X-rays by two different mechanisms. The recovery process by restitution of the broken chromosomal fragments and the protection against initial radiation damage were the possible protective mechanisms displayed by thiourea in this plant material.

A quantitative analysis was carried out of structural chromosome aberrations in human perpheral lymphocytes exposed in vitro to 180 kV X-rays or 50 MeV protons. Statistical treatment of experimental findings by least-squares technique showed a regressional relationship between dose administered and yields of various chromosome aberration types. Fitting of the data to four mathematical models indicated, for both radiation types, that two-break aberrations, total number of aberrations and total of breaks are best fitted by the polinomial of second degree Y equals bD + CD-2, while one-break aberrations and number of aberrant cells are best fitted by the model Y equals a + bD. For all chromosome aberration types numerical values of the coefficients in these models are presented.

Cells differentiated from a human metastasizing melanoma have been irradiated simultaneously with pulsed high frequency currents (27.12 MHz, 400--600 pulses/s, pulse duration 65mus, average power 25--38 Watt) (Diapulse), and gamma radiation from a Co-60 source. Simultaneous pulsed high frequency field and gamma radiation acted in a way resembling a cell-protecting mechanism, enhancing the number of surviving cells to the extent of about 15 percent as compared with the cell number scored after pure Co-60 gamma-radiation treatment. Irradiation with pure high frequency currents resulted in increasing cell death for a period of up 4 minutes; subsequently, this seemed to be almost independent of time. The number of cells which survived, as compared with the controls, was found to be approximately 80 percent, near a distance of 6.5 cm from the symmetry axis, perpendicular to the plane of the radiating element.

The authors have followed the excretion of pyrimidine doexyribonucleosides in the urine of patients with generalized stages of Hodgkin's disease. They proved an increased excretion of deoxyuridine and thymidine in these patients compared to healthy persons. In the course of 14-days of combined chemotherapy a statistically significant increase in the excretion of DNA catabolites followed was found.

The levels of IgG, IgA and IgM were measured in the blood serum of uranium miners in a minin-district, where after a geological disturbance exposure to a high level of ionizing radiation took place. The mean exposure to 222-Rn daughters after first year was 7.35 WLM, after the second year 0.13 WLM only. Serum was sampled before miners started their occupation, for the second time after the first year and for the third time after the second year. The levels of IgG and IgM significantly decreased after one year of exposure, while the IgA changed only slightly. After the second year the levels of IgG and IgM significantly rose. IgG exceeded the initial levels: a regenerative hypercompensation took place. On the other hand IgA at the same time decreased. The IgG levels are only slightly correlated with radiation dose rate; for IgA and IgM the correlation is lacking. Individual Ig levels appear to be very variable. The reduction of IgG reached hypogammaglobulinemic levels in some miners after the first year and was followed by a propensity to infections of the respiratory tract. The significance of these observations is discussed from the immunological, radiological and radiohygienical point of view.