Enterohepatic circulation of a new oral cephalosporin, FR10612, and its effect on serum and tissue levels in rats.

Serum levels of FR10612 given orally to rats persisted significantly longer than did those of cephalexin. Since the elucidation of this phenomenon observed in rats is considered to be pertinent to the understanding of the drug kinetics of FR10612 in other animals including man, the present study was undertaken. From the dose-response curve of the serum levels of FR10612 in rats, it is apparent that the maximum oral absorption is obtained in the range of 100-400 mg/kg. Even when the doses were increased from 100 to 1,000 mg/kg, the tissue levels with the exception of the kidneys, did not increase significantly. However, the persistence of the tissue levels was enhanced. The serum and tissue levels of FR10612 in rats after repeated massive dosings did not increase accumulatively. From the experimental results of FR10612 in rats with ligated bile ducts and the results obtained after intravenous injection, it seems clear that the prolonged in vivo levels of FR10612 in rats after oral dosing are closely related to its enterohepatic circulation.


Action of caffeine and theophylline on staphylococcal penicillinase synthesis.

Both caffeine and theophylline acting in subinhibitory concentrations inhibit the synthesis of penicillinase in Staphylococcus aureus. Neither of these compounds inactivate the enzyme. Inhibition of penicillinase synthesis is attributed to the lack of formation of penicillinase rather than the elimination of the extrachromosomal plasmid.


[The Nakayama technique of shunt creation for chronic hemodialysis. Experience, complications and possibilities of their removal].

The Brescia-Cimino fistula is carried out as an end-to-end anastomosis for mechanical flow reasons. The Nakayama anastomosis in the upper plexus anesthesia is carried out as a fast and simple apparatus method. Between 1973 and June 1977, 114 Nakayama anastomoses were performed in 80 patients. Till June 1977, 61 were still usable. Time and cause of occlusion were analyzed. Early occlusion (within 30 days) was mainly caused by faulty operation. Late occlusion (within 4 months) was mainly caused by thrombosis at the tantalum ring and improper usage. Shunt occlusion was remedied by a new connection on the same or on the other arm, by vein replantation, or by construction of a vein loop. The arteria femoralis was placed in subcutaneous position when blood vessel conditions were unfavorable. Tests with Spark's prosthesis and autologous vein transplantation produced no usable vessels.


[Hemodialysis--the arteriovenous fistula, distal to the wrist joint].

The arterio-venous fistula distal to the proc. styloides radii in the "tabatière" offers a most useful additional and very peripheral vascular access for chronic hemodialysis. It in no way compromises the further construction of arteriovenous anastomoses in be forearm in fistula failure. The results of 26 such fistulas are reported.


[Selective proximal vagotomy (SPV). Experience and technic using the LDS device].

In the period between January 1974 and 1977, a total of 358 selective proximal vagotomies were performed in patients with gastroduodenal ulcers avoiding pyloroplasty if possible. This report is concerned with intra- and postoperative experience with Burge's operating technique, incorporating LDS instruments from the USSC. The use of the instrument in preparing the proximal stomach is discussed. The instrument is recommended for reducing the time needed for emergency and simultaneous operations and for performing vagotomy in high risk patients.


[The solvent-dried dura mater. A new dura transplant in the animal experiment].

After the excision of 7 X 5 mm abdominal muscle sections in an experiment using rats, rehydrated, solvent dried dura grafts of the same size were implanted. After three hours the tissue reaction of the transplant areas were continuously examined under a light and electron microscope for 14 months. A gradual graft decomposition advancing in a coating form from the periphery to the center and a simultaneous replacement with collagenous connective tissue of the body resulted due to an absorbent granulation tissue rich in cells and blood vessels after the initial infiltration of neutrophil granular leukocytes caused by the operation. A fibrous-rich connective tissue plate, in part forming two layers and thereby serving as a reminder of the former dura graft is decomposed in the abdominal muscles of the rats without infection or rejection and replaced with endogenous connective tissue. The duration of this decomposition and transformation process is contingent on the size of the graft and the tissue reactivity in the surrounding transplant area.


Association of centrioles and chromosomes observed in preparations of whole-mounted human chromosomes.

