Leukopenia-induction capacity of 6-MP metallo-purine complexes in the rat.

Six-MP and its palladium and platinum complexes of this compound were administered intraperitoneally to 28 day old Sprague-Dawley rats in dosages of 15 mg/kg, 26.85 mg/kg, respectively for 21 days. The leukopenia induction capacity of 6-MP was greater at the end of day 7 while the 6-MP-Pd complex evidenced a more drastic leukocyte reduction at the end of day 21. The platinum complex was less toxic, as demonstrated by greater weight gain, while treatment with the palladium complex resulted in approximately the same weight gain as that observed in rats treated with pure 6-MP.


Bismuth toxicity in man - I. Bismuth blood and urine levels in patients after administration of a bismuth protein complex (Bicitropeptide).

In the course of a double-blind clinical trial of treatment involving a bismuth protein complex (Bicitropeptide), an antacid and placebo, blood samples (33 patients) and urine samples (43 patients) were collected for bismuth analysis from patients on bismuth therapy at the beginning of the trial (week 0) and at weeks 3 and 6. Base line blood (2 - 11 ng/l) and urine (2 - 29 ng/l) values were not zero and appeared to have reached "saturation" values in many cases after 3 weeks (Blood : 4 - 33 ng/l and Urine 60 - 600 ng/l). After 6 weeks, blood values were 5 - 20 ng/l and urine values 63 - 780 ng/l. It is concluded that these blood and urine levels are not associated with significant toxicity in man.


Influence of age on norepinephrine-induced vascular contractions as a function of extracellular calcium.

Age has been shown to produce various morphological and biochemical changes within the vasculature as well as changes in the responsiveness of the vasculature to various drugs. In the present study, the influences of age and extracellular calcium on norephinephrine-induced aortic contractions in male rats were examined. The aging process resulted in a decrease in sensitivity and responsiveness of rat aorta to norepinephrine-induced contractions. The progressive decrease in maximum contractile force (mg force/mg tissue) in response to norepinephrine as the result of aging occurred in all the different extracellular calcium concentrations used. In addition, the EC50 for norepinephrine in aortae from younger animals was directly related to the extracellular calcium concentration. As the animals, however, became progressively older (49-63 weeks) the aortic tissues became less sensitive and the calculated EC50 for norepinephrine was not altered by changes in the extracellular calcium concentration.


Synaptosomal dopamine from phenylalanine in brain: effects of some dopaminergic agents.

This report demonstrates for the first time that the synthesis and release responses to some dopaminergic agents may be elicited from that synaptosomal dopamine which may be formed by the hydroxylations of phenylalanine. Amphetamine and Cogentin increased the release of dopamine formed from 14C-phenylalanine in rat caudate nucleus synaptosomal preparation and concomitantly stimulated the synthesis. Amfonelic acid also caused a net release of that dopamine. Reserpine markedly increased the medium level of formed dopamine and at the same time inhibited the synthesis of the amine. Triton X-100 detergent almost completely inhibited the substrate uptake and the formation of dopamine. In conclusion, the results suggest that synaptosomal particles represent an unit capable of synthesizing dopamine from phenylalanine and that the synthesis from this precursor may be under the regulatory control of the particles to some degree.


Change in myocardial metabolism in man by a new stimulator of carbohydrate oxidation.

The effect on human myocardial metabolism of (S)-4-hydroxyphenylglycine, a substance which in animal experiments has been shown to stimulate carbohydrate metabolism mainly by activation of pyruvate dehydrogenase was studied in five healthy volunteers by coronary sinus catheterization. 90 min after i.v. injection of the drug myocardial extraction of glucose and lactate was doubled, myocardial oxidation of plasma free fatty acids (FFA) significantly reduced and myocardial RQ increased accordingly. This a pronounce shift towards carbohydrate oxidation was achieved with a dose which gave no side effects.


Effects of intraventricular beta-endorphin on GABA system in some areas of chick brain.

In chicks with cannulae chronically implanted into the III cerebral ventricle, the effects of a single dose (10 micrograms) of beta-endorphin on GABA and free glutamic acid content, GAD and GABA-T activities in the diencephalon, brain-stem and brain hemispheres were studied at the time of maximal behavioural stuporous state and analgesia. A significant decrease in GABA concentration both in the diencephalon and brain-stem, accompanied by a significant increase in GABA-T activity in the same areas, was shown to occur. No changes were observed in GAD activity and in glutamic acid content in the studied areas of the brain. In conclusion, present experiments suggest that some central effects of a beta-endorphin may be due to an interference with GABA-ergic transmission.


The role of altered tissue norepinephrine concentration in the hereditary obese-hyperglycemic syndrome of mice.

The purpose of this study was to determine if the elevated concentration of norepinephrine in the hypothalamus of the obese-hyperglycemic mouse plays a role in the development of this syndrome. We treated normal and obese mice with the monoamine oxidase inhibitors pargyline or clorgyline for 25 weeks. This resulted in significant inhibition of monoamine oxidase in their hypothalamus, cerebral cortex, kidney, heart and epididymal fat. There was a significant increase in the norepinephrine concentration of the hypothalamus of the normal mice and the cerebral cortex of the obese mice. The obese mice receiving clorgyline had an increase in plasma glucose (313 +/- 9 mg/dl). However, the increase in tissue norepinephrine concentration did not result in increased weight gain or alterations in organ weights in the mice. Thus, the elevated hypothalamic norepinephrine concentration in obese mice is probably not the cause of their obesity.


Dipyridamole levels in plasma of man and other species.

Measurements were made of the concentration of dipyridamole in the plasma of man, dogs, pigs, and pigeons at different times after oral administration of the drug. In dogs and in man, there was considerable variation in the plasma levels of the drug in different subjects. Pigs and pigeons always had much lower levels of the drug in plasma than did men and dogs given comparable doses. After intravenous injection of dipyridamole to pigs, a large proportion of the drug appeared to leave the plasma almost immediately; subsequently, the half-life of the drug remaining in the plasma was quite similar to that previously reported in man. The administration of aspirin with dipyridamole sometimes resulted in higher blood levels of the drug in dogs, man, and pigs, but the effects were small. The wide variations in plasma drug levels observed indicate that in future human or experimental trials designed to evaluate the antithrombotic effect of dipyridamole, plasma levels of the drug should be routinely monitored.


Comparative pharmacokinetics of theophylline and dyphylline following intravenous injection in rabbits.

The pharmacokinetics of theophylline and dyphylline in four rabbits were investigated following intravenous injection. Each rabbit received theophylline (10 mg/kg) first then dyphylline (25 mg/kg) two weeks afterwards as an intravenous bolus injection. The serum concentration-time data for both theophylline and dyphylline were best fitted to the two compartment open model. The half-lives of theophylline and dyphylline were 5.5 +/- 1.3 and 0.74 +/- 0.10 hr, respectively. The apparent volume of distribution (Vdbeta) and total body clearance (TBC) of dyphylline (Vdbeta = 1008 +/- 156 ml/kg; TBC = 942 +/- 118 ML/HR/KG)a = 1008 +/- 156 ml/kg; TBC = 942 +/- 118 ml/hr/kg) were much higher than those of theophylline (Vdbeta = 545 +/- 160 ml/kg; TBC = 69 +/- 10 ml/hr/kg). Thus both theophylline and dyphylline showed pronounced difference in their pharmacokinetic profile.


Monoamine oxidase and pyruvate oxidase inhibitory properties of some newer thiosemicarbazones and their anticonvulsant activity.

Seventeen 4-[3-(N-cyclohexylamino)propyl]-1-substituted-3-thiosemicarbazones were synthesized and evaluated for their ability to inhibit rat brain monoamine oxidase (MAO) and pyruvate oxidase in vitro. Anticonvulsant activity exhibited by these thiosemicarbazones (100 mg/kg,i.p.) against pentylenetetrazol-induced seizures ranged from 10-50%.


Effect of 1,25(OH)2D3 and 24,25(OH)2D3 on experimental rickets.

The vitamin D3 metabolite 1,25(OH)2D3 alone may not be able to reverse defective bone mineralization, while a combination with another metabolite, 24,25(OH)2D3 might be necessary to display the known effect of vitamin D on bone. Growing rachitic rats were treated with 25 ng vitamin D3/d, 10 ng 1,25(OH)2D3/d, 10 ng 24,25(OH)2D3/d, 5 ng 1,25(OH)2D3/d and 5 ng 24,25(OH)2D3/d in combination and 10 ng 1,25(OH)2D3/d and 10 ng 24,25(OH)2D3/d in combination. After 10 days of treatment the epiphyseal plate width of femura and the distance of tetracycline fluorescence bands were measured microscopically on undecalcified sections of the bone. The calcium content of femur epiphysis was measured by neutron activation analysis. Neither parameter showed on greater effect of the combination of 1,25(OH)2D3 and 24,25(OH)2D3 than of 1,25(OH)2D3 alone.


VI. Efforts at stabilization of rat liver phenylalanine hydroxylase.

The reaction of purified rat liver phenylalanine hydroxylase (PheH) with a variety of diazonium, monofunctional and bifunctional reagents or covalent coupling to several polyamino acid and dextran supports resulted in no improvement in stability.


14C-Thiourea binding in the rat lung.

Results of the present study demonstrate that in vitro covalent binding of radioactivity from the edematogenic agent [14C] thiourea to rat lung protein can occur under aerobic and anaerobic conditions. Binding of thiourea to lung protein is associated with a reduction in glutathione. The binding of [14C] from thiourea to lung protein is temperature dependent.


Distribution of succinyltrialanine p-nitroanilide hydrolase in human tissues.

The activity of succinyltrialanine p-nitroanilide hydrolase in human tissues was greatest in kidney (384.2 x 10(3) U/gram wet tissue) followed by spleen, small intestine, liver and pancreas.


[The endotracheal intubation of rabbits with xylazine and ketamine (author's transl)].

The intubation of rabbits is difficult. This is due to the anatomical structure of these animals. We intubated 40 New Zealand rabbits with a body weight of 2.0 to 2.8 kg with endotracheal tubes of an inner diameter 3.0 to 3.5 mm. Premedicating agents were Xylazine 1 ml/kg and Atropine 0.25 mg/kg. For induction of anaesthesia we used Ketamine in a dilution of 5 mg/ml and in dosages of 2.5 to 5.0 mg/kg. The intubation was performed with the aid of a Foregger childrens laryngoscope and a Wis-Hippel blade. For maintenance of anaesthesia we used a mixture of nitrous oxide/oxygen administered through a Kuhn system. In addition to this inhalation anesthetic Ketamine 1 to 2 mg was injected intermittently i.v. The recovery time with this method was extremely short in comparison to the use of intramuscular injections of Ketamine as monoanesthetic.


[Gastric blood flow in animals. I. Normal blood flow (author's transl)].

