Role of central catecholamines in the control of blood pressure and drinking behavior.

The role of central nervous system (CNS) catecholamines in the development of hypertension and the control of drinking behavior was assessed in rats by depleting these amines with 6-hydroxydopamine (6-OHDA). Intraventricular administration of 6-OHDA completely prevented the development of one-kidney renal hypertension and abolished the associated increase in water consumption. 6-OHDA-treated rats showed deficits in drinking behavior when challenged with subcutaneous injections of angiotensin II (AII) and hypertonic sodium chloride. The acute pressor responses produced by intraventricular injections of AII and carbachol were virtually abolished by central catecholamine depletion. However, drinking produced by central cholinergic stimulation remained intact while AII drinking was significantly reduced. These data demonstrate that the integrity of CNS catecholamines is required for the development of one-kidney renal hypertension and the increased drinking which accompanies it. In addition, destruction of central catecholamine-containing neurons allows for a specific dissociation of the pressor and drinking responses produced by central cholinergic but not AII stimulation.


Analysis of short-term plasticity at the perforant path-granule cell synapse.

Short-term plasticity was investigated at the perforant path-granule cell synapse in the hippocampal slice preparation. A successive decrement in the amplitude of the extracellular EPSP was obtained at all stimulus frequencies above 0.05 Hz. This effect of repetitive stimulation has previously been shown to fulfill the requirements for habituation processes. If each stimulus within an habituation train was followed by a second identical test stimulus the response to the test stimulus was larger than that to the paired conditioning stimulus. This short-term plasticity has been called paired pulse potentiation. The test response potentiated only with respect to the paired conditioning response and not with respect to previous test responses. Neither form of plasticity appeared to result from changes in the amplitude of the afferent fiber volley. Both habituation and paired pulse potentiation result from an interaction of at least three changes in the efficacy of transmission after a conditioning stimulus: (1) an initial depression, (2) an intermediate relative potentiation and (3) a late depression which decays slowly. Paired pulse potentiation could be demonstrated only if the interpair interval corresponded to the period of maximal late depression and the interstimulus interval to the period of relative potentiation. The amplitudes of intermediate relative potentiation and late depression (and inhibition of transmission by 2-amino-4-phosphonobutyric acid (APB)) were inversely related to the control response amplitude. This relationship likely derives from nonlinear stimulation of postsynaptic ionic currents at higher stimulus intensities. In contrast, the initial depression increased with response amplitude. This is consistent with a mechanism dependent on the postsynaptic membrane potential, such as refractoriness to succeeding stimuli. When the response amplitudes in the presence and absence of 2.5 mM APB were equalized by adjusting the stimulus intensity, no difference was found in the magnitude of either form of plasticity. Since APB probably inhibits transmission at this site through competitive antagonism at the postsynaptic receptor, this observation suggests that habituation and paired pulse potentiation are generated presynaptically.


Distribution of alpha-melanocyte-stimulating hormone in the rat brain: evidence that alpha-MSH-containing cells in the arcuate region send projections to extrahypothalamic areas.

The distribution and concentration of alpha-MSH in the rodent brain has been determined by radioimmunoassay. The limbic system contained substantial quantities of alpha-MSH. Forty per cent of the alpha-MSH present in the brain was localized in the hypothalamus, with the highest concentration of alpha-MSH in the arcuate nucleus. More than 40% of the extrahypothalamic alpha-MSH in the brain was found in the following areas: midbrain (16%), preoptic area (13%), septum (7%), and thalamus (7%). To determine the source of the hypothalamic and extrahypothalamic alpha-MSH, the anterior hypothalamic preoptic area of the brain was surgically separated from more caudal diencephalic structures, and the arcuate region of the hypothalamus was surgically isolated from the remainder of the brain. Following these deafferentations, no significant reduction in hypothalamic alpha-MSH levels was observed; however, a significant reduction in extrahypothalamic alpha-MSH level was demonstrated. This dramatic decrease of alpha-MSH in extrahypothalamic areas of the rodent brain strongly suggests that the bulk of the extrahypothalamic alpha-MSH arises from neuronal perikarya in the arcuate region. These findings are consistent with the hypothesis that a population of neuronal cell bodies producing alpha-MSH originate in the arcuate region of the hypothalamus and that they send axonal projections to many areas of the limbic system and brain stem.


Development of neocortical circuitry: quantitative ultrastructural analysis of putative monoaminergic synapses.

The distribution, numbers and morphology of presumed monoaminergic (MA) synapses were examined in somatosensory cortex of neonatal rats and mice (newborn to 16 days of age). MA synapses were identified using an ultrastructural cytochemical marker, 5-hydroxydopamine (5-OHDA), which results in the appearance of small granular vesicles (SGV) in their presynaptic terminals. From birth to 7 days of age, 20--30% of all synapses sampled in somatosensory cortex contain SGVs. However, few SGV synapses are seen in 8-day-old cortex and by 12 days of age, SGVs are no longer detectable in cortex. A specific laminar distribution for these SGV synapses -- which is distinct from the overall synaptic distribution -- is first seen at 3 days of age and is essentially unchanged until 7 days postnatally. During this entire period, the SGV synapses predominate in the primordium of layer IV, where they account for 50--70% of all synapses. Morphometric analysis of SGV synapses indicates that there are differences in junctional symmetry, vesicle shape and configuration of the contact zone between SGV and non-SGV synapses, as well as between SGV synapses themselves in the various cortical layers. The laminar distribution and morphological characteristics of SGV synapses suggest that the MA projection to neocortex exhibits a high degree of spatial specificity during its ingrowth. Also, the relatively high proportion of SGV synapses in the first postnatal week may reflect a potent influence exerted by the MA inputs on immature neocortex. The decreased numerical density of SGV synapses after 7 days of age is probably due to the development of the blood-brain barrier to 5-OHDA.


Enrichment-isolation, cortex length and the rank order effect.

In a previous paper we have proposed a developmental theory to account for the neurological changes which result from differntially rearing animals in either enrichment or isolation. On the basis of brain weight measurements we suggested that the primary cause of the differential development could be traced to retarded neurological growth in the isolated animals. The present 9 studies test the generality of this theory by applying it to the cortex length changes induced in rats by differential rearing periods of between 18 and 160 days. In the light of this new data the theory has been revised to the extent that the developmental ceiling for the dependent variable is now considered to change with age instead of being fixed. Two major consequences of this revision are as follows. Firstly that the environmentally induced changes in cortical development are seen as persistent. Secondly that the Rank Order Effect is shown to be transitory phenomenon which exists only when some, but not all of the isolate values have been restricted in their development.


Intertectal crossing of optic axons after tectal fusion in neonatal rats.

Surgically-induced fusion of the superior colliculi along the midline was performed in newborn rats to provide a bridge for optic axons from one eye to cross the tectal midline. The results indicate that although tectal fusion is a necessary condition of optic axons to cross from one side of the midbrain to the other, it is not sufficient by itself to induce crossing unless the optic input from the opposite side is also removed. This finding is discussed in relation to tectal lesion studies and is compared with our previous observations of the corticotectal pathway.


Incidence of liver haemorrhage among white leghorn strains fed on diets containing different types of rapeseed meals.

1. There was a marked strain difference in the incidence of hepatic haemorrhage in White Leghorn hens receiving dietary rapeseed meal (RSM). 2. Tolerance to high dietary contents of RSM also varied between individual birds within a strain. 3. Glucosinolates were implicated in the development of hepatic haemorrhage among hens receiving dietary RMS but the exact relationship was not clear.


Heart rate response to egg rotation in the domestic fowl embryo.

1. In eggs turned about 12 times daily, around the long axis of the egg and through about 180 degrees, significant increases in heart rate occurred during turning on the 15th and 17th, although not on the 16th, d of incubation. 2. On and after the 18th d heart rate increases were more marked and occurred both during and after turning. 3. When a single group of embryos was turned every day for the last 4 d of incubation there were significant increases in heart rate on the last 3 d: this repeated retesting had no effect on the response to turning.


Blood enzyme activities in different breeds of geese.

1. Enzyme activities were studied in blood plasma from Rhenish, Italian, Landes and Masseubian geese. 2. Strains used for liver production (Landes, Masseubian) showed higher activities of aspartate transaminase (AST) [EC 2.6.1.1], alanine transaminase (ALT) [EC 2.6.1.2] and fructose aldolase (FRA) [EC 4.1.2.13] while breeds with high egg production (Rhenish, Italian) had higher activities of both alkaline phosphatase (ALP) [EC 3.1.3.1] and acid phosphatase (ACP) [EC 3.1.3.2]


Effects of storage conditions in vitro on the assay of chick liver glycogen.

1. The reproducibility of an enzymic method for assaying chick liver glycogen was found to be +/- 1.6%. 2. Storage of liver at either -21 or -70 degrees C for up to 4 weeks, after freezing in liquid nitrogen, had no significant effect on glycogen concentration. However, the concentration of free glucose increased by about 50% during this time. 3. Storage of liver in ice-cold saline for up to 3 h proved unsatisfactory because of a significant loss of glycogen. 4. There was no significant difference in immediate glycogen concentration in liver tissue that was freeze-clamped, frozen in liquid nitrogen or collected into ice-cold saline. The free glucose concentration was higher, when estimated immediately after, with the latter two methods of collection of liver tissue.


Plasma growth hormone concentrations in growth-retarded, cortisone treated chickens.

1. Weekly variations in body weight, relative body-weight gain and plasma growth hormone (GH) concentrations were determined in control and cortisone-treated (5 mg cortisone acetate/bird d) chickens between 3 and 10 weeks of age. 2. Treatment with cortisone between 3 and 5 weeks of age markedly suppressed growth but did not inhibit GH secretion. 3. After the cortisone injections were stopped these birds grew more rapidly than the controls. However, this period of "catch-up growth" was not accompanied by alterations in plasma GH concentrations.


Protein requirement of laying Japanese quail.

1. Two feeding experiments were conducted to determine the crude protein requirement of laying Japanese quail. Birds were fed to provide 293 kJ ME and 2, 3, 4, 5, 6 or 7 g protein/d. 2. As protein intake increased from 2 to 5 g egg production increased. 3. Quadratic relationships between protein intake and egg production and protein intake and egg weight were derived. 4. To maintain a production of 90 eggs/100 bird d and an egg weight of 9.3 g required 4.9 g protein and approximately 264 kJ ME/d.