Pairs of centrioles are a frequent finding in whole-mounted, critical-point-dried chromosome preparations from normal and irradiated human lymphocyte cultures. Most frequently they are found in association with a group C chromosome, although apparently free diplosomes are not uncommon. Fibers that in every respect are the morphologic equivalent of those seen in the body of the chromatid connect to the thick-walled open-ended part of the parent centriole. These features argue for the possibility that fibers connecting centrioles are an integral part of nuclear or chromosomal chromatin. It was observed that the smaller (daughter) centriole was connected and held in the well-known angular configuration to the thick-walled opne end of the parent centriole by a few, probably only two, colchine-resistant fibers.


In situ detection and characterization of DNA polymerase activities in the nucleus of eukaryotic cells.

We have developed a cytoenzymological method for localizing DNA polymerase activities in situ and for studying their responses to various chemical agents or environmental conditions. The incubation mixtures and the stimulatory or inhibitory agents added to these media were defined with reference to in vitro biochemical tests used to detect and to characterize DNA polymerases-alpha or -beta found in eukaryotic cells. This method has already been used to study DNA polymerase activities during cell differentiation or cell senescence. Apart from two exceptions found with lower organisms, the nuclear DNA polymerase activity was always higher under conditions which favoured the in vitro expression of DNA polymerase-beta rather than DNA polymerase-alpha. --In the various cell types studied, the cellular DNA polymerase activities were almost exclusively found in the nuclei. It is hoped that this methodology will be useful for obtaining more complete biochemical data on the intracellular localization of various DNA polymerases.


Presumed histoplasmosis.

In a follow-up study of 30 eyes of 25 patients, three types of lesions could be distinguished: 1) the classical pigment ring, found in 13 eyes of 12 patients; 2) the cystous type, observed in 4 eyes of 4 patients, and 3) the multilocular type, found in 13 eyes of 9 patients. Up to the present, the cystous type of histoplasmosis has not been described.


Hereditary proximal colonic cancer.

Ten families prone to cancer of the colon (in the absence of familial polyposis coli) have been investigated. A significantly greater frequency of carcinomas of the proximal colon was evident relative to non-familial colonic cancers (65% versus less than 35%, P less than .001). Moreover, family members with proximal colonic cancers experienced significantly enhanced survival, compared with family members with distal colonic or rectal cancers. Findings consistent with a genetic predisposition included early mean age at onset (45 years) and a high frequency (40%) of multiple primary cancers in the patients studied. The results are in accord with reported findings in 11 similar kindreds from the literature, and strongly suggest the existence of a heritable variety of colonic cancer in which the proximal colon is at particularly high risk. Extraordinary early diagnostic measures, including colonoscopy, are indicated for members of such families.


Photic injury to the retina and the manifestation of acute posterior multifocal placoid pigment epitheliopathy.

Findings in retinas of animals suggest a correlation between the pathological process of certain hereditary dystrophic diseases and the effect of light on the retina. One may speculate whether clinical conditions exist--apart from hereditary retinal dystrophies--in which the retina becomes more sensitive to light from strong artificial or natural sources, which are otherwise innoxious. Two case histories will be presented, clinically diagnosed as acute posterior multi-focal placoid pigment epitheliopathy in which a direct relationship seems to exist between the appearance of the fundus changes and the light impact. The role of electrodiagnostic procedures in the differential diagnosis will be discussed.


Resolution of the appendiceal mass in Nigerian Igbos.

Appendicitis is reputed to be rare or unknown in African communities, but this is not true of the Igbos of Nigeria, West Africa. This paper reports the histologic features of appendices from eight Igbo patients who underwent interval appendectomy two to six months after conservative treatment for appendiceal masses that resolved satisfactorily. Resolution was complete histologically in the two children in the series. In five adult patients, one or more sections of the appendix contained residual inflammation or luminal obliteration. In the remaining adult patient, schistosomiasis coexisted with both inflammation and obliteration.


Subscleral trepanation in the treatment of glaucoma.

A consecutive series of 121 subcleral trepanations was studied for one year after surgery. The intraocular pressure in glaucoma simplex was less than 21 mm without therapy in 91% of Dutch white cases and in 71% of black Surinam cases. Histological examination revealed that corneal trepanations also gave good results.


Comparative evaluation of two new applanation tonometers-preliminary study.