Total and regional gastric blood flow were measured in 15 dogs under control conditions (mean AOBP 100 mm Hg) using microspheres labelled with different isotopes (125J, 141Ce, 85Str, 46Sc) of 8 mu size. The mucosa in fundus and corpus showed significantly higher blood flow compared to the antrum. There was no difference in the muscular layer for either part of the stomach. It is concluded from these data that differences in regional blood flow in the unstimulated stomach of the dog are related to different energy-demands within the stomach.


Calcium secretion in the isolated perfused canine pancreas.

The quantitative relation of calcium and protein secretion was studied on the isolated perfused canine pancreas at different secretory states of hydrokinetic and ecbolic stimulation and various extracellular Ca++-concentrations. 1. Calcium and protein secretion are correlated at both ecbolic and hydrokinetic stimulation as well as by biological or synthetic secretion. 2. Enzyme-associated calcium was estimated at 35 nmol/mg protein and did not vary under differing stimulatory and secretory conditions. 3. During variable concentrations of synthetic secretin basal protein and calcium concentrations in the pancreatic juice show a hyperbolic relationship to the respective rates of fluid secretion. At flow rates beyond 3 ml/5 min the calcium concentrations asymptotically tend to 0.46 mEq/l while protein concentrations nearly decrease to zero. Moreover, the y-intercept of the regressionline correlating the calcium and protein concentrations gives with 0.48 mEq/l Ca++ additional evidence of the existence and magnitude of an enzyme-independent calcium fraction, which seems to remain constant over the whole range of secretory rates. 4. The omission of perfusate calcium does not abolish the calcium-protein correlation either at hydrokinetic or at ecbolic stimulation, but diminishes the enzyme-independent calcium fraction. 5. Enhancing perfusate Ca++-concentrations augments calcium output byt fails in stimulating enzyme secretion. It is concluded that at exclusively hydrokinetic stimulation basal secreted protein with a definite amount of chelated calcium is diluted by variable rates of pancreatic juice containing enzyme independent Ca++ at a constant concentration. During different secretory states of hydrokinetic or ecbolic stimulation the respective proportions of enzyme associated and independent calcium vary, and thus determine changes in the calcium-protein ratios. Extracellular calcium can only influence the non-protein-bound calcium fraction of the pancreatic juice presumably by diffusion from the extracellular fluid through the ductal epithelium rather than by an active secretory mechanism.


Effects of acute hemodialysis-induced changes in sodium balance on the renin-angiotensin system in renovascular and spontaneously hypertensive rats.

In two-kidney Goldblatt hypertensive, spontaneously hypertensive, and normotensive control rats the activity of the renin-angiotensin system was tested during variation of sodium balance. Acute, exactly calculable and selective changes of total body sodium were achieved by hemodialyzing the conscious rats using dialysate with either high or low sodium content. The activity of the RAS was evaluated by blood pressure response to AT II blockade (saralasin bolus injection; 25 micrograms/kg b.w., i.v.) and the plasma-renin activity. During sodium depletion blood pressure maintenance became renin-dependent; sodium loading caused a decrease of renin-angiotensin activity in renovascular hypertension. A weak direct correlation between deprssor response to saralasin and the PRA could be established in the different sodium-depleted and -loaded states.


A hitherto unreported paramyxovirus of turkeys.

A newly isolated avian virus is described which was obtained from a flock of laying turkey hens with respiratory disease and accompanying egg production drop. Characterisation of the virus indicated it to be of the paramyxovirus group and to be related through antigenic crossing with Newcastle disease virus. Examination of turkey sera from five separate flocks indicated natural infection with the paramyxovirus to be relatively widespread. Experimental infection of turkeys produced only mild respiratory disease.


In vitro response of lymphocytes of normal and ovine squamous cell carcinoma-bearing sheep to phytomitogens and tumour extracts.

A comparison was made of the blastogenic responses of peripheral lymphocytes (BRPL) of normal sheep with those of sheep bearing ovine squamous cell carcinoma (OSCC). In normal tumour-free sheep, BRPL to phytomitogens were found to vary in different age groups, and BRPL to OSCC extracts were found to become significantly elevated in sheep over one year old. In tumour-bearing mature sheep, BRPL to phytomitogens and to OSCC extracts decreased significantly with increasing maturity of tumours. The results are interpreted to show that increasing tumour volume, due to natural growth or enhancement, associates with increasing suppression of cell-mediated responses, and that such suppression may be a cause and a result of increased tumour volume.


Effect of removal of ovine squamous cell carcinoma on peripheral lymphocyte stimulation by tumour extracts and phytohaemagglutinin.

Mock-operation of normal tumour-free sheep was not associated with significant changes in blastogenic responses of peripheral lymphocytes (BRPL) to phytohaemagglutinin (PHA-P) or tumour extracts (TA). In age-matched tumour-bearing sheep, tumour removal was associated with a significant prolonged increase in BRPL to PHA-P and TA about three weeks after operation. This increase was significantly greater in sheep with mature than with early tumours. No increase in BRPL occurred in sheep with secondary lesions. Challenge of tumour-removed sheep with TA 15 weeks after operation was associated with a significant anamnestic-type short-term surge in BRPL to PHA-P and TA, which was significantly greater in sheep which had previously borne advanced tumours. Mock-operated normal mature sheep challenged with TA also showed a lowgrade anamnestic-type response of BRPL to PHA-P and TA. The results are discussed in terms of the mechanisms of BRPL suppression, and of specific reactions in normal sheep.


Effect of cyclophosphamide on tumour growth and cell-mediated immunity in sheep with ovine squamous cell carcinoma.

Cyclophosphamide (CY) is shown to associate with partial or complete regression of ovine squamous cell carcinoma (OSCC), the rate of regression varying directly with CY dosage and inversely with maturity of tumour at the start of therapy. CY treatment given coincidental with injection of tumour extracts (TA) completely neutralised the tumour enhancement effects regularly associated with TA injections, and caused tumour regression comparable to that seen in sheep treated with CY alone. In discussion of the results, which incorporate parallel studies on cell-mediated responses, it is suggested that immunosuppression during tumour growth is due to formation of B suppressor lymphocytes and that CY treatment of OSCC may exert beneficial effects through its immunosuppressive action on such lymphocytes as much as its direct cytotoxic action on tumour cells.


Suppression of blastogenic response of peripheral lymphocytes by serum from ovine squamous cell carcinoma bearing sheep.

Sera from sheep with ovine squamous cell carcinoma are shown to contain a factor which nonspecifically inhibits blastogenesis of T lymphocytes. This blastogenic inhibitor is stable at 56 degrees C for 30 min, passes a 430 nm filter, and increases in concentration (or efficiency) with increasing tumour volume. Tumour removal is associated with effective circulatory disappearance of the inhibitor and coincides with recovery of cell-mediated responses within five weeks. The inhibitor adsorbs readily to leucocyte populations from normal and tumour removed sheep. It is suggested that the blastogenic inhibitor is mediated by the tumour to cause immunosuppression through an undetermined B lymphocyte suppressor pathway, and acts as a mechanism protecting the tumour from immune rejection by T lymphocytes.


Designation of aerotolerant Campylobacter-like organisms from porcine and bovine abortions to the genus Campylobacter.

Unusual helically-curved bacteria isolated from porcine and bovine abortions measured 1.8 microns long and 0.4 microns wide, failed to produce poly beta-hydroxybutyric acid granules and had DNA base compositions within the span 29--34 moles per cent. From this evidence, it was concluded that these organisms are members of the genus Campylobacter.


The influence of environmental temperature on the rate of development of Ascaris suum eggs in Great Britain.

The rate of development of Ascaris suum eggs was recorded during 18 months in England. Every second or third week unembryonated eggs were placed in an unheated animal house and their development was observed at weekly intervals. Eggs underwent no development during November to May. Embryonation was most rapid during June, July and August. The shortest time for eggs to reach the infective stage was two weeks in 1976 and four weeks in 1977. A relationship was apparent between the rate of development of eggs and the seasonal occurrence of pigs in chronic focal interstitial hepatitis, a condition associated with infection by A suum larvae.


The passive transfer of immunity to Taenia ovis in lambs via colostrum.

Colostrum from ewes that had been repeatedly exposed to cestode infection, whether or not their immunity was boosted by vaccination with Taenia ovis, transferred a strong immunity to the lambs. Susceptible ewes, not recently exposed to tapeworm eggs, gave no protection to their lambs via the colostrum. There was no evidence that colostrum-deprived lambs were more susceptible to infection with T ovis than lambs that received colostrum from non-immune ewes. Colostrum from naturally immune vaccinated ewes gave good protection to lambs for up to six weeks but thereafter the effect was variable. The immunity that developed in susceptible ewes after vaccination with activated embryos was not passed on to the lambs via the colostrum.


The effects of irradiation on Babesia maintained in vitro.

Blood infected with Babesia radhaini, B major or B divergens was irradiated to different absorbed doses between 0 and 120 krad, and then maintained in vitro in the presence of 3H hypoxanthine for 24 h. The effects of irradiation were measured by the ability of the parasites to incorporate 3h hypoxanthine and, in the case of B rodhaini, by the ability of the parasites to infect mice. B major and B divergens were slightly more radio-resistant than B rodhaini, but all showed a progressive fall in ability to incorporate 3H hypoxanthine with increasing doses of irradiation, except at low doses of irradiation when there was increased uptake of 3H hypoxanthine. In the case of B rodhaini there was close correlation between the ability of the parasites to incorporate 3H hypoxanthine and their infectivity for mice. Both types of activity were abolished at doses of 40 krad and above.


The effect of route of infection on acquired resistance to Fasciola hepatica in the rat and sheep.

Rats and sheep were infected with Fasciola hepatica by subcutaneous, intramuscular or oral (intraruminal--sheep) inoculation with encysted metacercariae and the development of flukes from these primary infections assessed. Additional rats and sheep similarly infected were challenged with encysted metacercariae orally (rats), or intraruminally (sheep) to assess the level of acquired resistance generated by previous infection by each of the three routes of administration. In both rats and sheep 0--5 per cent, 0--5 per cent and 20--25 per cent of metacercariae given by the subcutaneous, intramuscular or oral (intraruminal--sheep) routes were recovered as flukes in the liver four and 12 weeks after infection of rats, or 17 weeks after infection of sheep. Primary infection of rats with F hepatica by each of the three routes generated strong protection against oral challenge whereas no protection was generated in sheep, irrespective of route of infection.


Cross-protection between the cysts of Echinococcus granulosus, Taenia hydatigena and T ovis in lambs.