Effect of deficiencies of single essential amino acids on nitrogen and energy utilisation in chicks.

1. Diets 50% deficient in single essential amino acids were fed to chicks from day 8 to day 18 after hatching to evaluate body-weight gain, food consumption, body composition, nitrogen (N) and energy utilisation. 2. Body-weight gain was reduced most severely by deficiency of isoleucine followed in decreasing order by threonine, arginine, valine, histidine, tryptophan, methionine plus cystine, phenylalanine plus tyrosine, leucine and lysine, and possible reasons for the differences are discussed. 3. Body-weight gain and food efficiency were highly correlated with food consumption but metabolisable energy value of diets was not affected by single essential amino acid deficiencies. 4. Generally N retention (N retained/N consumed) and energy retention (energy retained/energy consumed) reflected food consumption, except for a lower N retention by chicks fed on the methionine plus cystine-deficient diet and for a lower energy retention by chicks fed on the valine deficient diet. 5. The amino acid deficient in the diet was present at very low concentration in the blood plasma.


Canine hematology and biochemistry reference values.

Reference hematology and biochemistry values for 53 variables are presented from 51 clinically healthy dogs, 26 female and 25 male, approximately six to 24 months of age and of mixed breed. These dogs were sampled because of their good health status and the opportunity to collect the volume of blood required to complete the variable analysis of interest. Collection of blood specimens and laboratory analysis was done in a standard described manner, the latter including a continuing quality control program. For each variable the data were examined for homogeneity and when present, outliers (n = 9) were excluded. Parametric analysis was used to calculate the reference interval for those variables which had a Gaussian distribution or could be changed to a Gaussian distribution by any of four transformations. For those variables in which Gaussian distribution was not present or attained, nonparametric analysis was used. Due to the small size of the population sample, the uncertainty of breed and the exact age of each dog, breed, age and sex effects were not examined. Reference values should be used to assist interpretation of observations obtained from an animal or animals of comparable origin, i.e. similar subpopulation, and only if the same laboratory techniques are followed. Until each laboratory is able to generate reference values using adequate sample size and current methodology for the numerous subpopulations of interest, reference intervals such as these are useful to clinicians and researchers.


Experimental rabies in skunks: oral, nasal, tracheal and intestinal exposure.

Striped skunks (Mephitis mephitis) were exposed to challenge virus standard rabies virus by feeding infected mouse brain in suspension or as intact brain free choice, by forced feeding of suspension, and by intranasal, intratracheal and intraintestinal instillation of suspension. All of five skunks exposed intranasally, two of five exposed intratracheally and two of ten exposed by forced feeding developed rabies. None of the skunks exposed to challenge virus standard virus, by other methods, became rabid. Most of the survivors, when challenged intramuscularly with street rabies virus at six months, developed rabies. The results indicate that the skunk is much more susceptible to challenge virus standard rabies virus given intranasally than by the other methods used. When disease occurs following oral administration, infection may be associated with prolonged contact with buccal mucosa or accidental contact with nasal mucosa. Survivors had little or no protection when challenged intramuscularly with street rabies virus.


Parental and revertant Brucella canis induced changes in the rabbit.

Chronic brucellosis was produced in the rabbit by parental and penicillin-induced L-phase revertant of Brucella canis. Animals in the experimental groups were injected with 1.2 x 10(8) organisms/ml of appropriate strains by specified routes at intervals. At a maximum of 12 weeks postinfection, animals were killed and samples were taken for bacteriology, serology, histology, immunofluorescent and electron microscopy. Results revealed faecal shedding in some animals from 72 hours up to three weeks postinfection. High agglutinating antibody titres of 1:1280 were sustained in all infected animals. Histopathological and ultrastructural changes attributed to the invading organisms were apparent and evidence of mitochrondriopathic changes are provided. The implication and indirect role of L-phase in brucellosis are discussed.


The preparation of a polyvalent feline calicivirus antiserum.

A polyvalent antiserum capable of neutralizing 82 isolates of feline calicivirus made from cats in various parts of North America was produced by the sequential inoculation of SPF cats at three-week intervals with feline calicivirus strains F-9, 68-2024 and FS, followed by a final booster inoculation two weeks after the third inoculation with all three strains combined. Sera raised against the same strains but individually and then pooled failed to show such broad cross-neutralizing capacity. The polyvalent serum should prove useful for the confirmation of an isolation of feline calicivirus.


Oxygen affinity in stored canine blood: the effect of prednisolone.

Erythrocyte 2,3 diphosphoglycerate (DPG) levels and P450 measurements were made on canine blood stored in acid citrate dextrose solution at weekly intervals for four weeks. A negative correlation (-0.904) was found between weekly DPG and P50 values. The mean P50 measurement of 28.2 mm Hg on day 0 was significantly (P less than 0.001) greater than values measured on days 14, 21 and 28. Mean DPG values in the blood at the time of collection of 8.59 micrometers/gHB were only significantly (P less than 0.005) greater compared to values measured on day 28. On day 27, 0.5 mg of prednisolone sodium succinate per ml of blood was added to certain blood samples. This treatment did not result in an increase in P50 and DPG values on day 28.


Some intestinal parasites of Arctic fox, Banks Island, N. W. T.

Small intestinal parasitology of 50 trapped Arctic fox taken on Banks Island, The Northwest Territories, showed a prevalence of Taenia crassiceps (78%), Toxascaris leonina (60%), Echinococcus multilocularis (2%) and Coccidia (2%). Attention is drawn to the absence of Toxocara sp. and of Uncinaria sp.


The virus neutralizing activity of antibodies specific to the envelope and nucleocapsid of equine herpesvirus type 1.

Antibodies specific to the envelope or nucleocapsid of the Kentucky-D strain of equine herpesvirus type 1 were isolated from convalescent horse serum by immunoadsorption on cyanogen bromide-activated Sepharose conjugated with equine herpesvirus type 1 envelopes or nucleocapsids, with subsequent elution by glycine buffer. In double immunodiffusion and immunolectrophoresis reactions, the eluted proteins appeared to belong to the IgG fraction of horse serum. Antibodies directed against the viral envelope neutralized equine herpesvirus type 1 in a plaque neutralization test, while antibodies against the nucleocapsid showed no virus neutralizing activity.


Release of exogenous gamma-[3H]aminobutyric acid during seizure activity in chronically denervated and normal cat cortex.

The hypothesis that the seizure susceptibility of chronically denervated cortex is due to interruption of recurrent inhibitory pathways was tested by examining the release of 3H-labeled gamma-aminobutyric acid ([3H]GABA) from chronic slabs and normal cortex of cats. Seizure activity was maintained throughout the test periods in both normal and chronically isolated cortex. When methacholine was used to evoke seizure activity, [3H]GABA release was depressed in both normal and epileptic cortex, suggesting that the mechanism of seizure genesis by cholinomimetics involves suppression of inhibitory neuron activity. Pentylenetetrazol-induced seizures evoked a small, equal increase in [3H]GABA efflux from epileptic and normal cortex. Continuous electrical stimulation evoked a large, and again equal increase in [3H]GABA release. Preseizure efflux of [3H]GABA was the same from chronic slabs and normal cortex in all experiments. Since the interruption of recurrent inhibitory pathways by chronic denervation would result in a decreased resting and seizure-evoked release of [3H]GABA, results obtained do not support the above-mentioned hypothesis.


Calcium antagonists and contractile responses in rat vas deferens and guinea pig ileal smooth muscle.

The effect of depletion of extracellular Ca2+ (Ca2+ext) on the loss of responsiveness of the guinea pig ileal longitudinal muscle (g.p.i.l.m.) and the rat vas deferens (r.v.d.) to K+ and cis-2-methyl-4-dimethylaminomethyl-1,3-dioxolane methiodide (CD), and K+ and noradrenaline (NA), has been examined and compared with the effects of a variety of local anesthetics and calcium antagonists. The results indicate that qualitative similarities are apparent with respect to the dependence of agonist-induced activity on Ca2+ext in both the g.p.i.l.m. and r.v.d. Distinct differences, however, in the Ca2+ translocation processes in these two tissues, in response to the different agonists, can be shown by the use of a variety of 'calcium antagonists' thus indicating that such translocation processes are both tissue and agonist selective. It is thus noted that, contrary to the Ca2+ depletion studies, D 600 and the usually more potent BAY-1040 showed no discrimination of action or potency in their ability to inhibit components of the NA response in the r.v.d. In contrast, D 600 and the more potent BAY-1040 selectively inhibited the tonic component of the K+ response. Treatment with SKF 525A and parethoxycaine (PC) in the g.p.i.l.m. and SKF 525A in the r.v.d. resulted in a nonselective inhibition of responses of the tissues to all stimulants. However, in the r.v.d. PC potentiated NA action, and its methobromide (MeBr) derivative potentiated both NA and K+ action and also, like PC, partially shifted to the left the dose-response curve to Ca2+ in NA-depolarizing Ca-free Tyrode's. The quaternary MeBr and the tertiary 2-chloroethyl (2Cl) derivatives of SKF 525A and PC were selectively more effective against CD- than K+ supported contractile activity in the g.p.i.l.m. and the 2Cl derivatives were more effective against NA than K+ responses in the r.v.d. The 2Cl derivative of PC also was more effective in antagonizing the Ca2+ dose-response curve in high-CD or high-NA than in high-K+ Ca2+-free Tyrode's.


Age-dependent changes in the response of the lamb ductus arteriosus to oxygen and ibuprofen.

Circular strips of ductus arteriosus from lambs of gestational age between 90 and 144 days (term 147 days) were studied in vitro at low (8--16 torr (1 torr = 133.322 Pa)) and high (426--622 torr) PO2. Potassium- and oxygen-induced contractions increased with the gestational age and attained a maximum at term. At low PO2, ibuprofen, a blocker of prostaglandin synthesis, produced a dose-dependent contraction of the ductus at all ages and enhanced the potassium-induced contraction of the immature ductus (90--124 days). Both effects were relatively greater in the 103- to 107-day gestational group. At that age, ibuprofen also potentiated the oxygen-induced contraction. These findings, while confirming that a prostaglandin is involved in ductus patency, indicate that the prostaglandin-relaxing mechanism becomes functional at an early stage of gestation and reaches maximal activity before term. The existence of an active, prostaglandin-mediated relaxation in the preterm ductus may account, in part, for the reduced responsiveness of the vessel to oxygen. It is confirmed that ibuprofen and other nonsteroidal antiinflammatory drugs are well suited for the management of the premature infant with patent ductus arteriosus.