Three separate intra-ocular pressure assessment preliminary studies utilising the Goldmann, E.M.T. 20 and the Digilab Model 30R pneumatonometer were carried out on a total of 114 eyes with glaucoma, and in 184 normal eyes in 162 patients. In general the E.M.T 20 gave a lower result that the Goldmann but both compared well within the normal intra-ocular pressure range. Within the normal intra-ocular pressure range the pneumatonometer generally gave a 1-3 mm Hg higher reading than the Goldmann but in the glaucomatous eyes this difference became much less and readings tended to be similar with both tonometers. The fixed calibration of the E.M.T. 20 and its accuracy for pressures in the 20 mm Hg range make it an ideal instrument for screening for glaucoma but it is not suitable for the accurate stabilization of glaucoma patients under treatment. The accuracy of the pneumatonometer in the range of intra-ocular pressure above 22 mm Hg render it the instrument of choice for the diagnosis and control of glaucoma patients. Added advantages of the pneumatonometer were the resilience of the probe to accidental damage and the ability to record the ocular pulse.


A reconsideration of the ischiorectal fossa.

The ischiorectal fossae of one fresh and 47 preserved cadaver specimens were dissected to elucidate its fascial boundaries, neurovascular relationships, spatial orientation, and possible functions. Based upon measurements of approximately half of the dissected specimens, a three-dimensional model of the ischiorectal fossa was developed to clarify visually its fascial relationships and orientation within the perineum. Seven fetal specimens were also dissected for comparative purposes. A distinct fascial septum, the lamina terminalis, connecting the medial and lateral walls of the fossa to form its anterior boundary, was consistently found as a dense fibrous component attaching inferiorly to the posterior aspect of the urogenital diaphragm. The functional significance of the ischiorectal fossa in supporting the urogenital diaphragm, in anal activities, and in sparing the compression of the neurovascular supply to the perineum is discussed.


Combined therapy for cancer of the anal canal: a follow-up report.

We believe this preoperative combined therapy is highly effective in treating squamous-cell carcinoma of the anal canal, and that a subsequent larger cooperative study with controls is indicated. This pilot study suggests that some individuals may be spared abdominoperineal resection when treated in the manner described.


Multiple mucosal neuroma (MMN) or multiple endocrine neoplasia (MEN) type 3 syndrome. Ocular manifestations: a case report.

Case report of a young man showing neuromas of the palpebral and bulbar conjunctiva and markedly thickened nerve fibers in both cornea. Multiple neuromas were seen on the lips and in the oral cavity. A medullary carcinoma of the thyroid was found. These symptoms pointed to the diagnosis of a MMN or MEN type 3 syndrome. There were no signs of phaeochromocytoma, however, which also belongs to this syndrome. The ophthalmologist, who may be the first to see such a patient as a child, should be aware of the malignancies which develop around puberty and of the strong and dominant heredity of this disease.


Hallermann-Streiff syndrome.

Blodi (1957) and François (1958) recognized this syndrome as a distinct entity differing from the mandibulo-facial dysostosis (Franceschetti's syndrome). Although there are approximately 60 cases reported in the literature, only very few cases have been obtained for histological study. A report of a case with ophthalmopathological examination is given.


The Tolosa-Hunt syndrome.

The signs and symptoms of the Tolosa-Hunt syndrome are described and the results of orbital phlebography discussed. Emphasis is placed on the importance of systemic administration of corticosteroids, both as a diagnostic test and as a therapeutic measure. A case history is presented.


Duane's uniocular micro-tremor or superior oblique myokymia of Hoyt and Keane.

Two cases of intermittent unilateral motor disturbance of the superior oblique muslce are presented and compared with cases reported previously by Duane, Clark and Hoyt & Keane and briefly mentioned by Duke-Elder in his System of Ophthalmology. The first case is a girl with longstanding history of oscillopsia, vertical and tortional oscillatory diplopia. No abnormal eye movements were observed but objective evidence of the disturbance was obtained in the form of electromyography during which relationship of the superior oblique was established. In contrast, the second case experienced episodes of static vertical and tortional diplopia similar to the case reported to by Clark. Again the relationship in the condition was unilateral involving the superior oblique muscle. There was no corroboratory evidence to support the diagnosis of an intermittent superior oblique tendon sheath syndrome. Hoyt & Keane's theory based on their electromyography findings that the lesion is in the lower motor neuron unit is reported and the significance of the oscillopsia as corroboratory evidence is discussed.


Vertical motor fusion.

