[Value of the oral TRH test for the evaluation of thyroid function in impaired TSH reserve. Preliminary report]. Oral TRH (40 mg) exerts a marked and protracted stimulatory effect on TSH release. The potency of oral TRH in stimulating TSH and T3 was evaluated in 26 euthyroid patients with absent or impaired TSH response in the i.v. TRH test (200 micrograms). All were given i.v. and oral TRH at an interval of at least 3 days. Based on the response to i.v. TRH, they were divided into "non-responders" (TSH increment less than 1.0 microU/ml) and "low-responders" (TSH increment 1.0--3.7 microU/ml). The results were compared with those in 11 patients with overt hyperthyroidism. 10 "non-responders" were additionally tested with 400 micrograms TRH i.v. to study the effect of a supramaximal dose. Most patients unresponsive to i.v. TRH had a pronounced response to oral TRH (TSH increment 0.1 +/- 0.1 and 4.0 +/- 0.9 microU/ml (mean +/- SEM) respectively, p less than 0.005). The "low-responders" in the i.v. test had a significantly enhanced response to the oral dose (2.4 +/- 0.3 and 7.6 +/- 1.6 respectively, p less than 0.005). The euthyroid patients with treated Graves' disease with a weak response to i.v. TRH showed a distinct response to the oral dose. On the other hand, plasma TSH in patients with overt hyperthyroidism failed to increase either after intravenous or after oral TRH. In contrast to oral TRH, the supramaximal dose of 400 micrograms i.v. TRH did not enhance the TSH-response in the "non-responders". In most patients with absent or impaired response to i.v. TRH, a marked increase in T3 could be demonstrated (0.5 +/- 0.1 ng/ml and 0.6 +/- 0.1 ng/ml in "non-responders" and "low-responders" respectively, p less than 0.01); thus, oral administration allows simultaneous stimulation of TSH and triiodothyronine. Oral TRH can be considered the test of choice for the investigation of patients with diminished TSH reserve.


[In vitro study on the problem of optimal gentamicin therapy in leukopenic patients: short injections or parenteral infusions?]. Killing curves of Pseudomonas aeruginosa were performed in an in vitro system simulating in-vivo gentamicin kinetics, i.e. decay of the antibiotic concentration with a 2.1 h halflife time. Minimal inhibitory concentrations (MIC) of gentamicin killed 99.999% of the initial Pseudomonas inoculum whereas 99.99% were killed at a continuously falling gentamicin concentration (starting from the MIC level) in the same period of time. Regrowth of persistent germs occurred only after 6 hours in cultures exposed to falling gentamicin concentrations, and after 8 hours in cultures kept at the MIC. Thus, a postulated superiority of gentamicin infusions over intermittent gentamicin therapy could not be demonstrated in vitro. Intervals between bolus injections of gentamicin should probably not be longer than 6 hours.


Current radiodiagnostic concept of ankylosing spondylitis. Nine radiodiagnostic rules are drawn from the X-rays of 2125 ankylosing spondylitis patients. The significance of early diagnosis of the 'multicolored' saroiliac X-ray is looked onto; the syndesmophyte, squaring-phenomenon, barrel-shaped vertebra, Romanus and Andersson lesions, and the ossification of ligaments are discussed. The changes at the apophyseal and the costovertebral joints, unimportant for early diagnosis, are explored.


Effect of mannitol on the traumatized spinal cord. Microangiography, blood flow patterns, and electrophysiology. The effects of mannitol on the spinal cord blood flow patterns in experimental traumatic paraplegia were correlated with microangiographic and electrophysiologic studies. At 1 hour following a therapeutic dose of mannitol (3 g/kg), an improved fluorescent intramedullary vascular pattern was detected among the mannitol-treated animals relative to those that were not treated. Within 4 hours, perfusion of many areas of the lateral white matter of the spinal cord often approximated normal in the mannitol-treated group. This pattern of perfusion was in striking contrast to that seen in the spinal cord of untreated animals, which displayed an almost total lack of fluorescing vessels at this later time. These findings correlated with an increased vascular caliber as revealed by microangiography and were postulated to be the result of a decrease in vasospasm and an expanded intramedullary blood volume following the administration of mannitol. Although mannitol therapy did not reverse the loss of the cortical evoked response observed during the 4-hour interval studied, the observation of improved blood flow patterns in the white matter is encouraging and warrants further study.


Cefoxitin in the treatment of gonorrhea. Cefoxitin is active in vitro against beta-lactamase-producing strains of Neisseria gonorrhoeae; therefore, its efficacy in the treatment of uncomplicated genital gonorrhea was evaluated in a study of ten men and 15 women. Cefoxitin was administered in two intramuscular doses given 5 hr apart, patients alternately receiving either 1 g or 2 g of cefoxitin in each injection. Probenecid (1 g) was administered orally with both injections to five women, and with the first injection only in the remaining patients. All cases of gonococcal cervicitis or urethritis were cured, and all rectal carriage was eliminated. Four of seven patients had persistent oropharyngeal carriage after treatment. There was no discernible difference between the efficacies of the 1-g and 2-g regimens. It was concluded that the cefoxitin regimens used are effective for therapy of uncomplicated genital or anorectal gonorrhea, but not for eradication of oropharyngeal carriage of N. gonorrhoeae.


Association between the auxogroup of Neisseria gonorrhoeae and the minimal inhibitory concentration of penicillin. The auxogroups and the minimal inhibitory concentrations (MICs) of penicillin for 885 recently isolated strains of Neisseria gonorrhoeae were determined. Auxogroups were established according to the growth requirements of the strains for proline (Pro-), uracil (Ura-), hypoxanthine (Hyx-), citrulline (Cit-), or citrulline replaceable by ornithine (Orn-). The seven most common auxogroups studied were: Pro-Cit-Ura- (38.8%), Orn-Hyx-Ura- (24.1%), nonrequiring (NR) strains (13.4%), Pro- (9.7%), Orn- (5.2%), Cit-Hyx-Ura- (4.2%), and Pro-Onr-Hyx-Ura- (2.0%). The distribution of MICs of penicillin for the complete set of 885 strains had a bimodal distribution, with a minor peak at 0.01 microgram of penicillin/ml and a major one at 0.16 microgram/ml. The auxogroups, however, had different patterns of distribution of MICs of penicillin. Five patterns of distribution were found among eight auxogroups identified. (1) Orn- and NR auxogroups showed a broad distribution of MICs, with peak at 0.08 microgram/ml. (2) Of the Cit-Hyx-Ura- and Orn-Hyx-Ura- auxogroups, greater than 98% of strains were susceptible to less than or equal to 0.04 microgram of penicillin/ml. (3) All strains of the Pro-Orn-Hyx-Ura- and Pro-Cit-Hyx-Ura- auxogroups were susceptible to less than or equal to 0.08 microgram of penicillin/ml. (4) More than 95% of strains of the Pro-Cit-Ura- auxogroup required greater than of equal to 0.08 microgram of penicillin/ml for inhibition of growth. (5) The Pro- auxogroup showed a bimodal distribution, with a major peak at 0.01 microgram of penicillin/ml and a minor one at 0.32 microgram/ml.


Colonization of the pharynx with Neisseria gonorrhoeae: experience in a clinic for sexually transmitted diseases. At a clinic for treatment of sexually transmitted diseases, 1,453 patients were examined for pharyngeal colonization with Neisseria gonorrhoeae. A history of oral sex was reported by 895 (61.2%) of the patients. N. gonorrhoeae was isolated from the pharynges of 42 (2.9%) of the 1,453 patients. Twenty-seven of the 42 patients with N. gonorrhoeae-positive cultures gave histories of oral sex, and all 42 patients reported orogenital contact when questioned again at a follow-up visit. Seven patients with positive cultures had pharyngeal symptoms; all seven practiced fellatio. Eleven of the infected men were asymptomatic heterosexuals whose only orogenital contact was cunnilingus.


Effects of low cobalamin diet and chronic cyanide toxicity on cobalamin distribution in baboons. This paper reports the bodily distribution of total cobalamin and individual cobalamins at the termination of an experiment on the effects of a low cobalamin diet and chronic cyanide or thiocyanate administration in baboons. The results show that the distribution of cobalamins in the tissues of the baboon can be altered by a low cobalamin diet and also by chronic intoxication with cyanide, whether or not the animals are on a low cobalamin diet. All animals on the low cobalamin diet showed a reduction in total and individual cobalamins. In blood plasma and erythrocytes, kidney, spleen, testis and brain, the proportion of methylcobalamin tended to be disproportionately reduced in cobalamin-depleted animals. This reduction was lessened or prevented by the administration of cyanide. Neither cyanide not thiocyanate produced a significant increase in the proportion of cyanocobalamin in plasma, though thiocyanate produced a large increase in cyanocobalamin in erythrocytes. In liver, cyanocobalamin was more than doubled by the administration of cyanide to cobalamin-depleted animals.


Dipetalogaster maximus (Hemiptera, Triatominae) for xenodiagnosis of patients with serologically detectable Trypanosoma cruzi infection. In patients serologically positive for Trypanosoma cruzi infection the three bug species/instar combinations used in xenodiagnosis showed third-instar Dipetalogaster maximus to be more efficient in detecting circulating trypanosomes than the first instar of the same species which, in turn, is more sensitive than third-instar Triatoma infestans. The sensitivity of the pool technique of faecal examination compared with individual dissection was investigated. Four pool examinations (the product of 20 bugs) were equivalent to 10 individual bug dissections. Because of the ease of providing large numbers of bugs for mass xenodiagnosis, first-instar D. maximus has replaced third-instar T. infestans in our routine work. The value of third-instar D. maximus as a xenodiagnostic agent needs further investigation.


Experimental Trypanosoma cruzi infection in rhesus monkeys 111. Electrocardiographic and histopathological findings. In five rhesus monkeys surviving 'Peru strain' or 'strain 7' Trypanosoma cruzi infection for six to eight years, positive xenodiagnosis results and high indirect fluorescent antibody titres (4096 - 65536) persisted until the animals were killed. Abnormal electrocardiograph patterns in two monkeys (H and K) were possibly compatible with myocardial damage. Histopathological changes attributable to T. cruzi infection were minor in four monkeys but severe in one (R). In this animal, infected with what was judged previously to be the less virulent of the two T. cruzi stocks used ('strain 7'), there was severe myocarditis, with myofibre degeneration, and lesions of the oesophagus. Elevated serum levels of five enzymes were not detected in any of the chronically infected monkeys.