Improved isolation of villus and crypt cells from rat small intestinal mucosa.

An enzymic method is described which allows the isolation under comparable conditions of crypt and villus cells from rat jejunum with normal morphologic appearance and high metabolic activity when compared with previous preparations. The method is based on a differential scraping of short lengths of everted small intestine to yield two villus cell fractions and a gut wall residue. The scrapings and the gut tube are incubated for the same length of time in a HEPES-buffered modified Hanks' balanced salt solution containing hyaluronidase, DNase, and soybean trypsin inhibitor. The cells of the crypt region are recovered by a further scraping of the digested gut wall. Cells from all fractions are dispersed by gentle agitation, washed, and harvested by centrifugation. The final crypt and villus cells are 95--99% viable by dye exclusion and exhibit 5--20% cross-contamination on the basis of differential marker enzymes. The isolated crypt and villus cells prepared by the new procedure are suitable for comparative studies of metabolic activity in the absence of chelation-induced structural and metabolic abnormalities.


Effect of somatostatin suppression of glucagon secretion on glucose production in sheep.

The effect of somatostatin (SRIF) on glucagon and insulin secretion was examined in fed and fasted sheep. This was related to changes in glucose production. Infusion of SRIF at 80 micrograms/h caused a marked reduction in plasma glucagon concentrations. However, the insulin response to SRIF infusion was not consistent; its concentrations decreased occasionally, but often did not change. The depression of glucagon was not associated with a significant reduction in blood glucose concentrations in either fed or fasted sheep, but was associated with a reduction in glucose production by 12--15%. The inhibitory effect of insulin on glucose production was not markedly increased by glucagon deficiency. Infusion of insulin at 1.17 U/h with SRIF decreased glucose production only an additional 10%. Thus, it appears that under basal conditions pancreatic hormonal influences on hepatic glucose production were relatively small in sheep. This implies that under normal conditions in sheep, substrate supply has a much greater impact on hepatic glucogenesis than do hormones.


Interactions of methylxanthines, nonxanthine phosphodiesterase inhibitors, and calcium with morphine in the guinea pig myenteric plexus.

In an earlier study, theophylline was shown to antagonize the morphine-induced inhibition of electrically induced contractions of the longitudinal muscle-myenteric plexus preparation from the guinea pig ileum. In the present study, acetylcholine (ACh) released from the myenteric plexus was measured directly using a radioenzymatic assay. Theophylline antagonized the morphine-induced inhibiton of ACh release. A similar antagonism was also observed with caffeine and 3-isobutyl-l-methylxanthine (IBMX). All three methylxanthines also increased ACh release. The nonxanthine phosphodiesterase (PDE) inhibitors 4-(3-butoxy-4-methoxy)-2-imidazolidinone (Ro 20-1724) and l-ethyl-4-isopropylidenehydrazino-1 H-pyrozolo(3,4-b)-pyridine-5-carboxylate, ethylester, HCl (SQ 20,009) generally did not antagonize the morphine-induced inhibiton of ACh release. The PDE inhibitor SQ 20,009 but not Ro 20-1724, enhanced the release of ACh. Both high calcium concentration and the divalent cation ionophore A23187 antagonized the inhibitory action of morphine on ACh release. These observations suggest that alteration in calcium fluxes rather than the inhibiton of PDE mediate the methylxanthine-induced antagonism of morphine in this preparation.


Effect of alcohol on thermal balance of man in cold water.

The effects of alcohol on core cooling rates (rectal and tympanic), skin temperatures, and metabolic rate were determined for 10 subjects rendered hypothermic by immersion for 45 min in 10 degrees C water. Experiments were duplicated with and without a 20-min period of exercise at the beginning of cold water immersion. Measurements were continued during rewarming in a hot bath. With blood alcohol concentrations averaging 82 mg 100 mL-1, core cooling rates and changes in skin temperatures were insignificantly different from controls, even if the exercise period was imposed. Alcohol reduced shivering metabolic rate by an overall mean of 13%, insufficient to affect cooling rate. Alcohol had no effect on metabolic rate during exercise. During rewarming by hot bath, the amount of 'afterdrop' and rate of increase in core temperature were unaffected by alcohol. It was concluded that alcohol in a moderate dosage does not influence the rate of progress into hypothermia or subsequent, efficient rewarming. This emphasizes that the high incidence of alcohol involvement in water-related fatalities is due to alcohol potentiation of accidents rather than any direct effects on cold water survival, although very high doses of alcohol leading to unconsciousness would increase rate of progress into hypothermia.


The origin of two components in contraction of guinea pig papillary muscle in the presence of noradrenaline.

In experiments on isolated guinea pig papillary muscles the effects of verapamil (5 mg/L) and caffeine (1 g/L) on the two-component contraction were investigated. The muscles were continuously superfused with normal Tyrode's solution containing 2 mg of noradrenaline/L at 20--22 degrees C. The first derivative of contractile response and transmembrane action potential were simultaneously recorded. Verapamil suppressed the amplitude of the second component and had no influence on the first component of contraction. Caffeine eliminated the first component and increased the second component of contraction. It was suggested that in the activation of two-component contraction calcium ions from two different pools take part: (1) those released from sarcoplasmic reticulum, and (2) those that crossed a cell membrane during the plateau of the action potential.


Activation by adenosine-5'-triphosphate of glutamic decarboxylase from a subcellular fraction of mouse brain.

Glutamate decarboxylase from a mouse brain P2 fraction undergoes a twofold activation in the presence of 0.5 mM ATP. No such stimulation by ATP occurs if the enzyme is assayed in the presence of excess pyridoxal phosphate as cofactor. The ATP-induced stimulation is almost completely eliminated if the enzyme is dialysed before its assay. [lambda-32P]ATP present during the enzyme measurement is converted to [32P]pyridoxal phosphate. These results demonstrate that the activation produced by ATP is the result of the generation of cofactor during the course of the assay. This phenomenon may be a reflection of a control mechanism of glutamate decarboxylase activity.


Ketamine kinetics: decerebrate vs. intact cats.

Pharmacokinetic parameters of a ketamine (10 mg/kg, iv) bolus in decerebrate and intact cats were compared. A two-compartment open model best described the data in both groups. The apparent volume of distribution of the peripheral compartment, the apparent volume of distribution of the drug in the body, and the half-life of the postdistributive phase were significantly less (p less than 0.05) in the decerebrate animals. These results emphasize the importance of correlating behavior and neuronal activity with plasma or blood concentrations of drug in animals rather than assuming that, for a given drug dose, blood (and thus tissue) levels of the agent will be similar regardless of how the animal is prepared for study.


Theophylline antagonizes flurazepam-induced depression of cerebral cortical neurons.

Intravenously administered theophylline (50--100 mg/kg) antagonized the depressant actions of adenosine and flurazepam on rat cerebral cortical neurons. When assessed in conjunction with recent reports that theophylline competes with diazepam for binding sites in brain tissue, this finding suggests that one action of the benzodiazepines may be exerted at a purinergic receptor associated with central neurons.


Results of radical nephrectomy in 178 cases of renal cell adenocarcinoma.

One hundred and seventy-eight patients with renal cell adenocarcinoma were classified by stage and treated by radical nephrectomy. A transabdominal approach was used in 92% of cases and lymphadenectomy was not performed unless ipsilateral hilar nodes were involved. Survival rates are presented in the form of life-table curves. These curves indicate that survival depends on the stage of the disease at the time of initial treatment; about 80% of patients with stage 1 lesions (tumour confined to the kidney) survived for 10 years compared with only 30% to 35% of stage 2 (involvement of perinephric fat) and stage 3 (involvement of renal vein or regional lymph nodes) patients and less than 10% of stage 4 (metastatic spread) patients. Radical nephrectomy appears to be the best method of treatment for patients with stage 1, 2 or 3 lesions. Simple palliative nephrectomy may be indicated in selected patients with stage 4 lesions.


Renal cell carcinoma in children.

The authors reviewed the records of eight children with renal cell carcinoma and correlated the clinical presentation, pathological and radiologic findings, stage and treatment of the disease with patient survival. Angiography revealed tumours of sparse neovascularity, associated with varied histologic patterns. Patient survival was dependent on the stage of the disease at the time of treatment; treatment of localized disease was effective but of metastatic disease was generally poor. Tumour staging appeared to be the only reliable indicator of prognosis. Children with renal cell carcinoma differ from adults in that a palpable mass in a child does not necessarily indicate that there is metastatic disease.


Radiation therapy for adenocarcinoma of the prostate.

Forty-eight patients with different stages of adenocarcinoma of the prostate were treated by external beam therapy. Biopsy results are correlated with stage of disease, original grade of tumour and with the findings on examination. The authors discuss the significance of histologic progression of the disease particularly in relation to prognosis. They review the place of staging lymphadenectomy before radiotherapy and the overall morbidity associated with treatment.


Surgical management of renal cell carcinoma at the Vancouver General Hospital: 20-year review.

Over a 20-year period 143 patients with renal cell carcinoma were treated surgically at the Vancouver General Hospital. The results of simple nephrectomy are compared to those of radical nephrectomy. The authors conclude that radical nephrectomy (including node dissection) is a useful staging procedure but provides little or no long-term therapeutic benefit over simple nephrectomy. They stress the need for new adjunctive therapy.


Management of primary bladder cancer by a multidisciplinary team.

Results of management of a closed series of primary bladder carcinoma over a 20-year period by a multidisciplinary team are presented. Patients were classified by the TNM method before treatment. These experiences indicate that stage and grade are relevant to prognosis and treatment. The TNM classification can be precise and practical when used diligently by a treatment team. Although no new methods of treatment are offered, the treatment now available may be utilized to better effect if programmed to allow care of the patients by a team, especially if the team explores the limits of radiation and surgery in their hands.


Trans-sphincteric approach to the rectum.