An analysis is given of the eye movements which take place in vertical fusion. These movements are compared with the movements that occur in horizontal fusion. The differences and similarities that can lead to a model are stressed.


Electro-ophthalmology and side-effects of drugs.

Diagnostic procedures have to be directed towards the prevention of irreversible changes. In this respect, patients using chloroquine have to be examined at least once a year. The most sensitive methods for detecting early reversible changes are the electro-oculogram and static perimetry. The latter is probably more specific. Concerning ethambutol, the patients themselves are aware of the onset because a decrease in visual acuity and a central scotoma are early and reversible symptoms. In these cases electro-ophthalmology is of help when the diagnosis is doubtful. Iatrogenic effects of other drugs are not seen regularly in our electro-ophthalmological departments.


Desinsertion of the superior oblique in A-patterns.

A-patterns have been treated by various techniques, with variable results. A desinsertion of the superior oblique at its insertion temporal to the superior rectus has proved to be a satisfactory treatment. This is combined with horizontal surgery. The results of this surgery in 137 cases are analysed and the complications outlined.


Nystagmus induced by intermittent photic stimulation (flash induced nystagmus (FIN).

In man, as has been shown previously in rabbits and monkeys, a nystagmus can be elicited by monocular intermittent photic stimulation. The direction of nystagmus (FIN) is always towards the stimulated eye. This nystagmus strongly resembles latent nystagmus. Here the fast phase is always directed towards the 'non-occluded' eye. The FIN may, therefore, be used as a model for the study of mechanisms underlying these pathological conditions. For further elucidation of FIN, studies were made in rabbits.


Results of transantral decompression in hyperthyroid exophthalmos.

For the moment, transantral orbital decompression is the best procedure for the treatment of manifest exophthalmos because it is a simple and effective method with hardly any postoperative complications. If some ocular motility disturbances do not disappear spontaneously postoperatively, they can be treated successfully by muscle surgery. We found that the postoperative reduction of exophthalmos further improved during the first year with an average of 3 mm. For this reason, it is not advisable to section the infraorbital nerve in order to obtain a better immediate reduction. We are convinced that this operation is justified for some patients with a manifest exophthalmos for cosmetic reasons only. Good preoperative photographic documentation is necessary in each case.


Slit lamp ophthalmodynamometry.

A short clinical trial of the 'Dynoptor' Slit Lamp Ophthalmodynamometer has shown it to be a practical instrument. A mean O.A.P. of 52.3 mm/hg has been recorded.


The prism loupe used as a low-vision aid and in ocular surgery.

The prism-magnifier developed and constructed by Biessels has been used as a low-vision aid since 1971. It has been derived from the Carl Zeiss (W. Germany) 8 x 20 mini prism-binoculars. The system has several advantages. The prism-magnifier also enables the eye surgeon to perform microsurgery without the disadvantages of a stand-microscope.


Changes in the structure of intra-ocular nylon.

When using a nylon thread for the attachment of a pseudophakos to the iris, it may happen that the suture is slung tightly around the implant-lens. In such a case this constitutes a clinical experiment where is one and the same eye one part of the nylon thread is in its normal state (the cut-off ends) and the rest is in a stretched state, both under the same environmental conditions and for the same length of time. The differences in structure of the parts of the nylon thread are thus fully comparable. Clinical observatons show that when the nylon thread is under tension it will be eroded by chemical influences. It does not make any difference whether the nylon is used for corneal, scleral or intra-ocular suturing. The duration of the observations is still too shor to predict the behaviour of nylon which is not stretched.


Cryptococcal eye disease.

A survey is given of the clinical picture of an infection with Cryptococcus neoformans. The symptoms and therapy are reviewed and the case history of a 13 year old boy suffering from this fungus infection is discussed.


Controversial aspects of ablative photocoagulation in diabetic retinopathy (d.r).

In recent years ablative treatment of advanced diabetic retinopathy has gained more and more adherents. However, most cases of proliferative retinopathy, even if they are advanced, can be treated successfully by restricting xenon-or laser-coagulation to pathologic areas, while sparing healthy-looking parts of the retina. It is felt that destruction of large parts of the retinal periphery should be reserved for special cases only. In those cases where the fundus is clouded by abundant hemorrhages and vitrectomy does not seem advisable, ablative treatment should be tried ab externo by means of diathermy or cryoapplication.


Diabetic retinopathy and light-coagulation.

