Cytotoxicity and mutagenicity of alkylating agents in cultured mammalian cells (CHO/HGPRT system): mutagen treatment in the presence or absence of serum.

Cytotoxicity and mutation induction at the hypoxanthine-guanine phosphoribosyl transferase locus in Chinese hamster ovary cells (CHO/HGPRT system) were measured for a range of concentrations of 6 alkylating agents [methyl and ethyl methanesulfonate (MMS, EMS), N-methyl- and N-ethyl-N'-nitro-N-nitrosoguanidine (MNNG, ENNG), and methyl- and ethyl-nitrosourea (MNU, ENU)] to determine the effect of the presence or absence of serum during the time of mutagen treatment. Cultures were treated with the mutagens for 5 h, a time period which results in no growth inhibition in the absence of serum, to estimate the potential decrease in effective mutagen dose to the cells which might result from reactivity with the serum proteins. With all 6 agents, identical results were found for cytotoxicity and for mutagenicity regardless of the presence or absence of serum during treatment. This finding demonstrates that the use of serum in cell-culture medium does not present any problems in apparent dosimetry studies, at least with these alkylating agents.


Endonucleolytic activity for gamma-irradiated DNA in normal and ataxia telangiectasia fibroblast cell extracts.

The increased sensitivity of ataxia telangiectasia cells towards ionizing radiation may be related to their inability to incise DNA near sites of radiation-induced base damages. When compared to 3 unaffected controls, crude extracts from 5 lines of fibroblast cells derived from ataxia telangiectasia patients were capable of incising gamma-irradiated DNA to the same extent as normal cells as determined in a nicking assay, using the circular replicative form of phiX174. However, the types of alterations introduced into DNA by gamma-irradiation could be distinguished from sites of base loss due to depurination or depyrimidination and from sites of base modification by OsO4. The specific endonuclease involved was demonstrated to be distinct from the apurinic endonuclease by its rate of temperature inactivation.


Resistance of plateau-phase human normal and xeroderma pigmentosum fibroblasts to the cytotoxic effect of ultraviolet light.

Clonogenic survival response to 254-nm ultraviolet light was measured in 2 strains of repair-proficient normal human fibroblasts and 4 strains of xeroderma pigmentosum (XP) fibroblasts belonging to complementation groups A, C, D and variant. In all strains except XPA, cells irradiated in plateau phase and subcultured immediately were much more resistant to the lethal effect of UV than cells irradiated in the exponential phase of growth. Typically, 10-20% of plateau-phase cells were extremely resistant. When the cultures were held in plateau phase for 24 h after irradiation and before subculture, there was a further enhance of survival. By use of a UV-specific endonuclease assay, no difference was found in the number of DNA lesions induced in exponentially growing and plateau cultures by the same dose of UV light. Thus plateau-phase cells appear to be more efficient in their DNA-repair capability than cells in exponential growth. XP group A cells were uniquely found to be deficient in the processes which lead to plateau-phase resistance. Since plateau-phase repair was not lacking in XP groups C, D and variant, it may be related to a DNA-repair process different from that which is responsible for the overall UV sensitivity of these cells.


Inducation of chromosomal aberrations in cultured mammalian cells by nickel compounds.

The effects of 4 Ni compounds, nickel chloride, nickel acetate, potassium cyanonickelate, and nickel sulfide were studied in a line of mammary carcinoma cells from the C3H mouse. All 4 were easily taken up by the cells and reacted with protein, RNA, and possibly DNA. Measurements of leucine, uridine, and thymidine uptake during exposure showed that the syntheses of protein and DNA were more sensitive than RNA. Chromosomal aberrations were observed during the recovery period following the end of the treament with Ni. The implications of these results were discussed with respect to the carcinogenicity of the compounds and to the recommended protocols for mutagenicity testing by chromosomal aberrations.


Induction of sister-chromatid exchanges in Chinese hamster ovary cells by thiol and hydrazine compoudns.

Cysteine, cysteamine and glutathione all induce sister-chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells when applied to cell cultures at concentrations between 10(-4) and 10(-2) M. Acute exposure of cells th thiol compound for a period of 2--3 h resulted in a unique dose--response relationship in each instance. This consisted of two peak SCE frequencies, one at either extreme of the concentration range. Each peak corresponded to a 2--3-fold increase over the spontaneous level. A chronic exposure of 24 h, in contrast, resulted in a dose--response relationship consisting of a single peak SCE frequency (representing a 4--5-fold increase over the spontaneous level) at a concentration of approx. 4 x 10(-4) M. The effect of Cu2+ ions included in the medium at a concentration of 10(-5) M was to increase the toxicity and, at some concentrations, the SCE levels occurring after either acute or chronic exposure to thiols. Hydrazine and its derivatives, dimethylhydrazine and isonicotinic acid hydrazide (isoniazid), as well as hydrogen peroxide, also induce SCEs in CHO cells. A 2--3-fold increase over the spontaneous level was observed, depending upon the particular treatment protocol applied. SCE yields after 3 h treatment with dimethylhydrazine and isoniazid were increased if Mn2+, but not Cu2+, was included in the tissue culture medium at a concentration of 10(-5) M. SCE yields after a 24-h treatment with dimethylhydrazine in which Mn2+ was present in, and absent from, the medium were similar. Catalase was observed to reduce the SCE levels resulting from treatment with hydrogen peroxide, dimethylhydrazine and isoniazid. The effect of catalase upon SCEs induced by dimethylhydrazine and isoniazid in the presence of Mn2+ was more evident than when Mn2+ was not included in the culture medium. The significance of these results with respect to the possible active chemical species produced and the mutagenic/carcinogenic risk associated with thiol and hydraizine compounds is discussed.


Mutagenicity studies with nitrofurans. I. Mutagenicity of nitrofurylacrylic acid for mammals.

Cytogenetic analysis of mouse bone-marrow cells, the dominant lethal test in mice and the cytogenetic analysis of human peripheral lymphocytes in vitro were used to study the mutagenicity of 3-(5-nitro-2-furyl)acrylic acid (5-NFA) for mammals. The bone-marrow cytogenetic analysis was performed in female mice exposed to 5-NFA administered intraperitoneally in single doses of 15--120 mg/kg and in 5 repeated doses of 15 and 30 mg/kg, intragastrically in single doses of 30--240 mg/kg and 5 repeated doses of 30 and 60 mg/kg, and perorally for 12 weeks to 5-NFA concentration of 10, 100 and 1000 mg 5-FNA/1 in drinking water. The bone-marrow analysis was performed in this case after 12 days, 3, 4, 6, 8, 10 and 12 weeks exposure. No increase in chromosome damage attributable to dosing with 5-NFA occurred in any of these experiments. Experiments in which mice were exposed to 5-NFA in drinking water for 12 weeks and then treated with a single i.p. dose of 2 mg of the mutagen TEPA [trix-(1-aziridinyl)phosphine oxide] per kg revealed that, at a concentration of 1000 mg 5-NFA/1, the clastogenic activity of TEPA was reduced to that in untreated animals. The dominant lethal test was performed in male mice exposed to 5-NFA applied intraperitoneally in single doses of 40--120 mg/kg and in 5 repeated doses of 10--30 mg/kg, intragastrically in 5 repeated doses of 20--60 mg/kg, and perorally for 4 weeks in drinking water containing 5-NFA at concentrations of 10, 100, 316 and 1000 mg/l. No significant differences were detected between the exposed and control groups of animals. Experiments in which male mice were exposed to 5-NFA in drinking water and treated after the 4-week exposure to 5-NFA with 1 mg TEPA/kg revealed that a concentration of 1000 mg 5-NFA/1 reduced TEPA-induced dominant lethality to within control values. A reduction in male fertility was observed after the single or repeated 5-NFA doses, but no changes when 5-NFA was applied in drinking water. The cytogenetic analysis of human peripheral lymphocytes exposed in vitro for the last 24 h of culture to concentrations of 1--100 micrograms 5-NFA/Ml did not show any compound-related chromosomal changes. The results of dominant-lethal and bone-marrow cytogenetic studies in mice after consumption of drinking water containing 1000 mg of 5-NFA/1 for 12 weeks and dosed subsequently with TEPA suggests that 5-NFA has some antimutagenic activity. Because none of the studies reported revealed any compound-related genetic activity, the results suggest that 5-NFA is not a chromosome-breaking agent in mammals.


Pathological observation on experimental swine dysentery.

Experimental swine dysentery caused by 4 cultured strains (S73/2, DJ183, DJ70 and DK762) of Treponema hyodysenteriae was studied pathologically. The distribution and quantity of treponemes were examined on tissue sections stained by the Warthin-Starry method. Of the organs the colon contained the largest number of treponemes and the cecum and rectum the second largest number. Histopathological lesions were restricted to the large intestine. They ranged from mild catarrhal colitis in the mild case to desquamative, hemorrhagic colitis in the severest case. The severity of lesion was closely associated with the quantity of treponemes present. There was no difference in quality of the lesion between any two of the strains used in this study. Electron microscope revealed a large number of free treponemes present in the intestinal lumen and crypts. Treponemes were seen more frequently in the cytoplasm of goblet cells than in that of intestinal epithelial cells. They were also observed in desquamated degenerative epithelia. A small number of them were found in intact epithelia. Morphologically, the treponeme had a granular protoplasmic cylinder at the center which was surrounded by a thin envelope. Between the cylinder and the envelope there were axial fibrils.


Pathological and microbiological studies on calf pneumonia occurring in mass rearing facilities.

Pathological and microbiological studies were conducted on lesions in the lungs of 194 calves from mass rearing facilities. Macroscopically, the lesions were classified into six forms: nonlesion, atelectasis, mild pneumonia, moderate pneumonia, advanced pneumonia, and advanced pneumonia accompanied with abscess. Histopathological examination revealed bronchopneumonia in most of the calves. Lesions more advanced than moderate pneumonia were complicated with desquamation, severe exudation, and necrosis. Bacteriologically, Pasteurella sp. was isolated often in combination with Staphylococcus sp. from about a half of the atelectatic cases. With the development of pneumonic lesions, Pasteurella sp. was isolated at a high frequency in combination with Haemophilus sp., Streptococcus sp., and Corynebacterium sp. Prominent necrosis was more often seen in cases with Pasteurella haemolytica isolated than in cases with only Pasteurella multocida isolated. Mycoplasma sp. and Ureaplasma sp. were isolated from distinctly pneumonic lesions. Advanced pneumonic lesions were observed in many calves over 30 days of age. The importance of environmental and managerial improvement was also emphasized, since calf pneumonia tended to break out in facilities under unsatisfactory conditions in the present work.