In 28 cases the trans-sphincteric approach has been used to remove lesions of the lower and mid-rectum; in 4 cases the combined abdominal and trans-sphincteric approach was used. Complications were minor and were easily treated and the operation was well tolerated by poor-risk patients. No patient had altered anal continence. The author emphasizes the need for careful identification and reconstruction of the anatomical structures. The trans-sphincteric approach gives excellent exposure of the mid- and lower rectum and has been particularly useful in managing large villous adenomas. The trans-sphincteric approach alone is not adequate for the treatment of cancer, but makes possible sphincter-preserving resections of lesions that might otherwise be treated by more radical procedures.


Elastin and granulation tissue.

The contraction of granulation tissue is an important factor in wound healing. The tract of an abdominal drainage tube closes at the rate of 1 mm/h once the tube is removed. Specialized myofibroblasts are generally believed to be responsible for this process and the presence of elastin in granulation tissue has been debated for many years. A 3-mm polyethylene tube was inserted through the left lobe of the liver in 41 rats. A tube of granulation tissue formed around the plastic. This granulation tissue was isolated, after periods ranging from 8 to 20 days, by removing the left lobe of the liver and scraping away the surrounding liver tissue. Biochemical assay for elastin revealed that normal hepatic tissue does not contain any detectable amount of elastin. All 41 samples of granulation tissue contained elastin with a mean value of 8.5 X 10(-6) g of elastin per milligram of tissue. Normal rat aorta contains 31.4 X 10(-6) g of elastin per milligram of tissue. These tubes of granulation tissue were histologically normal and the presence of elastin was recognized using elastin stains. The exact role of elastin in granulation tissue is uncertain but this experiment clearly demonstrates its generation and presence there.


Treatment of carotid cavernous fistula by intravascular occlusion using a balloon catheter.

The surgical treatment of carotid cavernous fistula gradually evolved into a "trapping" technique. This technique includes ligation of the cervical internal carotid artery, clipping of the intracranial portion distal to the fistula and often embolization of the isolated segment. The development of embolization techniques using intravascular balloon catheters greatly simplified this treatment. The authors report a case of spontaneous carotid cavernous fistula in which obliteration was achieved by an intracarotid balloon catheter. This was inserted by direct puncture of the carotid artery, which had been exposed by a simple neck incision. The patient's visual acuity was preserved. The efficacy, ease and safety of this method are emphasized.


Involvement of small intestine in familial polyposis coli.

Extracolonic intestinal manifestations of familial polyposis coli have been described in recent years, but the exact frequency is still unknown. To date the more common sites of extracolonic polyposis appear to be stomach and duodenum with true adenomas being somewhat rare in jejunum and ileum. The authors report a further two cases of ileal polyposis in siblings from a family with familial polyposis coli and conclude that this condition cannot be considered as a disease exclusively of the large bowel. They emphasize that examination of the upper gastrointestinal tract and small bowel must be included in the investigation and follow-up of patients with familial polyposis coli.


Early surgical management of acute cholecystitis.

Between 1971 and 1977, 361 patients underwent early elective cholecystecomy for acute cholecystitis, and the complications and mortality were studied according to the length of time from admission to operation. A substantially greater proportion of the complications, and the only deaths, occurred in the patients operated upon more than 7 days after admission. The mortality rate was 0.6%. Nine additional high-risk patients underwent cholecystostomy. There were four postoperative deaths in this group, all related to the debilitating underlying conditions. The mortality for the entire series was 1.6%. These results compare favourably with those following delayed elective operations for acute cholecystitis. Early elective operation, using cholecystectomy when possible and cholecystostomy when necessary, is recommended for general use in experienced hands. This practice is safe and sound particularly when the diagnosis is made more certain preoperatively by the use of intravenous cholangiography.


Aspirin prophylaxis of venous thromboembolic disease following fracture of the upper femur.

In a prospective study of 51 patients with fractures of the femoral neck, aspirin was used as a prophylactic measure against thromboembolic disease. Thrombi were detected by cuff impedence plethysmography, Doppler ultrasonography and ascending venography. Thrombi were identified in 20 (39.2%)  of the patients. There was no significant difference between the frequency with which thrombi occurred in men and in women. Blood salicylate values were the same for patients who had and who did not have thrombi. There were no instances of pulmonary embolism. The frequency of deep vein thrombosis was comparable to that in a previous series of untreated patients from the same centre. It appears from this study that in these cases prophylaxis against venous thromboembolism using aspirin in a dosage of 600 mg bid is ineffective.


Testicular scanning: its efficacy in diagnosing intrascrotal lesions.

Radionuclide scanning is a relatively new diagnostic aid for evaluating intrascrotal lesions. The authors present a retrospective analysis of 34 patients who underwent testicular scanning from 1973 to 1978. While the technique may be helpful, misleading results are not uncommon and caution should be exercised in interpreting the results. In this series 22% of scans obtained in cases of testicular torsion and acute epididymitis failed to provide the correct diagnosis. In view of the serious consequence of testicular loss when surgical exploration is delayed, testicular scanning should not be relied upon to the exclusion of other more traditional methods.


Sensory feedback in a myoelectric upper limb prosthesis: a preliminary report.

Upper limb prostheses are often rejected because they do not provide the sensory feedback available from a normal hand. A system for providing sensory feedback has been developed at the University of New Brunswick for use with the three-state myoelectric controls prepared in the Bioengineering Institute there. Strain gauges mounted on the forefinger of an electric hand provide information which is processed electronically to cause a tingling sensation in the patient's stump, proportional in its intensity to the pinch force in the finger. This system has been used by a patient at the Ontario Crippled Children's Centre in Toronto, since June 1976. She uses it consistently with great satisfaction and enthusiasm. It gives her a sense of competence and confidence she does not have without it.


Colorectal neoplasm: a rare complication of ureterosigmoidostomy.

A 24-year-old woman had a rectal neoplasm which occurred 20 years after she had undergone ureterosigmoidostomy for exstrophy of the bladder. Only 41 cases of bening or malignant tumours of the large bowel developing after ureterosigmoidostomy have previously been reported in the literature. Adenocarcinoma of the colon is most frequently found and can develop even after urine has been diverted away from the colon. The presenting symptoms are either those of ureteral obstruction or of colorectal neoplasm. This rare complication remains intriguing and the possible pathogenetic mechanisms are discussed.


Intraoperative transmural myocardial biopsy: a simple technique.

A Tru-cut disposable biopsy needle was used in 10 pigs, 3 cadavers and 63 humans to obtain transmural ventricular myocardium for diagnostic and research purposes. The technique proved simple and safe. In every case an adequate amount of full-thickness myocardium was obtained which was examined by light and electron microscopy and used for enzyme studies and glycogen measurement.


Electrohydraulic cystolitholapaxy.

The electrohydraulic lithotrite generates high voltage discharges which, in a liquid medium, are converted to hydraulic shock waves capable of fracturing bladder stones. Electrohydraulic litholapaxy was successful in treating 28 of 30 patients with bladder stones. In nine patients other procedures were performed during the same anesthetic. In one patient, a calculus was removed from within a narrow-necked bladder diverticulum. Compared with conventional mechanical lithotripsy with serrated, jawed instruments, electrohydraulic lithotripsy is a safe, easy to learn and effective technique for treating bladder stones.


Studies of crystalluria in recurrent calcium lithiasis.

The authors have studied the distribution and total volumes of large and small crystals in the urine of healthy individuals and of those who form stones. Studies carried out on randomly obtained specimens were as reliable in identifying differences as were fasting specimens. Stone forming individuals had a greater number of large crystals and a greater total volume of crystals in the urine than had healthy persons. The urine of stone forming patients who had received treatment showed no difference in crystal volume from that of a similar group who had not been treated, and the same was true of a group of stone forming patients studied before and 6 months after the start of treatment.


The abdominal surgeon and the ureter.

Iatrogenic ureteral injuries are not common but may occur whenever the retroperitoneum is opened. The best time to treat these injuries is when they occur. The abdominal surgeon is responsible for the immediate treatment of ureteral injuries that he causes and should be able to take care of most of them. The author describes methods for preventing and managing ureteral puncture, crushing injury, kinking and ligation of the ureter, partial and complete transection of ureters, excision of both short and long segments of the ureter and ureteral devascularization.


Symposium on portal hypertension and its complications: current management. Preoperative assessment and predictors of encephalopathy.

None of the preoperative predictors of encephalopathy proposed so far to evaluate the risk of portacaval shunting in cirrhotic patients has been of value. The authors have found, in preliminary studies, that measurement of the hepatic extraction of indocyanine green (ICG), which correlates highly with the "functional" portal blood supply, could be of prognostic value: cirrhotic patients with a near-normal value for ICG extraction often have encephalopathy after portacaval shunting whereas those with a low ICG extraction value seldom have encephalopathy. These preliminary data suggest that cirrhotic patients with markedly decreased ICG extraction have a lesser risk of encephalopathy since their portal blood supply is already shunted away from hepatocytes before the operation because of anatomic changes in the liver microcirculation.


Current status of the peritoneovenous shunt for the management of intractable ascites.

Renewed interest in the management of intractable ascites has led to the use of a peritoneovenous shunt for its control. Analysis of Canadian experience with this technique in the last 2 years has demonstrated that there are problems associated with it that have not been reported in the surgical literature. A group of 60 patients who underwent peritoneovenous shunting at several Canadian centres was analysed. The operative mortality was 20% but was related to the underlying disease rather than to the operative procedure. Although the initial response to shunting was excellent in 53%, long-term patency (more than 3 months) was achieved in only 43%, but the procedure greatly improved the quality of life in those patients. The indications for shunting, the complications, results and cumulative patency rates are discussed.


Hemoccult test as a routine screening procedure for colorectal disease in the private clinic setting.

Increased attention is being focused on the earlier detection of malignant and premalignant colorectal lesions in an attempt to increase the survival rate of patients with these diseases. This study evaluates the use of the Hemoccult test as a screening procedure in a private clinic. A protocol for its implementation is presented. Of the 631 patients entered into the study, 514 (81.5%) returned completed slides. In 14 (2.7%) of these 514 patients, the slides gave positive results, and 10 of the 14 patients underwent thorough investigation. No malignant tumours were found as a result of the test. Six (1.2%) of the 514 patients had one or more benign polyps.


Acute spinal cord injury: analysis of epidemiologic factors.