Low-dose electron image reconstruction of negatively stained contractile phage sheath from Bacillus subtilis (PBS-Z). The structure of the contractile sheath of the defective phage from B. subtilis (PBS-Z) has been investigated by low-dose electron microscopy and image reconstruction. The extended and contracted sheath particles were imaged by means of two negative stains which consisted of uranyl- and phosphotungstate-containing solutions of a pH of 4.2 and 7.0 respectively. Images of identical parts of the same type of specimen were recorded at a total electron dose of 80 C/m2 (5 electrons/A2) and 4 x 10(3) C/m2 (250 electrons/A2). The low-dose reconstructions of the extended and contracted sheath structure in the two stains show good correspondence and made it possible to draw the following structural conclusions. The sheath protein in both types of structure has an elongated shape, and in both structures the long molecular axis lies in a plane perpendicular to the helical sheath axis. The orientation of the protein in the extended and contracted sheath is different; the long axes differ by about 35 degrees in orientation. The reconstructions did not permit conclusions about different conformational states of the protein in both structures. These data, together with the packing parameters of the protein subunits in the contractile sheath [1], form the complete structural analysis of this biological structure by electron microscopy. The radiation damage effects which have been monitored in analyzing image pairs to the full extent may be summarized as follows. (1) Diameters of the sheath structure increase, which indicate flattening. (2) There is no loss in resolution, and layerline altitudes of the Fourier-transformed images do not change. (3) Uranyl stain behaves differently compared to phosphotungstate. In both negative stains the structural noise level increases upon irradiation as follows from the increase in phase residuals of the digital layerline data. In uranyl-stained images also more aperiodic noise appears. (4) The Fourier amplitudes of the principal layerline maxima shift towards lower spatial frequencies; phases of corresponding maxima generally remain constant. This pattern is more pronounced in the extended sheath data; there is no rationale describing these positional shifts. Moreover, in the case of contracted sheath the amplitudes of Fourier components also change more in absolute value. Therefore the damage effects also seem to depend on the type of structure embedded in the stain. (5) In the reconstructed images these radiation effects create artificial stain-excluded volumes of a type and at a radius which depend on the stain and structure.


Induction of infective stages of Theileria parva by exposure of host ticks to high temperature. It was demonstrated that Theileria parva parasites infective to cattle could be induced by exposure of infected adult Rhipicephalus appendiculatus ticks to 37 degrees C. The production of the sporozoites of T parva was not as efficient as by feeding ticks on rabbits.


[Development of enterococci and coli bacteria in Bulgarian yogurt]. The effect of lactic acid fermentation in Bulgarian yoghourt was studied by the development and decline of hygiene level indicating microorganisms--enterococci and coli-bacteriae. It was established that for the first 6 h after production of Bulgarian yoghourt, the quantity of enterococci (Str. faecalis, resp. Str. faecium) increases 5--6 times on the average, after the 12th hour it begins slowly to decrease and the number is reduced two times during storage for 7 days at 7--10 degrees C temperature of 6 days at 18--22 degrees C. The reduction in enterococci number is not fully correlated with the stage of lactic acid fermentation. Coli-bacteriae (E. coli) do not grow in number at the time the milk is turned into yoghourt. Their initial quantity diminishes along with the advance of the lactic acid process and after 24 h of milk storage at 18--22 degrees C or after 48 h at 7--10 degrees C they cannot be detected at all. The conclusion is drawn that enterococci are more suitable as hygiene level indicating microorganisms for hygienic evaluation of Bulgarian yoghourt, as compared to coli-bacteriae, due to their greater viability and longer survival in the product at the time of its production and during storage. It is recommended to perform the investigations on coli-forms not later than the 24th hour after yoghourt productions begins.


Biotransformation of diclofenac sodium (Voltaren) in animals and in man. I. Isolation and identification of principal metabolites. 1. The anti-inflammatory agent diclofenac sodium (o-[(2,6-dichlorophenyl)amino]phenylacetic acid sodium salt) is extensively metabolized by rat, dog, baboon and man. The main metabolites were isolated from the urine of all species and from the bile of rat and dog and identified by spectroscopy. 2. Metabolism involves direct conjugation of the unchanged drug, or oxidation of the aromatic rings usually followed by conjugation. Sites of oxidation are either position 3' or 4' of the dichlorophenyl ring or, alternatively, position 5 of the phenyl ring attached to the acetic acid moiety. 3. In the urine of rat, baboon and man conjugates of the hydroxylated metabolites predominate, but the major metabolite in dog urine is the taurine conjugate of unchanged diclofenac. 4. In the bile of rat and dog, the main metabolite is the ester glucuroniade of unchanged diclofenac.


Biotransformation of diclofenac sodium (Voltaren) in animals and in man. II. Quantitative determination of the unchanged drug and principal phenolic metabolites, in urine and bile. 1. Quantitative determinations of unchanged diclofenac and two of its major phenolic metabolites were made by reverse isotope dilution analysis on urine of rat, dog, rhesus monkey, baboon and man and on bile of rat, dog and man. Isotope dilution analysis was performed before and after various methods of enzymic and chemical hydrolysis. 2. The same samples were also analysed by two-dimensional t.l.c. and subsequent autoradiography, to estimate the remaining phenolic metabolites. 3. In contrast to rat, rhesus monkey, baboon and man, which excrete mainly hydroxylated metabolites, the dog does not oxidize diclofenac. Dog urine contained a relatively stable taurine conjugate of diclofenac, and in the bile an ester glucuronide was excreted, which decomposed even in weakly alkaline soln. 4. The unstable ester glucuronide found in dog bile was also demonstrable in rat bile. It presumably hydrolyses in the duodenum, releasing diclofenac which undergoes enterohepatic circulation.


The disposition of the synthetic prostaglandin analogue cloprostenol ('Estrumate') in the rat and marmoset. 1. Following subcutaneous administration of the synthetic prostaglandin analogue [14C]cloprostenol to the rat (200 micrograms/kg), the dose was quantitatively recovered from the excreta: 52% of the dose was present in the urine and 43% in faeces. After intravaginal administration (200 micrograms/kg) 42% of the dose was recovered from the excreta, equally divided between urine and faeces, and 40% (range 25--66%) of the dose was recovered from the site of application. The radiolabelled compounds present in faeces were eliminated initially via the bile. 2. The max. observed plasma concn. of total 14C in the rat was 84 ng equiv./ml at 30 min after subcutaneous administration of cloprostenol (200 micrograms/kg). A component which co-chromatographed with cloprostenol on t.l.c. was rapidly cleared from plasma with a half-life of 54 min. After intravaginal administration of cloprostenol (200 micrograms/kg), low and persistent plasma concn. of 14C were detected. 3. The metabolic fate of cloprostenol in the rat and marmoset has been studied with radiolabelled and non-labelled drug mixed such that fragments detected by mass spectrometry exhibited characteristic 12C:14C isotope clusters. Metabolites derived from cloprostenol contained these characteristic doublets. 4. In the rat cloprostenol is metabolized by beta-oxidation to tetranor-cloprostenol. Unchanged cloprostenol and a conjugate of tetranor-cloprostenol were minor urinary metabolites. In the rat biotransformation of cloprostenol in the cyclopentane ring occurred; the tetranor acid of 9-keto-cloprostenol was identified in urine. In the marmoset unchanged cloprostenol and dinor-cloprostenol were major urinary components.


Studies on the different metabolic pathways of antipyrine in rats: influence of phenobarbital and 3-methylcholanthrene treatment. 1. The amounts of antipyrine and its metabolites excreted in 24 h urine after i.v. injection of 10 mg antipyrine into male Wistar rats were quantified after enzymic hydrolysis with beta-glucuronidase/aryl sulphatase. In 24 h 2.7% of the administered dose was excreted as unchanged antipyrine, 13.3% as 4-hydroxyantipyrine, 7.4% as norantipyrine, 28.9% as 3-hydroxymethylantipyrine and 1.1% as 3-carboxyantipyrine. 2. Treatment with phenobarbital decreased the antipyrine half-life from 65 to 30 min, but did not significantly change the urinary metabolite profile. Only the amount of 3-carboxyantipyrine was significantly different and increased from 1.1 to 2.6% dose. 3. 3-Methylcholanthrene treatment resulted in a decrease of antipyrine half-life from 72 to 37 min. After treatment 4-hydroxyantipyrine was increased from 13.4% to 25.6% dose, whereas 3-hydroxymethylantipyrine was decreased from 26.8% to 8.5% and 3-carboxyantipyrine from 1.3% to 0.2% of the dose respectively; norantipyrine was unchanged. 4. It is concluded that different types of hepatic cytochrome P-450 may be involved in the formation of 4-hydroxyantipyrine on one hand and the formation of 6-hydroxymethylantipyrine on the other. Another possibility is that in methylcholanthrene-treated animals another haemoprotein is formed that results in the formation of more 4-hydroxyantipyrine and less 3-hydroxymethylantipyrine. In any case, the urinary metabolite profile of antipyrine can be used to study changes in the activity of different cytochromes in drug metabolism studies.


Fate of 2,5,4'-trichlorobiphenyl in rats. 1. Following the administration of daily oral doses (1 mg/kg) of 2,5,4'-trichloro-[14C]biphenyl to rats for 14 days, the compound was rapidly excreted, only small amounts (3--4%) being stored in the organs. 2. The majority of the biphenyl was metabolized (greater than 85%) and the major metabolites excreted were identified as hydroxy-, dechloro- and conjugated derivatives.


The induction of hepatic and extrahepatic xenobiotic metabolism in the rat and ferret by a polychlorinated biphenyl mixture (Aroclor 1254). 1. The effect of a single i.p. dose (500 mg/kg) of a polychlorinated biphenyl mixture (Aroclor 1254) on hepatic and extrahepatic xenobiotic metabolism in male rat, and male and female ferret, was studied. 2. Aroclor 1254 treatment induced hepatic microsomal N-demethylase activities, and cytochrome P-450 and protein content in both rat and ferret. Liver size and aniline 4-hydroxylase were also increased in rat, but not ferret. The polychlorinated biphenyl mixture appeared to be a mixed-type inducer of hepatic xenobiotic metabolism in both species. 3. Aroclor 1254 treatment produced large increases in activities of benzo(a)pyrene hydroxylase and 7-ethoxycoumarin O-deethylase in whole homogenates of the liver, small intestinal mucosa, kidneys and lungs of both species. Maximal stimulation of xenobiotic metabolism occurred in the kidney of both the rat and ferret. In contrast, UDP-glucuronyltransferase activity was only stimulated in liver, intestine and kidney of the rat and in liver and intestine of the ferret. 4. These results suggest a general species similarity in the response to the polychlorinated biphenyl mixture between the rat and ferret.