Lambs were infected orally at 14 weeks of age with either Taenia hydatigena, T ovis or Echinococcus granulosus eggs. To induce high levels of resistance to oral reinfection, they were then injected intramuscularly with eggs of the homologous species four weeks and eight weeks later. The degree of immunity was then tested by oral challenge with eggs from either the homologous or an heterologous species. Autopsy results indicated that prior infection with an homologous species induced a very high degree of immunity to challenge infection. Prior infection with all combinations of heterologous species resulted in a lesser degree of immunity, which appeared to have acted on the establishment phase of development and did not influence cyst survival.


A mouse model of Pasteurella haemolytica infection and its use in assessment of the efficacy of P haemolytica vaccines.

A method for infecting mice with Pasteurella haemolytica is described. Mice were inoculated intraperitoneally with P haemolytica incorporated in gastric mucin, killed at various time intervals thereafter and viable counts of bacteria were performed on liver suspensions. P haemolytica grew at an exponential rate in the livers of normal mice. Mice vaccinated against P haemolytica A1 were protected against homologous challenge and viable counts decreased rapidly in their livers. Mice given trivalent P haemolytica vaccine (types A1, A2 and A6) were protected against challenge with P haemolytica types A1 and A6, but were not protected against challenge with types A2 and A9. These results correlate with findings in sheep.


In vitro sensitivities to antimicrobial drugs of ureaplasmas isolated from the bovine respiratory tract, genital tract and eye.

The sensitivity to 18 antimicrobial drugs was examined for 66 strains of Ureaplasma sp isolated from respiratory tracts of calves suffering from enzootic pneumonia, urinary tracts of bulls and eyes of cows suffering from infectious bovine kerato-conjunctivitis. Furamizole, tiamulin fumarate, erythromycin lactobionate, malidomycin C, doxycycline hydrochloride, kitasamycin tartrate, tylosin tartrate, T-2636C, tetracycline hydrochloride, oxytetracycline hydrochloride, chlortetracycline hydrochloride, oleandomycin phosphate, furazolidone, spiramycin adipate, chloramphenicol and thiophenicol showed strong inhibiting activity on all the test strains. Among them, furamizole, tiamulin fumarate and erythromycin lactobionate were most active. Kanamycin sulphate showed weak activity on all the strains tested. The differences in origin of the test strains did not affect their sensitivity to any of the drugs.


A microtitre technique for the assay of malignant catarrhal fever virus and neutralising antibody.

A microtitre technique for the quantal assay of a cell-free strain of malignant catarrhal fever virus was developed, using serially passaged bovine embryonic kidney cells. End-points were determined after 12 days' incubation and the mean titre recorded for a single virus stock stored at -70 degrees C over a six-month period was 10(5.5) +/- 0.2 (SD). In neutralisation tests serum/virus mixtures were best held at 37 degrees C for 1 h in microtitre trays before the addition of cells; assays were highly reproducible, figures of 10(1.5) +/- 0.2 being obtained for a single reference serum.


Pathogenicity of some Mycoplasma and Acholeplasma species in the lungs of gnotobiotic calves.

Cloned cultures of 16 strains, representing nine different species of Mycoplasma and Acholeplasma, were inoculated intratracheally into gnotobiotic calves. Strains of M bovirhinis, M canadense, M verecundum, A axanthum and A modicum did not produce visible pneumonic lesions and were not reisolated from the lungs. Strains of M alkalescens and M arginini colonised the lower respiratory tract but failed to produce visible pneumonia. M bovigenitalium (strain M991/70) and M dispar (strain Gri226) both colonised the respiratory tract and induced pneumonic lesions estimated to involve up to 8 per cent (M bovigenitalium) and 17 per cent (M dispar) of the lung. Histologically M bovigenitalium produced a cuffing pneumonia and M dispar produced a interstitial alveolitis.


Assessment of the attenuation produced by irradiation of Fasciola gigantica metacercariae in hamsters.

Severe pathological changes were seen in hamsters given metacercariae of Fasciola gigantica irradiated at doses below 4 krads. No adult flukes were recovered from hamsters given metacercariae irradiated at doses above 4 krads and little hepatic damage was caused. It was not ascertained whether resistance resulted following these latter infections.


Phosphorus content of bovine rib: influence of earlier biopsy of the same rib.

Serial sampling of bovine rib is undertaken experimentally to monitor changes in the degree of skeletal mineralisation. The validity of this approach depends on the assumption that the previous sampling of a bone does not influence the composition of a sample obtained subsequently. To test this, the effect of a prior biopsy sampling on phosphorus content of the remaining bone was determined at various times after the initial sampling. A preliminary biopsy sample was taken with a 1.5 cm diameter trephine from the left 12th rib of 40 cattle; experimental samples were taken from the same rib of 10 of the cattle at three, six, nine and 12 months later, for comparison with similar samples taken concurrently from the right 12th rib. The phosphorus content of the second left rib was significantly lower than that of the right (control) rib at the three-month interval, particularly where the sampling site was ventral, rather than dorsal, to the site from which the initial biopsy was obtained. No effects of previous biopsy sampling were observed after six, nine or 12 months.


Observations on the egg output resulting from continuous low level infections with Ostertagia circumcincta in lambs.

Faecal egg counts were determined twice weekly for two groups of four-month-old worm free cross Suffolk lambs experimentally infected with 100 and 320 Ostertagia circumcincta larvae, five times per week for 20 weeks. The group mean egg count in both groups rose to a maximum of approximately 500 eggs per gram during weeks 12 to 14 and had fallen to less than half of that value at slaughter. There was no statistical difference in egg output between these two groups or between them and a comparable group of lambs receiving 4000 Ostertagia circumcincta larvae per day. No significant changes in live weight gain or serum pepsinogen levels were observed in the lambs given 100 and 320 larvae per day.


Evaluation of oxfendazole against natural infections of gastrointestinal nematodes in Nigerian calves.

The efficacy of oxfendazole was tested in naturally infected Sokoto-Gudali calves at a dosage of 2.8 mg per kg. At this dosage level, oxfendazole showed 100 per cent efficacy against adult and immature forms of Haemonchus spp, Trichostrongylus spp, Bunostomum phlebotomum and Oesophagostomum radiatum. Although efficacy of 100 per cent was recorded for the adult form of Cooperia spp, only 48 per cent reduction was recorded for its immature stages. Similarly, a percentage reduction of 75 was recorded for adult Trichuris spp. No larvae hatched out of a seven-day vermiculite culture of faeces collected from the treated calves 24 h after treatment.


A serological comparison of Pasteurella haemolytica vaccines containing different adjuvants.

Five adjuvants were compared for their ability to enhance the serological response of sheep to capsule extract of Pasteurella haemolytica biotype A serotype 6. Vaccines of this antigen were inoculated with incomplete Freund's adjuvant, complete Freund's adjuvant, incomplete Freund's adjuvant containing a water soluble extract of Mycobacterium tuberculosis, aluminium hydroxide gel or a combination of aluminium hydroxide gel and incomplete Freund's adjuvant. This latter vaccine induced significantly higher titres of antibody as measured by an indirect haemagglutination test than did any of the other vaccines. The aluminium hydroxide gel alone was shown to be the poorest adjuvant. The local reactions at the sites of inoculations produced by the aluminium hydroxide gel in incomplete Freund's adjuvant vaccine were not severe and were not detectable beyond one month after vaccination in the majority of the sheep.


Indices of stress in housed experimental sheep.

Six trained sheep were used in isotope dilution studies to determine the relations between glucose and lactate metabolism. The animals were judged by their behaviour and by their arterialplasma glucose and cortisol concentrations to be unstressed before and during each experiment. In each animal, however, the concentration of lactate in an arterial plasma sample taken immediately before an experiment was greater than the mean arterial plasma lactate concentration found during the course of the experiment. This increase in the concentration of lactate may be a sensitive index of apprehension in sheep which are well accustomed to being handled and which by other criteria appear to be unstressed.


Lack of functional recovery from spinal cord trauma following dimethylsulphoxide and epsilon amino caproic acid therapy in dogs.

The spinal cords of 20 normal dogs were exposed via dorsal laminectomies at L1 and damaged with a direct impact force of 440 g cm. One hour later treatment with dimethylsulphoxide (DMSO) was started on 10 dogs and with epsilon amino caproic acid (EACA) on the other 10 dogs. Administration of the DMSO ceased at 41 h after trauma and EACA at 49 h. The results showed that neither drug had a significant beneficial effect on the functional recovery of the spinal cords, when compared to a control group of similarly traumatised dogs.


The effect of nitroscanate tablets of Echinococcus granulosus and Taenia hydatigena infections in dogs.

Tablets of micronised nitroscanate (nominal particle size 2--3 microns) were given to a total of 190 dogs that had been experimentally infected with either Echinococcus granulosus or Taenia hydatigena. The efficiency of the drug in tablet form in freeing dogs from tapeworms, was investigated. The dose rate at which 50 per cent of normally fed dogs can be expected to be freed from E granulosus was found to be 89 mg/kg (95 per cent confidence limits 55 mg/kg to 140 mg/kg). The 90 per cent effective dose rate was not determined within the range 32 mg/kg to 250 mg/kg. The dose rate at which 90 per cent of normally fed dogs can be expected to be freed from T hydatigena was 37 mg/kg (95 per cent confidence limits 23 mg/kg to 60 mg/kg).


Investigation of Haemonchus contortus infections in sheep. Comparison of irradiated larvae and transfer factor treatment.

A comparison is made between the resistance conferred to Haemonchus contortus challenge by irradiated larval treatment and transfer factor (TF) treatment in four-month-old lambs and seven-month-old lambs. As in previous investigations the irradiated larval treatment failed to confer resistance to the four-month-old lambs challenged with 10,000 third stage larvae while similar irradiated larval treatment in seven-month-old lambs reduced the worm burdens by 40 per cent compared to controls. The TF treatment produced a 34 per cent reduction in the challenge infection in the four-month-old lambs and a 45 per cent reduction in the seven-month-old lambs compared to the control lambs. It is concluded that TF activity operates independently of immune competence.


Comparative red cell metabolism in the domestic dog and the dingo.

A comparative study of the red cell characters, glycolytic enzymes and intermediates was made in the domestic dog and the dingo. No significant differences were found in any of the parameters studied except the enzyme level of NADH-MR which was significantly lower in dingoes (P less than 0.05).


Solanum torvum as a causative agent of enzootic calcinosis in Papua, New Guinea.

Inclusion of dried powdered leaves of Solanum torvum Swartz (collected in Papua, New Guinea) in the diet of rats induced hypercalcaemai rapidly and hyperphosphataemia more slowly; soft tissue calcification was most evident in the kidney and lung. Solanum torvum may be a causative agent of enzootic calcinosis in cattle in Papua, New Guinea.


The half-life of glutamate dehydrogenase in plasma of dry and lactating dairy cows.