The authors studied the epidemiologic aspects of acute spinal cord injury in 358 patients admitted to the Toronto General and Sunnybrook hospitals between 1948 and 1973. The ages of the patients ranged from 14 to 89 years (median 32 years) and the male:female ratio was 4.5:1. The most frequent causes of injury were traffic accidents (34.4%), accidents at work (29.3%), sports-recreational injuries (15.4%) and falls at home (9.8%). Several epidemiologic factors were identified which are important for developing programs to reduce the frequency of cord injury. In particular young persons should be made more aware of the risks they run as automobile drivers and of the hazards of diving in shallow water, middle-aged workers in the construction industry are at risk of spinal cord injury from falls and elderly farmers are at risk of falling from lofts or being crushed by overturned tractors.


Metastatic endometriosis in abdominal scars.

The author presents two examples of metastatic endometriosis occurring in an abdominal scar. These case reports illustrate the two main theories of the pathogenesis of the condition: transportation and metaplasia. The diagnosis is straightforward in the classic case in which a painful mass fluctuates with the menstrual cycle, but a biopsy may be needed to confirm the diagnosis when the history is atypical. The treatment of choice, for those who require treatment, may be hormonal manipulation, surgery or irradiation, or a combination of these.


Solitary pulmonary nodules due to sarcoidosis.

Two patients, a 67-year-old woman and a 33-year-old man, had asymptomatic solitary nodular masses in the lung detected by roentgenographic examination. The preoperative investigations failed to make a firm diagnosis or to rule out the presence of a malignant lesion. In both patients the lesions were resected and found to contain noncaseating granulomas. Electron microscopy and immunochemical studies for lysozyme supported the diagnosis of solitary nodular sarcoidosis. Such roentgenographic presentations of sarcoid are rare.


Postmastectomy lymphangiosarcoma: experience with three patients and electron microscopic observations in one.

The clinical features are presented of three patients in whom lymphangiosarcoma developed after radical mastectomy followed by local irradiation. The median time between radical mastectomy and the diagnosis by biopsy of lymphangiosarcoma was 9.9 years. No form of therapy, including high-dose combination chemotherapy, appeared able to control the disease. All three patients died with residual lymphangiosarcoma and in two it was the direct cause of death. These results stress that prevention of postmastectomy lymphangiosarcoma is vital. This can be accomplished by avoiding radical mastectomy followed by local irradiation. Ultrastructural observations in one case suggest that the tumour has a primitive vasoformative origin.


Follicular carcinoma in a thyroglossal duct.

The case of a 24-year-old woman with follicular carcinoma arising de novo in a thyroglossal duct is reported. A review of the literature disclosed seven case reports of thyroglossal duct carcinoma with a mixed papillary-follicular pattern. There are three criteria for the diagnosis of follicular carcinoma of a thyroglossal duct: presence of a thyroglossal duct, absence of carcinoma within the thyroid gland and angioinvasion. A plan of treatment, based on the literature survey, should include Sistrunk excision of the tumour if possible, and subtotal thyroidectomy should be performed to eliminate the presence of a primary thyroid carcinoma.


Orthopedic surgery today.

The history of orthopedic surgery in Canada is briefly reviewed. It appears that the problems which were posed in the 1960s and early 1970s have diminished in importance. They related to the shortage of orthopedic manpower and to the lack of a sound scientific base within universities. There appears now to be an adequate number of orthopedic surgeons to handle the needs of the population, and Canadian training programs are providing replacements at an appropriate rate. Future problems will in all probability relate to the interrelationship between society and the medical profession. Academic freedom and mobility of medical manpower must be preserved at all costs and the orthopedic profession must adapt to an ever-changing situation if future developments are to be as satisfying as our very exciting past.


Primary malignant tumours associated with renal cell carcinoma.

Of 360 patients with primary renal cell carcinoma seen at the Vancouver General Hospital between 1957 and 1976, 33 had associated primary malignant lesions. A review of the 166 patients who had ablative surgery revealed that they were four times more likely to have a synchronous primary malignant tumour than the other patients. The incidence of asynchronous primary malignant tumours was not increased. This may be related to the fact that the patients' full life charts were not available. In 18 patients dying of other causes in whom an incidental renal cell carcinoma was found, 5 (28%) died of other malignant tumours. In a comparable age group from the general population, 19% are at risk of death from malignant disease. The frequency of synchronous contralateral renal cell carcinoma in our series was 50 times greater than the frequency of primary renal cell carcinoma in a corresponding sector of the general population.


Oral fluid therapy: sodium and potassium content and osmolality of some commercial "clear" soups, juices and beverages.

Analysis of nearly 90 commercial "clear" fluids, including soups, juices, fruit-flavoured drinks and ices, carbonated beverages and gelatins, showed a range of 0.1 to 251 mmol of sodium and 0.0 to 65 mmol of potassium per litre; the osmolality ranged from 246 to more than 2000 mOsm/kg of water. Knowledge of these values is useful in the home or hospital management of patients for whom control of fluid and electrolyte intake is indicated. The results of the analyses are presented in tabular form for use by physicians and nutritionists when counselling patients to ingest clear-type fluids for various illnesses. Examples are given using these data to show how clear-fluid therapy can be tailored in one such illness--gastroenteritis (infectious diarrhea).


Five-year survival of women with breast cancer in northern Alberta.

Five-year survival rates for all 519 women with breast carcinoma in northern Alberta in 1971 and 1972 were analysed with the use of data from the computerized northern Alberta breast registry and the Alberta cancer registry. The relative 5-year survival was 73%, which is higher than most rates reported from other centres. Lymph node involvement was significant as a prognostic factor, with the relative 5-year survival falling from 92% in the group without lymph node involvement to 58% in the group with three or more involved nodes. The prognosis was also significantly affected by the stage of the disease according to the 1973 TNM classification: the 5-year survival rates ranged from 88% for patients with stage 1 disease to 17% for those with stage IV disease. Women 40 to 59 years of age had a higher survival rate (79%) than those under 40 years (65%) or over 60 years (66%) of age. Analyses by 5-year age groups showed that women 35 to 39 years old had a particularly poor survival rate (59%). Postmenopausal women less than 55 years old had a higher survival rate than did perimenopausal or premenopausal women in the same age group. Further follow-up is indicated to correlate possible high-risk factors with survival.


Physiologic significance of hemodynamic measurements and their derived indices.

The fundamental value of hemodynamic monitoring is that it provides direct physiological measurements. The appropriate use of these requires an understanding of normal cardiac physiology and its alterations in certain disease states. An appreciation of the determinants of cardiac output, coronary blood flow and myocardial oxygen consumption will improve the interpretation and subsequent manipulation of these values when one is confronted with them clinically.


Basic equipment requirements for hemodynamic monitoring.

Hemodynamic monitoring in the critically ill patient requires the use of sophisticated electronic devices. To use this equipment one should have a general understanding of the principles involved and the requirements of a reliable system. This communication serves to explain the requirements of the various components of a hemodynamic monitoring system and to demonstrate how they interact to produce accurate and safe electronic signals from mechanical wave forms obtained from the patient.


Hemodynamic monitoring: catheter insertion techniques, complications and trouble-shooting.

Hemodynamic monitoring is an important aspect of contemporary intensive care of the critically ill patient. The potential problems associated with invasive monitoring fall into two general categories: those related to technical pitfalls and those related to patient complications. An awareness of these problems combined with technical expertise and an understanding of cardiovascular physiology can minimize complications and make hemodynamic monitoring a safe and useful procedure.


Does hemodynamic monitoring complement conventional methods of assessment in the critically ill cardiac patient?

Conventional clinical methods give qualitative information about left ventricular function in the critically ill patient. However, the information gathered from the physical examination and noninvasive methods is subject to important pitfalls with respect to both its nonspecificity and interobserver variability. The advent of hemodynamic monitoring has highlighted these difficulties and provided more quantitative information that is relevant in both diagnosis and treatment of the critically ill patient.


Hemodynamic monitoring in acute myocardial infarction.

The main cause of in-hospital death in patients with acute myocardial infarction is the "power failure syndrome". Hemodynamic monitoring provides precise and current data on the filling and output status of the left ventricle and, when indicated, the right ventricle. The information obtained is used to determine the hemodynamic status more precisely than is possible from conventional clinical assessment. It permits categorization of patients by hemodynamic status; the hemodynamic subset classification of Forrester, Diamond and Swan is a powerful tool in guiding therapy and establishing prognosis in individual patients. In addition to guiding the initiation of therapy, hemodynamic monitoring is useful in the continuing assessment of potent and complex treatment. This therapy is directed at resolving hemodynamic derangements without unfavourably altering the myocardial oxygen supply-demand relationship. Specific clinical indications for hemodynamic monitoring may include confusing or complicated clinical situations in which diagnostic problems exist, complicating mechanical derangements, severe congestive heart failure, cardiogenic shock and clinical research in acute myocardial infarction.


Contributions of hemodynamic monitoring to the treatment of chronic congestive heart failure.

Optimal therapy for congestive cardiac failure requires identification of correctable factors that aggravate it as well as an understanding of its etiology. Increased sympathetic nervous system activity, reduced renal blood flow, and cardiac hypertrophy and dilation are the main compensatory processes that occur in response to cardiac failure. Although they may be of initial benefit in supporting a reduced stroke volume, they may ultimately prove self-defeating. New drugs for the treatment of severe congestive heart failure include dopamine, which has a selective nonadrenergic dilator effect on the renal vascular bed, and dobutamine, which has potent inotropic effects, lowers the left ventricular filling pressure and does not increase the heart rate or the systemic vascular resistance. By reducing both the resistance to left ventricular ejection and the venous return to the right heart, vasodilators result in improved peripheral perfusion and reduced pulmonary congestion. Optimal therapy for refractory cardiac failure can be rationally determined by characterizing the hemodynamic profile through measurement of the mean arterial pressure, the left ventricular filling pressure, the cardiac output and the systemic vascular resistance. The specific therapy can then be effectively and safely delivered by a careful analysis of the dose-response relation as identified by hemodynamic monitoring.


Hemodynamic monitoring and care of the patient of high risk for anesthesia.