Avian metabolism of halogenated biphenyls. 1. The metabolism of several halogenated biphenyls has been studied using poultry as a model system. The substrates 4-chlorobiphenyl and 4-bromobiphenyl each yielded two metabolites (4'-chloro-4-biphenylol, 4'-chloro-3,4-biphenyldiol; 4'-bromo-4-biphenylol, 4'-bromo-3,4-biphenyldiol), while 4,4'-dichlorobiphenyl yielded only one metabolite (4,4-dichloro-3-biphenylol). 2. Metabolites were not found in eggs collected for 7 days following the administration of the substrate.


Effect of hypocalcemic and hypercalcemic substances on the parathyroid histology of the lizard, Uromastix hardwickii (Gray). The effects of hypocalcemic and hypercalcemic substance on activity of the parathyroid and plasma calcium and phosphorus levels in the lizard, Uromastix hardwickii are described. The cellular hypertrophy and degranulation of cytoplasm in the parathyroid cells along with decrease in plasma calcium level appeared after sodium citrate and ethylenediaminetetraacetate (EDTA) treatment. On the other hand, degenerative changes are observed after calcium chloride treatment. It is suggested that the secretion of parathyroid is regulated by the circulating blood calcium level.


[The influence on water-electrolyte balance through osmotherapy for decreasing intracranial pressure]. On the basis of a group of neurosurgical patients showing a differing composition, various procedures of the dehydrating therapy in the pre- and postoperative phases for decreasing the increased intracranial pressure were studied. In addition to the continuous recording of the intracranial pressure, the electrolyte and water balance was measured by recording the plasma, urinary, and cerebrospinal-fluid electrolytes and their osmolarities and the urinary output was determined. Besides, specific measurements of the haematocrit, of the central venous pressure and the arterial mean pressure brought pathophysiological findings on the dehydration. The comparison of conventional substances such as mannite and sorbite of different concentrations per time showed various disturbances of the electrolyte and water balance; therapeutic guiding rules could be elaborated under consideration of these experiences. On the basis of the intracranial pressure/volume relationship, the effectiveness of the dehydration should not only be assessed by the reduction of the intracranial pressure since the extent of the alteration of the electrolyte and water balance and the haemodynamically active changes are quite different. Finally, disease pictures should be taken into consideration in which the basic morphological and functional conditions have been lost and the limits of the therapeutic procedure are exceeded.


[Mechanism of switching over simple and systemic conditioned reflexes to time in animals]. Switching over of simple reflexes and of a system of reflexes to "pure" time was studied on 12 rabbits, 2 dogs and one monkey. Instrumental conditioned reflexes (pulling a ring or pressing a pedal) were elaborated in response to 5; 4, 2 and 1.5 minutes time intervals; a system of conditioned reflexes was elaborated to different time intervals: 1.5--2.5--3.5 min and 4--2 min. Switching over agents were a metronome (300 beats/min), noise of a ventilator plus light of an electrical bulb, as well as different quantities or qualities of alimentary reinforcement. Turning in of the one and turning out of the other agents caused switching over of the food-procuring activity from one rhythm to another. The mechanisms of this complex form of integrative brain activity are discussed.


[Why do the very aged become so old?].

[Why do the very aged become so old?]. Some men can obtain hundred years or more, but the grounds are as yet unknown. Till now medical research has given no specific clues. Intensive consideration shows that life under quite natural (no longer found), not too hard social and climatic conditions (more maritime than arid) and in mountainous regions is decisive. It is clear that few territories of the earth come into consideration. The specific mental situation of mountain dwellers which contrasts in important points to that of the inhabitants of flat country, plays a decisive part.


The stimulation of the mitochondrial respiration by citrulline synthesis. 1. The influence of ammonia and ornithine on the oxygen uptake and the formation of citrulline was investigated with isolated rat liver mitochondria. The experiments were performed in a cytosol-like saline medium at 38 degrees C. 2. Under these conditions an increase of the respiration rate by ammonia and ornithine was observed, but a small response to external ADP, only. The missing stimulation by ADP was due to a partial inhibition of the respiratory chain by traces of zinc (approximately 1 microM) present in the medium. This inhibition was only detected at low concentrations of mitochondria. 3. For activation of respiration by ammonia plus ornithine two different processes were responsible: (i) chelation of the inhibiting zinc by ornithine, which could be prevented by EDTA; (ii) ADP production in the matrix space during formation of carbamoyl phosphate, which could be prevented by oligomycin but not by carboxyatractyloside. 4. This stimulus of the carbamoyl phosphate formation and of the equivalent citrulline synthesis on the mitochondrial respiration ran to 12% of that increase caused by phosphorylation of external ADP. The maximum rate of citrulline formation was limited by the activity of carbamoyl phosphate synthetase. 5. Added ADP suppresses the production of citrulline probably by the exchange of extramitochondrial ADP versus intramitochondrial ATP. The data suggest a common adenine nucleotide pool delivering ATP to the adenine nucleotide translocase as well as to the carbamoyl phosphate synthetase.


[Tractional diverticulum of the urinary bladder as a component in recurring inguinal hernias]. The tractonal diverticulum as contained in recidivating inguional hernia occur rather often. They are created most often during plastic surgical treatment most frequently in inguinal hernia repairs in which a suture partially or completely passes through the urinary bladder and fixes it to the layers of inguinal canal when it is being sutured. They also occur when the bladder is accidentally pinched while the sutures are being pulled taught. The diverticulum so created almost never yields characteristic symptoms, and for this reason it is most often diagnosed intraoperatively. Because of this, the surgeon must keep in mind the possible existence of such a diverticulum when reoperating a recidivating hernia localized in the lower abdomen especially those near the bladder. It is important that such a diverticulum be carefully dissected and that the bladder be adequately closed with a layers of catgut sutures. An accidental -- overlooked lesion of the urinary bladder during operation can have a fatal outcome. For this reason such lesions must never be overlooked, and should be resolved during the hernioplasty itself.


Failure of metoclopramide to influence LH, FSH and TSH secretion or their responses to releasing hormones. Intravenous metoclopramide (MET) (10 mg) induced a brisk PRL response with a mean +/- SEM peak of 85.3 +/- 7.7 ng/ml maximal at 30 min. L-Dopa, but not atropine pre-treatment, attenuated the prolactin (PRL) response to MET. This indicates that the antidopaminergic properties of MET mediate PRL secretion. MET did not influence basal levels of TSH, LH or FSH. Neither did it affect their response to the respective releasing of hormones. Our results indicate that dopaminergic blockade induced by iv MET, does not influence the secretion of the pituitary glycoprotein hormones.


Serum levels of retinol, retinol-binding protein, carotenoids and triglycerides in children with beta-thalassemia major. Levels of retinol (vitamin A), carotenoids and triglycerides in the serum of 50 children with homozygous beta-thalassemia have been studied, as well as the ability of the small intestine to absorb a test meal containing retinol palmitate, triglyceride, d-xylose and glucose. On the other hand, 8 patients underwent a dark-adaptation test, and in 40 children with homozygous beta-thalassemia the levels of retinol-binding protein in the serum were estimated. The mean levels of retinol, carotenoids and triglycerides in the serum of the patients were: 23 +/- 4.1 micrograms/dl (controls: 36.3 +/- 4.9), 44 +/- 15.5 micrograms/dl (controls: 103 +/- 24), 117 +/- 20 (controls: 126 +/- 26), respectively. The absorption from the small intestine of retinol, triglycerides, glucose and d-xylose was normal. 6 out of 8 patients studied for visual function showed an abnormal dark-adaptation test, and these 6 children had low serum retinol levels. Finally, the mean serum levels of retinol-binding protein in the patients were 4.74 +/- 0.53 mg/dl (controls: 5.63 +/- 0.58). The low retinol levels were correlated with the low retinol-binding protein values which, in turn, could be due to the abnormal liver function of the patients.


Interaction between beta-thalassaemia and Hb G Philadelphia associated with alpha-thalassaemia. A man who did not produce and beta-chains did not suffer from a severe beta-thalassaemia. He was heterozygous for Hb G Philadelphia. It has been suggested that this haemoglobin variant was associated with alpha-thalassaemia and that interaction between alpha-thalassaemia and beta-thalassaemia decreased the imbalance of alpha/beta-globin biosynthesis and thereby the severity of the beta-thalassaemic disorder. Association of Hb G Philadelphia and alpha-thalassaemia in this man and his family is now demonstrated using bone marrow and reticulocytes of the propositus and one of his sons and reticulocytes only of another son.


Thrombotic thrombocytopenic purpura in early pregnancy. Remission after plasma exchange. A 24-year-old Chinese female developed fever, fluctuating neurological and renal manifestations, microangopathic hemolytic anemia, and thrombocytopenia during the 11th week of her first pregnancy. Therapy for thrombotic thrombocytopenic purpura (TTP), initiated during the 15th week of her pregnancy, including corticosteroids, platelet aggregation inhibitors, hysterotomy, and splenectomy was ineffective. However, dramatic improvement and remission occurred after plasma exchange of 3,560 ml was performed with the Haemonetics Model 30 Blood Cell Separator.


Levamisole and autoimmunity in angioimmunoblastic lymphadenopathy. A case of angioimmunoblastic lymphadenopathy (AILD) with important autoimmune symptoms disappearing under Levamisole therapy is reported. Since Levamisole is thought to have no direct effect on B cells, it is supposed that in AILD it regulates B lymphocyte activity via the restoration of impaired T cell functions.


Prolonged busulfan-induced remissions in chronic myeloid leukemia. Two prolonged remissions were achieved in a patient with chronic myeloid leukemia by two short courses of busulfan treatment. The first remission lasted for 7 years; the second one lasts already 14 years. In the interval periods no treatment was administered.


Acute lymphatic leukemia with mediastinal involvement. Mediastinal involvement was found in 11 (group A) of 43 patients affected with acute lymphatic leukemia when early thoracic roentgenograms of these patients were reviewed. Several clinicobiological characteristics of these patients were compared with those with a normal mediastinum as shown in their roentgenograms (group B). Statistically significant differences were observed between group A and group B not only as far as age was concerned (13 years group A, 7.4 years group B) but also in the ratio males/females (10:1 group A, 10:20 group B) and with regard to the leukocyte counts (266 x 10(9)/liter group A, 20 x 10(9)/liter group B). In addition, patients from group A showed a greater 'tumoral mass' and a more prominent extrahematological involvement (45% group A, 15% group B). In these cases 'convoluted' cells were frequently discovered and the blastic cells exhibited significantly lower scores of PAS-positivity and more marked acid phosphatase activity than those in group B. Although the rate of complete remissions (CR) obtained in both groups was similar (80% group A, 93% group B), marked differences were observed not only in the duration of CR but in the period of survival after CR as well, both factors being more prolonged in group B patients. 50% of patients with mediastinal involvement (group A) relapsed in the first 6 months of the evolution of the disease.