The clearance of glutamate dehydrogenase from plasma was measured weekly for three weeks in three dry and three lactating cows. The clearance was exponential with a mean clearance constant of 0.0488/j and means (+/- SE) half-life of 14.2 (+/- 0.77) h. There were variations among cows and among measurements in the same cow but there was no difference between the mean half-lives of GDH in lactating and dry cows. Because of the long half-life the small variations among individual cows are unlikely to affect the interpretation of increased plasma GDH activity.


Effect of orciprenaline on hypoxic pulmonary vasoconstriction in dogs.

The effect of orciprenaline on hypoxic pulmonary vasoconstriction and arterial oxygen tension (PaO2) was studied in 8 dogs by measuring the redistribution of blood flow in response to unilateral alveolar hypoxia. The distribution of blood flow was recorded continuously by measuring the radioactivity of the mixed expired gas from each lung during the continuous intravenous infusion of xenon-133. The hypoxic vasoconstrictor response was significantly depressed by an infusion of 1.0 micrograms/kg/min of orciprenaline but not by a dose of 0.1 micrograms/kg/min. PaO2 during unilateral hypoxia was significantly lower during the infusion of the high dose of orciprenaline than it was in the control periods before or after the infusion. A bolus dose of 0.5 mg significantly increased blood flow to a lung with established hypoxic vasoconstriction and also caused a significant reduction in PaO2. Since these effects were produced in the absence of airway pressure or pulmonary vascular pressure changes, it is concluded that orciprenaline may depress the hypoxic pulmonary vasoconstrictor response in dogs.


Observations on regional ventilation and perfusion in kyphoscoliosis.

Studies of regional ventilation and perfusion have been made in 10 patients with kyphoscoliosis. In 7 of the 10 patients ventilation was more severely impaired in the region of the maximum convexity than in the opposite lung. Perfusion was not impaired to the same degree. The resulting locally diminished ventilation-perfusion ratios may account for the hypoxemia and increased PA-aO2 gradient seen in patients with kyphoscoliosis. It is suggested that the local distortion of the chest wall, with the splayed out ribs, may account for the local change in lung mechanics.


Pulmonary hypertension in rats with papain emphysema.

Lung emphysema was produced in 80 rats by tracheal chronic constriction and repeated instillations of 0.1% papain solution intratracheally. 17 animals survived 90 days of the experiment; a complete examination was performed on 14 experimental and 11 control animals. 9 rats of the experimental group had pulmonary hypertension, in 5 other rats the pulmonary arterial blood pressure was not different from that in the controls. The experimental animals with hypertension had arterial hypoxemia and increased weight of the right ventricle. All experimental rats (with and without pulmonary hypertension) had increased air spaces in the lung and thickened media of distal pulmonary vessels. After breathing 100% oxygen for 20 min, the pulmonary arterial blood pressure in animals with pulmonary hypertension decreased but did not reach the control level. The decrease of the mean pulmonary arterial blood pressure after oxygen breathing correlated well with the initial level of pulmonary hypertension and with the degree of hypoxemia during air breathing.


[Correlations between the changes in the affinity of hemoglobin of oxygen and the anaerobic metabolism during muscular exercise in 20 silicotic patients (author's transl)].

This study investigated the changes in hemoglobin affinity for oxygen -- P50 standard [P50 (7.40)]; P50 in vivo (P50 IV), and 2,3-diphosphoglycerate concentration (2,3-DPG) -- and the anaerobic metabolism during a short muscular exercise in 20 silicotic patients. P50 (7.40) and 2,3-DPG remained unchanged at the end of the exercise but P50 IV increased significantly. A negative correlation was found between the increase in the arterial lactates and the increase in P50 IV. Such a shift to the right of the oxyhemoglobin dissociation curve probably improves the tissular oxygenation and can be regarded as a compensatory mechanism in patients with pulmonary impairment during exercise.


Normal values of transfer factor and transfer coefficients in healthy males and females.

A population study was performed to obtain local normal values of the transfer factor for a respiratory laboratory providing a routine hospital service. Statistical analysis of the results obtained showed similar results to those of previous investigators for the transfer factor and alveolar volume. The transfer factor was found to be dependent on height, age and sex, while the alveolar volume depended only upon height and sex. Unlike previous investigations, however, the present study showed that the transfer coefficient was the same for women as for men and was related solely to age.


Pulmonary function in rabbits with BCG-induced lung disease.

This study was performed to determine whether the lung histological changes which occur in rabbits following intravenous injection of killed Bacilli Calmette-Guérin (BCG) are accompanied by measurable changes in pulmonary function. We measured pulmonary function in New Zealand white rabbits 3 weeks after intravenous injection of BCG and in normal rabbits. After a tracheostomy and carotid artery catheterization was performed, each anesthetized rabbit was placed in a body plethysmograph for pulmonary function testing. Following the measurements, the lungs were removed for weighing and histological evaluation. In the BCG-treated rabbits, the lung weight/body weight ratios were 152% greater, the pulmonary resistance was 104% higher, dynamic compliance was 45% lower, minute ventilation was 28% greater, and the delta AaPO2 gradient was 13 torr higher than in the normal control rabbits. Histological evaluation of the BCG-treated animals revealed diffuse pulmonary involvement with non-caseating granulomas.


Anatomically localised re-expansion pulmonary oedema following pneumothorax drainage. Case report and literature review.

We describe the 15th recorded case of ipsilateral pulmonary oedema following re-expansion of a pneumothorax. In contrast to previously described cases, the oedema was exclusively confined to the right middle and lower lobes, with complete sparing of the right upper lobe. This strict anatomical localisation can best be explained by the presence of a discrete temporary obstruction of the bronchus intermedius during the critical period of rapid pneumothorax re-expansion. We believe that this case lends strong support to previous contentions that bronchial occlusion plays a crucial role in the genesis of re-expansion oedema.


Obstructive lung disease from acute sulfur dioxide exposure.

A previously healthy, non-smoking young man is presented who was briefly exposed to a high concentration of sulfur dioxide. An immediate episode of pulmonary edema was followed by a silent interval with subsequent development of a severe, irreversible obstructive syndrome. This history, together with radiographs showing hyperinflation and sequential physiologic studies indicative of obstruction without bronchospasm and without loss of parenchyma suggest bronchiolitis obliterans as the causative lesion. The literature concerning this syndrome and its relationship to toxic inhalation is briefly reviewed.


Lung mechanics during spontaneous ventilation in premature and fullterm rabbit neonates.

Rabbit neonates were tracheotomized on day 27--30 of gestation, and lung mechanics during spontaneous ventilation was registered with a fluid-filled esophagus catheter for pressure recording and a pneumotachograph connected to the tracheal cannula via a Fleisch tube. The first breath of all neonates had a very long inspiratory phase (less than or equal to 1.12 sec), with insufflation pressures amounting to 42 cm H2O in the mature animals. The expiration phase of the first breath was usually 'passive', i.e. there was no positive expiratory esophagus pressure. In animals delivered on day 27--28 there was, as a rule, no difference between inspiratory and expiratory tidal volume during the first few breaths, whereas such difference was regularly registered in mature animals; this phenomenon probably corresponds to the establishment of FRC. Dynamic lung compliance increased with both gestational and postnatal age, up to 60 min after delivery. Shortly after birth, pulmonary resistance was higher in immature animals than in fullterm ones, but at later intervals, there was no difference between survivors of various gestational age.


Distal airway responses to changes in oxygen and carbon dioxide tensions.

The reactivity of subpleural strips of lung parenchyma reflects primarily the tone of the smooth muscle in the peripheral airways. Lung strips taken from ten dogs relaxed when the oxygen level in the gas bubbling through the bath was reduced from 95% to 18%. Subsequent hypocapnia (carbon dioxide reduced from 5% to 0%) induced contraction of all strips. These changes were reversed when the oxygen or carbon dioxide tensions were restored to control levels. Addition of either indomethacin or meclofenamate, two chemically dissimilar inhibitors of prostaglandin synthetase, reduced the resting tone in each of six strips and prevented the hyperoxic constriction which was observed in paired, control strips (oxygen increased from 18% to 95%). Blockers of histamine and catecholamines had no effect. The reactivity of the distal airways to changes in gas tension provides a mechanism by which ventilation and perfusion can be matched. The action of indomethacin and meclofenamate indicates that a prostaglandin-like substance may be involved in the maintenance of distal airway tone and in the constriction produced by hyperoxia. The addition of prostaglandin F2 alpha or E1, after meclofenamate, in a further nine pairs of strips did not restore the hyperoxic constriction. This suggests that prostaglandins may mediate, rather than merely facilitate, the response.


The effect of pulmonary edema on gas trapping in excised rat lungs.

The object of this study was to determine how pulmonary edema affects the volume of gas trapped in excised lungs as they are slowly ventilated. In this study trapped gas is defined as the volume of gas that cannot be removed from the lungs with a negative transpulmonary pressure of -5 cm H2O (Frazer and Weber, 1976). Experimental pulmonary edema was produced by ventilating rats using high inspiratory positive pressure breathing (HIPPB) as described by Webb and Tierney (1974). The amount of gas trapped in both edematous and control lungs was then compared as the lungs were inflated-deflated under identical conditions in 6 different 4 cycle sequences. During each sequence the lungs were deflated to an end expiratory pressure of either +6, +4, +3, +2, 0.0, or -5 cm H2O. It was found, that gas became trapped at more positive values of end expiratory pressure in lungs having pulmonary edema than in control lungs. These results were interpreted as evidence that the airways close sooner, at more positive transpulmonary pressures, in edematous lungs than in control lungs.


Relative decay rate of inspiratory muscle pressure and breath timing in man.

The decay rate of inspiratory muscle pressure (PmusI) was measured during the postinspiratory period of zero flow (TEz) occurring under a discontinuous inspiratory elastic load with the following tests, (a) Voluntary changed breathing frequency (f) at similar end-inspiratory muscle pressure (PmuseI), (b) as above plus dead space, hence greater PmuseI, (c) breathing spontaneously through a dead space or during exercise to obtain different f at similar PmuseI. The decay rate of PmusI relative to PmuseI (RDRI) at increased f was similar to the corresponding relative decay rate of transdiaphragmatic pressure. Hence, the increase of f did not elicit phasic activity of expiratory muscles during TEz. RDRI increased proportionally to f: i.e. for a given f, the decay rate of PmusI was proportional to PmuseI. RDRI increased hyperbolically with decrease of expiratory time and was not directly related to inspiratory time. In each subject these relationships were unique for different tests. These findings show that increase of Pmusel alone does not shorten the persistence of PmusI during expiration, whereas a timing factor, by increasing RDRI, allows shortening of expiration without the intervention of expiratory muscles.


Thoracic dorsal rhizotomy in the anesthetized cat: maintenance of eupnic breathing.