Rapid changes in enkephalin levels in rat striatum and hypothalamus induced by diazepam.

The acute treatment of rats with diazepam induces pronounced changes in brain enkephalin concentrations, as was estimated for methionine(met)-enkephalin and in some representative experiments for leucine(leu)-enkephalin, employing highly specific radioimmunoassays. Diazepam selectively increased the enkephalin concentrations in the hypothalamus by about 35%, and lowered it in the corpus striatum by roughly 25%; no changes could be detected in the medulla oblongata/pons or midbrain. The drug-induced changes displayed a rapid onset. Peak effects were reached by 2 to 5 min after injection. Changes observed in the hypothalamus were only short lasting and were apparently parallelled by diazepam concentrations in the brain, whereas the decrease in the striatum was of markedly longer duration. Presently, the mechanism underlying all these changes is unknown. Whereas an increase in enkephalin concentrations in the hypothalamus may be discussed in terms of the anti-stress effect of benzodiazepines, the observed drop in striatal enkephalin is not obviously to be correlated to behavioural changes induced by these drugs.


Propranolol in conscious spontaneously hypertensive rats. II. Disposition after subcutaneous and intracerebroventricular administration.

The disposition of dl-propranolol was studied in spontaneously hypertensive rats (SHR), both after subcutaneous (s.c.) and intracerebroventricular (i.c.v.) injection of 1 mg/kg. 1. Upon s.c. injection propranolol appeared rapidly in plasma. A maximum concentration of 374 +/- 33 ng/ml (N = 10) was reached 5 min after injection. After a distribution phase with a half-life of t 1/2 alpha = 17 min propranolol was eliminated with a t 1/2 beta = 59 min. 2. Both propranolol and its metabolites were taken up rapidly into all tissues studied. Highest concentrations (10.4 +/- 1.5 micrograms/g, N = 5) were found in lungs 30 min after injection. 3. Neither propranolol nor its metabolites accumulated in any of the tissues examined. 4. Upon i.c.v. injection of propranolol, a maximal concentration of 573 +/- 47 ng/ml (N = 3) was reached in plasma already 2 min after injection. In this case t 1/2 alpha was 13 min and t 1/2 beta was 80 min. 5. Dialysis experiments indicated that propranolol is bound to plasma proteins for 92% in the concentration range of 20--100 ng/ml. With increasing concentrations binding diminishes progressively. At the highest concentration tested (345 ng/ml) only 76% was bound. It is concluded that s.c. and i.c.v. injection of an identical dose of propranolol gives a similar plasma concentration-time profile. Moreover, it is suggested that the pharmacokinetic behaviour of propranolol in SHR does not explain the delayed antihypertensive effect of this drug.


Studies on the inhibitory effect of indomethacin and meclofenamate on the adrenalectomy-induced increase in plasma renin concentration.

Bilateral adrenalectomy combined with a sodium-deficient diet caused a time-dependent increase in plasma renin concentration in rats. Seventy-two hours after adrenalectomy the inhibitors of prostaglandin biosynthesis indomethacin and meclofenamate diminished the plasma renin concentration by about 50%. This effect was independent of the amount of renin released. Indomethacin and meclofenamate fully retained their ability to reduce the plasma renin concentration when the renal sympathetic nerves or the macular densa cells of the kidneys no longer contributed to renin release. It is concluded that in adrenalectomized rats renal prostaglandins effect the baro-receptor-mechanism in the afferent arterioles and thus enhance renin release.


Capsaicin-sensitive innervation of the guinea-pig taenia caeci.

1. Stimulation (2--50 Hz) of the mesenteric nerves of the guinea-pig taenia caeci gave rise to contraction of the muscle obtained from animals pretreated with the adrenergic neuron-blocking agent guanethidine. Contraction was the response to stimulation at low frequencies (2--5 Hz) in about half of the untreated preparations as well. 2. The response was abolished by hyocine (4.5 x 10(-7) M), but was unaffected by the ganglionic blocking agent mecamylamine (4.9 x 10(-5) M). Physostigmine (2.4 x 10(-8) M) enhanced the contractions. 3. Capsaicin (9.8 x10(-6) M) elicited a contraction of the taenia caeci followed by a long-lasting tachyphylaxis. Contraction in response to stimulation of the mesenteric nerves was absent after this pretreatment. 4. Neither the response to direct excitation of the cholinergic neural elements of the myenteric plexus, nor the relaxation caused by stimulation of adrenergic fibres were influenced by capsaicin. "Purinergic" relaxation produced by field stimulation (0.5--10 Hz) remained also unchanged. 5. No functional evidence has been found for the presence of parasympathetic preganglionic fibres among the perivascular nerves applying the taenia. 6. It is concluded that capsaicin-sensitive nerves excite cholinergic neurons of the myenteric plexus.


Effect of procainamide on transmembrane action potentials in guinea-pig papillary muscles as affected by external potassium concentration.

Effects of procainamide (PA), 0.18, 0.37 and 0.74 mmol/l, on the transmembrane potential were studied in isolated guinea-pig papillary muscles, superfused with modified Tyrode's solution (external K concentration, [K]0 = 5.4 mmol/l) at the basic driving rate of 1 Hz. PA, at 0.37 mmol/l, significantly reduced the maximum rate of rise of action potential (Vmax) with no change in the resting potential. When 2.7 mmol/l [K]0 of the superfusate was exchanged for 15 mmol/l [K]0 solution a decrease in Vmax induced by 0.37 mmol/l PA became more prominent with decrease in resting potential. The reduction of Vmax at steady state was less at lower driving rates (0.25 and 0.5 Hz) and more at higher driving rates (2-5 Hz) than at 1 Hz in 2.7, 5.4 and 10.0 mmol/l [K]0 solution. Such changes were enhanced concentration-dependently by PA at 5.4 mmol/l [K]0. Also, the changes became more significant with an increase in [K]0 from 2.7 mmol/l to 5.4 mmol/l and then to 10.0 mmol/l. The recovery process of Vmax proceeded with two components. The time course of the slow component seen in the Vmax of the first response after interruption of basic driving stimulation at 1 Hz, followed an approximate monoexponential function. The time constants were 6.3, 4.4 and 5.8 s in the presence of 0.18, 0.37 and 0.74 mmol/l PA at 5.4 mmol/l [K]0 and 3.4 and 3.7 s both in the presence of 0.37 mmol/l PA at 2.7 and 10.0 mmol/l [K]0. Vmax values after 30 or 60 s interruption of stimulation were 80-92% of the predrug Vmax value at 1 Hz. The time constants of the first component, estimated by the peeling-off methods at the driving rate of 0.1 Hz, were 11, 31 and 5-22 ms in the presence of 0.37 mmol/l at 5.4, 10.0 and 2.7 mmol/l [K]0 and did not differ significantly from the time constants in control preparations. The results were found to be consistent, to a certain extent, with the model proposed by Hondeghem and Katzung (1977).


The effects of antiinflammatory steroids on the response of the guinea-pig isolated ileum to acetylcholine, histamine, nicotine, 5-hydroxytryptamine and electrical stimulation.

High concentrations of antiinflammatory steroids (2.5-40 microgram/ml) reversibly inhibited the electrically induced contractions of the guinea-pig isolated ileum. At 40 microgram/ml they also reversibly inhibited contractions elicited by acetylcholine, histamine nicotine and 5-hydroxytryptamine. PGE1 (2.5 ng/ml), PGE2 (2.5 ng/ml) and PGF 2 alpha (25 ng/ml) antagonized these effects. The inhibition of contractions elicited by direct agonists were less pronounced than those elicited by indirect or partly indirect agonists. The inhibitory effect of steroids may be related to non-specific actions on biological membranes. An overall sensitization of the smooth muscle by PG's may explain their antagonism to inhibition by steroids.


4,4'-Dihydroxyphenazone as an urinary metabolite of phenazone in different species including man.

4,4'-Dihydroxyphenazone (4-hydroxy-1-4'-hydroxyphenyl)-2,3-dimethyl-3-pyrazoline-5-one) was isolated as a metabolite of phenazone (antipyrine) after acid hydrolysis of rat urine. This was characterized and identified by NMR, MS, IR, UV, Fp and epsilon270. After dosage with phenazone, 4,4'-dihydroxyphenazone is excreted in conjugated form by man, rabbit, guinea pig and rat. In the rat it is further shown, that conjugates of 4,4'-dihydroxyphenazone are formed by glucuronidation as well as by sulfatation. The metabolite seems to add substantially to the overall metabolic pattern of phenazone in these species.


Organ cultures of embryonic target-tissues exposed transplacentally to chemical substances as a test-system for rapid evaluation of carcinogenicity.

Organ cultures of embryonic target-tissues transplacentally treated by chemical substances are proposed as a test-system for a rapid evaluation of carcinogenicity of environmental pollutions. The results of transplacental effect of some different substances (urethane, polycyclic hydrocarbons, N-nitrosocarcinogens, aminoazo compounds, cyclic amines, aflatoxin B1, pesticide DDT and some noncarcinogenic analogs) on organ cultures of embryonic lung, kidney, liver and brain (hyppocamp) are presented. Transplacental effect in organ cultures depended on the used carcinogen, its dosage, duration of cultivation and on the susceptibility of animals and explanted tissue. The tested carcinogens induced in organ cultures of embryonic target-tissues: 1. specific morphological alterations (diffuse and focal hyperplastic pretumoral alterations of epithelium and tumors); 2. alteration of cell proliferation and 3. an increase of viability and survival of explanted embryonic tissues. This criteria and proposed test-system are critically evaluated with respect to its practical use.


The role of autosensibilization of lymphoid cells in genesis of antitumor resistance.

C3HA mice were inoculated with a mixture of syngeneic transplantable hepatoma 22a cells and syngeneic splenocytes of mice immunized with normal syngeneic tissues or subjected to partial hepatectomy. Control mice were inoculated with a mixture of tumor cells and splenocytes of intact or sham operated mice. A considerable inhibition of tumor growth was observed in the experimental series. Immunization of mice with normal syngeneic tissues as well as partial hepatectomy results in sensibilization of splenocytes not only to normal tissue antigens, but to the antigens of hepatoma 22a cells too. This was shown by the reaction of indirect inhibition of glass adherence of peritoneal cells. The data obtained are considered to be one more possible prove of a special form immune surveillance which controls the state of cytodifferentiation being active in the organism. The involvement of this form of immune surveillance in the genesis of antitumor resistance is discussed.


The passage of lymphatic leukemia L1210 cells injected into glass bead labyrinth: their flow and retention.