Hemodynamic monitoring and care of the patient at high risk for anesthesia require a careful and systematic approach. During preoperative evaluation the patient at increased risk must be identified and correctable problems must be solved. The patient's current medications must be reviewed because they may influence the choice of anesthetic approach and may alter the physiologic response to the stresses commonly associated with anesthesia. In addition to conventional clinical and electrocardiographic monitoring, perioperative hemodynamic monitoring may be desirable for patients at special risk, who are likely to have significant associated medical problems or to undergo complicated surgical procedures. No ideal induction agent exists, and hypotension secondary to peripheral vasodilation or myocardial depression, or both, is a potential problem. Patients with an inordinately high risk may benefit from mechanical circulatory assistance prior to induction of anesthesia. Attention to oxygenation, blood volume replacement and the prevention of hypertensive episodes are particularly important during anesthesia so that optimal cardiac performance is ensured and ischemia avoided. The stresses during emergence from anesthesia contribute to lability of the cardiovascular status and hypoxemia. The period of risk does not conclude with immediate recovery from anesthesia but extends through the postoperative phase. Careful monitoring and attention to the control of pain, prevention of hypotension and hypertension, adequate oxygenation, early mobilization and resumption of the administration of cardiac medications are important factors in a successful outcome.


A possible case of osteodystrophia fibrosa cystica in a horse.

A case of unilateral front leg lameness with bone changes in the pedal bone suggestive of osteodystrophia fibrosa cystica is reported in an eight year old crossbred gelding. The changes were diagnosed at postmortem examination. The known possible causes are briefly reviewed.


Familial glomerulonephritis in Doberman pinscher dogs.

Progressive renal disease in 13 related Doberman pinscher dogs had the histological criteria of membranoproliferative glomerulonephritis. Polyuria, polydipsia and weight loss were the usual initial abnormalities and were observed at one year of age or less in seven of 11 dogs diagnosed antemortem as having renal disease. There was no sex predilection. All dogs were traced to a common male dog no more than four generations previously.


Treatment of feedlot cattle in Alberta for gastrointestinal nematodes.

The effects of a single treatment at entry with three anthelmintics on rates of weight gain and feed conversion efficiency over a 70 day period were studied in 200 feedlot steers. None of the anthelmintic treatments used appeared to confer any improvement in the above parameters under the conditions of this experiment. The results are discussed in relation to routine anthelmintic treatment in western Canada.


Steroid receptor content in human prostatic carcinoma and response to endocrine therapy.

Biopsy material from primary prostatic carcinoma from 25 patients was analyzed with regard to cytosol content of methyltrienolone (a synthetic androgen) binding sites and the receptor content has been correlated to the clinical response to endocrine therapy. A dextran-coated charcoal technique was used and binding data were calculated from Scatchard plots. In 20 of the tumors detectable levels of methyltrienolone receptor were noted. One of the receptor-positive patients died during radiation therapy before onset of hormonal treatment, and a second patient, who had a highly differentiated carcinoma, so far has not received any endocrine therapy. Of the remaining 18 patients 15 responded well to castration, treatment with estrogens, or Estracyt (approximately 80%). The biopsies from two of the three receptor-positive non-responders contained the lowest measurable receptor levels. Five specimens lacked detectable amounts of methyltrienolone receptor. Four of these patients did not respond to therapy (approximately 80%), but one was "false" negative. Our data indicate that steroid receptor analysis may become an important tool in predicting the value of endocrine therapy in human prostatic carcinoma.


High dose cytosine arabinoside (HDARAC) in refractory acute leukemia.

Thirteen leukemic patients with disease refractory to conventional chemotherapy were treated with 1.0 to 7.5 g/m2 of Cytosine Arabinoside (Ara-C) over 29 drug cycles. Drug infusions were spaced at 12-hour intervals; a maximum of four doses was administered over 36 hours. After single dose tolerance had been established, three or four dose cycles were given at 2- to 30-day intervals. There were three partial remissions (PR) and one complete remission (CR) in a treatment group of four patients with AML, five with ALL, two with lymphoma converted to leukemic phase, one CML in blast crisis, and one promyelocytic leukemia. Five of the patients were septic and considered terminally ill at the time of treatment. All other patients had evidence of drug responsiveness. The nadir of the white count occurred from 3 to 12 days after treatment, with subsequent recovery of the peripheral granulocyte count between days 12 and 28. Toxicity included nausea and vomiting (GI symptoms) in twelve patients, central nervous system (CNS) disturbances in eight patients, one episode of inappropriate antidiuretic hormone syndromes (SIADH), one of hyperuricemia, and fever in eleven patients. There was no evidence of hepatic or renal dysfunction. These high doses of Ara-C appear useful for treatment of patients with refractory leukemia. Hospitalization is brief and toxicity acceptable.


The value of serial carcinoembryonic antigen (CEA) in predicting response rate and survival of patients with gastrointestinal cancer treated with chemotherapy.

Elevated serum levels of carcinoembryonic antigen (CEA) were found in 70% of 141 patients with advanced gastrointestinal (GI) cancers. Serial CEA measurements were performed on 70 patients before and during chemotherapy. The majority were treated with 5-FU and Methyl-CCNU (33 patients), 5-FU (19 patients), or 5-FU and mitomycin-C (8 patients). In 49 patients with colorectal carcinoma who had elevated serum CEA prior to chemotherapy, 18 had objective partial tumor remission, 16/18 (89%) showed definite decrease in CEA level, one had no change, and one had an increase CEA titer. Thirty-one patients had either stable disease (10 patients) or increasing disease (21 patients) while on chemotherapy. Of these patients four showed decrease in CEA, eight had no change, and 19 had increase in CEA levels as compared to pretreatment value. The survival of patients with a decrease in CEA during chemotherapy was statistically significant (p = .03) as compared to survival of those with no change or increasing CEA levels. In 21 patients with other GI cancers, the correlation between the clinical response and change in CEA level observed was not as definite as in patients with colorectal carcinoma.


Septic endarteritis due to intra-arterial catheters for cancer chemotherapy. I. Evaluation of an outbreak. II. Risk factors, clinical features and management, III. Guidelines for prevention.

A cluster of three cases of staphylococcal septic endarteritis originating from percutaneously inserted brachial artery catheters for regional cancer chemotherapy prompted an epidemiologic and clinical study of bacteremic infections associated with this therapeutic modality. Nine cases were identified over a 3 1/2-year period (1.6% of all catheterizations), all caused by Staphylococcus aureus. The cluster followed discontinuation of hexachlorophene for scrub of the extremity prior to cannulation; phage-typing suggested the three cases were caused by the patients' own strains of Staphylococcus. These infections produced a distinctive clinical syndrome which facilitates implicating the catheter in the genesis of fever occurring in a patient receiving intra-arterial chemotherapy: early localized pain (89%) and hemorrhage (78%), and Osler's nodes distally (44%), later followed by local inflammation (78%), purulence (56%) and signs of systemic sepsis (100%) (each factor, p less than or equal to .005). Duration of cannulation did not influence susceptibility to infection. However, difficult cannulations or need for repositioning the catheter (p = .0096), prior radiation therapy (p = .033), leukopenia (p less than .05) and hypoalbuminemia (p less than .05) were all associated with septicemia. In the 25 months since implementation of specific control measures, there have been no further catheter-related septicemia in 310 catheterization (p less than .001). Guide-lines for prevention and management of these infections are provided.


The effect of in vitro irradiation on mitogenic responsiveness of peripheral blood lymphocytes from untreated patients with Hodgkin's disease.

Peripheral blood lymphocytes from six untreated patients with Hodgkin's disease were exposed to various doses of ionizing radiation in vitro and thereafter tested for reactivity to PHA and ConA using DNA synthesis as a marker of viability. While the responsiveness of Hodgkin's disease lymphocytes was abolished by moderate radiation doses, the proliferative activity of healthy controls' lymphocytes was reduced in a biphasic fashion suggesting the presence of one relatively radiation-sensitive and one relatively resistant cell population.


Sarcomas in ovarian mucinous tumors: a report of two cases.

Two sarcomas that appeared as distinct solitary nodules in the walls of ovarian mucinous cystic tumors are described. One of the tumors was a fibrosarcoma associated with a mucinous cystadenoma; the other was an undifferentiated sarcoma in a mucinous cystadenocarcinoma. Both patients died within 1 1/2 years of their operations with distant metastasis; one of them had had metastatic sarcoma in the para-aortic lymph nodes at the time of exploration. These two cases are the only well-documented examples of this unusual combination of tumor types.


Ovarian mucinous tumors with sarcoma-like mural nodules: a report of seven cases.

Seven cases of mucinous ovarian tumors with sarcoma-like nodules in their walls are reported. The age of the patients ranged from 18--81 years. Each of them had a large abdominal mass which proved on exploration to be a Stage Ia cystic ovarian tumor. All the specimens contained one or more discrete nodules in their walls, most of which were soft, dark brown, and hemorrhagic. On microscopical examination the epithelial component of four of the tumors was of borderline malignancy and of three was well-differentiated carcinoma. Three patterns were encountered in the nodules: pleomorphic and epulis-like in four cases, pleomorphic and spindle-celled in one case, and giant cell-histiocytic in two cases. These patterns simulated those of malignant giant cell tumor of soft parts, spindle cell sarcoma, and well-differentiated rhabdomyosarcoma, respectively. Postoperative follow-up ranging from 1 to 11 1/2 years (average 7 1/2 years) revealed no evidence of recurrence. Reports of seven similar tumors were found in the literature. Although follow-up has been less complete in these cases, none of the tumors is known to have spread beyond the ovary. These data suggest that mural nodules of the types described are not sarcomatous but could represent a reactive process that has no effect on the prognosis of the patient.


Myelolipoma in a heterotopic adrenal gland: light and electron microscopic findings.

A symptomatic myelolipoma of the heterotopic adrenal gland was diagnosed as the cause of nephrotic syndrome and was surgically removed. Remission of the nephrotic syndrome promptly ensued. Ultrastructurally, the tumor consisted of well-differentiated cells resembling adrenal cortical cells, bone marrow cells in various stages of differentiation, and lipid cells. Some cells that contained fat were of adrenal cortical origin, but the derivation of most lipid cells and of bone marrow elements could not be deduced from the present ultrastructural findings.


Cytophotometric studies of the nuclear DNA content in cartilaginous tumors.