In order to assess the level of participation of thoracic afferents in the determination of the eupnic breathing pattern, thoracic dorsal rhizotomies from T1 through T13 were performed in cats anesthetized with alpha-chloralose or sodium pentobarbital, with or without intact vagi. While recording several respiratory parameters, no consistent changes in the spontaneous breathing pattern could be demonstrated either 10--20 min or 90--100 min following disruption of thoracic afferent input. Thus, respiratory frequency, tidal volume and total ventilation were unaffected by rhizotomy. Inspiratory (TI) and expiratory (TE) durations and TI/TE ratios remained constant. Tracheal air flows during inspiration and expiration and intrapleural pressure were not altered. Finally, end-expiratory %CO2 and %O2 did not change after section of the thoracic dorsal roots. Only arterial blood pressure was found to fall as a function of time into the experiment. Since the results were identical in vagotomized and in vagi intact preparations, thoracic reflexes were not being masked by vagal dominance in eupnea. Rather, thoracic afferents, including intercostal muscle spindle afferents, appear to be ineffective in shaping the pattern of quiet breathing in anesthetized cats. This is unlike situations of loaded or stressed breathing where these afferents assume a more active role in the modulation of rate and depth mechanisms.


Mechanism of the isoproterenol hyperpnea in the cat.

To clarify the role of peripheral chemoreceptors in the abrupt hyperpnea induced by isoproterenol injection, we measured, in anesthetized cats, the time course of VE, PETCO2, H.R. and B.P. following i.v. bolus injection of 0.5--2 microgram isoproterenol before and after bilateral section of the carotid sinus (csx), aortic (ax) and vagus (vx) nerves. We compared the hyperpneic response of isoproterenol to that of 100 microgram injections of NaCN (CN), a drug known to stimulate peripheral chemoreceptors, during air and 100% O2 breathing. The ventilatory response to isoproterenol persisted for over 90 s, whereas the CN response lasted only 30 s. Also 100% O2 markedly attenuated the CN hyperpnea but had little effect on the ventilatory response to isoproterenol. The maximum increase in ventilation in response to isoproterenol was reduced by approximately 1/3 by csx, 1/2 by combined csx and ax, and 2/3 by combined csx, ax and vx. The residual hyperpnea after csx, ax, and vs is delayed in time and lagged behind the increase in PETCO2. It is concluded that the peripheral chemoreceptors and possibly vagal afferents play a major role in the hyperpnea caused by isoproterenol, but in their absence central chemoreceptors respond to the increased PaCO2 induced by the elevated cardiac output to stimulate ventilation.


Anaerobic energy metabolism during severe hypoxia in the lungless salamander Desmognathus fuscus (Plethodontidae).

In the lungless salamander Desmognathus fuscus, mean body weight 4.5 g, the changes in total body concentration of adenosine triphosphate (ATP), creatine phosphate (CP) and lactate (LA) were measured during exposure to a severely hypoxic atmosphere (PO2 = 25 Torr) for 48 h at 13 degrees C. ATP and CP decreased, reaching a minimum at 3 h of exposure, and LA increased, attaining maximum values after 12 to 24 h of hypoxia. Thereafter recovery was observed and control values of ATP, CP and LA were reached after 48 h of sustained hypoxia. This behavior is attributed to a biochemical adjustment to hypoxia of the metabolic machinery which leads to normalization of chemical energy stores in spite of O2 uptake being persistently reduced to 30% of its normoxic level. The anaerobic energy yield derived from splitting of ATP and CP and from LA formation corresponded to about 2/3 of the oxidative energy deficit during the first 3 h of hypoxia. Thereafter anaerobic mechanisms were responsible for insignificant contributions to the energy balance.


Experimental surgery of the nose, anteroposterior changes of the mucosa on altering the air-flow.

In 20 rabbits one nostril was surgically closed and the mucous membrane studied 4--90 days after the operation. The density of goblet cells was determined anteriorly and posteriorly on whole mounts, epithelial changes on serial sections from 4 different localities on the septum. Anteriorly on the open side damage to the cilia initiated epithelial processes of repair, viz. hyperplasia of basal cells, transformation of these cells into columnar cells, and differentiation into mucous and ciliated cells. On the 16th day the epithelium was again columnar and ciliated. As a consequence of continued trauma new cycles were initiated, but not even after 90 days was there any squamous epithelium. In the middle and posteriorly on the septum no changes were demonstrated, indicating a marked, but gradual decrease in the anteroposterior direction of the influence by the air-flow upon the mucosa. On the closed side there was increased secretory activity and normalization of the epithelium which was changed most anteriorly in normal rabbits.


Use of intranasal pledgets for localization of cerebrospinal fluid rhinorrhea. (notes on technique).

The site of cerebrospinal fluid leaks from the nose can be localized by means of radioactive substances. The technical aspects are important for success.


Long-term results of Vidian neurectomy.

A number of publications appeared in the sixties claiming success of Vidian neurectomy in patients with chronic vasomotor rhinitis and recurrent polyposis nasi. During the period from October 1970 through February 1975, a total of 27 Vidian neurectomies was performed in 14 patients (seven males and seven females). Two groups of seven patients each were operated on; seven patients with chronic vasomotor rhinitis and seven patients with recurrent polyposis nasi and rhinitis. Symptoms were quantitatively recorded pre- and postoperatively and patients were followed up 15--66 months. The Rotterdam results appear in the long run inferior to those published in the literature.


Reconstruction of the facial fenestration in the Caldwell-Luc maxillary sinus operation.

The result of the inadvoidable removal of bone in the canine fossa during antral fenestration is a large bone defect. Scar tissue grows across this defect and sometimes obliterates and interferes with the antral physiology. This paper presents our experience with the reconstruction of the defect by means of the osteotomised canine fossa bone with adhering soft tissues. In this way the antral volume remains unchanged and irritation of the infraorbital nerve often caused by the scar tissue of the facial fenestration as well as other pathological sequelae after the Caldwell-Luc operation are avoided.


Studies of the gas exchange and pressure in the maxillary sinuses in normal and infected humans.

The total gas pressure in experimentally occluded maxillary sinus was continuously recorded during 90 minutes on 7 healthy human subjects. PO2 and PCO2 were measured before and after the total pressure recording. In 3 cases the volume changes in the sinus were measured. The total gas pressure after an initial increase to about 35 mm H2O decreased to a steady state of about 70 mm H2O below atmospheric pressure. The volume changes in sinus showed a corresponding alteration. The gas measurements showed a decrease of PO2 of 25 mm Hg and a rise of PCO2 of 21 mm Hg. In 3 patients with acute purulent sinusitis there was seen a pressure of about 10 cm H2O above the atmospheric pressure.


Postoperative mucoceles of the maxillary sinus.

Apparently, the incidence of postoperative maxillary sinus mucoceles is greater in Japan than in the Western world. Between 1967 and 1976 at the Tokyo Medical and Dental University Hospital, Department of Otorhinolaryngology, 132 patients had the diagnosis of mucoceles of the maxillary sinus. Of these patients, 131 (99%) had histories of previous maxillary sinus surgery. A number of etiologic mechanisms are probably involved in producing these mucoceles.


Comparison of the gas quantities in the blood of patients with nasal packing for epistaxis, after nasal surgery and experimentally.

The authors examined blood pO2 and pCO2 in patients whose noses had been tamponaded because of epistaxis, nasal surgery and in animals whose noses had been artificially obstructed. A marked fall of pO2 and an increase of pCO2 were found as well as certain differences of the gas quantities between the first and second groups of patients. For this phenomenon an explanation is given.


Inhibition of testosterone-induced prostate growth in the rat by melatonin-free pineal extract.

Administration of the melatonin-free pineal extract to rats concomitantly receiving testosterone propionate caused partial inhibition of the ventral prostate growth induced by testosterone. Administration of the pineal extract to rats likewise caused a statistically significant decrease in the ventral prostate weight under basal conditions. The mechanism of action is discussed.


Circadian rhythms of corticosterone and nucleic acids in the rat adrenal in relation to age.

For 3 successive days, at 0600, 1200, 1800 and 0000, the circadian variations of corticosterone, RNA and DNA were followed up in the adrenals of 3 lots of prebuertal (30 days old), adult (120 days old) and old (28 months old) white Wistar male rats. There is a correlation between the circadian rhythm of corticosterone secretion and the circadian rhythms of RNA and DNA synthesis all along ontogenesis. These rhythms appear to be formed at 30 days of life, but they still differ from the ones in the adult rats by the levels recorded in the second half of the nocturnal period. In old rats the adrenal circadian variations have a considerably smaller amplitude, their curve taking a plateau form. The results support the hypothesis of the circadian rhythm ontogenesis in the rat adrenal.


Aspects of carbohydrate metabolism after pinealectomy in normal and pancreatectomized pigeon.

In order to examine the regulatory function in glucidic metabolism of the pigeon pineal gland the authors used the model of complete pancreatectomy associated or not with pinealectomy and treatment with Epifizan. It results that the pineal gland has a hypoglycemic action and partially compensates the lack of the endocrine pancreas.


Evolution of endemic goiter in the Valea Jiului area after 30 years of iodine prophylaxis.

After 30 years of iodine prophylaxis the incidence of goiter in the Valea Jiului area was reassessed. A number of 7,892 pupils aged 7-16 years were examined, of whom goiter was found in 32%. Before iodine prophylaxis started the incidence was 91.8%. The present survey shows that the small-sized goiters markedly prevail over middle-sized ones, while large-sized goiters became extinct. The diffuse to nodular goiter ratio changed by the disappearance of the nodular forms. The neurologic and psychic complications in goiter-bearing children disappeared. Attempts to correlate taste sensitivity to thiocarbamide with goiter failed. Examination of the digito-palmar dermatoglyphics showed a greater incidence of the higher atd angle, with transition forms of sulcus palmaris.


A study of assay conditions for palmitoyl-CoA synthetase and carnitine palmitoyltransferase in homogenates of human blood platelets.

The assay conditions for palmitoyl-CoA synthetase (P-CoA S) and carnitine palmitoyltransferase (CPT) in homogenates of human blood platelets have been studied. The assay based on trapping of palmitoyl-CoA by carnitine in the presence of exogenous CPT gave higher activity of P-CoA S than the assay based on direct isolation of the palmitoyl-CoA formed. The activity of CPT was higher on exogenous palmitoyl-CoA than on endogenous palmitoyl-CoA formed from palmitic acid and CoA in the presence of endogenous P-CoA S. The activity of CPT was strongly dependent on the incubation time and the amount of platelets used. The initial activity of this enzyme in human blood platelets was higher than previously assumed.


Electronoptical aspects of the thyroid cold nodule.