In diabetic retinopathy, a low resistance of flow between choroid and retina is found which goes with an increased intake of tissue fluid into the retinal vessels and the appearance of retinal oedema. Light coagulation destroys the choriocapillaris which does not regenerate. As less fluid becomes available to be sucked up by the retinal vessels, the oedema will now disappear and consequently, the retinopathy subsides.


Purtscher's disease.

An 8-year-old boy was run over by a caravan and showed the typical fundus lesions described by Purtscher in 1910. Fundus picture, fluorescein angiograms and clinical course are presented, followed by a discussion on the different theories concerning the aetiology.


[Demonstration of HBs antigen with the hepanostika test, an enzyme immunoassay (author's transl)].

Sensitivity, specificity and practicability of the Hepanostika test, a newly developed enzyme immunoassay by organon Teknika for the demonstration of HBs-antigen, was compared with results of the Aursria II 125 test. Smallest demonstrable concentration of the antigen in the Hepanostika test eas 3.125 ng/ml with antigens of subgroup ad and 2.08 ng/ml in those of subgroup ay, while it was 1.04 ng/ml for both subgroups with the Austria test. Among 2930 blood donors 85 antigen carriers were discovered by both tests, while with the Hepanostison test, a passive haemagglutination test from Oranon, only nine were discovered. In serial blood samples of patients with various disease there was only a slight difference between the two tests. The Hepanostika test had 1.6--3.88% nonspecific reactions, compared with 0.5-0.8% with the Ausria II 125 test. Both tests thus gave much more specific results than passive haemagglutination. The Hepanostika test is thus a satisfactory alternative to the Ausria test. Because of its high sensitivity it can be recommended for the diagnosis of HBs antigen among blood donors and in clinical laboratories.


[Novonal (diaethylallylacetamide) poisoning (author's transl)].

Novonal, a hypnotic dispensed without medical prescription in West Germany, has in the past two years been used relatively often in suicide attempts. It is quickly absorbed after oral intake, with a blood half-life of 6-11 hours, most of it being excreted by the kidneys after metabolic degradation. Analysis of 23 cases of Novonal intoxication revealed that cardiac arrhythmias, hypotension and respiratory depression may occur with 6 g Novonal (contained in a pocket of 20 tablets) and must thus be rated as potentially lethal. In severe cases of poisoning haemoperfusion or haemodialysis may be useful. Pharmacological data suggest that forced diuresis is ineffective.


[HB's-antigen and anti-HBs in hospital staff (author's transl)].

In 826 employees from six hospitals and three theoretical clinical institutes of Düsseldorf University HBs-antigen and anti-HBs were determined. HBs-antigen was not significantly more frequent than in a control group. On the other hand anti-HBs was much more common in hospital staff. In probands with histories of liver disease and blood transfusions there was a significantly higher incidence of anti-HBs. Different occupations within the hospitals showed different anti-HBs frequencies.


[The effectiveness of antibiotic treatment for Salmonella enteritis and Salmonella excretors].

The role of antibiotic treatment was evaluated in 190 hospitalized patients with Salmonella enteritis and 80 with asymptomatic Salmonella infection (without typhoid or paratyphoid). The results indicate that antibiotic treatment does not shorten the duration of excretion (compared with non-treated patients). Because of the danger of prolonged bacterial excretion under antibiotic treatment in complication-free Salmonella enteritis as well as the possible development of resistant Salmonella strains, antibiotic treatment of Salmonella infections (other than typhoid or paratyphoid) should be limited to systemic forms. Treatment of complication-free Salmonella enteritis and Salmonella excretors should be limited to intestine-cleansing measures.


[Treatment of acute myocardial infarction with sodium nitroprusside (author's transl)].

In 12 patients with acute myocardial infarction, seven of whom had high and five low blood pressure measurements, sodium nitroprusside infusions were given to reduce the myocardial oxygen consumption. The dosage was between 20 and 300 mug/min. Sodium nitroprusside led to a considerable reduction of the systemic arterial pressure, while the left ventricular filling pressure was less influenced. In normotensive patients the filling pressure could often not be sufficiently lowered as a too severe reduction of arterial pressure occurred beforehand. In hypertensive patients the relationship between left ventricular filling pressure and arterial pressure was better: in all patients the arterial pressure could be lowered to normal values and the filling pressure also became normal in most cases. Angina pectoris improved markedly in all patients. These results show that sodium nitroprusside has a satisfactory effect on the haemodynamics in hypertensive infarct patients, whereas it is less suitable for the treatment of normo- or hypotensive patients.