Effect of vitamin E on platelet aggregation in diabetic retinopathy. The effect of vitamin E on platelet aggregation was investigated in a group of 10 patients with diabetic retinopathy. Adenosine diphosphate induced platelet aggregation was inhibited in the patients' group as well as in the controls in the presence of vitamin E. An increased platelet aggregation was obtained with arachidonic acid in both groups when platelet-rich plasma was incubated prior with vitamin E. The clot retraction inhibition test parallels the findings of aggregation obtained with the platelet aggregation meter.


Multiple myeloma and acute leukemia.

Multiple myeloma and acute leukemia. A patient suffering from multiple myeloma without treatment with cytoxic drugs or irradiation, died within 4 months, from acute leukemia. The appearance of acute leukemia in a patient with multiple myeloma without previous treatment is very unusual. The relation of these two conditions is briefly discussed.


Hyperviscosity syndrome in a patient with plasma cell leukemia. A patient with plasma cell leukemia and IgG (K) M-component, who developed a hyperviscosity syndrome is reported. To our knowledge, this complication has not yet been reported in plasma cell leukemia.


Platelet transfusion requirements of children with newly diagnosed lymphoblastic leukaemia. The platelet transfusion requirements of 70 unselected children with lymphoblastic leukaemia were studied from the time of diagnosis to the achievement of complete remission, or to death if no remission was obtained. Platelets were not transfused unless clinically significant bleeding occurred in association with a platelet count of less than 20.0 x 10(9)/l, and on this basis only 31 transfusions were given to 11 (15%) patients for 17 episodes of apparent or presumed bleeding. No deaths occurred due to haemorrhage, and 67 (95%) patients achieved complete remission. These findings suggest that such children do not need prophylactic platelet transfusions, which are commonly given despite their inherent risks and sequelae.


Myeloproliferative disease of childhood associated with a trisomy 21 clone. Myeloproliferative disease of childhood is frequently associated with chromosomal anomalies, usually of the C group. Clinical features are similar to those of the juvenile type of chronic myeloid leukemia. A child with this disease is described. Marked myeloid proliferation, anemia, thrombocytopenia and hepatosplenomegaly were present; leukocyte alkaline phosphatase and fetal hemoglobin were moderately elevated. Chromosome analysis of bone marrow cells revealed a mosaicism 47,XX,+21/46,XX. Down's syndrome was ruled out by the child's normal phenotype and dermatoglyphic analysis. The cytogenetic finding is probably evidence for the clonal origin of the trisomy 21 cell line.


Endogenous erythroid colony formation by peripheral blood mononuclear cells from patients with myelofibrosis and polycythemia vera. Peripheral blood mononuclear cells from patients with polycythemia vera or myelofibrosis with myeloid metaplasia were studied for their erythroid colony growth characteristics in plasma clot cultures. In both diseases, erythroid colonies formed early in culture in the absence of added erythropoietin (endogenous colonies). In no instance did early, endogenous colony formation occur with peripheral blood cells from normals or patients with secondary polycythemia. A normal response to erythropoietin was observed with both control and patients' peripheral blood cells. Spleen mononuclear cells obtained from one patient with myelofibrosis also produced endogenous colonies and showed a response to erythropoietin. This study suggests that culture of peripheral blood mononuclear cells might serve as a useful tool in discriminating polycythemia vera from secondary polycythemia.


Bone marrow biopsy in patients with malignant neoplasms other than lymphomas or leukemia. 104 patients with various cancer, excluding malignant lymphoma and leukemia, underwent bone marrow biopsy using a Jamshidi needle, regular type. In 100 patients an adequate pice of bone marrow was obtained. In 24 patients metastases were detected in the bone marrow. Metastases were found in 10 of 38 (26.3%) patients with breast cancer, in 5 of 17 (29.4%) patients with lung cancer, in 5 of 10 (50%) patients with cancer of the prostate, in 1 patient with rhabdomyosarcoma, 1 with chordoma and in 2 of 14 patients who underwent biopsy in search of unknown cancer. 71% of the patients with positive findings in the bone marrow had clinical signs of bone involvement, 80% had positive X-ray film and 78.9% had positive skeletal isotope survey. Hemogram, serum alkaline phosphatase, serum calcium level and sedimentation rate were of no value in predicting whether the marrow was involved or not. No complications were documented following biopsy. The use of the Jamshidi bone marrow biopsy needle for staging and early detection of metastases in a select group cancer patients is suggested.


Alterations of the cell surface morphology in human T-rosetting lymphocytes. An ultrastructural study. A study of E-rosette ultrathin sections has been undertaken in an attempt to analyze changes induced during the T-lymphocyte-sheep red blood cell interaction on the rosetted lymphocyte surface architecture. The formation of nonimmune rosettes implies different types of attachment between lymphocytes and sheep red blood cells which can affect the rosetted lymphocyte surface morphology: (a) Junctions not involving morphological changes which correspond to bands or point-to-point contact sites. (b) Junctions displaying localized morphological changes, which are revealed mainly in the form of microvilli or digitations. (c) Junctions involving broad morphological changes, revealed primarily by the development of various microvilli or other more complex structures. In both cases, the alterations are found only in those areas of the lymphocyte membrane-bound sheep red blood cells. The modifications that affect the rosetted lymphocyte make the validity of the E-rosette test questionable for studies aiming at the analysis of the lymphocyte surface architecture.


Microbicidal function of the neutrophils in hairy-cell leukaemia. The ability of neutrophils from patients with hairy-cell leukaemia to kill Candida guilliermondii and Staphylococcus aureus in vitro was investigated. Of 10 patients, 8 showed defective candida killing, 5 defective bacteria killing, in comparison with normal controls. Study of those patients who underwent splenectomy suggests that neutrophil function can be improved by splenectomy. The possible causes of defective function in this disease are discussed.


Terminal transferase in leukemia of adults. Terminal deoxynucleotidyl transferase (TdT) determinations were carried out on peripheral blood leukocytes or bone marrow cells from 61 adult patients with various types of leukemia. TdT activity was undetectable in the cells of patients with acute myelocytic or acute myelomonocytic leukemia but was present in 12 of 13 patients with acute nonmyelocytic leukemia. None of 3 patients with acute myelocytic transformation of chronic myelocytic leukemia (CML) manifested TdT activity while 4 of 6 patients with lymphoid transformation had such activity. More patients with TdT in their leukemic cells responded to treatment than those without TdT activity. However, our findings suggest that TdT activity may be less useful in management of leukemia than has sometimes been supposed.


Acute agnogenic myeloid metaplasia with chromosomal abnormalities. A case of a 37-year-old woman presenting with acute agnogenic myeloid metaplasia (AAMM) is described. The disease had a stormy course and was characterized by moderate splenomegaly, persistently depressed WBC counts, extramedullary hemopoiesis and presence of a high percentage of atypical myeloblasts in the peripheral smear. Platelets were persistently low, reticulocytes significantly below normal, notwithstanding anemia. Hot tended to fall progressively to intolerably low values in the absence of transfusion. The chromosomal mapping of peripheral blood revealed the presence of a trisomy of chromosome No. 8. This abnormality already demonstrated in two previous cases of acute myelofibrosis and the clinical course of the disease suggest that acute myelofibrosis and AAMM could be the same disease while chronic myelofibrosis should be considered a separate entity. Also, it is possible that AAMM with trisomy of chromosome No. 8 and stormy clinical course may be a different entity from the acute myeloproliferative disorders associated with other chromosomal abnormalities.


Chronic myeloid leukaemia and a myasthenic syndrome. This is the first report of a case of chronic myeloid leukaemia (CML) complicated by myasthenic syndrome. The patient suffered two prolonged periods of idiosyncratic busulphan-induced marrow aplasia, the first occurring 5 months after busulphan was stopped. Between these two episodes, and at a time when no therapy was required for the leukaemia, myasthenic syndrome developed. After the patient recovered from the second episode, the myasthenic syndrome disappeared, and, despite subsequent recrudescence of CML, there were no further myasthenic symptoms, and treatment with neostigmine was discontinued.


Thrombocytosis, thrombocythaemia and iron deficiency in patients with polycythaemia vera. 6 patients with polycythaemia vera who also developed concomitant iron deficiency are reported. When oral iron therapy was given, there was a marked reduction in the previously elevated platelet counts in 4 patients; during 2-9 years of observation of these patients there was a significant inverse relationship between haemoglobin concentration and platelet count. In the other 2 patients the elevated platelet counts did not fall when iron therapy was given. The significance of these different patterns of response in relation to the causal mechanism of elevated platelet counts in patients with polycythaemia vera is discussed.


Anti-lymphocyte antibody levels in chronic lymphocytic leukaemia. A radioimmunoassay for measuring levels of lymphocyte autoantibody in chronic lymphocytic leukaemia (CLL) has been developed. Antibody in the form of crude IgG was extracted from patients' sera and iodinated. The assay utilizes its cross-reactivity with other CLL cells. Levels were measured in 23 patients. The results show that an inverse relationship exists between the quantity of circulating CLL autoantibodies and the number of mouse red blood cell rosetting lymphocytes (M cells). The preliminary findings do not correlate with disease activity although it is our impression that patients who are maintaining higher levels of autoantibody and fewer M-rosetting cells have nonprogressive disease.


Serum ferritin and mean corpuscular volume measurement in the diagnosis of beta-thalassaemia minor and iron deficiency. The value of serum ferritin and mean corpuscular volume (MCV) measurement in distinguishing between iron deficient, beta-thalassaemia trait and normal subjects has been studied. Normal subjects had normal ferritin and MCV, iron-deficient ones had low ferritin and low or normal MCV, and thalassaemics had normal ferritin and low MCV. By the combined use of these two measurements it was possible to identify individuals belonging to one of the three categories with an accuracy of over 95%. Although definitive diagnosis of beta-thalassaemia trait requires the demonstration of abnormal haemoglobin A2 levels or reduced beta-chain synthesis, serum ferritin and MCV measurements are useful screening procedures for the initial diagnosis of beta-thalassaemia trait and iron deficiency. Because of the very small amounts of blood required for both of these measurements, they are particularly suitable for surveying large numbers of subjects in populations with a high prevalence of hypochromic-microcytic anaemias.


[Brain rat histoenzymological changes induced by microsphere injection during ischemia (author's transl)]. The cerebral thrombosis of the rat with 35 micrometer labeled microspheres gives infarcted areas easily seen. After 15 min, in these areas, there is no change in NADH diaphorase-, succinic-dehydrogenase-, mono-amino-oxidase-, glucose-6-phosphate-dehydrogenase-, isocitric dehydrogenase-, lactic-dehydrogenase-, ATPase, alpha galactosidase-, acid phospatase activity. After 2, 4, 6 h all these activities diminish in the neuropil but they are preserved in the neurones for diaphorase, succinic-dehydrogenase and mono-amino-oxidase. The margin of infarcted areas shows a strong staining for acid phosphatase. Before 2 h there is not enzymatic changes neither oedema. This experimental model seems trustly and could be developped.