The authors studied the ultrastructure of benign and malignant forms of the thyroid cold nodule. In the benign cold nodule the most striking feature was an irregular endoplasmic reticulum with large cisternae and scarce ribosomes, this meaning an impaired protein synthesis. Frequent lysosomes and phagolysosomes occurring in the apical zone of the cell were present. In the malignant form of the cold nodule, nuclear abnormalities, a reduced endoplasmic reticulum and a highly increased number of abnormal mitochondria were found. The increased number of mitochondria in the carcinoma is a compensatory reaction to the frequent abnormalities found in these organelles. No transitional ultrastructural stages could be established between benign and malignant cold nodules. In practice the nature of a cold nodule is established by thyroid surgery and histologic examination.


Measurement of 25-hydroxyvitamin D in serum and its relation to sunshine, age and vitamin D intake in the Danish population.

A competitive protein-binding assay for 25-hydroxyvitamin D (25-OHD) based upon a specific binding protein in the cytosol from rachitic rat kidneys is described. A diethyl ether extraction followed by separation by freezing was used. The extracts were chromatographed on short silicic acid columns, which separated 25-hydroxycholecalciferol from cholecalciferol, 24,25-dihydroxycholecalciferol, and 1,25-dihydroxycholecalciferol. A small aliquot of the 25-OHD fraction was used in the assay and free and bound vitamin were separated by dextran coated charcoal. The lower detection limit was 0.8 ng/ml (2.0 nmol/l). The levels of 25-OHD were measured in 596 healthy subjects and a seasonal variation was demonstrated. This variation, however, was only found in those without regular vitamin D intake, whereas the level of 25-OHD remained constant throughout the year in subjects with regular vitamin D supplement. The levels of 25-OHD were lower in the elderly subjects compared to younger ones, but seasonal variation was observed in both groups. In the summer months there was a significant correlation between age and the 25-OHD level. The mean levels of 25-OHD in Denmark are within the range of means found in the United States and Sweden but are higher than those reported from England, Belgium and France. This indicates a relatively high vitamin D intake in the Danish population and a low risk of nutritional vitamin D deficiency.


Effect of oral zinc intake on delta-aminolaevulinic acid dehydratase in red blood cells.

Earlier results regarding the in vitro and in vivo effects of zinc on delta-aminolaevulinic acid dehydratase (ALAD) activity in red blood cells were confirmed in healthy human subjects after oral intake of zinc for 12 weeks. In one group of seven healthy adults, oral intake of zinc for 12 weeks. In one group of seven healthy adults, oral intake of zinc, as the sulphate salt (2.07 mmol zinc/day) for 6 weeks, resulted in a 44% increase in the activity of ALAD in erythrocytes. Plasma zinc levels also increased during the experimental period and reached a maximum of 29 mumol after 6 weeks and remained constant thereafter. In another group, the intake of zinc in a lower dose, (0.69 mmol zinc/day) for 12 weeks, showed a similar tendency, although the increase in the enzyme activity, as well as the plasma zinc levels, was relatively much less. The plasma copper levels decreased significantly in the second group after the zinc intake and reached a low value of 11 mumol at the end of the experimental period. The Cu:Zn ratio also decreased considerably towore valuable indicator of zinc status than plasma zinc levels alone.


Gel filtration pattern of immunoreactive glucagon secreted by the isolated, perfused, porcine pancreas.

The isolated pancreatic glands from six pigs were perfused in a single pass system and then stimulated with arginine. Samples of the early response perfusate were subjected to gel filtration. Glucagon was determined radioimmunologically in the column effluents using four different antisera with various capacities to recognize other molecular forms of pancreatic type glucagon immunoreactivities. One antiserum crossreacted with purified gut type glucagon. More than 93% of the assayed glucagon in the effluent was eluted within the distribution of pancreatic glucagon when chromatographed under identical conditions. In fifteen experiments there was no detectable immunoreactivity corresponding to the void volume, whereas in the remaining seven experiments less than 7% was eluted at this position. The immunoreactivity in the void volume was detected variably by the four antibodies. No immunoreactivity was detected between the void volume and the elution position of pancreatic glucagon. It is concluded that the arginine stimulated porcine pancreas almost exclusively secretes one molecular species of glucagon, which probably is the 29-amino acid peptide.


Presence of isorenin in human pineal gland.

A renin-like enzyme was identified in adult human pineal gland preserved post mortem in acetone. The mean value of the isorenin content was equivalent to 470 +/- 75.4 ng. ang II/g Pt/h.


Effects of fasting and tryptophan force-feeding on the activity of hepatic nuclear RNA polymerases in rats.

The effects of fasting, and subsequent force-feeding of L-tryptophan on the activity of hepatic nuclear DNA-dependent RNA polymerases were studied in adult (5-6 weeks old), and old (5-6 months) male Wistar rats. Liver nuclei, nucleoli, and nucleoplasmic fraction were isolated from rats following a single tube-feeding of tryptophan or water, and were assayed in vitro for the activity of different RNA polymerases. Whereas in adult rats 24 h of fasting caused a significant reduction in the activity of RNA polymerase I and II, in old rats the activity of only polymerase II was decreased after 24 h of fasting. In fasted adult rats administration of tryptophan promptly restored the activities of both polymerases to the respective normal fed levels, while in old rats none of the polymerases were affected by tryptophan. In fasted adult rats the pattern of response for both forms of polymerases to a single tube-feeding of tryptophan, over a period of 5 h, was found to be biphasic. When ribonuclease activity of nuclei was suppressed by performing incubations at low temperatures (17-30 degrees C) the difference between the two groups for polymerase I was greatly reduced, and for polymerase II the difference was fully abolished. Pre-treatment of fasted adult rats with cycloheximide (1.5 mg/kg) was found to abolish the 30 min tryptophan-mediated stimulation of both polymerase I and II activities. In cycloheximide pretreated rats the activity of polymerase II, but not polymerase I returned to its original level 5 h after tryptophan force-feeding.


Exercise testing in Sweden: a survey of procedures.

This report surveys the techniques of exercise testing of patients in twenty out of twenty-four (83%) Clinical Physiological Departments in Sweden. The study shows that bicycle ergometry is the predominant technique used. In the vast majority of hospitals, the standards of practice employed are high and adequate safety precautions are observed. However, criteria for exclusion from and interruption of exercise testing differ from one hospital to another. Limit values for heart rate, breathing frequency and blood pressure are by no means standardized. The criteria for distinguishing between normal and pathological electrocardiographic response vary. We conclude that in order to reduce complication rates and prevent accidents there is a need for further evaluations of the optimal use of exercise stress testing.


Circulatory homeostasis in rats after bile duct ligation.

The bile duct was ligated in rats, and their tolerance against a small blood loss was evaluated 7 days later. A 10% blood loss precipitated a large and sometimes fatal reduction in arterial blood pressure, while no reduction was seen in shamoperated rats. The plasma and erythrocytes were labelled by isotopes and the animals were rapidly frozen in liquid nitrogen. The splanchnic and pulmonary blood volumes were estimated from the isotope content in blood and tissue. These vascular beds will normally reduce their blood volumes during a blood loss and thus serve as vascular depots. In the bile duct occluded animals, the partition of blood is changed. More blood is to be found in the splanchnic vessels, and the depot function of the lung vessels is partly used for compensation. When these rats were bled, their liver blood volumes were not reduced, and only a small further reduction took place in the lung vessels. It is concluded that rats with bile duct occlusion will suffer considerably from small blood losses. This may be due to a lacking depot function of the splanchnic vessels.


A computerized semi-automatic evaluation system for quantitation of electroimmunoassays.

A fast and accurate evaluation system for quantitation of plasma proteins from electroimmunoassay plates is described. The protein concentration is determined from the height of its stained antigen-antibody precipitate by means of a coordinate digitizer connected to a COMPUCORP 445 minicomputer. The plasma protein concentration is calculated from the equation of the best second-order least square regression of data from a standard dilution curve. The values from one type of protein analysis can either be stored on a discette for future examination or printed out each day in a tabular form on a typewriter. A double evaluation of plasma concentrations from plates of two different proteins showed a coefficient of variation (CV) better than 4.5%. A correlation between values obtained by this technique and those obtained by the manual reading procedure has also been done. The correlation coefficient varied between 0.95 and 0.99 depending on the type of protein.


Metabolism in hypothermically perfused human kidney carcinoma: utilization and production of amino acids and glucose.

The metabolism of human kidney carcinoma was studied during hypothermic perfusion. Ten kidneys with carcinomas of different size were perfused in a Gambro perfusion machine for 6 days at +8 degrees C to +10 degrees C. The tumourous kidneys were allocated to one of two groups depending on the relative size of the tumour. Tumours occupying more than 40% of the total kidney volume were designated as "large tumours" and tumours occupying less than 40% as "small tumours". The net glucose uptake was greater during perfusion of kidneys with large tumours than during perfusion of kidneys with small tumours. A lower gluconeogenesis was found in kidneys with large tumours compared to perfusion of kidneys with small tumours and this could explain a large part of the difference in net glucse uptake. The uptake of fatty acids per unit kidney weight was lower during perfusion of kidneys with large tumours. A considerable uptake and release of amino acids were found in both groups. The uptake  of proline, aspartate, glycine, and arginine as well as the release of alanine and serine was lower during perfusion of kidneys with large tumours. The nitrogen balance was negative in both groups, with a net release of amino acids to the perfusate. The results suggest a higher glucose uptake, a lower gluconeogenesis, a lower fatty acid uptake and a decreased metabolization of amino acids in the tumour compared to the renal tissue. The model appears promising for studies of human kidney carcinomas at various experimental conditions.


Moderate and extreme haemodilution in open-heart surgery: electrolytes, urea, creatinine and osmolality.

Two different programs of treatment, called moderate and extreme haemodilution, respectively, have been compared in patients undergoing aortic valve replacement. Serum electrolytes, urea, creatinine and osmolatity were satisfactory in both groups during and after surgery. A substantial retention of sodium took place in the moderately diluted patients. The extreme group lost more potassium in the urine than the moderate one. A small post-operative rise in creatinine indicates a slight kidney damage in the moderate group. Increased serum urea following moderate dilution might partly be due to increased protein catabolism.


Moderate and extreme haemodilution in open-heart surgery: evaluation of haemolysis, cell damage and protein changes.

Clinical chemical data from patients operated upon in moderate and extreme haemodilution have been compared. Haemolysis was more pronounced during and after moderate dilution that in extreme dilution. A slight liver damage was found post-operatively after moderate dilution. Several changes were of about the same magnitude in both groups: Serum CK increased, reaching maximal activity 3-18 h after operation. An acute phase reaction of plasma proteins took place post-operatively, except that the concentration of complement C-3 dropped during the first days after operation. The serum levels of phosphate were positively correlated to several of the acute phase proteins.


Kinetics of bilirubin oxidation with peroxidase, as applied to studies of bilirubin-albumin binding.