[New aspects in the treatment of puerperal mastitis (author's transl)].

36 women with postpartal breast engorgement were treated with a single oral dose of 2.5 mg bromocriptine (Pravidel). Significant relief was recorded in 28 patients, 6 patients required a second dose of 2.5 mg bromocriptine, whereas 2 patients failed to respond. Antibiotics were at first avoided in the treatment of puerperal mastitis. 26 patients with all characteristics of breast inflammation were treated exclusively with bromocriptine: for 3 days 2.5 mg t.i.d., for the following 11 days 2.5 mg twice daily. The temperature dropped below 37C in 25 patients within 12-24 hours, tension and pain disappearing simultaneously. One patient did not respond after 36 hours, so that an antibiotic was administered additionally; in another patient who had been admitted to the hospital six days after the onset of the clinical symptoms of breast inflammation, bromocriptine failed to prevent abscess formation. The results indicate that in most cases of puerperal breast inflammation no antibiotics are required. Puerperal mastitis can be treated effectively by the exclusive administration of bromocriptine.


[Influence of molsidomine on exercise-ECG'S In coronary insufficiency (author's transl)].

Molsidomine was shown to have a strong pain-relieving action in 22 coronary patients investigated one hour after oral intake of 2 mg of the substance. During comparable maximal exercise load the ST interval lowering was reduced from an average of 0.22 mV to 0.09 mV (P less than 0.0005). At the termination of exercise it was still reduced from 0.23 mV to 0.12 mV (P less than 0.0005). At the same time the exercise tolerance increased from 570 to 717 Watt-minutes (P less than 0.0025). Pectanginal complaints were clearly reduced at the same exercise loads, 11 patients became symptom-free at the same load. Even when exercise loading was stopped at higher loads a decrease of the severity of angina pectoris could be shown. Seven patients became symptom-free at that stage. The heart rate was not influenced markedly at rest and during exercise. Systolic blood pressure was reduced from 135 mm Hg to 118 mm Hg (P less than 0.0005), and in comparable submaximal loads from 177 to 165 mm Hg (P less than 0.005).


[Levels of immunoreactive insulin in laser irradiated rats].

The authors described the results from a study on immonoreactive insuline in rats after their irradiation in the region of the pancreas with rubine laser with beam energy of 0, 13 Joul/impulse. The irradiation was made singly with 7--10 impulses. The level of immunoreactive insulin was raised to 33,83 microliter I/ml in nonirradiated rats and to 48 microliter/ml per 24 hours after irradiation and reached its maximum of 54 microliter/ml after 48 hours of its irradiation, but then returned to its normal values after 72 hours. The same elevation of insulin was found also in rats, irradiated in the region of liver, kidney and heart. The discovered histomorphologic findings in the tissues after irradiation revealed activation of mesenchyme, interpreted as a reaction of dystrophic changes, caused by laser beams. The elevation of insuline was connected with changes in hypophysial-adrenal system, presenting the type of the general adaptation syndrome, and, on the second place, site of the realesed mediators (sympathycomymetics) in this stress reaction.


[Radiometric method of determining the phagocytic activity of macrophages in vitro].

The authors describe a radiometric method for determination of phagocytic activity of macrophages, using as an object for phaging hen erythrocytes labeled with 51Cr. The basic principle consists of quantitative determination of phaged cells by means of measuring the activity, found in the phagocytes. The method is described in details and the obtained results in normal mice and such with experimental leucosis NKLI are compared with those, checked by the classical methods for determining phagocytic activity in vivo and in vitro. On the basis of these data the authors indicate the advantage of the method, prepared by them, because it alows objective checking of phagocytosis on a large number of cells and thus increases the possibilities of obtaining significant results.


[Electrophoretic study of different types of phytohemagglutinins].

The author compared the number and the percentage distribution of the preparations faseolaxin (FHA-F), produced in this country by the method of Coneva and phytohemaglutinines from the firms "Difko" VASTO-M and VASTO-P, by means of disc electrophoresis and acrylamide gel. He found similarity in the fractions of FHA-F and VASTO-P. The difference was in the quickly mobile components, which were respectively 6,5% and 14,5% of the total amount. The examination of the initial extract for obtaining FHF-F showed that the method of Coneva had advantages in respect of the purity of the preparation.