Leukemia L1210 cells and normal lymphocytes were injected into the glass bead packing perfused with a medium containing serum proteins in concentration sufficient to greatly reduce the surface adhesion. The passage of radioactively labeled cells introduced as a concentrated suspension, was studied by the analysis of transit-dilution curves. It was demonstrated that a fraction of cells was retained in the labyrinth; other parameters characterizing the cell flow were similar to those of the medium. The mechanism of the arrest of cells is discussed: it is related to geometrical features of the labyrinth and the hydrodynamic forces influencing the cell surface interactions. Intense washing of the glass bead column results in the release of only a minor fraction of cells which were previously arrested. When the L1210 cells which have passed through the labyrinth without being trapped are reinjected into another glass bead layer, their retention is similar to that observed after the first injection; it appears, therefore, that the L1210 cells are uniform as concerns the properties which are important for surface interactions under flow conditions.


Effect of chloro- and bromo-derivatives of isocrotonic acid of bioenergetic processes in Ehrlich ascites cells and isolated mitochondria.

The effect of nine chloro- and bromoderivatives of isocrotonic acid on some bioenergetic processes in both Ehrlich ascites cells and isolated rat liver mitochondria has been investigated. Substances studied in the concentration range 25--200 microM significantly inhibited incorporation of both 14C-adenine and 14C-valine into acid-insoluble material of Ehrlich ascites cells. The rate of 14C-precursors incorporation being directly related to the concentration of the inhibitor. Gamma,gamma-bis-4-ethylphenyl-alpha,beta-dichloroisocrotonic acid fully inhibits both aerobic glucose utilization and lactic acid formation at 200 microM concentration. At lower concentrations, however, glycolysis is stimulated. Maximal stimulation of rat liver mitochondrial respiration in state 4 with succinate as substrate was reached at concentrations as low as 10 microM. On the other hand, these substances were able to release by the oligomycin inhibited respiration of rat liver mitochondria. Our data suggest that cytotoxic and cancerostatic action of isocrotonic acid derivatives lies primarily in the exclusion of key processes in the energy metabolism of Ehrlich ascites cells and isolated mitochondria.


Excretion of melanogens and zinc during the growth of melanoma in hamsters.

Melanogens which are considered as probable precursors or their metabolites in the metabolic pathway toward melanin are excreted in an increasing amount during the melanotic melanoma growth in hamsters. Moreover, an increased excretion of zinc was observed. The evaluation of dependence between zinc and Thormählen positive melanogens excretions during the melanoma growth suggests an exponential type of dependence. Likewise as in the case of human melanoma the hyperzincuria proved to be a laboratory sign of tumor disease progression in Syrian hamsters as well. The cause of an increased zinc excretion during the melanoma growth seems to consist in an increased lysis of pigment cells. The presumed destruction of tumor cells was not accompanied by a higher excretion of magnesium, though. Concentration of creatinine proved to be a useful mean for expressing of standard excretion of various substances also in hamsters.


Stress and Ehrlich ascites tumor in mouse.

The aim of the study was to investigate the interaction of the psychosomatic stress and the Ehrlich ascites tumor (EAT) growth in mice. The stressor consisted of combination of a light signal followed by a mild electric shock. The first experiment was performed on CBA mice irritated for 0, 2 and 4 weeks respectively, prior to intraperitoneal transplantation of the EAT. In the second study, mice of BALBc strain were used. Stress was applied 4 weeks before the tumor transplantation and continued throught the experiment. Both the irritated and the nonirritated animals were subjected to either intraperitoneal or subcutaneous inoculation of the EAT. In both experiments, mice were left to live until their spontaneous death. In the first experiment, after a 2-week irritation the experimental animals showed a significantly longer survival time as compared to the controls. Longer or shorter duration of the irritation had no significant effect on the results obtained. Results yielded by the second experiment showed no significant difference in the time of survival of the irritated and nonirritated animals after the i. p. transplantation, whereas after the s. c. inoculation of the EAT, the irritation significantly increased the survival period. The EAT in irritated mice was observed to have invaded the vitals later and less frequently than in the nonirritated animals. Quantitative histological analysis of some endocrine and lymphatic organs revealed signs of stress in the experimental animals. The EAT transplant, per se, had a stressogenic effect too.


Invasive thymoma (a case report).

A 10-year old Nigerian boy was admitted to hospital with a history of swelling in the neck, change of voice, dysphagia and dyspnoea of 2 weeks duration. He died on the 2nd day of admission. Autopsy revealed a thymoma infiltrating the thyroid, trachea and neck muscles and transforming the tracheal lumen into a slit like space. The condition is considered worthy of record on account of its rarity and of the short clinical course terminating in death. The authors feel that the most important factor in determining the prognosis of thymoma is the presence or absence of gross invasion.


Cell surface adhesiveness of mouse sarcoma lines evaluated by latex particle adherence assay: correlation with growth behavior and electrophoretic mobility.

Using the latex particle adherence assay and five mouse sarcoma cell lines of the identical origin, etiology and genotype but differing in malignancy we attempted to correlate the degree of cell surface adhesiveness with growth behavior and electrophoretic mobility of cells. Higher tumorigenicity of four of the cell lines (Mc11--Mc14) was associated with lower cell surface adhesiveness and, conversely, lower malignancy of the fifth line (Mc15) with higher cell surface adhesiveness. No simple correlation or causal relationship was found among the electrophoretic mobility of the lines and other cellular characteristics.


Human lymphoblastoid cells in long-term cultures: electron microscopic study.

Fine structure of lymphoblastoid cell lines (LCL) derived from leukocytes of three patients with acute myelosis and one patient with undifferentiated acute leukemia were studied repeatedly by electron microscope. The majority of cells in all lines was of the same primitive lymphoblastic type as refered to in literature regardless to their origin. Morphology of the cells did not change with time of cultivation for several months, by freezing and thawing and by new recultivation after prolonged cryopreservation. No morphologic signs of contamination by viruses were found. No evident morphologic signs of differentiation to mature granulocytes or "mature" lymphocytes or plasmatic cells were observed.


Combined therapy of L1210 leukemia with Damvar and cytostatics.

Damvar, the delta-(2-amino-6-hydroxy-3,4-dihydro-4-oxo-5-pyrimidinyl) valeric acid, administered alone s. c. or i. p., has no effect on L1210 leukemia. In DBA2 mice with L1210, Damvar administered in combination with 5-fluorouracil, or with 6-mercaptopurine, or with cyclophosphamide, in optimal doses, enhances or intensifies the antileukemic effects of the above cytostatics.


Modification of adriamycin cardiotoxicity by Damvar.

In experiments performed in mice, Adriamycin (15 mg/kg i. p.) produced serious damage of the heart muscle. Damvar (2 x 200 mg/kg orally) a new cytostatic drug combined with Adriamycin decreased conspicuously its cardiotoxicity.


Effects of cyclophosphamide on the prenatal development of the Swiss strain mice.

Groups of pregnant mice were given cyclophosphamide at daily doses from 6.4 to 40.8 mg/kg from the 11th to the 15th day of gravidity. Significantly lower weight and length of fetuses were noted after each of the above dosis as against the controls, while the volume of the amniotic fluid was significantly increased. The number of resorptions rose significantly with the growing dose, the embryotoxicity proving 100-percent effective in both the highest doses. Malformations were followed in live fetuses. Evident malformations resulting from cyclophosphamide application were those of the head (hydrocephalus, exencephalus, exophthalmus, median cleft palate, micrognathia), of the extremities (syndactylia, polydactylia), caudal malformation (stunted and crooked tail) and an overall developmental retardation of the fetuses. Skeletal anomalies comprised synostosis, retarded ossification, deficiency or redundance of some bones of the head, trunk and limbs.


White and red spleen pulp recovery in mice after continuous irradiation.

The process of spleen recovery after the continuous irradiation with higher daily doses up to the total dose 9570 mGy was studied in histological slices. Histological picture seen immediately after the irradiation gives evidence that significant changes occur in spleen white and red pulp. The lymphopoiesis recovery is slow and lasts till day 60, resp. 90 after irradiation. Erythropoiesis and myelopoiesis recovery of the red pulp is more intensive and is completed within 14-28 days in all three examined groups.


Tumor differentiation and immunocompetence in cervical cancer patients.

The authors investigated cell-mediated and humoral immunity parameters of 161 and 131 cervical cancer patients in connection with the histological differentiation of the tumor. As regards the carcinoembryonic antigen and acute phase proteins no difference was found between differentiated and undifferentiated types of tumors. Significantly higher levels of IgA, IgM, 3rd component of the complement and of skin reactivity to phytohemagglutinin were observed in patients with differentiated tumors.


Mental changes in women with gynecologic cancer.

In 47 women with gynecologic cancer a questionnaire method was used for investigation mental changes in these patients. Alteration of value orientation, self-image, sexuality, attitude to cancer, etc., were analyzed in the group of the followed patients.


[Use of microangiography in postmortem angiographic examination of the brain].

By means of microangiography investigations of small blood vessels were carried out postmortem in cases of brain strokes. It was observed that a part of the precapillary and capillary vessels had irregular, tortuous course, formed "glomeruli" or intertwinning patterns. Histological examinations of the same sections done by means of conventional methods showed very intense changes in the vascular walls in the form of their striking fibrosis and hyalinization. These changes were, most probably, responsible for the changed course of small brain vessels in old people. Microangiography is a method making possible observation of small precapillary and capillary vessels, assessment of their course under physiological and pathological conditions, demonstrating changes in their lumen (narrowing or occlusion). In serial sections it could be possible to determine accurately the range of tissue supplied by different vessels.


[Effect of hemodialysis on the creatine kinase activity in inflammatory muscular diseases].

In 10 patients with polymyositis at different stages of the intensity of clinical changes the effect of serum dialysis on CPK activity was studied. The controlgroup comprised 5 patients with Duchenne type myopathy and 11 healthy subjects. In 80% of patients with polymyositis a fall in CPK activity was observed after dialysis, similarly as in all patients with Duchenne type dystrophy and in healthy subjects. In the ramaining patients with polymyositis a significant rise in CPK activity occurred after dialysis. These patients were in the acute stage of the disease and had not yet been treated.


[Use of azathioprine in the treatment of chronic form of Guillain-Barré syndrome].

After discussing the clinical problems of the chronic form of Guillain-Barré syndrome the authors describe 8 own cases, treated with azathioprine 100 mg daily. In 3 cases drug tolerance was poor and the treatment had to be stopped. Considerable improvement was achieved in 3 cases, slight in 1, and no improvement in one patient.


[Neurological syndromes in the course of systemic lupus erythematosus].