In the determination of unbound bilirubin by rate of oxidation with peroxidase, errors may be caused by (1) phenol, propylparaben, and phenothiazines (free radical acceleration), (2) haemoglobin (peroxidase effect), and (3) ascorbate (inhibition). Such errors may be diminished by dilution 1:40, or with an anti-oxidant, tert-butyl-p-hydroxyanisole, and ascorbate oxidase.


Plasma glucagon responses to insulin-induced hypoglycaemia and arginine in normal and alloxan diabetic rats.

A decreased plasma glucagon response to insulin-induced hypoglycaemia was found in the normoglucagonaemic alloxan diabetic rat. 0.021-0.240 ng/ml was accepted as the range of normoglucagonaemia. The reduction of the glucagon response was not due to destruction of the alpha 2-cells by alloxan, since a normal response to arginine could  be demonstrated. The decreased glucagon response to hypoglycaemia in the insulin deficient normoglucagonaemic alloxan diabetic rat suggests that this alpha 2-cell dysfunction may be caused by insulin lack.


Haemodynamic effects of treatment and withdrawal of spironolactone in essential hypertension.

The effect of spironolactone (50 mg b.i.d.) in essential hypertension was studied by measurement of effective renal plasma flow (ERPF), blood urea nitrogen (Ur+), serum creatinine (Cr), cardiac index (CI), plasma volume (PV), body weight (BW), mean arterial blood pressure (MAP), total peripheral resistance index (TPRI), plasma renin activity (PRA) and plasma aldosterone (PA) in two groups of patients. Ten cases had determinations before, after 5 weeks and 4 months of treatment; fourteen cases who had been treated at an average of 18 months, had measurements while on treatment and 5 weeks after cessation of the drug. Among the ten patients ERPF fell in six and increased in four patients during treatment, but was statistically unchanged in the total group. Ur + and Cr were also unchanged by treatment. ERPF was unchanged after withdrawal of the drug. During treatment BW decreased 3.5%, PV decreased in nine and increased in one patient, while PRA and PA increased 426% and 202%, respectively. After cessation of the aldosterone blockade, BW increased 1.9%, PV 10.5% while PRA and PA fell 60% and 48.9%, respectively. MAP fell in eight out of ten patients during treatment. This fall was associated with a fall in CI or TPRI, or both. After withdrawal of the drug, MAP increased in nine and decreased in five of the patients. The data shows that this dosage of spironolactone gave minor adjustments of the systemic and renal circulation in spite of the consistent changes in BW, PV, PRA and PA.


Effect of propranolol on total exchangeable body potassium and total exchangeable body sodium in essential hypertension.

Total exchangeable body potassium (KE) was determined in fifteen patients with essential hypertension, and total exchangeable body sodium (NaE) in ten, before and after propranolol administration for 2-3 months. Blood pressure was reduced; serum potassium increased, but KE was unchanged. Serum sodium and NaE were unaffected during therapy. It is concluded that the increase in serum potassium during propranolol treatment could not  be attributed to potassium retention, but is possibly due to a displacement from the intra- to the extracellular fluid compartment. The antihypertensive effect of propranolol could not be related to changes in NaE.


Leg temperature profiles with a simplified thermographic technique in the diagnosis of acute venous thromboses.

A simplified thermographic technique has been developed to provide continuous leg temperature profiles by manual scanning with a noncontactile infrared radiation transducer connected to a linera potentiometer for determination of the transducer position. The clinical value of the technique in the diagnosis of acute venous thromboses has been estimated in seventy patients and thirty controls, using plethysmography and phlebography as methods of reference. The thermographic diagnosis  was based on side differences in temperature levels within different segments of the limbs, as calculated from the temperature profiles by means of planimetric technique. Standardized temperature profiles from the medial side of the limbs were found to demonstrate a side difference above the reference level in fifty-seven of fity-nine patients with acute venous thromboses, which means a diagnostic sensitivity corresponding to that of conventional thermography. Skin temperature profiles were superior to plethysmography, particularly in the diagnosis of thromboses located distally. Falsely positive results were obtained, as expected, in some cases of varicose veins or acute arthritis and skin infections. The presented type of thermography has obvious qualifications as a screening method in the early diagnosis of acute venous thromboses, being far less expensive but never the less more suited for objective numerical analyses and evaluation than conventional thermography with scanning cameras.


A non-invasive method for recording His-Purkinje activity.

A simple non-invasive method for recording of activity from the His-Purkinje system (HPS) is described. The electrical activity was derived from bipolar orthogonal surface leads. The signal was strongly amplified, bandpass filtered, delayed and averaged in an analogue averager before presentation. The equipment is mobile. The characteristics of the equipment are described. There was good agreement between invasive and non-invasive recordings. Out of seventeen subjects studied ten had a measurable HPS signal. Muscle tension and deep breathing tended to obscure the non-invasive recordings. The best lead for the measurements was lead X.


Assessment of an automated enzymatic method for ethanol determination in microsamples of saliva.

An automated enzymatic (ADH) method is described for ethanol determination in saliva. A 10 microliter sample volume is sufficient for analysis and by means of a Technicon Auto-Analyzer, sixty samples per hour may be run. It has been shown that ethanol is stable in saliva for at least 21 days when the samples are stored in a refrigerator at +4 degrees C, chemical preservatives were not required. The standard deviation of a single determination increased with increase in ethanol concentration in the sample. At a mean saliva ethanol concentration of 11.96 mmol/l, the standard deviation was +/- 0.169 mmol/l, corresponding to a coefficient of variation of 1.4%, implying a high precision. The recovery of alcohol added to saliva was 100.1% of the attributed concentration. Aliquots of the same saliva specimens were analysed using the enzymatic method (y) and by a head-space technique (x) for comparison. The regression equation was y = -0.067 + 1.002x (r = 0.993) inferring no systematic differences. The ADH method introduced has been used to determine the saliva ethanol concentration time course in man after alcohol ingestion.


Dissociation rate constants and fractional binding of tracer estimated for three antibody populations in unstripped and stripped antiserum.

The dissociation rate constants of a high-affinity thyroxine antiserum were estimated on the basis of curves showing the dissociation of labelled thyroxine-antibody complexes as a function of time. The dissociation curves were fitted by computer to an equation with a sum of three exponentials. The analysis of the curves gave estimates of the dissociation rate constants for fast, medium and slowly dissociating antibody populations, and also estimates of the size of the fraction of tracer bound to each of the three populations of antibodies. The coefficients of variation for the estimates were of the order of 10%, and the estimates were reproducible. The dissociation rate constants for the thyroxine antibodies were 0.55, 0.045 and 0.0058 h-1 at 23 degrees C. When labelled thyroxine and antiserum were incubated for increasing periods of time, there was an increase in the fractional binding of tracer to the slow-dissociating antibodies. The use of stripped antiserum as against unstripped antiserum also improved the fractional binding of tracer to the slow-dissociating antibodies. The stripping effect was slight for three other antisera which contained relatively fast dissociating antibodies.


Stool porphyrins determined by high pressure liquid chromatography and by fractional hydrochloric acid--ether extraction.

When stool copro- and protoporphyrin were quantitated by spectrophotometry, after fractional hydrochloric acid-ether extraction, up to 30% of the protoporphyrins were recovered in the coproporphyrin extract. In disorders with elevated stool protoporphyrin excretion (e.g. erythropoietic protoporphyria), this method therefore may give falsely elevated coproporphyrin values. When the stool porphyrins were determined by high pressure liquid chromatography there was no carry-over of protoporphyrin to coproporphyrin. The recoveries were 82 and 87%, and the coefficients of variation 5.6 and 3.1% for proto- and coproporphyrin, respectively. Moreover, in specimens containing a more complex mixture of porphyrins, a complete separation of the C2-C8 porphyrins and porphyrin isomers was obtained in a single run. High pressure liquid chromatography should therefore be considered the method of choice to obtain a quantitative profile of stool porphyrins in the routine laboratory.


The hepatic secretion of lecithin: cholesterol acyltransferase in rats with increased secretion of triglycerides due to ventromedial hypothalamic lesions.

Lecithin:cholesterol acyltransferase (LCAT) is postulated to take care of excess cholesterol formed during metabolism of triglyceride (TG)-rich lipoproteins. To test this hypothesis the relationship between secretion of LCAT and TG have been investigated in rats with ventromedial hypothalamic lesions which lead to increased hepatic secretion of TG. 1. The increased plasma concentration of TG in rats with ventromedial hypothalamic lesions was positively correlated to the activity of LCAT in plasma. 2. Incubation of hepatocytes isolated from such rats revealed a positive linear correlation between secretion of TG and of LCAT. 3. The secretion of unesterified cholesterol was neither correlated to the secretion of the acyltransferase nor to the TG.


The effect of splanchnic block on renin production and renal haemodynamics in hypertensive patients.

In eighteen patients with hypertension the effect of a splanchnic block was studied with respect to the plasma renin activity (PRA) in the renal vein and to the renal haemodynamics. A significant reduction of the PRA was noted during splanchnic block, both in kidneys with arterial stenosis, and in those without. The decrease in renin activity took place despite a simultaneous decrease in renal vascular resistance, which in itself should increase the secretion of renin. This supports the view that the sympathetic nervous system dominates over the baroreceptors in patients with hypertension at the pressure levels investigated and if the sodium intake is restricted.


The effect of long-term arterial occlusion on energy metabolism of the human quadriceps muscle.

The effect of 1.5 to 2.5 h tourniquet ischemia on energy metabolism of the quadriceps muscle was studied using percutaneous needle biopsy technique in sixteen patients operated on for an inveterated knee injury. During occlusion there was a moderate decrease in ATP with an increase in ADP and AMP. This change resulted in a decreased energy charge potential. At the same time phosphorylcreatine (PC) decreased markedly while creatine (Cr) increased giving a constant total creatine (TCr). An accumulation of lactate during occlusion with values up to 80 mmol/kg d.m. (dry muscle) was seen. A 15% reduction in glycogen was calculated. After release of the tourniquet the active phosphate concentration and the energy charge potential returned to basal levels within 5 min and most of the metabolites in the glycolytic sequence were also normalized. Muscle lactate content was normal after 30 min of intact circulation. The results suggest that longterm tourniquet ischemia induces marked changes in energy metabolism in skeletal muscle, but that the changes are rapidly and completely reversible with restoration of blood flow.


The effects on urinary kinin excretion of oral salt and water loads in dogs.