[Influence of salivary gland hormone on the number of leukocytes and level of calcium in the blood of experimental rabbits].

The authors examined the influence of single venous doses of hormone from the saliva glands on the calcium level and leucocytes in the blood of nonnarcotized experimental rabbits. They investigated the effect in the following doses: 20, 10.5 and 1 mg/kg of body weight. The indicated two indices were examined 2, 4, 6 and 10 hours after the injection of the preparation. The venous administration of all exa mined doses of the hormone from the saliva glands caused statistically significant lowering of leucocytes on the second hour and respective increase on the sixth and tenth hour since the onset of the experiment. The hormone of the saliva glands lowered the amount of calcium ions in blood, but the difference was not always statistically significant in various doses and time intervals.


[Condensed and dispersed chromatin in the nuclei of thyroid follicular cells under normal conditions and following thyrotropic stimulation].

The author examined the changes in the nuclear size, in its form and optical density as well as the changes in the condensed and dispersed chromatin of the follicular cells of the thyroid gland after thyroid stimulation by means of the method of scanning cytophotometry. He found that after a 20-day treatment of the animals with methythyouracyl-an agent, which blocks thyroid hormonal synthesis and in this way raised the level of the thyreothropic hormone in circulation, the size of the cell nuclei was increased and at the same time its concentration of DNA was reduced. The amount of the particles of the condensed chromatin after thyreotropic stimulation diminished, but the integral space remained unchanged and the area of the dispersed chromatine was mainly increased. The obtained data are discussed in view of the possibilities of the scanning cytophotometry for evaluation of the functional activity of the cell.


[Morphologic study of teflon implanted in the prelaryngeal space of dogs].

The authors described their experimental studies on dogs, using aliomaterial teflon- in forming FTM slap in the prelaryngieal space for the purposes of the reconstructing plastica of the larynx. The teflon was a suitable material because of its good tolerance and well occuring reactions of the pathologic organization, combined with the processes of resorption and its substitution with connective tissue. The authors found the period of 10 to 20 days as the earliest and most suitable period for the usage of FTM slap.


[Muscular bioelectric activity, synchronous with respiration, following physical loading in trained and untrained individuals].

The authors aimed to examine the occurrence of biopotentials of muscles of the extremities, synchronous with respiration, and their duration after dynamic functional loadings with various length of time and intensity in trained and nontrained individuals. They carried out 60 examinations on two groups of students from the Higher Physical Institute: trained and nontrained. The following indices were recorded: muscle bioelectric activity of m. biceps brachii dex., m. quadriceps femoris dex., m . gastrocne-mius dex. and respiration before and after three types of functional loading of veloergometerfirst (2 X 30 sec. with 20 seconds of rest between them after 100 rotations/minute and 245 watts of strength) and second (5 X 1 minute with 30 seconds of rest after each minute after 90 rotations and 200 watts) were of speed character, but the third (20 minutes after 60 rotations per minute and 117 watts withminute of rest after each 5 minutes of work), developing the trait of endurance. On the basis of the obtained results the authors found that muscle bioelectrical activity, synchronous with vespiration, waw observed in the largest percentage of the examined persons after loading with speed character and in smaller percentage-after exercises for endurance, in which its duration was less as well. This precentage on its side was greater in nontrained persons in comparison with trained persons, in whom the phenomenon disappeared more quickly.


[Cytogenic survey of 600 mentally retarded hospitalized patients].

A collaborative study (including the patients of 4 mental hospitals) was done in an attempt to evaluate the incidence of chromosomic anomalies in a large group of mentally retarded patients. A cytogenetic study was performed in 600 mentally retarded patients selected among 3.311 psychiatric patients. Chromosomic anomalies were found in 54 (9 per cent) mentally retarded patients. There were 43 autosomic anomalies (32 had trisomy 21) and 11 sexual chromosomes anomalies. This large series is consistent with the results found in the litterature. However of interest is the fact that this anomalies were frequently associated with affective deprivation, relational distorsion, disturbed family milieu and low social economic status during childhood.


[Physiological and psychological effects of biological feed-back training (alpha and EMG) among drug using college students].