Anaphylaxis in the monkey: pulmonary oedema after pre-treatment of beta-receptor stimulants. Aggregate anaphylaxis was induced in seven ovalbumin-sensitized monkeys, with high tires of ovalbumin specific haemagglutinating antibodies. After pretreatment with an intravenous (i.v.) injection of 0.25 mg/kg terbutaline (n = 6) or an infusion of isoprenaline (n = 1), anaphylactic shock was induced by i.v. challenge with specific antigen. Haemodynamics, regional blood flows, respiratory mechanics, blood gases and haematological changes were studied during the following 30 min. Severe shock developed following ovalbumin challenge and the cardiac output was reduced by a mean of 74%. Pulmonary vascular resistance increased 11-fold. Pulmonary dynamic compliance decreased, but there was only a minor increase in pulmonary resistance. Hypoxaemia and severe metabolic acidosis developed. Circulating platelets and leucocytes decreased markedly. Three animals died with fulminant pulmonary oedema. In conclusion, the reaction pattern was similar to that found in studies of monkeys that received no prior treatment. However, the occurrence of pulmonary oedema suggests that the effects of large doses of terbutaline on the heart, combined with the high pulmonary vascular resistance, resulted in more severe pulmonary changes than took place in untreated animals.


Comparative effects of repeated and prolonged inhalation exposure of beagle dogs and Cynomolgus monkeys to anaesthetic and subanaesthetic concentrations of enflurane and halothane. Male and female Beagle dogs and Cynomolgus monkeys were exposed to anaesthetic (1.5 MAC) and subanaesthetic (1/100 MAC) levels of enflurane and halothane for 3 hours on alternate days for 4 weeks. One-half of the animals were killed following the last exposure and the remainder after 4 weeks of recovery. The animals' condition was assessed during anaesthetic periods by measuring respiration, ECG, blood pressure, temperature and EEG. Haematology, urinalysis and clinical chemistry parameters were evaluated. Gross and microscopic pathological examinations were conducted at the end of the exposure and recovery periods. Two female monkeys in the mid- and high-dose halothane groups died during the study. No deaths were observed in the enflurane group. No quantitative differences were observed in respiration rate, heart rate, blood pressure and EEG activity of animals anaesthetized with enflurane or halothane. Muscle twitches were observed in some mid- and high-dose dogs inhaling enflurane, but not in monkeys. A number of liver function tests became abnormal in mid- and high-dose halothane-treated dogs and high-dose halothane-treated monkeys. This was not observed with enflurane. Histopathologic alterations were confined to the liver of animals exposed to halothane. In dogs, the lesions were characterized by centrilobular hepatocyte degeneration and/or necrosis, fibroblastic proliferation, hepatocyte enlargement, fat deposition and glycogen depletion; and in mid- and high-dose monkeys by moderate to marked hepatocyte vacuolation and fat deposition. Except for one high-dose dog, these lesions were not seen in animals killed after 4 weeks of recovery. No histopathologic alterations were observed with enflurane.


Anatomy of the auditory tube and related structures in the rhesus monkey (Macaca mulatta). The primate nasopharynx-auditory tube-middle ear complex is being used by several researchers to model both normal and pathologic functions of the human auditory tube. An extensive search of the literature has indicated little detailed information on the primate tube/middle ear system. This study was undertaken to define the anatomical characteristic of the system in the rhesus monkey (Macaca mulatta) and to determine the limits on the use of the monkey as a model of human tubal function. Although the direct application of morphologic data to account for the observed function of a system is a tenous one, the data on the rhesus monkey auditory tube appear to be consistent with those published for other mammals. The tensor veli palatini muscle appears to be the only muscle to act directly on the tube and effect tubal dilation. The muscle is attached to the lateral membranous tubal wall along its extrabullar extension. The muscle has an inferior attachment to the posterior hard palate and thus possesses a vector directed inferolaterally; contraction would appear to pull the membranous wall inferiorly and laterally, resulting in tubal dilation. The auditory tube relationships of the salpingopharyngeus, levator veli palatini, and internal pterygoid muscles are described. Their possible role in primate tubal function is minimal at best.


Para-articular ossifications associated with melorheostosis Léri. A case of para-articular ossifications associated with melorheostosis gave differential diagnostic problems, as the only symptom referred to the ossifications in the left knee region.


Treatment of para-articular ossification after total hip replacement by excision and use of free fat transplants. Six patients with para-articular ossification after total hip replacement were treated by excision and free fat tissue transplantation. The results of treatment were good and at the follow-up examinations, 2 to 8 years after the operation, a good range of movement of the hip joint was noted in all cases. It was apparent that the free fat transplant had prevented the recurrence of the para-articular ossification.


Clinical and social status following injury to the lateral ligaments of the ankle. Follow-up of 144 patients treated conservatively. Out of 174 patients treated conservatively for injuries to the lateral ligaments of the ankle 144 were seen at follow-up after 3.1--6.1 years (mean 4.2 years), and clinical as well as social sequelae were recorded. The diagnostic criterion was a difference in talar tilt of 6 or more degrees between the injured and uninjured foot on inversion stress radiographs. Occupational and athletic injuries, almost equally represented, made up a total of 64 per cent. Residual symptoms were present in 21 per cent, mainly in the form of functional instability, but only four patients (3 per cent) reported daily complaints. One patient had developed reflex dystrophy, and this was the only patient who had been referred for further orthopaedic treatment. There was a close correlation between pain on movement in the ankle joint and residual symptoms which were, incidentally, unrelated to the degree of primary talar tilt. All the patients seen at follow-up had normal range of movement in the talocrural and subtalar joints. Two patients with residual symptoms had stopped working, while in the others the working ability was unaffected. The period off work had been twice as long for patients having heavy and fairly heavy work as for those doing light work. All football players with residual symptoms had had to give up playing, but only a few had daily complaints. This indicates that some symptom-free patients have in fact latent symptoms, elicited only by fairly severe strain.


Radiological and muscular status following injury to the lateral ligaments of the ankle. Follow-up of 144 patients treated conservatively. An average of 4.2 years after conservative treatment of injury to the lateral ligaments of the ankle 144 patients attended a follow-up examination which included radiography and measurement of the strength of plantar flexion. Prior to treatment all of the patients had a difference in talar tilt of 6 or more degrees between the injured and uninjured side. At follow-up there was instability in 28 patients, or 19.4 per cent, but no correlation between instability and residual symptoms. Nine patients had an anterior "drawer sign" exceeding 2 mm, but this was also without relation to residual symptoms. Radiological evidence of osteoarthrosis was found in five patients, but four of them had a stable ankle joint and only one had residual symptoms. The mean age of the patients with osteoarthrosis was twice that for the entire material. Two patients had osteochondritis of the talus. The strength of plantar flexion was measured in 124 patients. There was significantly less strength in the injured than in the uninjured leg, but there was no statistically significant correlation between residual symptoms and reduced strength or between radiological instability and reduced strength. According to the results of the present study and a previous one (Hansen et al. 1979) and to the results reported in the literature, we find no reason to alter our present principles regarding the diagnosis and conservative treatment of injury to the lateral ligaments of the ankle.


The role of endogenous cortisol in patients with non-thyroidal illness and decreased T3 levels. The aim of the study was to elucidate if endogenous cortisol, as previously suggested, could be involved in the mechanism behind the reduced serum T3 levels seen in euthyroid patients with various non-thyroidal illnesses. The correlation between the serum levels of T3 and cortisol was investigated in 41 hospitalized patients with non-thyroidal illness during hyperpyrexia. The results showed a correlation coefficient of -0.94, indicating a close reciprocal association between the two hormones. Cortisol may thus be one factor associated with the decreased T3 levels seen in euthyroid patients with non-thyroidal illness. The results also indicate a close parallelism between the total and free T3 levels during hyperpyrexia.


Blood supply of the rat hypothalamus. VI. Posterior region of the hypothalamus (nucleus hypothalamicus posterior, nuclei praemammillares, nucleus supramammilaris, mammilary body). It was shown by the double ink-filling technique that the arteries of the rat premammillary region and mammillary body arise from the a. communicans posterior while these areas are drained by the anterior interpeduncular vein. Disregarding some minor overlaps and anastomoses, the blood supplies of the two territories are independent of each other and from the neighbouring areas of the hypothalamus, diencephalon and mesencephalon. Arteries of the premammillary region arise from the premammillary artery, except for some branches of the posterior tuberal and interpeduncular arteries. The mammillary body is supplied by three mammillary arteries (anterior, posterior and lateral). The premammillary region drains into the anterior and posterior premammillary veins. Venous blood of the mammillary body is collected by the anterior and posterior mammillary veins which end in the anterior interpeduncular vein. The circulation of individual premammillary and mammillary nuclei is described in detail.


Dichlorvos intoxication and gastric secretion. Gastric acid secretion, pepsin concentration in gastric juice and acetylcholinesterase and histidine decarboxylase activities in gastric mucosa of rats treated with dichlorvos (DDVP) were investigated. The increase of HCl secretion, the decrease of acetylcholinesterase activity and enhanced activity of histidine decarboxylase were observed. It is suggested that a higher gastric acid secretion is secondary to histamine production in gastric mucosa, induced by acetylcholine yields gastrin yields histidine decarboxylase mechanism.


[Analysis of results with Depamide in children with psychomotor instability (hyperkinesis (author's transl)]. This study results from observations, for 10 years, of children with psychomotor instability, also called hyperkinesis, generally due to "minimal brain dysfunction". A clinical summary emphasizes instability and difficult coordination of all aspects of personality. A pathogenic hypothesis concerns one of the stimulation function which may be abnormal, as the control and regulation of personality, partly located, at the subcortical level, and creating secondary symptoms and reactional ones. The results of therapy are interpreted according to a clinical research protocol. It proposes a global appreciation, an appreciation of the duration of therapeutic effect through the study of variation of specific criteria, and a general appreciation correlating both aspects. Through this stern methodology and the mean duration of treatment of 2 years, the results are significant in 55% of the cases. Compared to other drugs, Depamide seems more valid. Furthermore, this drug is without secondary clinical and psychological effects.