Ten dogs received 1 l of 37 degrees C tap water by stomach tube. Urine flow rate increased from 17 +/- 6 ml in the control hour to 285 +/- 25 ml in the second hour following the water intake. The diuresis was paralleled by increased urine kinin excretion from 23 +/- 9 ng/h to 94 +/- 17 ng/h. Urine kallikrein and urine sodium excretions remained unmodified. In seven dogs urine sodium excretion was increased from 0.87 +/- 0.22 mmol/h to 14.9 +/- 1.9 mmol/h by intragastric administration of 2% NaCl. Urine flow moderately increased from 15.1 +/- 2.5 ml/h to 64.3 +/- 15.0 ml/h. Urine kinin excretion was unchanged. The results suggest a relationship between high rates of urine flow and urinary kinin excretion.


Biphasic venous emptying from the calves in venous-occlusion plethysmography.

The pathophysiological significance of the biphasic venous emptying curves from the lower limbs in venous occlusion plethysmography was examined in three patients peroperatively by clamping the iliac veins in different locations. The clinical significance of biphasic curves was analysed in fifty-four patients, thirty-one of whom were pregnant and twenty-three had a suspected deep vein thrombosis. It was found that the primary venous emptying time (PVET) was helfpul in locating the obstruction. Patients with femoral and pelvic vein thrombosis had shorter PVET than patients with pregnancy or other pelvic vein obstructions. With PVET of 0.5 sec, or shorter, thrombosis should be strongly suspected. The ratio between the slow and fast emptying phases was useless in localization of the intrapelvic process.


Determination of alkaline phosphatase (EC 3.1.3.1) on the SMAC using diethanolamine in a modified manifold.

The SMAC method for alkaline phosphatase was modified inorder to determine the enzyme activity according to the Scandinavian recommended method [1]. The method is not strictly 'Scandinavian', but the correlation with the strict Scandinavian method performed on the LKB 8600 Reaction rate analyzer was excellent. The modified method was linear up to at least 2000 U/l.


Cannulation of small lymph vessels using a tissue glue.

A tissue glue was used to facilitate cannulation of small lymph vessels. A ligature around a lymph vessel distends the vessel proximally, but when the vessel is incised the friable vessel wall collapses. This is prevented by a small drop of a tissue glue applied to the vessel. The technique permits rapid cannulation of small vessels.


Re-examination of the dose-reponse relationship for the renal effect of acetozolamide.

To examine the effect of acetazolamide on tubular reabsorption of bicarbonate, plasma concentrations of bicarbonate, potassium and PCO2 were kept constant in volume expanded dogs. Intravenous infusion of acetazolamide reduced glomerular filtration rate (GFR) at all dose levels; after a dose of 30 mg/kg body wt GFR was reduced by about 30% and was not reduced further by increasing the infused dose of acetazolamide up to 500 mg/kg body wt. When control GFR was restored by raising systemic blood pressure, increments in filtered and excreted bicarbonate were not significantly different. At control GFR a linear relationship was obtained between bicarbonate reabsorption and log dose when acetazolamide was administered intravenously in doses ranging between 0.3 and 500 mg/kg body wt (r = 0.93). We conclude that a log dose-reponse relationship applies over a 25 times larger dose range than previously assumed.


Effect of long-term physical training on total red cell volume.

Six months of military training elicited a significant 4% mean increase in total red cell volume (TRC) measured by the 51Cr-labelled red cell method. This increase was associated with a mean 16% increase in predicted maximal oxygen uptake (VO2max). The increases in TRCV and predicted VO2max were inversely related to their initial levels. A statistically highly significant correlation between TRCV and predicted VO2max was observed (r = 0.59). The trained group had larger initial TRCVs than the sedentary group and the subjects who became well conditioned had a significant increase in TRCV, which contrasted with the unchanged TRCV in the subjects who did not become well conditioned. The greatest increase in TRCV (11%) was found in corporals, who had the hardest training. A statistically significant correlation between the changes in TRCV and estimated plasma volume was observed (r = 0.62), P less than 0.001). Owing the 1.8% increase in body weight the TRCV and predicted VO2max in terms relative to the body weight did not demonstrate the changes as clearly as did the absolute values. The factors affecting the TRCV increase are discussed.


Insulin and substrate exchange in the forearm during prolonged forearm work.

Forearm exchange of insulin and uptake of oxygen, glucose and free fatty acids (FFA) were studied during 120 min forearm work in six healthy male volunteers. At rest the arterial-deep venous difference of insulin was zero. At the onset of work release of insulin occurred, which continued at constant rate throughout the work despite unaltered arterial insulin concentration. Extractions of oxygen, glucose and FFA were of similar magnitudes at 120 as at 15 min work, while lactate release decreased with time. It is concluded that (1) a significant insulin release from muscle tissue or its vascular bed occurs and continues at undiminished rate during prolonged work, (2) a substantial amount must be bound in the tissue, unless local synthesis takes place and (3) despite this loss of insulin from the forearm no major change in glucose and FFA extraction occurs with duration of work.


Studies of renal urea cycle enzymes. I. Renal concentrating ability and urea cycle enzymes in the rat during protein deprivation.

Activities of renal urea enzymes were studied in normally fed (21% dietary protein) rats and rats deprived of protein (6% dietary protein) for 3 weeks. Protein deprivation resulted in growth retardation and defective urine concentrating ability. Compared to rats on an optimal diet containing 21% of protein, the protein starved animals had decreased concentrations of protein and urea in serum, reduced urinary excretion of urea and decreased levels of all five urea cycle enzyme activities in the liver. In the kidney, however, protein malnutrition resulted in a significant increase in arginase specific activity from 11.5 +/- 1.1 to 16.3 +/- 1.5 (M +/- SD) whereas the other urea cycle enzymes remained unchanged. It is postulated that this increase in renal arginase might be an early compensatory mechanism to preserve a net synthesis of urea in a situation involving arginine deficiency, thereby preserving an intact hypertonic gradient in the renal medulla.


Studies of renal urea cycle enzymes. II. Human renal arginase activity and location of the adaptive changes of renal arginase in the protein deprived rat.

Rats fed 6% protein for 3 weeks with growth retardation and urinary concentration defect had 3 times higher arginase activity in the kidney cortex (10.8 +/- 28, M +/- SD) compared with controls fed 21% protein (3.3 +/- 0.9, M +/- SD). In the outer medulla there was a 50% increase of arginase activity whereas no change was observed in the inner medulla and papilla. Arginase activity in fresh human cortical tissue was of the same magnitude as in the rat. The results are in agreement with the hypothesis that intrarenal urea synthesis contributes to the maintenance of the intrarenal urea gradient in the protein deprived state. The response in the protein deprived rat might thus be an adaptation to a situation with substrate deficiency.


Pteroylpolyglutamate hydrolase of human granulocytes. I. Partial purification and kinetic studies.

Pteroylpolyglutamate hydrolase was demonstrated in the lysosome-like cytoplasmic granules of human granulocytes. Partial purification of this enzyme from granulocytes, obtained from patients with chronic myeloid leukaemia, was achieved by chromatography of the granule extract on Sephadex G-75, Bio-Rex 70 and hydroxylapatite. The enzyme preparation obtained was slightly contaminated with myeloperoxidase. Synthetic pteroyltetraglutamate was used as a substrate for the enzyme. The pH optimum was 5.1; the Km was 6 x 10(-3) mol/l; and the enzyme was activated by divalent cations, e.g. Ca++, Mg++ and Mn++. Pteroylpolyglutamate hydrolase is suggested to be involved in the destruction of microorganisms in granulocytes during phagocytosis.


Changes in plasma amino acid distribution and urine amino acids excretion during prolonged heavy exercise.

Venous plasma and urine amino acids and urea were measured in ten well-trained men, aged 23--45 years, in connection with a 70 km cross-country ski race, lasting 4.39--6.04 h, leading to slight dehydration. The estimated urea production rate during the race was of the order 7.6 mumol/min, kg b.wt, i.e. twice the rate for such men on ordinary protein intake, during ordinary activity, thus suggesting increased protein catabolism. The race led to a fall of the total plasma amino acid concentration to about 60% of the pre-race level. In particular, the branched chain amino acids (valine, iso-leucine, leucine) and alanine were markedly reduced, whereas the S-containing amino acids (taurine, cystine, methionine) and the aromatic (phenylalanine, tyrosine, trytophan, histidine) and glutamine/glutamate were increased, unchanged or only moderately reduced. It is concluded that prolonged heavy exercise is accompanied by increased protein catabolism and changes in the plasma amino acid concentrations similar to those observed during prolonged starvation, but differing from those seen at heavy exercise of less than 2 h duration or prolonged exercise of moderate intensity.


Quantitative radiocardiographic evaluation of cardiac dynamics in man at rest and during exercise.

113Inm radiocardiography in conjunction with a gamma camera and a digital computer is applied to measurements of cardiac output, stroke volume, ejection fraction, end-diastolic volume, pulmonary blood volume, pulmonary transfer time and dispersion both at rest and during muscular exercise. A modified gamma function is used in calculations of radiocardiographic curves. In twelve supine male subjects the maximal increase of cardiac output was 220%, stroke volume 30%, ejection fraction 15%, and pulmonary blood volume 30%. The present method provides a non-invasive tool for cardiovascular examinations during exercise.


Serum thyroxine, triiodothyronine and thyroid stimulating hormone after prolonged heavy exercise.

Serum thyroxine (T4), triiodothyronine (T3) and thyroid stimulating hormone (TSH) was measured before, immediately after and on the following days after a 70 km cross-country ski race in two groups of ten well-trained men, one aged 21--29 years, taking 5.01--7.03 h, and one aged 51--57 years, taking 6.07--7.38 h. T4 was definitely increased immediately after the race, but fell to below the initial level on the following day and was not restored to the pre-race level until 4 days after the race. T3 showed essentially the same pattern, though less pronounced, a major part of the changes being possibly due to plasma volume variations. TSH showed a tendency to rise immediately after the race, but rose further to 175% of the initial level on the following day and was not restored to the initial level 4 days after the race. The pattern of changes were independent of age. It is suggested that the prolonged rise in TSH is probably due to an exercise-induced increased peripheral need for thyroid hormone.


Rapid micromethod for flourometric determination of neutral lipids on thin-layer chromatograms.

A rapid fluorometric procedure for in situ evaluation of neutral lipids on thin-layer chromatograms is described. The lipids are rendered fluorescent by treatment with perchloric acid, and the intensity of the emitted light is recorded by flying spot scanning. Detection limits (2.8 x SD) are 0.10, 0.11, and 0.17 nmol for triglycerides, cholesterol, and cholesterol esters, respectively. Range of linearity is 0--3.4 nmol for triglycerides, 0--2.0 nmol for cholesterol, and 0--4.0 nmol for cholesterol esters. When standard in triplicate and 2 samples of each unknown are applied to the chromatogram, standard error of the mean is 2.7% for triglycerides, 1.7% for cholesterol, and 1.0% for cholesterol esters. The sensitivity of the method allows simultaneous determination of the three lipid classes in 5 microliter lipid extract representing 0.238 microliter human plasma.