Seven cases of SLE with concomitant neurological syndromes are reported. In 2 cases brain stroke with right-sided hemiplegia and aphasia developed, in the remaining cases brain-stem stroke with subarachnoid haemorrhage, progressive hemiparesis and signs of intracranial hypertension, chorea, status epilepticus in terminal uraemia were observed. In one case myasthenia coexisted. Severe neurological syndromes were preceded by signs of involvement of other organs and in most cases by low-grade signs of central nervous system involvement. Treatment with corticosteroids and immunosuppressants resulted in significant improvement without complete remission. A retrospective survey of clinical material showed that modern therapeutic methods have improved the prognosis in systemic lupus erythematosus independently of central nervous system involvement.


[Fertility in the population of women with epilepsy].

Retrospective inquiry investigations of 263 women with epilepsy at the age above 15 years demonstrated that the reproductive functions in these women were twice lower than in the general population of this region. The number of unmarried was 7% above that in the population, 25% of married epileptic women had no children, and most married women controlled the birth rate resorting frequently to artificial abortions. The index of perinatal mortality of the newborns, dead fetuses and early deaths) was over three times higher than in the population: 88.2 and 25.6 respctively. The risk of spontaneous abortion was 11.3%, the risk of stillbirth 3.9%, the risk of early neonatal death 4.6%. The risk of spontaneous abortion and early neonatal death was higher in the group of women taking anticonvulsants during pregnancy.


[Angiographic diagnosis of expanding processes in the posterior cranial fossa using a new topographic line].

The authors proposed a new rentgenometrie method allowing objective determination of the site of expanding lesions in the posterior cranial fossa. On the lateral angiograms of the vertebral arteries they determined the position of the choroid point of the posterior inferior cerebellar artery in relation to the line joining internal occipital protuberance with the upper ridge of acetabulum of the mandibular articulation. On the material of 50 subjects with expanding lesions of the posterior cranial fossa the authors determined interrelationship between the shift of the choroid point and the site of the lesion. They pointed out that the presented method can be of a considerable diagnostic value. In the presented material it allowed for the precise determination of localisation of the tumour in 86% of the cases.


[Post-traumatic cerebral artery thrombosis].

In the years 1965--1978 thrombosis of the intracranial vessels of different aetiology was diagnosed in 204 patients treated at the Department of Neurosurgery, Medical Academy in Warsaw. The authors selected from this group 8 cases described in greater detail in which there was an evident temporal relationship between trauma and the development of the disease. The severity of the sustained trauma was without a significant influence on the development of post-traumatic thrombosis. Clinical Manifestations increased in intensity usually within the first 48 hours and in only one case they appeared 2 weeks after trauma. In the clinical status of the patients of considerable interest was usually absence of disturbances of consciousness with presence of serious signs of focal central nervous system damage. Of decisive diagnostic significance was cerebral angiography which localized the site of thrombosis and excluded presence of post-traumatic intracerebral haematoma. In 7 cases thrombosis affected the main trunk or branches of the middle cerebral artery. The prognosis as to survival of such patients is generally good but in most cases disability of different degree developed following thrombosis.


[2 cases of ocular myopathy].

On the basis of two cases of progressive external ophthalmoplegia the authors discuss the clinical manifestations of this disease and call attention to diagnostic difficulties.


[Ocular manifestations of myotonia atrophica].

In a 55-year-old male with a history of over 20 years of exposure to lead clinical, electromyographic and histological investigations demonstrated myotonic dystrophy. Cataract and high-grade concentric narrowing of the visual field were found bilaterally. The latter change has been reported sporadically in this disease. Detailed laboratory investigations failed to confirm lead intoxication. No genetic background has been elicited which may suggest the possibility of toxic exogenous factors in this disease but is insufficient for accepting this possibility.


[Tolosa-Hunt syndrome (ophthalmoplegia dolorosa)].

In the reported case unilateral external ophthalmoplegia developed in a young woman, with concomitant pain and anaesthesia in the area innervated by the 1st branch of the trigeminal nerve. After ruling out an expanding lesion of the central nervous system, aneurysm, diabetes, myasthenia, multiple sclerosis and other diseases dexamethasone was administered in a total dose of 30 mg. Complete clinical remission was achieved. In the light of observations and a survey of the peritinent literature it has been accumed that the disease was caused by a non-specific process in the small vessels in the vicinity of the cavernous sinus.


[Case of Foster-Kennedy syndrome in the course of limited adhesive arachnoiditis].

A patient was observed with limited adhesive arachnitis of nontuberculous origin producing Foster-Kennedy syndrome. Ophthalmological, neurological and arteriographic investigations suggested unequivocally presence of a brain tumour. Limited non-tuberculous leptomeningitis is a very rare disease, difficult to diagnose and particularly difficult to differentiate against brain tumour. In the described case only intraoperative findings made possible the diagnosis.


[Case of cerebral aneurysm, arteriovenous fistula and cerebral hematoma].

A female patient is reported who had subarachnoid haemorrhage and in whom angiography demonstrated presence of an aneurysm and an arteriovenous angioma in the territory of the left middle cerebral artery. During surgical intervention an intracerebral haematoma was found additionally in the posterior part of the left temporal lobe. The postoperative course was uneventful. The patient was discharged without evidence of focal brain injury.


[Recurrent multifocal lesions of the nervous system after herpes zoster].

The authors report a case of zoster with signs of transverse myelitis and peripheral involvement of the facial nerve. The fact that tranverse myelitis developed late after zoster and was followed by facial nerve palsy is stressed. The involvement of these nervous structures occurred in a way suggesting exacerbations. In the light of literature data and the described case the authors state that zoster with complications in the form of multifocal nervous system involvement occurring at different time intervals is infrequent.


[Giant intracranial aneurysm].

The authors describe a case of a giant intracranial aneurysm of the left internal carotid artery in which signs of raised intracranial pressure predominated. In view of presence of internal hydrocephalus Holter's valve was implanted. The aneurysm was excluded from the circulation by trapping the afferent vessel. A good therapeutic result was achieved.


[Obstruction of the terminal cisterna as a result of surgery for intervertebral disk prolapse].

The authors describe two cases of obliteration of the terminal cistema as a complication developing late after removal of two intervertebral disc prolapse at the levels L4/L5 and L5/S1. Intensification of pains and neurological defects with development of sphincter disturbances developed 5 and 17 years after the operation. Repeated surgical intervention brought improvement. The authors stress that compression of the dural sac by a ring-like scar had contributed to disturbances in cerebrospinal fluid circulation in the terminal cistern and was probably the cause of its obliteration.


[Spontaneous regression of a posterior fossa dural arteriovenous malformation (author's transl)].

A 29-year-old woman was admitted to our hospital because of dizziness, nausea and convulsive seizure. She complained of left sided tinnitus. Neurological examination revealed right homonymous hemianopsia, and systolic murmur on the left retroauricular area. Angiograms revealed a dural AVM in the left posterior fossa. Feeders of AVM were enlarged left occipital artery and middle meningeal artery. Since then she was treated only conservatively, but angiograms performed two years and one month later showed disappearance of the dural AVM. She experienced no head trauma, and no subarachnoidal hemorrhage. She has never been treated by irradiation nor contraceptives. We could find no clear mechanism for the spontaneous regression of the AVM.


[Medulloblastoma with extracranial metastases--a case report (author's transl)].

A case of medulloblastoma with extracranial metastases was reported. A 20-year-old woman was operated on for cerebellar medulloblastoma twice during the past 5 years and a half. Two years after the second operation, she revealed the metastases to the cervical, axillar and inguinal lymphnodes, and to the skeletal system, such as the skull, scapula, humerus, sternum, spine, pelvis and femur. The cause of extracranial metastases in the very core in this case. While the tumor was located deep in the cerebellar hemisphere at the first operation, it spread over the cerebellar surface at the after the second operation, so that the tumor cells became infiltrative to the dura mater. Thus through lymphatic and circulatory system extracranial metastases occurred. The location of the tumor seems important in this case.


[A case of Maffucci's syndrome with intracranial chondroma (author's transl)].

A rare case of Maffucci's syndrome with intracranial chondroma was reported and the literature reviewed. A 16-year-old female high-school student was reffered to our service with 2 month history of diplopia and headache. She had been noticed to have multiple subcutaneous blueish nodules in the lower extremities and multiple body deformities in the four extremities since 6 months old. A biopsy of a skin lesion revealed cavernous hemangioma with calcified thrombi. Another biopsy from the deformed right femur showed it to be enchondroma. Skull series, carotid and vertebral arteriographies, and CT scan revealed a left parasellar mass, which had brought her sensory impairment of the left V1 and the left abducens palsy. The biopsy of the extradural mass in the medial portion of the left middle fossa proved it to be chondroma identical with the right femur lesion. So far as one year postoperative follow-up, she has been doing well with the postoperative sequela of mild left oculomotor paresis, having no evidence of malignant degeneration.


[Diagnosis of the chiasmal meningioma (author's transl)].

Not infrequently, it is difficult to differentiate the chiasmal meningioma from other suprasellar tumors, especially pituitary adenoma and craniopharyngioma. Authors examined 7 cases of chiasmal meningioma from neurological, endocrinological and neuroradiological points of view in comparison with the cases of pituitary adenoma and craniopharyngioma. As the results, the following features can be regarded as the differential characteristics of the chiasmal meningioma. 1) It was predominated in female of over 40 years of age. 2) Duration of the symptoms before admission was usually 2--3 years. 3) Disturbance of visual acuity and defect of visual field were initially unilateral in most of the cases, then extended to the other side when the disturbance of one eye had become severe. Visual field defect tended to be of irregular bitemporal hemianopsia with frequent involvement of peripheral nasal field. 4) Evidence of the endocrine disturbance were very scanty until the end stage. 5) Postero-superior elevation of A1 portion of the anterior cerebral artery in the tuberculum sellae meningioma was one of the pathognomonic features. 6) In the case of meningioma extending from tuberculum sellae to dorsum sellae or originated from dorsum sellae, PEG showed a finding of "capping on the dorsum sellae" and the tumor shadow over the posterior clinoid process took different feature from pituitary adenoma or craniopharyngioma.


[Diagnosis and pathological analysis of ruptured cerebral aneurysm by CT (author's transl)].