Hyperalimentation in alcoholic hepatitis. Enteral hyperalimentation in four patients with severe alcoholic hepatitis and anorexia increased spontaneous food intake, increased their nitrogen balance and the patients improved clinically. Seven patients with alcoholic hepatitis, who were clinically ill and able to eat only 410-1,100 calories per day, were given a 900 mosM/l. parenteral "hyperalimentation" solution by a peripheral vein (P-900). The intravenous nutrition provided daily 51.6-77.4 gm. amino acids in addition to oral intake. All patients improved. None developed detectable encephalopathy after 16-42 days of P-900 therapy. Five additional patients had ascites and alcoholic hepatitis. The daily infusion of 2,000 ml. P-900 was not associated with hyponatremia, renal failure or encephalopathy in four of these five patients who improved and continued their diuresis. P-900 therapy was discontinued in one because of progressive hyponatremia. The observations indicate that over and above the maximum tolerable oral nutrition, intravenous nutrition can be effectively utilized by clinically ill, jaundiced patients with alcoholic hepatitis without precipitating encephalopathy or interference with standard therapy of ascites.


Functional and morphological affinities of the subadult hand (O.H. 7) from Olduvai Gorge. Study of the O.H. 7 hand was based primarily on morphological comparisons with a large series of hand skeletons of extant hominoid primates. Most of the hand elements are fragmentary or have missing epiphyses and only comparisons based on qualitative morphological observations are possible. The distal phalanges are complete, however, and were analyzed metrically utilizing univariate and multivariate statistical techniques. To compensate for size differences among the Hominoidea a number of size adjustments were employed. None of the adjustments were totally satisfactory from theoretical and practical standpoints and none completely eliminated the influence of size. There is no entirely satisfactory procedure to eliminate size and it is advisable to use several techniques that are not closely related, to compare the results and interpret them with caution. In certain features the wrist and fingers resemble those of African apes; in others they are more like modern human hands; in still others they are unique. The scaphoid and the proximal articular surface of the trapezium retain ape-like features, as do the proximal and middle phalanges. The pollical carpometacarpal joint and the distal phalanges are closer in morphology to those of modern humans. The scaphoid, proximal phalanges and middle phalanges of rays II-V indicate a hand capable of a strong power grip. A number of features of the thumb and the distal phalanges suggest that the O.H. 7 individual was capable of more precise manipulation that extant apes. FLK NN-A, a first distal phalanx, does not closely resemble the first distal phalanx of any of the living Hominoidea. Multivariate distance analysis indicates, however, that it is closest in overall morphology to the pollical distal phalanx of modern humans. In some features not included in the metric analysis, FLK NN-A also resembles the hallucial distal phalanx of modern humans.


Quantitative comparison of the hominoid thalamus. I. Specific sensory relay nuclei. Studies to date have indicated few differences in sensory perception among hominoids. Sensory relay nuclei in the dorsal thalamus--portions of the medial and lateral geniculate bodies (MGBp, LGBd) and the ventrobasal complex (VB)--in two gibbons, one gorilla, one chimpanzee and three humans were examined for anatomical similarity by measuring and estimating the nuclear volumes, neuronal densities, numbers of neurons per nucleus, and volumes of neuronal perikarya. The absolute volumes of these nuclei were larger in the larger brains; however, with the volume of the dorsal thalamus as a standard, these sensory relay nuclei showed negative allometry. The gibbons had about half as many neurons as did the other hominoids. Although the human VB had slightly more neurons, the numbers of neurons in LGBd and MGBp did not significantly differ between the great apes and humans. The volumetric distribution of the neuronal perikarya were similar among these hominoids. Other thalamic nuclei had much more diverse numbers of neurons and relative frequencies of their neuronal perikarya. The sensory relay nuclei appear to be a group of conservative nuclei in the forebrain. These results suggest that as a neurological base for complex behaviors evolved in hominids, not all parts of the brain changed equally.


Further morphometric studies of the ulna from the Omo Basin, Ethiopia. A reanalysis of the L40-19 fossil ulna from the Omo Basin, Ethiopia is presented. Using covariance adjustment rather than ratios to correct metric data for variations due to body size, a comparative sample reflecting 21 contemporary Anthropoid taxa, and both distribution-free and multivariate statistical procedures, this study indicates that the earlier conclusion drawn by McHenry et al. ('76), viz., that the fossil is "unique" among Hominoids, is essentially correct. This study also concludes, however, that although the fossil is projected closer to Pan and Homo than to Pongo, the distances are considerably greater than found between behaviorally similar modern forms. Consequently, aside from assigning the fossil on morphometric grounds to the Hominoidea, little else can be said about its possible locomotor habits or its ancestry.


Growth, function and homology: aspects of dental replacement in toothcombed strepsirhines. In maturing juvenile lemurs and lorises, it was found that the anteriormost lower deciduous premolar migrates forward and may become associated with the teeth of the toothcomb; this is similar to previous observations on the dentition of indriines. The mesial shift of dp2 appears to be associated with the eruption of P2 but, more importantly, also with replacement of the deciduous by the permanent teeth of the toothcomb--which is a period of functional disruption at the front of the jaw. It is suggested that this growth-related phenomenon should not be confused with other aspects of dental development and eruption which might be indicative of homology.


Aspects of the middle and external ear of early South African hominids. A brief description of the exposed middle ear from two Swartkrans specimens demonstrates the feasibility of examining the inner auditory structures of existing fossil hominid material. These Swartkrans fossils provide the first clear view of the early hominid middle ear, and their structures appear to be morphologically distinct. The bony anatomy of the external ear of Australopithecus robustus is found to be unique among the South African hominids.


Fabry's disease. Primary diagnosis by electron microscopy. Fabry's disease is a lipid storage disease found in children and adults. The lipid is stored as a myelin-figure-like whorl of membranes in endothelial and smooth muscle cells, myocardium, fibroblasts, and epithelial cells of the glomerulus. The lipid deposits are identifiable by light microscopy, but are much easier to demonstrate by electron microscopy. The disease leads to vascular insufficiency because of narrowing and thrombosis of arteries and arterioles. The resultant vascular insufficiency leads to peripheral neuritis, myocardial infarction, peripheral infarction and cerebral infarction. Corneal clouding due to lipid deposits is also seen. Renal involvement is widespread, but renal failure occurs late.


Middle East lymphoma and alpha-chain disease. An immunohistochemical study. An immunoperoxidase study of the small intestinal mucosa of three patients with alpha-chain disease showed heavy infiltration of the mucosa by plasma cells containing alpha-heavy chain and J-chain but no light chains. An additional band-like and nodular mucosal infiltrate was also present and consisted of cells showing no evidence of cytoplasmic immunoglobulin synthesis. The cells comprising this infiltrate invaded and destroyed intestinal crypts, and immunoperoxidase staining showed them to be sharply distinct from the alpha-chain-containing plasma cells. In two cases of Middle East lymphoma, immunohistochemistry revealed a normal plasma cell population in the lamina propria of the small intestine. These results show that alpha-chain disease can be diagnosed in routine paraffin sections which should permit clarification of its true incidence in Middle East lymphoma. The demonstration of sharp distinction between the two types of mucosal infiltrate in alpha-chain disease is in contrast to previous immunofluorescence results and enables more ready identification of mucosal changes that may be important in the management of the disease.


Evaluation of various doses of testosterone on accessory reproductive organs and plasma testosterone in intact and gonadectomized rhesus monkeys (Macaca mulatta). The effect of 10 days i.m. treatment of testosterone propionate (TP) on plasma testosterone and accessory reproductive organs were studied in adult (6 to 6 1/2 kg) male rhesus monkeys, housed under natural light conditions using six different dose levels. The study was scheduled in the month of September and October. To maintain the weight of accessory reproductive organs and testosterone levels in castrates, different dose levels of exogenous testosterone propionate were required: 3.2 mg/d for seminal vesicles, 4.8 mg/d for ventral prostate and 3.2 mg/d for plasma testosterone titer. The levels of so-called "physiological" doses of exogenous testosterone varied for various target organs under consideration. TP at a dose of 0.4 mg/d had a depressing effect on plasma testosterone in intact monkeys. For higher doses, plasma testosterone increased roughly similarly in both intact and castrated monkeys. It suggests that with otherwise "physiological" doses of testosterone propionate, there is an almost complete blockage of endogenous testosterone secretion.


[Monitoring of extra- and intra-cellular compartment through total body impedance (author's transl)]. To evaluate the extra-cellular space, we measure the impedance (or resistance) of the extra-cellular electrolyte compartment with an alternating current at a fixed frequency of 5 kHz that can't pass through the cellular membrane. Total water is measured by the impedance to a current of 1 MHz which is conducted by extra and intra cellular hydro-electrolytic space. There is a good correlation between electrical impedance measurements and distribution of isotopic markers. The extra-cellular compartment was evaluated by diffusion of D.T.P.A. marked with 99mTc or with 111In and the total water by the diffusion of Antipyrin marked with 1,311 or 1,231. The findings indicate that there is not a significant difference between the results of the size of extra-cellular water measured by electrical impedance and D.T.P.A. diffusion (r = 0.75). Comparable results have been obtained in the determination of total water by electrical impedance measure and diffusion of Antipyrin (r = 0.90). We have also studied by method of electric impedance:--The state of hydratation in head injured patients and after pituitary surgery.--The lean body mass and hydro-electrolyte compartments in pregnancy. Electrical impedance measure seems to be a simple and reliable method to assess the hydric state of patients.


The effect of hemorrhagic shock on plasma amino acids and tissue energy substrates in the primate. Levels of plasma amino acids and muscle concentrations of energy substrates and metabolites after shock in the Macaca mulatta Rhesus monkey were investigated. The hemodynamic response to shock is similar to that of previously reported studies of primates in shock. Plasma glucose and ASAT increased significantly, while levels of ALAT and pyruvic acid did not change. Lactic acid was elevated. Muscle glycogen and concentrations of lactic acid were increased, and levels of pyruvic acid, creatine phosphate, and malate fell during shock. Levels of ATP in muscle were unchanged. Nine of the 23 arterial plasma amino acids analyzed decreased significantly. Aspartic acid was increased during shock. The increased levels of tissue carbohydrates and decreased concentrations of plasma amino acids observed in this study differ from results previously reported for other animal shock models. Changes in amino acid levels are similar to the results of some clinical studies.


[Changes in cholesterol esterification ratio during parenteral feeding including lipids (author's transl)]. Authors report the finding of an important change in the esterification of plasma cholesterol during parenteral nutrition using 10% intralipid. Thirty-seven patients with various disorders were included in the study. The results and possibility of deleterious effects are discussed.


[An atypical form of Waldenstrom's macroglobulinaemia with complete remission lasting for more than two years after multiple chemotherapy (author's transl)]. An authentic case of Waldenstrom's macroglobulinaemia without a tumoural syndrome is reported, with initial signs of peripheral pancytopenia. Complete and persistent remission appears to have followed multiple sequential chemotherapy. This very satisfactory and, according to data in the published literature, very rare result suggests that this type of treatment should be prescribed for all patients with macroglobulinaemia with poor prognostic clinical and histological characteristics.