The histopathological differentiation between chondromas and low-grade malignant chondrosarcomas can be difficult. For this reason we studied in 37 different cartilaginous tumors the mitotic index and the Feulgen DNA content using a scanning-integration cytophotometric technique. In 23 chondromas the Feulgen DNA content was diploid and showed a unimodal normal distribution. The number of mitoses was 0--0, 5%. The nuclei of a chondroblastoma were also diploid and the Feulgen DNA content was normally distributed. The mitotic index was 1% and few tetraploid nuclei, which were probably G2 nuclei, were observed. In two chondromyxoid fibromas, the average Feulgen DNA content was diploid and normally distributed. Several tetraploid nuclei were noted. The mitotic index was respectively 0.25% and 1.75%. Recurrence was noted in the first case. The Feulgen DNA content and mitotic index were clearly different in the chondrosarcomas. The distribution of the DNA content was bimodal or unimodal in low-grade chondrosarcomas. The mitotic index was less than 3%. In high-grade malignant chondrosarcomas, the histograms were broad unimodal or aneuploid. The mitotic index was above 5%.


Sebaceous lymphadenoma: ultrastructural observations and lipid analysis.

Sebaceous lymphadenoma is a rare, benign neoplasm of the parotid gland. In the 18 years since the initial report seven additional cases have been published. None includes ultrastructural studies or lipid analysis. Electron microscopy shows that the epithelial cells undergo a progressive maturation from basal to the typical lipid-laden mature sebaceous cells as in the cutaneous sebaceous glands. No morphologic differences are found between cutaneous sebaceous glands and the sebaceous glands in this parotid neoplasm. Thin-layer chromatography demonstrates the same type of lipids in the subaceous lymphadenoma as well as in cutaneous sebaceous glands. These findings suggest that the parotid salivary gland may be ectodermally rather than endodermally derived.


Mycosis fungoides and Hodgkin's disease occurring in the same patient: report of three cases.

The patients with the typical clinical course and pathology of Mycosis Fungoides (MF) were found also to have Hodgkin's Disease (HD), nodular sclerosing type. In two cases, HD was diagnosed 2 years after the diagnosis of MF; in the third case, both diseases were diagnosed simultaneously. Previous claims of MF transforming into second lymphomas are reviewed. The possible significance of our observed association of MF and HD is discussed.


Melanosis, melanocytic hyperlasia, and primary malignant melanoma of the nasal cavity.

A primary multifocal intranasal malifnant melanoma is reported in a 54-year-old black female. Diffuse pigmentation (melanosis) of nasal and maxillary sinus mucosa corresponds histologically to hyperplasia of dendritic melanocytes, from which cells the tumor is considered to originate.


Acinic cell carcinomas arising in salivary glands: a clinicopathologic study.

Fifty-one cases of acinic cell carcinoma (ACC) arising in major and minor salivary glands are reported (primary sites: parotid 37, submandibular, six, and oral cavity, eight.) These lesions usually produced painless slowly growing masses. Of 49 patients with follow-up information, 17 (35%) developed local recurrences following original surgical resection, and two (4%) had locally persistent disease. At last follow-up, 27 patients (55%) never had a recurrence, seven (14%) had experienced local recurrences but the tumors were apparently controlled by further surgical excisions, five (10%) were living with persistent disease, and 10 (20%) had died (one due to local tumor and nine due to metastases, usually to bones and lungs). The determinate 5-, 10- and 15-year survival rates were 78%, 63%, and 44%, respectively. Prognostic factors included: demonstrable tumor on lines of surgical excision, involvement of deep lobe of parotid, size of primary lesion, degree of mitotic activity and nuclear atypia, infiltrative rather than circumscribed borders, and lymph node involvement. Local recurrence was associated with an increased incidence of locally uncontrollable and metastatic disease. Type of initial therapy correlated with prognosis. Locally recurrent or persistent tumor was found in 14 of 15 patients treated with limited local excisions (including one biopsy only). Recurrences were seen in only three of 28 patients treated by wide local excisions and in two of six following radical en bloc resections. Seven of 17 patients with local recurrence were apparently cured by further more extensive resection. Radiotherapy did not appear effective in controlling these neoplasms.


Localized primary tumors of the pleura: an analysis of 40 cases.

A study of 40 localized primary tumors of the pleura in the files of the Canadian Tumour Reference Centre revealed a considerable diversity in their histologic structure. Collagenized, hemangiopericytoma-like and cellular areas were the main forms of growth pattern, with half of the tumors showing a mixture of two or more of these elements. Inclusions of non-neoplastic bronchioloalveolar epithelium were frequently seen in areas of tumor adjacent to lung substance but in only one tumor was there a neoplastic component of epithelial form. Eight tumors (20%) showed evidence of malignant behavior. All of these were large and cellular at the time of initial surgery and four had mitotic counts of 10 or more/10 H.P.F. in areas. The evidence suggests that the great majority of localized pleural tumors arise from submesothelial mesenchymal elements and it is believed that the term mesothelioma should not be used in reference to these growths.


Intraperitoneal free cancer cells and their viability in gastric cancer.

Free cancer cells in the peritoneal cavity of 100 patients with gastric cancer were examined by means of Douglas lavage, and their viability was estimated by 3H-thymidine uptake with autoradiographical technic. Furthermore, the effect of mitomycin-C on the viability of free cancer cells in the peritoneal cavity was studied. The appearance of intraperitoneal free cancer cells was dependent on the degree of invasion of cancer to the gastric serosa; that is, free cancer cells were not found in cases without serosal invasion, but were found in 48% with serosal invasion. The viability of free cancer cells in the peritoneal cavity was relatively high, but could be suppressed remarkably by intraperitoneal administration of 10 mg of mitomycin-C.


A report of the workshops on the current status of the histologic grading of prostate cancer.

A national multidisciplinary study of four major systems for the histological grading of primary prostatic cancer was completed during 1978. In a series of workshops culminating in a final review, criteria of grading were critically assessed against the background of patient survival data. The overall consensus was that the Gleason system should tentatively be adopted as the pathologic reference point for classifying patients. This system can be used in conjunction with other systems. It seems definable, reproducible, reasonably simple, and has clinical relevance as judged by correlations with patient survival. Further study may demonstrate advantages from incorporation of the nuclear or cytologic characteristics of tumor cells into the Gleason system. New techniques of acid phosphatase determination, bone scans, and assessment of the regional lymph nodes should provide better staging criteria for correlation with primary tumor histology in the furture. These workshops presented a unique opportunity for representative clinicians and pathologists in the United States to express their viewpoints in a comprehensive fashion on this timely and important topic.


Primary amyloidosis, pure red cell aplasia, and Kaposi's sarcoma in a single patient.

A patient who developed primary amyloidosis, pure red cell aplasia, and Kaposi's sarcoma is described. This is the second reported coincidence of Kaposi's sarcoma and pure red cell aplasia and the first coincidence of Kaposi's sarcoma and primary amyloid, thus enlarging the spectrum of plasma cell and immunoglobulin abnormalities seen in Kaposi's sarcoma. Because immunologic abnormalities have been described in all these diseases, it is felt that some primary immune dysfunction is the underlying cause of the three diseases in this patient.


Modification of muscle-preserving radical mastectomy.

A technical improvement of the muscle-preserving radical mastectomy for breast cancer is presented. In this procedure, the Sulcus interpectoralis, located between clavicular and sternocostal parts of the pectoralis major muscle, is split bluntly and spread apart. Then, the pectoralis minor muscle is severed near its attachment to the coracoid process and an axillary dissection is thereby easily and thoroughly accomplished. The effectiveness of lymph node dissection by this method was ascertained when the number of the lymph nodes removed by this procedure was compared with that removed by the conventional muscle preserving mastectomy (Madden's operation) and the radical mastectomy. Ninety-three patients treated by this operation have shown a satisfactory cosmetic appearance and a good prognosis when compared with patients treated by the standard radical mastectomy.


Peutz-Jeghers syndrome with intestinal carcinoma: report of the association in one family.

The Peutz-Jeghers Syndrome is a rare, genectically inherited disorder. There are insufficient data to establish this syndrome as a precancerous condition, but documented cases of gastrointestinal cancer arising in this syndrome have been reported with an incidence of 2--3%. Since the syndrome is transmitted as an autosomal dominant and is associated with cancer, family members so afflicted may show an increased cancer risk. This is the first reported case of a father and son with both Peutz-Jeghers Syndrome and colonic carcinoma.


Ureterosigmoidostomy followed by carcinoma of the colon.

Adenocarcinoma of the colon developing as a late complication or ureterosignoidostomy has been reported with increasing frequency. A patient is presented who developed adenocarcinoma of the colon 28 years after ureterosigmoidostomy for bladder exstrophy and 13 years after conversion of the ureterosigmoidostomy to an ileal conduit. The colonic tumor was documented at postmortem examination to be at the ureterosigmoidostomy site. Because of the potential late development of adenocarcinoma of the colon, careful follow-up of patients with ureterosigmoidostomies, particularly those performed in children many years ago, is indicated.


Malignant neoplasms in Saudi Arabia.

In a sample of 1000 consecutive malignant neoplasms in Saudis resident in the Western Region of Saudi Arabia, malignant lymphoma was the commonest of the life-threatening malignancies. The differences between malignant lymphoma in this sample and Western series include the greater frequency of lymphoma; the tendency for reticulum cell and poorly differentiated lymphomas to present as abdominal lesions; the earlier peak of prevalence of Hodgkin's disease, and the dissimilar proportions of its subtypes. The distribution of cancers in the gastrointestinal tract in our sample is almost the reverse of that encountered in the West in that cancer of the mouth and esophagus were more common than cancer of the lower intestinal tract. Lung cancer was relatively uncommon. The smoking habit is not so prevalent in Saudi Arabia as in the West and there is a need to maintain this situation by discouraging smoking. Cancer of the breast was by far the commonest major malignancy in the female, although most Saudi women have their first child early in their reproductive life. Skin cancers proved to be the most prevalent malignancy, and of these squamous cell carcinoma was the most common. The biases that affect studies such as ours in Saudi Arabia are stressed.


A critical analysis of response criteria in patients with prostatic cancer treated with cis-diamminedichloride platinum II.