This report describes the analysis of 216 CT pictures of 85 patients with ruptured aneurysms which consist of 29 anterior communicating, 27 internal carotid, 27 middle cerebral and 2 basilar arterial aneurysms, including 18 cases with multiple aneurysms. The intervals between CT scanning and the last subarachnoid hemorrhage were various from 6 hours to 4 months. The first CT scanning was made in 40 cases within 3 days, in 54 cases within 7 days and in 11 cases more than one month after the hemorrhage. CT findings showed no abnormality in 9 patients who were classified as Grade I (Hunt and Kosnik) and examined more than 2 weeks after the subarachnoid hemorrhage. Seventy-six patients had some abnormal findings in the first CT scans, which were 55 cases of subarachnoid clot, 16 cases of intracerebral hematoma, 24 cases of intraventricular clot, 16 cases of low density suggesting brain edema or softening and 42 cases of ventricular enlargement. There was a good correlation between CT findings and clinical grade of Hunt and Kosnik. In Grade I and II, abnormal findings other than subarachnoid clot were seldom seen. Iin Grade III, there were intracerebral hematoma (20%), low density (20%) and frequent ventricular dilatation; in Grade IV, massive intracerebral hematoma (80%); in Grade V, massive intracerebral hematoma and ventricular tamponade with blood clot; in Grade Ia, moderate ventricular dilatation and/or diffuse cerebral infarction. Cerebral vasospasm could be anticipated by CT pictures because it occurred frequently in the patients with massive and long-standing subarachnoid blood clot. The determination of the side and location of the ruptured aneurysm was possible in 82% of the patients who had subarachnoid clot, intracerebral hematoma or low density. This is useful to decide the side of the first angiography and the aneurysm to be approached at first in the cases of multiple aneurysms.


[Computed tomography in metastatic brain tumors and meningeal carcinomatosis (author's transl)].

The computed tomogrpahy has been proved to be highly reliable in diagnosis of CNS diseases. The findings in 26 cases of metastatic brain tumors, and 2 cases of meningeal carcinomatosis performed with Hitachi CT-H scanner are analized. Metastatic tumors are seen on plain CT as mainly isodense nodules (60%). But, on enhanced CT, they increase in their density (97%). Larger nodules of metastatic tumors (over 2 cm in diameter) are tend to contain less dense central area, so called central cavitation. The direction of the expansion and/or extension of the perifocal low density is characteristic to the location of the tumor. In cases of meningeal carcinomatosis, diffuse periventricular higher density can be recognized enhanced CT.


[A case of extra-intracranial bypass venous graft for giant internal carotid aneurysm (author's transl)].

A male patient, aged 42, (No. 780624) was admitted to the Department of Neurosurgery of Hirosaki University Hospital, complaining recent weight loss, intolerance to cold and visual disturbance of the right eye. Ophthalmological examination revealed the optic atrophy with decreased visual acuity and concentric visual defect of the right eye. Endocrinological examination showed almost general suppression of adenohypophyseal function except abnormal high level resetting of cortisol diurnal rhythm. Radiological examination revealed the accessory middle cerebral artery and giant internal carotid aneurysm of the right side which was displayed by contrast-enhanced CT scan, with the enlarged sella turcica. Good cross filling was seen in left CAG through the anterior communicating artery. Extra-intracranial end to end anastomosis of the right internal carotid artery was performed with long venous graft under general anesthesia with hypothermia and induced hypotension, on Oct. 26 '78. Unroofing of the right optic canal was very useful to preserve the optic nerve, and the body of the giant aneurysm was opened and sutured tightly to reduce its mass effect. Interlacing suture for the anastomosis of the cervical internal carotid artery was employed successfully. The blood flow of the bypass graft, measured as enough volume with square wave flowmeter during the operation, was also confirmed with postoperative angiography. After the episodes of gastrointestinal bleeding, hypotensive attack and hemorrhagic infarction of right frontal base, the postoperative final result was successful and the patient is doing well, 6 months after the operation.


[Polyuria and polydipsia in a young boy--a case study (author's transl)].

A 13-year-old boy with a teratoma in the sellar region was presented. This patient had gradually developed polyuria and polydipsia since 2 years prior to the first admission. Endocrinological examination showed a marked reduction of pituitary function. Careful neuroradiological examinations including CT failed to show any mass lesion in the sellar and suprasellar regions but a marked increase of the width of the third ventricle. CSF examination revealed only a slight increase of cell count (lymphocytes). The patient was discharged with hormonal replacement therapy. Seven months later the patient developed visual disturbance and mental disorders. On the second admission, plain skull films showed enlarged sella and CT demonstrated a mass in the suprasellar region. Preoperative diagnosis was suprasellar germinoma. At surgery a teratoma, probably arising from the pituitary fossa, was totally removed. Histopathology of the tumor showed tri-dermal tissues including melanotic progonoma and germinoma. The authors presented various problems of the patient and their solving processes.


[A study of regional cerebral blood flow by intravenous injection method of Xenon-133 (author's transl)].

Regional cerebral blood flow (rCBF) was determined in man by Xenon-133 intravenous bolus injection technique. This method is of value especially for patients with stroke. The measuring system constituted of a 16 channel cerebrograph (rCBF 1656, Meditronic, Denmark) and a minicomputer (AI Electronics, Japan). Then, for an estimation of rCBF, two compartment analysis was applied in which a special computer program was used for this purpose. Amount of Xenon-133 in expired air was used for calculation, since we confirmed that Xenon-133 clearance in expired air was similar to that in arterial blood except for those patients with obstructive lung disease and so on. In normal adults, rCBF of the gray matter was 67 +/- 13 ml/100 g brain/min. (95% confidence limits). Patients who had been TIA or RIND, revealed a decrease of rCBF of 33--49 ml/100 g brain/min. bilaterally, although they did not show any clinical signs at the time of measurement. Contrariwise, two cases of Moya-moya disease showed a normal value of rCBF at their silent periods.


[Nonsuture microvascular anastomosis--experimental arterial end-to-end anastomosis using plastic adhesive and a soluble PVA tube (author's transl)].

Microvascular anastomosis is now widely applied and many improved methods of the nonsuture anastomosis have been developed instead of the suture anastomosis for the purpose of saving time and making the reconstruction easier. We introduced a new nonsuture method of microvascular anastomosis using plastic adhesive and a soluble tube made of polyvinylalcohol (PVA). PVA, which had been utilized as a plasma expander, is a water-soluble polymer and its solubility is changeable depending on the degree of polimerization and percent saponification. We have made two kinds of soluble PVA tubes, the one has monolayer wall and the other double layered wall. The inner wall of the latter is more soluble than the outer wall. As plastic adhesives, we employed ethyl 2--cyanoacrylate, isopropyl 2--cyanoacrylate, and isobutyl 2--cyanoacrylate which were much superior to methyl 2--cyanoacrylate. Common carotid arteries of rats of 1.0 to 1.3 mm external diameter range were reconstructed and re-exploration was carried out at intervals of more than 7 days after operation. The anastomotic technique was very easy and it took about five minutes to reconstruct. In our last series, approximately 98 percent patency rate was achieved. The advantage of our method is that the blood stream is regained in the small soluble at the anastomotic site immediately after the release of hemostatic clamps.


[Contingent negative variation in patients with severe closed head injury--its diagnostic value as a quantitative evaluating method for certain aspect of posttraumatic syndrome (author's transl)].

CNVs were studied in 48 subjects with closed head injury followed by posttraumatic amnesia over than 7 days. Electrical motor-threshold stimulation of the median nerve or subjectively painful stimulation of the fingertip was used for imperative stimulus. An amplitude of CNV and its enhancement by painful imperative stimulus were measured and compared with those obtained from 34 normal subjects. In subacute stage within 3 months after the head injury, correlation between CNV abnormalities and an existence of some noticeable psychiatric disorders was found. In many of the subjects with CNV abnormalities, diffuse slow wave activities were observed in the background EEG, so that it was supposed that CNV abnormalities in subacute stage might reflect diffuse cerebral dysfunction and decreased vigilance. Any statistically significant correlation of CNV abnormalities to an existence of psychiatric disabilities, low score in WAIS and background EEG patterns could not be found in chronic stage 12 months after head injury. However, suppressed CNV was observed in all of 4 subjects who presented generalized epileptic patterns in the background EEG. Many of the subjects with suppressed CNV also showed a small effect of painful imperative stimulus on its amplitude. Statistically significant correlation between CNV abnormalities and work capacity was found. From these findings, together with previous observations (Tsubokawa et al. 19,36,40,44)), it is concluded that the measurement of the CNV is inimitable examination to evaluate certain psychiatric disability which is apt to be overlooked but, in fact, concerned intimately to the work capacity.


[Late manifestation of alternating Horner's signs in spinal cord injury due to dura-cord adhesion (author's transl)].

It has been said that late manifestation of transient alternating Horner's signs in cases of spinal cord injury is caused by intramedullary cavity formation in which some movement of fluid stimulates the sympathetic system corresponding to their positioning. We had a patient complaining of alternating Horner's signs which became manifest 8 years after the injury. We could not find any intramedullary cavity formation, in spite of a spinal puncture at operation, but the symptoms made a striking improvement after the operation simply by making free the spinal cord from the dura mater at operation. So we suppose that late manifestation of transient alternating Horner's signs will be manifested not only in cases of intramedullary cavity, but also in cases of dense adhesion between the spinal cord and the dura mater. In addition to this, we propose the new term "Poromyelia" for the intramedullary cavity because of its resemblance to "Porencephalia" in the cerebrum, and because of the confusing usage of the word "Syringomyelia" for this condition of "Poromyelia". It has been said that "Syringomyelia" in the spinal cord is similar to "Hydrocephalia" in the cerebrum.


[Liliequist membranotomy for patients with ruptured intracranial aneurysms (author's transl)].

In order to reconstruct the blocked CSF pathway, we attempted to excise the Liliequist membrane in 22 patients with subarachnoid hemorrhage resulted from ruptured intracranial aneurysms. After clipping the aneurysmal neck, the Liliequist membrane was reached through the space between the optic nerve and the internal carotid artery within the same operative field. As a result, the incidence of postoperative ventricular dilatation was remarkably reduced in comparison with control cases without Liliequist membranotomy. The necessity for the shunt operation for post-SAH hydrocephalus was also reduced. On the other hand, the incidence of postoperative subdural effusion increased in the group with Liliequist membranotomy. This suggests that the blockage of the arachnoid villi is probably the cause of disturbances in CSF absorption in some cases following subarachnoid hemorrhage. In such cases, the Liliequist membranotomy may be ineffective in restoring CSF circulation following subarachnoid hemorrhage.


Effect of a single injection of reserpine on kinetics of 3H-dexamethasone binding to receptors of the cat hypothalamus and hippocampus.