[Evaluation of urease and beta-glucosidase activity for the practical identification of mycobacteria (author's transl)]. The urease and the beta-glucosidase for the identification of the mycobacteria were evaluated using 1,019 strains received for reference purposes in this laboratory in 1978. We found that the urease test was useful in the differential identification of BCG which, contrary to Mycobacterium bovis, gave a strong positive reaction in 3 h. The test was also useful to discriminate M. scrofulaceum from pigmented strains of M. avium. The beta-glucosidase test discriminated between M. tuberculosis and M. bovis and was useful to distinguish the niacine-positive strains of M. africanum which were usually negative in this test. The beta-glucosidase test was particularly useful in the differential identification of M. fortuitum and M. chelonei. In this report, the frequency distribution of the species which were submitted to this laboratory in 1978 was also shown and the results obtained for each of the conventional test procedures was presented.


Transfer factor in immunodeficiency diseases. Results of therapeutic trials of transfer factor in a number of laboratories suggest clinical benefit and enhancement of immunological reactivity in patients with primary or secondary immunodeficiency diseases. Long term follow-up of 32 patients with the Wiskott-Aldrich syndrome suggested that transfer factor caused conversion of immunologic reactivity, apparent clinical benefit, and prolonged survival in some, but not in all patients. In 18 patients with disseminated (Stage III) malignant melanoma treated with surgery and transfer factor, survival was better than would ordinarily be expected for disseminated disease (78% with mean follow-up of 2 years). A randomized trial has been initiated which will answer the question of the efficacy of transfer factor as surgical adjuvant therapy in malignant melanoma. Studies in human subjects suggested that transfer factor does not cause enhancement of reactivity in normal subjects, when evaluated in a controlled, double-blind fashion. Similar controlled studies in immunodeficient patients are necessary to ascertain whether transfer factor does cause enhancement of immune responses in these patients. Based on these observations, a guinea pig model was developed in which transfer factor caused abrogation of tolerance to ABA-Tyrosine.


Biological activity of the pure thymus protein, LSHr. LSHr, a protein from thymus, was shown to be a single pure peptide of 80,000 daltons by its migration in Sephadex G-150, SEDImentation velocity ultracentrifugation, both regular and SDS gel electrophoresis, and isoelectric focusing as a single symmetrical peak. It promoted the differentiation of T-lymphocytes in in vitro and in vivo tests. Human bone marrow cells showed differentiation in response to LSHr treatment to express a surface marker unique to T-cells following incubation with 10(-14) to 10(-9) M LSHr. Control proteins showed no effect. In preliminary experiments, administration of microgram quantities of LSHr to nude mice for 2-3 weeks induced development of T-cell function as determined by antibody response to a T-dependent antigen, and a response of spleen cells to T-cell mitogen.


[Bacteriophage typing of 823 "Listeria monocytogenes" strains isolated in France from 1958 to 1978 (author's transl)]. This study was undertaken to establish a typing scheme for Listeria monocytogenes. A total of 823 strains, isolated in France from 1958 to 1978, were studied; 69.4% of these belonged to serotype 4. Using a set of 20 phages, the lytic activity, frequency and specific character of these phages were estimated and phage typing carried out. We were able to define a phage typing system for L. monocytogenes using 12 principal phages and 3 secondary phages. In order to discriminate phages types within serotype 1, the phages 1, 3, 4, 5, 6 and 7 were used, and for phage types within serotype 4, the phages 10, 11, 14, 15, 16 and 17. Secondary phages 8, 9 and 20 had a weak lytic activity, but their specificity was very high. The lytic patterns obtained with the phages 9 and 20 were restricted to strains of serotype 5. We established a complete correlation between the lytic pattern of phages 1 to 8 and serotype 1, just as there was a correlation between the lytic pattern of phages 10 to 19 and serotype 4. Using the set of 20 phages we were able to type 645 of 823 strains of L. monocytogenes. Thus we were able to type 78.4% of all the strains examined. This percentage was very different according to the serotype of the strains tested: 88% of strains of serotype 4 and 57% of strains of serotype 1. With this set of phages 552 of 645 typable strains could be subdivided into 8 principal phagetypes: 3 types within the serotype 1 and 5 others in serotype 4. This phage typing system can be used in some epidemiological situations, in taxonomic investigations or as bacterial markers.


[Effect of moderate protein-energy malnutrition in preschool children on various biochemical parameters. Use of biochemical indicators for early detection of malnutrition]. The efficiency of several biochemical parameters as indicators of moderate protein-energy malnutrition was investigated. 810 children aged under 5 years were studied in the forest region of southern Cameroon. The children were divided into groups of controls children and moderately malnourished children based on anthropometry. The means values of most of the biochemical parameters were decreased in the malnourished group. Prealbumin, Transferrin, Hydroxyproline index and Albumin/Globulins ratio showed the most significant decreases. There were highly significant (P less than 0.001) correlations between the parameters and all the anthropometric tests. It is concluded that biochemical tests studied are of value in detection of mild protein-energy malnutrition but only when used together and compared with levels in a control group of the same age and the same population. Because of the slight decreases, large distributions of individual values and interaction of factors others than malnutrition, interpretation of a single test appears to be very complex.


[Digestive duplications affecting the pharynx or fistulae of the fourth endo-branchial pouch. Four cases (author's transl)]. Four cases of children with recurrent latero-cervical epithelial cystic tumours which where identified as exceptional derivatives of the 4th endobranchial pouch on the basis of their connections with the pharynx and in particular the piriform fossa. The opportunity is taken to review the characteristics of equally rare digestive, duplications and congenital diverticula at a cervical and buccopharyngeal level. This diagnosis was made initially in the first of these cases.


Sporozoan infection in cultured Sparus aurata L. and wild Siganus luridus. White nodules containing intracellular ovoid Sporozoans were observed in internal organs (kidneys, liver and gut wall) of cultured Sparus aurata and in the liver of wild Siganus luridus in the gulf of Aquaba in the Red Sea. Nodules consisted of parasitised hypertrophic macrophage-like cells enclosed in a well-defined collagenous fibrous capsule. These parasites are evidently the cystozoite stage of a haemogregarine.


Defective activation of the pyruvate dehydrogenase complex in subacute necrotizing encephalomyelopathy (Leigh disease). Autopsy examination confirmed the diagnosis of subacute necrotizing encephalomyelopathy (SNE) in a 7-month-old male infant who underwent several metabolic studies before death. Intermittent lactic acidemia and fumaric aciduria, an extreme hyperglycemic response to an intravenous bolus of alanine, and an elevated total body flux rate of glucose (58.4 mumoles . kg-1 . min-1) suggested a disturbance in the oxidative decarboxylation of pyruvate. Enzymological studies of postmortem samples revealed low nonactivated pyruvate dehydrogenase activity in liver (19.4%) and brain (53.8%). The lowest brain pyruvate dehydrogenase activities were noted in the midbrain and pontine regions. Supramaximal activation of the hepatic pyruvate dehydrogenase complex (135% of control values) occurred in vitro. Spontaneous reactivation following in vitro inactivation of the complex with adenosine triphosphate was significantly less (p less than 0.02) in the patient's samples compared to controls. The biochemical defect was not apparent in fibroblasts. These enzymological observations point to an in vivo defect in the activation mechanism of the pyruvate dehydrogenase complex as the biochemical disturbance in SNE. The findings suggest that dichloroacetate may be beneficial in treating SNE.


Dorsal thalamic lesion in a noted case of human memory dysfunction. The extensively studied patient N.A. has had a severe verbal memory deficit since 1960, when he sustained a stab wound to the brain with a miniature fencing foil. His amnesia occurs in the absence of any other known cognitive defect. Recent CT scans have localized a lesion in the left dorsal thalamus of this patient in a position corresponding to the dorsomedial nucleus; there is no radiographic evidence of other damage in the diencephalon or cerebral cortex. The dorsomedial thalamus may be critical in the neuropathology of diencephalic amnesia and, in humans, may be required for normal memory functions.


Comparison of protein values in cerebrospinal fluid by nephelometry and radial immunodiffusion. Various parameters of three radial immunodiffusion systems, a kinetic nephelometer and two laser nephelometers were compared in a measurement of IgG and albumin in cerebrospinal fluid. Greater precision for IgG and albumin determinations was found with two RID systems. Correlation coefficients between methods ranged from 0.71 to 0.94. The generally poor correlations of methods, combined with the results of accuracy studies employing WHO standard reference dilutions and proportional errors demonstrated by linear regression equations, illustrate graphically the need for standardization in the field of immunochemical determinations. Our preliminary studies of the IgG/Alb ratio in cerebrospinal fluid of multiple sclerosis patients agreed with the work of others. In each case, the ratio was elevated or borderline high.


Acute intoxication with sodium valproate. Two epileptic patients developed an acute toxic encephalopathy consisting of altered behavior, deteriorating seizure control, and confusion while taking sodium valproate alone. Serum valproate levels were greater than 100 microgram/ml in both. Toxic symptoms resolved when the dose of valproate was reduced, with a consequent fall in serum concentration of the drug.


ABO and Rh blood groups in the Outer Hebrides. ABO and Rh (D--,dd) phenotype frequencies and gene frequencies are reported on 1547 pregnant women from different populations in the Outer Hebrides. There was significant heterogeneity of ABO gene frequencies in the Isle of Lewis, but not in or between other populations. More heterogeneity was apparent at the Rh locus, significant amounts being present between the populations of rural Lewis, between Lewis and Harris and between Lewis, Harris and the combined populations of North and South Uist, Benbecula and Barra. There was no evidence of heterogeneity due to religion in Benbecula or South Uist. Data on exogamy and endogamy suggest that migration between the various populations has been at a level sufficient to prevent or correct any tendency to genetic diversification. It is suggested tentatively that the heterogeneity observed may be the result of the massive emigration from the islands which has occurred over the last 150 years.


Kinetic studies on enzymatic acetylation of chloramphenicol in Streptococcus faecalis. The kinetics of chloramphenicol (CP) acetylation by CP acetyltransferase from Streptococcus faecalis was studied. CP was shown to be acetylated enzymatically to its 3-O-acetyl derivative (3-AcCP) in the presence of acetyl coenzyme A, after which 3-AcCP was converted nonenzymatically to its 1-O-acetyl isomer, 1-O-acetyl CP (1-AcCP). At equilibrium, the 1-AcCP and 3-AcCP were present in a 1:4 ratio. Subsequently the diacetylated product, 1,3-O-O-diacetyl CP [1,3-(Ac)2CP], was enzymatically produced from 1-AcCP by the same enzyme. Theoretical calculation of rate constants (k1, k2, k3) for each successive reaction is as follows: (Formula: see text). This calculation gave k1 = 0.4 min-1, k2 = 0.002 min-1, and k3 = 0.016 min-1. Experimental results agreed closely with these calculated values.