Cis-diamminedichloride platinum II (DDP), 50--70 mg/m2 iv, q 3w was administered to 25 patients with Stage D adenocarcinoma of the prostate. Since the assessment of tumor regression in a disease-oriented phase II study demands a clear end-point of response, case selection was restricted to patients who had objectively measurable lesions, i.e., nodes, skin, lung, and liver metastasis. Partial remission occurred in 3 (12%) and stabilization of disease in 1 patient. Responders lived 53 weeks vs. 20 weeks for non-responders. In the dosage and schedule used in this protocol, DDP was not an active agent in the treatment of prostatic cancer. Various patient characteristics are examined and correlations made between remission rates and survival in this study vs. 4 other response schemata. A critical analysis of patient selection, "lead time" -- diagnosis to chemotherapy, and the definitions of the terms "measurable" lesions, "evaluable" parameters, "objective response", stabilization of disease and response criteria employed in the 4 schemata are also discussed.


Cis-diamminedichloride platinum II (DDP) in the treatment of penile carcinoma.

Cis-diamminedichloride platinum II (DDP) was administered to eight patients with epidermoid carcinoma of the penis. Three of six adequately treated patients had an objective response: one patient achieved complete remission of 7 months duration and 2 patients had partial remissions of 8 and 2 months, respectively. DDP appears to be an active agent in the treatment of penile carcinoma.


Acute non-lymphocytic leukemia and acute myeloproliferative syndrome following radiation therapy for non-Hodgkin's lymphoma and chronic lymphocytic leukemia: cytogenetic studies.

Seven cases of acute nonlymphocytic leukemia (ANLL) and one of malignant myeloproliferative syndrome were identified from a pool of 189 cases of non-Hodgkin's lymphoma (NHL) and CLL treated primarily with extensive radiotherapy at the Clinical Center, the National Institutes of Health. Four patients also received chemotherapy, two for only short periods. The median time interval from the diagnosis of the primary malignancy to the development of leukemia was 61 months (range 33 to 98 months) and the median survival after the diagnosis of leukemia was two months (0 to 9 months). All eight patients were cytogenetically abnormal and serial chromosome studies revealed that hypodiploidy was the most commonly observed chromosomal abnormality. Abnormalities of chromosome no. 7 were seen in all five patients analyzed by the chromosome banding technique; four of them had monosomy 7. The next most frequently involved chromosome was no. 5. The complexity, extensive nature, and long duration of the cytogenetic abnormalities prior to the diagnosis of leukemia in these patients may be characteristic of secondary leukemia in radiation-treated lymphoma and the presence of such anomalies may predict leukemic transformation.


Breast carcinoma and basal cell epithelioma after x-ray therapy for hirsutism.

We report a 60-year-old woman with a history of x-ray therapy for generalized hirsutism at 20 years of age who at the age of 37 years developed the first of numerous basal cell epitheliomas on her trunk, including chest, on a background of radiation damaged skin. At the age of 51 years one of the basal cell epitheliomas was biopsied and an incidental histologic finding was a breast carcinoma. The basal cell epithelioma is clearly linked with x-ray exposure; breast cancer is less so although there is impressive epidemiologic evidence supporting an association between human breast cancer and radiation exposure. In view of an association between thyroid cancer and dermatologic x-ray therapy, further investigation of such an association with breast cancer should be considered. It may be wise to evaluate patients who received dermatologic x-ray exposure to their breasts for possible breast cancer and to consider radiation induced skin damage on or near the skin overlying the thyroid or breasts as a cutaneous marker of internal malignancy or potential internal malignancy.


The use of leukocyte cell line culture supernatant for skin reaction testing in malignant melanoma.

A study was conducted to determine some of the potential applications of a human leukocyte culture supernatant or "lymphokine" preparation in cancer patients. The application evaluated in this study was the use of this preparation as a skin test reagent for evaluation of the inflammatory response following intradermal injection. The preparation was derived from the supernatant of a long-term cultured lymphoblastoid cell line with migration inhibition factor (MIF) and other lymphokine activities. Dose response, histology and toxicity studies were done in 53 patients with malignant melanoma stage IIIB and IV. A dose response curve was observed for both erythema and induration at 12 and 24 hours, but not at 48 hours. An optimal intradermal dose for eliciting inflammation was determined and found to be five units. Histopathological evaluation of biopsy specimens showed a mixed cell reaction including granulocytes, eosinophils, lymphocytes and monocytes differing in lymphocyte content from the classical delayed type hypersensitivity (DTH) reaction in man. Compared with the response to recall antigens, only a weak correlation with the DTH response to the recall antigens was found. Our results support the conclusion that lymphokines may be used in the future to evaluate the ability to develop nonspecific inflammation in cancer patients, and that this inflammatory response can be obtained in a number of patients no longer capable of responding to recall antigens.


Antibody response to influenza immunization in adult patients with malignant disease.

Eight-two patients with solid tumors and lymphomas were immunized with New Jersey, Hong Kong, and Victoria influenza vaccines. Patients were divided into groups according to treatment: chemotherapy, radiotherapy, or no treatment. Four parameters were examined to assess the response to immunization: seroconversion, protective titer level, geometric mean titer, and response to multiple vaccines. Patients with lymphoma showed the lowest antibody response. Patients with solid tumors had antibody responses which were not significantly different from controls but were superior to lymphoma patients (p less than .01). Timing of chemotherapy, immunoglobulin levels, and lymphocyte counts did not appear to play a major role in determining the antibody response. Patients with neoplastic diseases should be immunized against the prevailing influenza virus. Patients with lymphoma should also receive antiviral prophylactic therapy during influenza epidemics.


Immune complexes in breast cancer patients as detected by C1q binding.

Levels of Clq binding activity have been measured in the sera of patients with benign and malignant breast disease. Cancer patients showed significantly higher binding activity than patients with gross fibrocystic disease. Clq binding levels were not related to levels of carcinoembryonic antigen, or rheumatoid factor. The Clq reactive material was identified as being precipitable with Protein A, and predominantly eluted in gel filtration fractions with a molecular weight of approximately 1 x 10(6). These studies indicate that Clq binding level may be of use in the differential diagnosis of benign and malignant breast disease.


Serum glycoprotein hormone alpha subunit levels in patients with cancer.

The serum glycoprotein hormone alpha subunit concentration was measured in 957 nonpregnant patients with benign disorders and 683 patients with unselected malignancies. Postmenopausal women had significantly higher alpha levels than premenopausal women or men. When the patients were subdivided according to age, sex or disease sites, significant population differences were found for women less than 50 years of age and patients with cancers of presumed neural crest origin. However, individual serum alpha levels in patients with benign disorders or malignancies demonstrated considerable overlap. No population differences in serum alpha concentrations were demonstrated between patients grouped according to stage of disease, suggesting that serum alpha were not directly related to tumor burden. Similarly, there was no statistical association between clinical improvement or deterioration and change in the serum alpha subunit concentration. These results indicate that measurement of the glycoprotein hormone alpha subunit concentration in the serum is not useful for screening patients for cancer or for monitoring the clinical course of patients with the vast majority of cancers.


Chromosome analysis of primary large bowel tumors: a new method for improving the yield of analyzable metaphases.

Colon tumors were processed immediately after surgical resection. Using L-Arterenol and sodium citrate in combination with standard chromosome culture techniques, 12 of 17 consecutive tumors (75%) had countable figures ranging from 5 cells to 59 cells. Seven of the 12 cases had over 25 countable cells. Chromosome counts did not vary more than +/- 4 for any one case. Seven tumors were karyotyped, 6 with banding techniques. One of these specimens had mosaic patterns. The chromosome counts varied: 2 were hypodiploid; 1 was pseudodiploid and 4 were hyperdyploid. There were some similarities in the karotypes although no identical karyotypes were seen in this series.


Relationship between bacterial binding to lymphocytes and clinical features in chronic lymphocytic leukemia.

In previous studies we showed that spontaneous bacterial adherence can be used to identify human lymphocyte subpopulations and to demonstrate variable binding patterns in chronic lymphocytic leukemia (CLL). In this study, 10 strains of bacteria of different genera and species were used in blood smears from 24 CLL patients to determine the percentages of lymphocytes that bind bacteria. From these percentages, binding indices were calculated. The symptoms and other laboratory tests were independently recorded and the stages determined. When the two sets of data were compared, relatively low binding indices were found in symptomatic patients or in Stages III and IV; relatively high binding indices were found in asymptomatic patients or in Stages I and II. We suggest that with progression of leukemia, lymphocytes with less "lectin" recognition potential are selected and escape any control mechanism of proliferation.


Vascular leiomyosarcoma: the malignant counterpart of vascular leiomyoma.

The clinical and pathological findings of six cases of leiomyosarcoma arising from blood vessels of different caliber are described. The term vascular leiomyosarcoma, having both a topographic and morphologic significance, is proposed for these tumors. The histologic pattern is characterized by a proliferation of atypical smooth muscle cells with a large number of intermingled blood vessels. Mitoses were counted per 10 high power field (hpf) and tumors were divided in three groups I, 10 to 20 mitoses, group II, 20 to 35 mitoses, and group III, more than 35 mitoses per 10 hpf. The mitotic index seems to be the most important pathological feature on which a prognostic evaluation for vascular leiomyosarcoma can be based. Tumors in group I had neither local recurrences nor metastases; the one tumor in group II had one local recurrence, but the patient is free of disease 6 years after surgical treatment; the three tumors in group III developed distant metastases and constitutional symptoms. Vascular leiomyoma, bizarre leiomyoma, and hemangiopericytoma are included in the differential diagnosis of vascular leimyosarcoma. The possibility that vascular leiomyosarcoma arising from small vessels represents the malignant counterpart of vascular leiomyoma is proposed.


Pineoblastoma: an electron microscopic study.

The ultrastructure of a human pineoblastoma is described. Tumor cells formed nests, palisading row and rosettes. Cells within nests were undifferentiated. Palisade and rosette forming cells had polarized cytoplasms and showed signs of differentiation and surface membrane specialization which included surface end-bulb-like protrusions of the cytoplasm, bulbous cilia with a 9 + 0 microtubular skeleton, and blunted microvilli. In the cytoplasm of tumor cells there were characteristic granular bodies, whorls of smooth endoplasmic reticulum and annulate lamellae. Some of these findings appear to be unique to pineal tumor and are reminiscent of photoreceptor cells in the pineal glands of lower vertebrates and human fetal pineal glands.