Cats were injected intraperitoneally with reserpine (5 mg/kg) or saline and sacrificed 16 h later. Hypothalamic and hippocampal cytosols were assayed for the kinetics of 3H-dexamethasone (3H-DM) binding. A parallel series was performed in which saline-injected cats were infused via venocatheter with hydrocortisone (HC). Reserpine-injected cats were infused with saline. The hypothalamic cytosol of reserpinized cats showed a marked decrease in 3H-DM binding capacity relative to that from saline-treated cats. Hippocampal cytosol 3H-DM binding capacity was unaffected by reserpinization. Infusion of high levels of HC reduced the amount of 3H-DM binding in the hypothalamus, but did not account for all the reduction found after reserpine treatment. HC infusion had no effect on hippocampal binding capacity. Reserpine treatment did not change the dissociation constant differences between the two brain regions. The data suggest that depletion of neurotransmitters by reserpine treatment from the hypothalamus, but not the hippocampus, significantly reduces the number of 3H-DM binding sites and that such a reduction is due, in part, to the effects of reserpine and not to high circulating levels of HC.


Adrenal medullary secretory response to stimulation of the medulla oblongata in the rat.

In rats anesthetized with sodium pentobarbital, adrenal venous blood samples were collected and analyzed for epinephrine and norepinephrine by the fluorometric method. Stimulation of the inferior fovea or adjacent areas resulted in a significant increase in epinephrine secretion. Stimulation of some other areas of the floor of the fourth ventricle was associated with a significant decrease in norepinephrine secretion with or without significant decrease in epinephrine secretion. In no instance was observed a significant increase in norepinephrine secretion in response to the medulla oblongata stimulation.


Alteration of the Agouti mouse coat color pattern by bromoergocryptine. Possible involvement of MSH.

In the Agouti mice C3H Avy the coat color of the dorsum changes from birth to maturity. In young animals the dorsal tegument is yellow whereas in adult mice it shifts to dark gray. The administration of bromoergocryptine, a dopamine agonist, as a single injection in a beeswax pellet prevented the color change resulting in the persistence of the immature pattern. After plucking an area of the dorsum of an adult animal, the regrown hair was dark; however, when bromoergocryptine was administered at the time of plucking the new hair was not dark but yellow. When MSH was injected in adult animals previously treated with the drug, the 'bleaching' effect of bromoergocryptine was abolished, suggesting that this substance did not act directly upon melanin synthesis. In bromoergocryptine-treated mice the MSH content of the pars intermedia was decreased and the ultrastructure of this lobe contained cells with signs of hypoactivity. These two observations suggested that the effect of the drug on the coat color might be ascribed to inhibition of the secretion of MSH. The results may indicate that in the Agouti C3H Avy mice MSH plays a physiological role in determining the coat color. On the other hand, in CH57BL mice bromoergocryptine did not elicit color changes suggesting that in this strain the normal color of the hair is not MSH-dependent.


[Clinical and instrumental study program of nodular diseases of the thyroid].

Authors have passed from a combined clinical and radioisotopic analysis to an integrated polyinstrumental approach by adding thermography and above all echography. In order to achieve the purpose Authors have confronted in retrospective a "clinico-radioisotopic group" of 103 cases, from 1965 to 1975, and an "integrated polyinstrumental group" of 53 cases, since 1976. Comparing the "clinico-radioisotopic method" with "polyinstrumental approach" the main results could be summarized as follows: the diagnostic specificity improved in benign lesions from 77% to 96%, however in malignant lesions it remained about the same (63%). Considering these results the Authors have subdivided thyroid nodules, mainly based on echography, in two distinct categories with the following orientation: I. Solitary Thyroid Nodule: a) definitely cystic -- demonstrated by echography; b) "cold" -- by conventional scintygraphy; c) "negative" -- by thermography; d) non uptake of tumor seeking radiopharmaceutical. The control, therapy and surveilance of these cases should be limited to needle aspiration of the cystic cavity followed, of course, by citologic examination. This aspirations is both diagnostic and possibly therapeutic. II. Solitary Thyroid Nodule: a) definite solid -- echography; b) "cold" -- convential scintygraphy; c) "positive" --thermography (possibly "negative"); d) non uptake of tumor seeking radiopharmaceutical. Here the therapeutic orientation is clearly surgical.


[Antiprolactin therapy in the treatment of benign lesions of the breast. Comparison of bromocryptine and methergoline].

The Authors have treated 11 patients with benign breast diseases (fibroadenosis or fibrocystic disease) with two prolactin inhibitor drugs -- metergoline and bromocriptine -- at the dose of 8 mg/die and 7,5 mg/die respectively for sixty days with a 30 days interval from one to the other. All patients, except one, had normal serum prolactin levels before the trial; during the treatment with metergoline no long-term changes in serum prolactin levels were observed; on the contrary, bromocriptine reduced significantly prolactin values for the whole duration of the therapy. Negative clinical results were obtained with the first drug, while bromocriptine allowed to reach an 80% of positive results at the end of the trial. Coming from previous experience, the Authors conclude that the positive therapeutic effect of bromocriptine treatment is connected with the maintenance of prolactin reduction.


[Hypomagnesemia with magnesium-dependent hypocalcemia and hypopotassemia in a case of alcoholic cirrhosis].

An account of the main causes of low blood magnesium and the predominant rôle of this ion in the organism is followed by the description of a case of encephalopathy due to magnesium deficiency in a chronic alcoholic with cirrhosis of the liver. This neuropsychological condition, together with its concomitant low blood calcium and potassium, rapidly regressed when magnesium sulphate was administered. Stress is laid on the desirability of giving attention to and preventing the onset of this electrolytic alteration in clinical practive.


[Elevation of the total blood CPK test in vomiting of various causes].

The Authors make a list of 17 cases of elevation of total CPK (creatine phosphokinase) in subjects with vomiting of different cause, supposing the exclusion of more kinowed causes be able to stir up the enzyme increase. The Authors place the above mentioned elevation in relation to muscular or traumatism on musculature delegate physiologically to vomiting. It is never observed any relation with entity of vomiting and elevation of CPK. The causes of elevation represent the 40% of examined subjects.


[Association of osteitis deformans (Paget's disease) and adenocarcinoma of the prostate].

A rare association of prostatic adenocarcinoma with osteitis deformans (Paget's disease) is reported. The diagnosis suspected on the basis of simultaneous increased concentrations of acid and alkaline phosphatases was documented only through repeated biopsies of prostate.


[An unusual case of pseudotabetic arthropathy].

After a brief introduction on Adie's disease, or pseudotabes, a rare case of pseudotabetic arthropathy which, in addition to the classical signs of Adie's syndrome, presented signs of a recurrent arthrosynovitis of the knee, is reported. This rare syndrome should be borne in mind in differential diagnosis with recurrent arthrosynovitis of other nature.


[Our experience with cardiac electrostimulation (1964-1979: 730 implants)].

From 1964 to 1979, 446 patients were treated with pace-maker implantation for a total of 730 devices. Epicardial stimulation was employed in 263 cases, endocardial in 160, and both in 23. The results, complications, treatment and indications are reported and discussed.


[504 implantations of aortic valve prostheses].

The results in 504 patients operated with aortic valve replacement are reported. In 153 patients other associated valvular diseases or complications were present. The mortality in non complicated case was 3%. The long term mortality (1--14 years) was 4%. The results and indications are discussed.


[Radical correction of the tetralogy of Fallot: 122 cases].

In 122 patients with Fallot tetralogy total correction was performed. 18 were previously operated with palliative surgery. The results were the following: hospital mortality: 8,5%; very good or good improvement: 78%; satisfactory in 13,5%.


[Surgery of ventricular aneurysms and akinetic zones].

Operation was performed in 180 patients with post-infarction ventricular aneurysm (12 cases) or akinesia (92 cases). Simultaneously in 2 cases mitral valve replacement was performed and in 2 cases ruptured ventricular septum was treated by patch. The results are reported and discussed.


[Calculosis of the biliary tract in childhood and adolescence].

A series of 55 cases of calculosis of the bile ducts observed in subjects aged 9-20 yr between 1963 and 1977 is presented. Haemolytic anaemia, familial predisposition, pregnancy, obesity, and deformity of the bile ducts are regarded as possible pathogenetic factors in accordance with the views of other workers.


[The treatment of varicose veins].

In the treatment of varicose veins and their complications most European phlebologists use today, unlike the past, surgery, sclerotherapy and compression without any preconceived preference, guided solely by the indications of choice of each method. Within this framework, it is generally admitted that surgery is by far the best treatment for incompetent saphenous terminations, main saphenous trunks and insufficient bulky perforating veins. Sclerotherapy, on the other hand, is given the task of eliminating the varicose tributaries of the removed saphenous conduits, as well for treating reticular non-saphenous varices, dermal varicosities and recurrent varicose veins after correct operations. As far compression treatment, it requires today respect for "posology" that is expressed in terms of mmHg of pressures to be exerted at different levels of the extremity; depending on venous and skin changes, semi-stiff sticky bandages or various types of elastic stockings will be chosen. Often two or more of the methods listed are used during the same treatment or in successive stages.


[Intestinal absorption of Ca47 in chronic renal insufficiency before and after treatment with 1,25 dihydroxycholecalciferol].

The effects of vitamin D3 follow its metabolisation in the liver and then in the kidney. Its most active metabolite is 1,25 (OH)2D3, produced by the liver precursor 25(OH)D3. In chronic renal insufficiency, demineralising osteopathy can be corrected by administering 1,25 (OH)2D3 to make up for its under-production by the kidneys. An assessment if is made of 47Ca intestinal transport in patients with chronic renal insufficiency before and after such treatment. It was found that the effects of the metabolite on calcium transport were dose-dependent.


[Budd-Chiari syndrome in the course of polycythemia rubra vera. Presentation of a clinical case].

An unusual case of Budd-Chiari syndrome during erythraemia is presented. Acute thrombosis of the suprahepatic veins became chronic with progressive improvement, shown clinically and radiologically in the form of partial recanalisation of thromboses of these veins and the porta. The pathogenetic relationship between polycythaemia and the Budd-Chiari syndrome is also discussed.


[Unusual association of hemolytic anemia and splenic metastases in a case of breast carcinoma].

An unusual case of splenic metastasis associated with haemolytic anaemia in a patient with breast cancer is reported. Attention is drawn to the rarity of invasion of the spleen, and an account is given of the causes of haemolytic anaemia in carcinomatosis. A spectacular response to splenectomy was observed in the case reported.


[Evolution and prognosis of retrobulbar optic neuritis as the initial symptom of multiple sclerosis].