Microbial transformation of A23187, a divalent cation ionophore antibiotic. A23187 is an ionophore antibiotic that forms dimeric complexes with divalent cations such an Mn2+ and Ca2+. Over 200 randomly selected soil microorganisms were incubated with A23187. None of these cultures was capable of transforming this compound. In contrast, many microorganisms were able to modify the methyl ester of A23187. The transformation products produced by one culture, Streptomyces chartreusis, were isolated and identified as 16-hydroxy-N-demethyl A23187 methyl ester, 16-hydroxy-A23187 methyl ester, and N-demethyl A23187 methyl ester. These ester derivatives lack most of the ionophore properties of the acids and cannot readily form dimeric complexes with divalent cations. However, they could be hydrolyzed by a mild treatment with ethanolic KOH to free acids that possess good ionophore activity. The use of the ester substrate in conjunction with the hydrolysis procedure is, at the present time, the only known method for microbiologically producing A23187 derivatives.


Effects of cerulenin on antibiotic-induced lysis of streptococcus faecalis (S. faecium). Addition of the antibiotic cerulenin to cultures lowered the minimal effective concentration of penicillin G or methicillin required to produce bacterial lysis and killing. This effect was most pronounced at subinhibitory antibiotic concentrations. Cerulenin had no significant effects on lysis or killing induced in the presence of D-cycloserine, fosfomycin, bacitracin, or vancomycin.


Composition and biological properties of lipopolysaccharides isolated from Schizothrix calcicola (Ag.) Gomont (Cyanobacteria). The most common cyanobacterium contaminating drinking water systems in southwestern Pennsylvania is Schizothrix calcicola. Lipoplysaccharides (LPS) were isolated from this species by hot phenol-water extraction. The polysaccharide moiety was composed of glucosamine, galactose, glucose, mannose, xylose and rhamnose. The lipid A part contained beta-hydroxylauric, myristic, pentadecanoic, palmitic, beta-hydroxypalmitic, stearic, oleic, and linoleic acids. In contrast to many LPS isolated from Enterobacteriaceae, the dominant component was not beta-hydroxymyristic but beta-hydroxypalmitic acid. The LPS induced Limulus lysate gelation and Schwartzman reaction but was nontoxic to mice. The identity of LPS was verified by alkali and lysozyme treatment. The results suggest that S. calcicola is one of the principal sources of endotoxins in water systems using open finished-water reservoirs.


Effect of mercuric ion on the growth, photosynthesis, and nitrogenase activity of Anabaena inaequalis. Anabaena inaequalis was sensitive to mercuric ion (Hg2+) in the ppb (nanogram per milliliter) range. Growth was inhibited significantly at concentrations of metal ion as low as 2 ppb, and 100 ppb was required to inhibit photosynthesis and acetylene reduction. Low levels of Hg2+ stimulated acetylene reduction and photosynthesis. The lysis of vegetative cells was the primary action of mercuric ions, resulting in the inhibition of growth, photosynthesis, and nitrogenase activity. There was a linear relationship between numbers of cells and the amount of Hg2+ required to induce culture lysis. Calculated on the basis of equivalent cell numbers, Hg2+ was toxic to A. inaequalis at 0.006, 0.009, and 0.100 micrograms of Hg2+ per 10(5) cells for photosynthesis, growth, and acetylene reduction, respectively.


TSH and PRL response to thyrotrophin-releasing hormone in children with chronic renal failure undergoing haemodialysis. Eight children (aged between 8 1/2 and 15 1/2 years) with chronic renal failure receiving intermittent haemodialysis, and 2 children with renal transplants were studied. The response of TSH and prolactin (PRL), and basal T4 and T3 values was measured. Basal TSH was normal, and rose only slightly after TRH stimulation. Plasma T4 and T3 were below normal levels in 6 children. Mean basal PRL was raised and could not be stimulated by TRH. This study demonstrates the involvement of the hypothalamus and pituitary in chronic renal disease. The cause of the abnormal secretion of TSH and PRL in chronic renal failure is discussed in the light of clinical importance.


A rapid quantitative analysis of tyrosine and its oxidation products by tyrosinase. A new technique based on liquid phase ion exchange chromatography on short column is proposed for quantitative determination of tyrosine and Dopa. alpha-Amino,beta-guanidinopropionic acid is used as an internal standard of coloration. The role of H2O2 and ascorbic acid on tyrosine and Dopa was checked. Ascorbic acid prevents the auto-oxidation of Dopa, H2O2 has no effect on tyrosine but oxidizes Dopa even in the presence of excess ascorbic acid. This method was tested in mushroom tyrosinase, with and without ascorbic acid. Assays performed with tyrosinase from rabbit ocular extracts clearly showed that they do oxidize tyrosine. Reliability of the method is comparable to radioassay.


Levels of organochlorine pesticides and polychlorinated biphenyls (PCBs) in mothers' milk collected in Osaka Prefecture from 1969 to 1976. Long-term investigations of polychlorinated hydrocarbon levels in mothers' milk were made from 1969 to 1976. The levels of p,p'-DDE, p,p'-DDT, dieldrin and PCB in mothers' milk were within the range reported by others. However, beta-BHC(Hexachlorocyclohexane) levels in the milk were 10 times that found in non-Japanese. A gradual decrease in the beta-BHC level in the milk was observed during this period. In contrast, the levels of p,p'-DDE, p,p'-DDT, dieldrin and PCB were consistent for the 7-year period. A significant correlation between the levels of PCB and p,p'-DDE in mothers' milk and blood was observed in the 1974-1976 samples. However, after prohibition of the use of chlorinated hydrocarbons, this relationship was less apparent in the 1972-1973 samples.


Surveillance of the daily PCB intake from diet of Japanese women from 1972 through 1976. A survey of the daily PCB intake from the total diet of Japanese women was made for the years 1972 through 1976. All but one sample of 177 samples analyzed were contaminated with PCBs. Only one sample exceeded the acceptable daily intake (ADI) of PCBs of 5 micrograms/kg body weight in Japan. The average daily intake of PCBs per person was approximately 10 micrograms, which was very low compared to the ADI value. The main source of PCBs in the diet in Japan was inshore fishes, in contrast to fresh water fishes as in the U.S.A. The data obtained from this surveillance showed no statistically significant change of daily PCB intake from the diet during this 5-year period. However, there has been a marked decrease in the estimated intake of PCBs since 1972. Gas chromatograph analysis of the residual PCB patterns in the diet showed that the patterns in the marine products were somewhat different from those in dairy, meat, and poultry products. The former was similar to the pattern of the PCB standards mixture and the latter was similar to the PCB pattern found in human milk and tissue samples from the Japanese population.


Contaminant levels in animal feeds used for toxicity studies. Samples of commercial feeds for laboratory rats, guinea pigs, cats, monkeys, rabbits, and hamsters were collected and analyzed qualitatively and quantitatively for selected antibiotics, trace metals, pesticides (organophosphates and chlorinated hydrocarbons), natural agents, and polychlorinated biphenyls (PCBs). The results indicated that antibiotics, parathion, diazinon, aldrin, and the aflatoxins were not detected, whereas, metals, chlorinated hydrocarbon pesticides (except aldrin), and PCBs were continually present. Malathion and estrogen were found occasionally.


Sorption and desorption of atrazine by three bacterial species isolated from aquatic systems. The isolates Acinetobacter spec., Cytophaga spec. and Pseudomonas fluorescens represent different morphological and physiological types of bacteria. They accumulate atrazine (2-chloro-4-(ethylamino)-6-(isopropylamino)-5-triazine) to different levels. Accumulation expressed by the ratio of atrazine sorbed per volume of bacteria to atrazine per the same volume of water amounted to 11 for Acinetobacter spec., 8.6 for Cytophaga spec. and 6.2 for Pseudomonas fluorescens. Accumulation ratios were proportional to the surface areas of the organisms. Single cells of Acinetobacter spec. sorbed amounts of atrazine comparable to the other species investigated, whereas cell aggregates, formed a few months after isolation, sorbed an order of magnitude less. A large portion of atrazine accumulated by the bacteria could be rapidly desorbed. A remainder of 10% was bound by Cytophaga spec. and Pseudomonas fluorescens. Acinetobacter spec. bound 70--80% of the atrazine sorbed. In the range of 0.3--3 mg/L atrazine, there was a linear relationship between the amount of non desorbable herbicide and its concentration in the incubation medium.


Acute epididymitis: etiology and therapy. Fifty patients with acute epididymitis were evaluated prospectively by history, examination, and microbiologic studies, including cultures for aerobes, anaerobes, N. gonorrhoeae, Chlamydia trachomatis, and Ureaplasma urealyticum. E. Coli was the predominant pathogen isolated from the urine of men over 35 years old and C. trachomatis and N. gonnorrheae were the predominant pathogens isolated from the urethra of men under 35. The etiologic role of E. Coli and C. trachomatis was confirmed by isolation from epididymal aspirates from a high proportion of men with positive urine of urethral cultures for these agents. C. trachomatis epididymitis accounted for two thirds of "idiopathic epididymitis" in men, and was often associated with oligozoospermia. Of nine female sexual partners of men with C. trachomatis infection, six had antibody to C. trachomatis, of whom two had positive cervical cultures for this organism, and the others had nongonococcal pelvic inflammatory disease. Antibiotic therapy with tetracycline was effective for the treatment of men with C. trachomatis epididymitis, and should be offered to their female sex partner.


Male reproductive tract sequelae of gonococcal and nongonococcal urethritis. Gonorrhea is the most frequent bacterial infection as well as the most frequently reported venereal disease. Nongonococcal urethritis has approximately the same incidence as acute gonorrhea in cases reported by many venereal disease clinics. The relative epidemiology of the two diseases, as well as their acute and chronic manifestations in the male genital tract (urethritis, prostatitis, and epididymitis), will be briefly discussed. Resultant obstructions of the lower genitourinary tract of possible consequence to male fertility, such as urethral stricture disease and strictures of the ejaculatory ducts, are described in terms of anatomy, pathophysiology, and treatment. The postulated and demonstrable effects of infectious agents on seminal fluid and sperm are reviewed, with emphasis on the recent literature concerning Chlamydia and Mycoplasma.


Culture methods for Neisseria gonorrhoea. Cultures on an appropriate medium are both highly sensitive and specific, but false-negative cultures can occur because of sampling procedures, laboratory errors, sensitivity of certain gonococci to the vancomycin contained in selective mediums, or loss of bacterial viability in transport.


[Metabolic regulation of nutrition].

[Metabolic regulation of nutrition]. The mechanisms regulating nutrient metabolism and their adaptation and compensation during stress conditions are discussed. The stress conditions considered are fasting and refeeding, pregnancy, growth and development, and malnutrition.