In 61 of 300 patients suffering from multiple sclerosis, disease onset was retrobulbar optical neuritis. Comparing the clinical data of these patients with those of the remaining 239 cases, the following typical features were observed: in patients with optical neuropathy, disease onset is more frequently acute and course, in the early years of the disease, is in fits and starts. Recurrence frequency is higher in these patients but not significantly so. Prognosis, deduced from the analysis of degrees of invalidity, does not differ substantially between the two groups. Current techniques of diagnosing multiple sclerosis in patients with retrobulbar optical neuritis are also discussed.


[Serum thiocyanate level as a discriminating element in evaluation of exposure to carbon monoxide].

Blood carbon monoxide concentration levels in two groups of subjects to a different degree of exposure are examined in the light of the subjects declared smoking habits and serum thiocyanate levels. The latter parameter proved an effective pointer to individual exposure to CO due to tobacco combustion. Assessment of the results showed that it could be proposed as an indicative and discriminating test of habitual exposure to CO, so as to enable expired CO and HbCO values to be interpreted in occupationally exposed subjects.


The stilbestrol-adenosis-carcinoma syndrome.

For the development of the DES carcinoma syndrome, two different mechanisms may be assumed. 1. Indirect effect via teratogenesis: squamous cell carcinoma develops from adenosis vaginae with the assistance of cofactors (Fig. 6). Till now, a conversion of adenosis to clear cell carcinoma has never been observed (Hilgers, 1977). Adenosis is probably a precancerous lesion only for squamous cell carcinoma. 2. Transplacental terato-oncogenesis: clear cell carcinoma as a mesonephric carcinoma develops from persisting wolffian ducts with a latent period of 15 to 20 years. DES here acts only as a promoter by way of the transplacental teratogenic mechanism, thus as a terato-co-carcinogenic factor (Fig. 6).


Electrocoagulation diathermy treatment of cervical intraepithelial neoplasia.

Although there are other physical methods of destruction which may be effective for small areas of dysplastic change, the author believes that D&C and electrocoagulation diathermy under general anesthesia is a more reliable and more effective method of destruction of abnormal T-Zone. It has the distinct advantage of being able to eliminate large areas, and in particular, changes of major atypia extending into the gland crypts. To date, no patient treated in this fashion has developed invasive carcinoma of the cervix.


Further evidence for high risk male and female groups in the development of cervical carcinoma.

Further evidence suggests that there exist high risk groups of men and women who are at a high risk of either transmitting the mutagen involved in the development of cervical cancer or for the development of this neoplasm.


Ultrasonically-aided percutaneous orbital aspiration.

Ultrasonography is the most effective diagnostic modality for locating and delimiting cystic orbital lesions, and may often provide an accurate tissue diagnosis. A case is presented demonstrating the ability of ultrasonography to aid in the percutaneous aspiration of selected orbital cystic lesions.


Pupillary dilatation in fractures of the floor of the orbit.

A sign involving pupillary dilatation preoperatively and postoperatively in fractures of the floor of the orbit is presented. Response to Pilocarpine 0.5% was immediate. This represents injury to the parasympathetic fibers in the nerve that travel to the inferior oblique muscle and interrupts the path of ciliary ganglion. This pupillary sign has been found so far in posterior orbital floor fractures.


Irrigating instruments for intraocular lens implantation.

A series of small instruments to assist with insertion of intraocular lenses and placement of lens fixation sutures has been described. Added to the main function of each, is the capability for infusion of fluid or injection of air and medication.


Scleral buckling with a soft xerogel implant: II. Experiments in vivo.

Experimental scleral buckling was obtained in rabbits by using soft xerogel implants placed either episclerally or intrasclerally. After implantation of 1 x 1.5 x 2 mm or 1 x 2 x 2.5 mm implants, buckle heights ranged from 1.3 to 4.0 mm. Intrascleral implantation produced a higher buckle than episcleral implantation. The follow-up period extended from 6 months to 1 year. No significant inflammatory reactions, wound dehiscence, or extrusions or intrusions of the poly(2-hydroxyethyl acrylate), PHEA, implant were observed either clinically or histologically. Our impression is that HEA can be a useful material for treatment of retinal detachment, particularly when a localized high buckle is required or for patients with thin and weak sclera.


Dacryoscopy.

A miniature caliber endoscope is described for introduction into the lacrimal excretory passages. Direct observation and diagnostic inspection of the contents and lining of the lacrimal sac and naso-lacrimal duct are possible with the instrument, and complement standard examination procedures of the lacrimal outflow system.


Need for bilateral electroretinography in unilateral trauma.

Electroretinography revealed unsuspected night blindness in a patient who had suffered unilateral trauma. This case illustrates the importance of testing both eyes, even when one appears normal.


Choyce intraocular lens placement under gonioscopic control.

Various gonioscopic lenses were tested in the operating room for viewing the size and foot placement of the Choyce Mark VIII intraocular lens. The Tennant and the Worst fiber optic devices were fairly adequate. The Thorpe surgical gonioscope was the easiest to handle, and provided a good view with the operating microscope.


A comparative evaluation of 9-0 monofilament and 9-0 braid polyglactin 910 in cataract surgery (intracapsular, extracapsular, and phacoemulsification).

This study describes the operative and postoperative performance of 9-0 monofilament and 9-0 braid Polyglactin 910 synthetic absorbable sutures in cataract surgery. The evaluation represents a clinical comparison of the sutures in 150 cataract surgical procedures. In a comparative evaluation each suture provided specific performance advantages: (table: see text). To date, the 9-0 monofilament and 9-0 braid Polyglactin 910 sutures are the smallest useful absorbable sutures developed for cataract surgery. While these sutures seem safe for use with phacoemulsification as sole wound closure materials, we recommend the use of nylon stints for intracapsular and extracapsular procedures until further experience is gained.


Seven years of secondary implants using the Choyce Mk VIII lens.

We have presented the results of 44 consecutive secondary lens implants using the Choyce Mk VIII lens. The longest follow-up is seven years--the shortest is one year. The visual acuities are shown, as are the complications. This is a small series, but the results are comparable to some larger series of primary implants, 2, 3, 4, 5. This series includes our first efforts at lens implantation and was undertaken at a time when the potential pitfalls were unknown. Most of our worrisome complications occurred in the early cases. Now that implant procedures are fairly well standardized, we feel that secondary implantation of a Choyce Mk VIII lens is an acceptable procedure with predictable results and should be included in the armamentarium of the implant surgeon.


The fate of eyes from which intraocular lenses have been removed.

The author removed 26 intraocular lenses in a series of 800 implantations (3.25%). The factors leading to lens removal and the clinical and visual end-results are analyzed and presented in tabular form. The most common factors leading to lens removal were: corneal edema, cystoid macular edema, uveitis, vitreitis, iris erosion/laceration, recurrent dislocation, updrawn pupil, glaucoma and blunt injury. Post-removal complications were: poor wound healing, high astigmatism, amblyopia, cystoid macular edema, retinal vascular occlusion, optic atrophy and phthisis bulbi. The average length of time between lens implantation and removal was 18 months. The vitreous loss rate was 35% during lens removal. On the average, an eye gained two Snellen lines of vision following removal of the offending lens; 69% had the same or better vision post-removal, and 64% of eyes with corneal edema/dystrophy improved.


Shell tamponade in filtering surgery for glaucoma.

The glaucoma shell tamponade technique in filtering surgery for glaucoma is a technique for (1) decreasing the incidence of flat anterior chamber and choroidal separation postoperatively, (2) promoting the development of a low diffuse filtration area, and (3) increasing the possibility of achieving very low resulting postoperative pressure. The glaucoma shell technique is applicable to all types of filtration procedures, including conventional filtering procedures utilizing no scleral flap and those utilizing a scleral flap, such as trabeculectomy. It can be used at surgery or can be applied in the postoperative period to deal with flat or shallow anterior chambers immediately at the time of onset. The shell tamponade technique can be utilized to aid in the management of some cases of leaking bleb in the early postoperative period or in the late postoperative period. The technique for operative and postoperative use of the glaucoma shell tamponade technique and its closely related pressure dressing is a demanding and exacting art. Because the technique increases the possibility of very low resulting tensions, its use should be considered especially for cases in which very low pressures are desired, such as some cases of extremely advanced cupping and field loss and low-tension glaucoma.


Microsurgical angulated irrigation and aspiration needle and handle.

An angulated irrigation and aspiration needle was designed to remove residual cortical material in an extracapsular cataract extraction.


Two-way 30-gauge air bubble cannula.

Removal of air from the anterior chamber in aliquot parts following anterior segment surgery is not an innocuous procedure without complications. A two-way 30-gauge cannula for simultaneous irrigation and aspiration in order to keep the anterior chamber at a constant volume thus avoiding too rapid decompression is described.


Surgical and strontium treatment of pterygium: recurrence and lens changes. Age statistics.

The results of a study of 975 pterygia treated surgically and immediately with Strontium 90 are presented. The recurrence rate (quiescent) was 6%. The actual recurrence requiring surgery was 0.82%. Technique of removal involves simple wide excision and immediate treatment with Strontium 90 over the entire area. Three thousand RADS is the maximum dosage. In most instances more than 3000 RADS is cataractogenic. Two methods of Strontium 90 production are discussed. Strontium 90 has a half life of 19.9 plus or minus .3 years. It decomposes to Yttrium 90 which has a half life of 62 hours. Tissue penetration is estimated by the use of polystyrene absorber which is considered to be a tissue equivalent. Age and sex occurrence is given from a survey of 832 patients. Newer developments that might replace Strontium 90 are briefly discussed.


Experiences with the Fox technique for the repair of senile entropion.

The author reports on the advantages of Fox's technique in the surgery of senile entropion on the basis of experiences with 30 interventions on 26 patients. In the evolution of senile entropion the structural changes in the orbicularis oculi muscle plays a decisive role, which leads to the malfunction of the muscle. The degenerative changes of the muscle are shown with electron microscopy. The author recommends the Fox technique because this type of intervention aims to abolish the cause of the aging process and not only the consequences of it as other methods do.


Extracapsular cataract extraction with simultaneous implantation of 300 Copeland iris plane lenses: five-year follow-up--a retrospective study.

Three hundred cases of extracapsular cataract extraction with Copeland iris plane lens implantation were reviewed. Two hundred sixty-six patients were followed objectively from 180-1,420 days with a mean follow-up of 1,026 days. 12.4% necessitated secondary operations, most of these being posterior capsulotomies. 89.5% of patients with a mean age of 73.6 years achieved visual acuity of 6/6-6/12. Using an extracapsular cataract extraction with a Copeland iris plane lens, the results obtained were considerably improved over that of intracapsular surgery.  A similar retrospective study of a larger series using extracapsular cataract extraction with the Binkhorst iridocapsular lens is currently being carried out.


Transcutaneous electrical nerve stimulation and the reaction to experimental pain in human subjects.

The effect of peripheral transcutaneous electrical nerve stimulation (TENS) on the reaction to experimental pain in human volunteers has been assessed. Placebo stimulation and electrical stimulation at moderate intensities failed to modify the response to the pain produced by conducted thermal stimuli. TENS at very high intensities did however elevate both the thermal pain threshold and the tolerance temperature. TENS at moderate intensities failed completely to alter the response to graded mechanical stimuli. The subjective pain assessment and the maximum pain tolerance produced by ischaemic pain after a submaximal effort tourniquet test were significantly modified by peripheral electrical stimulation at non-noxious intensities. The response to experimental pain can therefore be altered in man by peripheral electrical stimulation in a manner partly dependent on the sensory modality used for producing the experimental pain and on the intensity of the electrical stimulation.


Local analgesia by percutaneous electrical stimulation of sensory nerves.

Experimental C-fiber pain caused by radiant heat was applied to the skin area supplied by the left sural nerve of 20 subjects. Percutaneous electrical stimulation (PNS) was performed on the left sural nerve, the left superficial peroneal nerve and the right superficial radial nerve. Stimulation frequencies were: 3, 50, 100, 300, 500 and 1000 Hz. The analgesia resulting at the different stimulation sites was recorded according to a preset scale of estimation. Without considering the influence of the different frequencies, the best analgesic effects were reached if noxious heating and PNS were both performed on the left sural nerve; the anatomical conditions prevented us from distinguishing between the effects of possible peripheral blockade or spinal modification of pain. PNS of the superficial peroneal nerve seems to indicate spinal, possibly polysegmental, interactions between C-fiber pain and electrical stimulation of thick myelinated fibers. However, long loop effects may also play a part in local analgesia as demonstrated by PNS of the right radial nerve.


Inhibitory effects of nucleus raphe magnus on neuronal responses in the spinal trigeminal nucleus to nociceptive compared with non-nociceptive inputs.

The effect of stimulation in nucleus raphe magnus on neurones in the spinal trigeminal nucleus was studied in decerebrate cats. Short trains of raphe stimulation reduced or abolished the responses of neurones in nucleus oralis and nucleus caudalis to nociceptor stimulation (tooth pulp or cornea) but had a much weaker or insignificant effect on responses to non-noxious inputs (hair movement or low intensity stimulation of the infraorbital nerve). Maximum inhibition was seen 10--50 msec following the raphe stimulation and persisted up to 300 msec. The depression of neuronal responses was paralleled by an increase in the threshold of the jaw-opening reflex evoked by tooth pulp stimulation. The relation to stimulus-produced analgesia is discussed.


Effects of the synthetic enkephalin analogue FK 33-824 on pain threshold and pain tolerance in man.

Natural enkephalins exert weak and transitory analgesic effects. The synthetic enkephalin, FK 33-824 (FK), is less susceptible to metabolic breakdown and produces long-lasting analgesia in animals. The present studies examined the effects of FK on threshold and tolerance of electrically evoked pain in man under double blind conditions. 1.0 mg FK given intramuscularly (saline control) increased tolerance significantly without affecting the pain threshold, but also produced vasodilatation and feelings of oppression and heaviness (study I). In study II, where 50 mg betazole was employed as "placebo" because of its vasodilatatory effects, 1.0 mg FK increased pain tolerance significantly more than 0.25 mg FK while the threshold remained unchanged. Self-ratings of activation and well-being decreased; those of oppression increased, as did reaction time, equally after 0.25 and 1.0 mg FK but were not altered by betazole. In conclusion, 1.0 mg FK i.m. increases tolerance but not perception of pain, thus mimicking the analgesic effects of morphine.


Acupuncture: an evaluation in the painful crises of sickle cell anaemia.

An evaluation of acupuncture for pain relief was made in 10 patients with sickle cell anaemia during 16 pain crises. A model was developed in which the patient served as his own control and in which both patient and examiner were unaware of whether an acupuncture point or a sham site was treated. The results show (1) that pain relief was obtained in 15 of the 16 painful episodes regardless of whether an acupuncture point or a sham site was treated, demonstrating considerable overlap between the effects of needling acupuncture points and sham sites; (2) that needling at acupuncture points for pain relief is not significantly superior to treatment at sham sites; (3) that needling, per se, whether at acupuncture points of at sham sites can be useful for alleviating pain in sickle cell crises. The model could be useful for evaluation of pain relief by needling in other diseases.


The prevalence and nature of anemia among apparently normal subjects in Fiji.

A total of 4939 apparently healthy Fijian and Indian subjects living in Fiji were tested for anaemia by determination of the microhaematocrit of a sample of capillary blood. The prevalence of anaemia during childhood varied with age but was similar for Fijians and Indians of either sex. The overall prevalences were: 0-4 years, 20.3%; 5-9 years, 3.7%; 10-14 years, 23.5%. The prevalence of anaemia among Indian women (33.3%) was substantially higher than that for Indian men (6.9%), Fijian women (8.1%) or Fijian men (6.8%). Iron deficiency was the most common cause of anaemia and was established by laboratory studies in 203 (68%) of 298 anaemic subjects who were followed up. Iron deficiency was an important aetiological factor in 91 (93%) of 98 subjects with moderate or severe anaemia. Folate deficiency was found, usually in combination with iron deficiency, in 44 or 141 anaemic indian adults were followed up. Folate deficiency was uncommon in Fijian adults and among children of either race. Two cases of nutritional vitamin B12 deficiency, one case of pernicious anaemia, 6 cases of heterozygous thalassaemia and one case of heterozygous haemoglobin E were found among the anaemic Indian subjects. No cases of vitamin B12 deficiency anaemia, thalassaemia or haemoglobinopathy were detected among the Fijians. In 5 Indians and 7 Fijians the anaemia was associated with an underlying chronic disorder. This study emphasizes that in Fiji, as in other developing countries, nutritional anaemia is prevalent among asymptomatic subjects. Iron deficiency is by far the most common cause.


Unusual mycobacteria in 5 cases of opportunistic infections.

Five cases of infection due to an unusual mycobacterium are recorded, and the growth requirements and histological findings are discussed. On initial culture, these mycobacteria could be grown only on Lowenstein-Jensen medium containing ferric ammonium citrate, and the histology of the skin lesions was not always typical of mycobacterial disease.


Bioavailability study of diphtheria immunoglobulin (human).

A diptheria immunoglobulin has been prepared from selected blood donations to the Australian Red Cross Transfusion Services. A dose of 250 I.U. has been demonstrated to raise the titre of diptheria antitoxin in non-immune subjects to protective levels within 24 h, and these levels remain protective for at least 5 wk. Supplies are available from the various branches of the Australian Red Cross Transfusion Services.


Cystic chromomycosis of the skin.

Five patients with solitary cystic granulomatous lesions of the skin are described. Wood splinters and brown pigmented fungal elements were present in all 5 cases. "Cystic chromomycosis" is suggested as an appropriate title to avoid confusion with the cutaneous verrucous form, chromoblastomycosis.


Experimental granulomatous inflammation: I. Gross and light microscopical observations in freund adjuvant-sensitized Cavies following the injection of killed tubercle bacilli.

The tuberculous granuloma, induced by injection of microgram doses of killed mycobacteria into guinea pigs sensitized by injection of Freund adjuvant is immunologically mediated. Formation of the granuloma is preceded by development within 24 h of a lymphocyte-dominated mononuclear cell response typical of a delayed hypersensitivity (type IV immune response) reaction. About the sixth day, following a marked decrease in intensity of the cellular reaction, a nodule containing monocytes and macrophages develops at the injection site. With increasing numbers of monocytes and macrophages the nodule forms a non-caseating granuloma with giant cells but dominated by epithelioid cells and reaching a maximum size about 3 wk after injection. Thereafter the granuloma undergoes gradual demolition being replaced and surrounded by fibroblasts and collagen deposition. The very delayed nature of this immune response as well as its histological character appear clearly to separate it from classical cell-mediated and humoral immune responses. These facts justify the hypothesis of a third type of (usually protective) immune response characterized histologically by the development of an epithelioid cell granuloma and determined by the nature of the antigenic material and the reactivity of the host. The initial polymorphonuclear leucocyte reaction to injection of mycobacteria, being similar in sensitized and control animals, does not appear to be under immunological control.


Experimental granulomatous inflammation: II. Effect of injection of intact and disrupted killed tubercle bacilli into Freund adjuvant-sensitized Cavies.

The reaction of Freund adjuvant-immunized cavies to subsequent injection of Mycobacterium tuberculosis H37Ra is confirmed as an immunologically mediated phenomenon. Ultrasonic disruption of mycobacteria to be injected as "challenge" markedly increases the intensity of the consequent 24-48 h reaction and subsequent fibrosis in Freund adjuvant-sensitized cavies and has an apparently inhibiting effect on the extent of subsequent granuloma formation with marked reduction of the density of epithelioid cells. From this study, the 24-48 h reaction to injection of M. tuberculosis into sensitized animals appears clearly to be separable from subsequent granuloma formation depending upon the integrity or otherwise of the injected myocobacteria used as the challenge injection material.


The mast cell: III. Distribution and maturation in various organs of the young rat.

The changing population-density of mast cells in various organs was plotted for rats aged 1/2 to 90 days and correlated with histochemical studies on the stage of maturation of cells. Mast cells are present at birth in liver and spleen and are particularly associated with foci of haemopoiesis. In bone marrow mast cells are absent at birth but become progressively more numerous with increasing age of the animal. The association of mast cells firstly with foci of extramedullary haemopoiesis and secondly with medullary foci coupled with their detection in peripheral blood strongly suggests that mastopoiesis may be analogous with granulopoiesis. In thymus mast cells are usually associated with interlobular connective tissue stroma, but in the parenchyma they are found toward the medullary side of the cortico-medullary junction. Such a distribution suggests the possible origin of mast cells from lymphocyte or thymocyte. In other tissues examined mast cells are frequently associated with connective tissue stroma and blood vessels.


Mucins and carcinoid tumours.

Mucin was demonstrated in 11 of 16 carcinoid tumours of usual histological appearances. The mucin was characterized histochemically and shown to be similar to that which is produced in the gastrointestinal as well as the respiratory tract. This relative ubiquity of mucin in carinoid tumours has not hitherto been appreciated and more obviously "mixed" tumours have been regarded as rareties. The importance of these findings with respect to the neural crest theory of origin of enterochromaffin cells is discussed.