Twenty-four volunteer college students, who were regular drug users, were randomly allocated to three training groups of equal size: alpha feedback, EMG feedback and a joked control group. Subjects, who were unaware of which feedback condition they received, were asked to practice at home during a six month follow-up period to achieve a relaxed state similar to that experienced during training. No group was successful in retaining gains made in their alpha levels during each session. The EMG group, however, significantly reduced their muscular activity during training and retained the improvement during follow-up. The alpha and joked groups did not significantly improve their EMG during training but at follow-up achieved the same levels as the EMG group. There was evidence to suggest a reduction in drug use among light and medium users that was maintained during follow-up. Significant and lasting improvements were made by each group in the duration and quality of their sleep. Anxiety levels were also reduced.


[Manic depressive psychosis and hemispheric dominance with bipolar left handedness and episodic aphasia].

The author report on a manic depressive patient 66 years old which dysplayed aphasic troubles during depressive phase. As the patient was left handed and considering recent development in hemispheric specialisation, this trouble can be viewed as indicating a right hemisphere disturbance which is likely to be involved in the affective disorder.


[Lithium and water metabolism].

Interaction between lithium+ and water balance was studied in nine patients suffering manic-depressive trouble. Nephrogenic diabetes insipidus with polyuria and polydipsia was induced by Li+ in one case only. No trouble was apparent in eight cases. However, the applied method of investigation by lacking, and next, excess of water, vasopressin and ADH tests, measurements of urinary osmolarity and clearances, showed up a trouble of concentration in four cases, improved by ADH. The Li+ frequently (50%) induces a trouble of urinary concentration, without polyuria; it is brought to light only by biological investigations. Its origin is double, nephrogenic, which is the most important, and central by a pituitary component. In the other hand, the change in water metabolism, studied by the same tests, showed us a decrease of the clearance Li+ after lacking of water (deshydratation), and an increase after water surcharge. That result is not concordant, chiefly in regards to the water surcharge, with former experiments. It appears that our method (division by horary periods for measurement of clearance, study of circadian cycle of urinary Li+) permits some observations more precise than global gathering and measurement of clearances. That method also allows to make evident a circadian cycle of renal clearance of Li+, according to, for some part, with the renal movement of water. That remark would also have some consequence on lithium-therapy practice.


[Clinical effects of long-term lithium treatment on sleep, appetite and sexuality].

The authors try to determine the incidence of long-term lithium treatments on sleep, appetite and sexual behaviour. The study was conducted in fifty outpatients of both sexes who have been for at least six months on lithium only and whose mood disturbances are stabilized. In two thirds of the cases of this clinical study, lithium seems to have beneficient qualitative and quantitative effects on sleep as opposed to other psychotropic drugs which cause discomforting sleepiness. Lithium seems to influence appetite slightly although it is responsible for the gain in weight in a fourth of the treated outpatients. Half of the subjects consider that lithium modifies their sexuality towards a decrease of the desire without modifying their capacities of realization. In a comparison study conducted with the psychotropic drugs that had been administered before, the repercussions of lithium on sexuality appear thus opposite to those of psychotropic drugs, major tranquilizers and antidepressants which impair the capacities without reducing the desire. Despite the specific side effects on some instinctive functions, lithium seems to be a treatment well lived by the subjects.


Enzymatic responses of transplanted tumour cells towards estrogen, progesterone and testosterone.

The influence of estrogen, progesterone and testosterone on the activities of alkaline and acid phosphatases, adenosine triphosphatase and succinate dehydrogenase were determined by cytochemical methods in sarcoma 180 and Ehrlich's carcinoma cells transplanted in male and female Swiss mice. The results revealed differential effects of the sex hormones on different enzymes which seemed to depend on the type of tumour cell studied and the sex of the host mice.


A transient increase in renal clearance of phosphate in response to continuous infusion of salmon calcitonin in rats.

The effects of intravenous carrier-free salmon calcitonin on renal clearances of phosphate, calcium, magnesium, sodium and potassium were studied in male parathyroidectomized (PTX) and intact rats. Both natural and synthetic hormone, when infused at constant rates (0.005 approximately 0.5 MRC U/hr), produced a rapid increase (peaking at about 60-90 min) in phosphate clearance. However, the maximal increase was transient in nature in PTX rats. In intact rats, the phosphaturic response was somewhat more pronounced and the decline after the peak was rather modest. When a large amount (4 MRC U) of calcitonin was given in divided doses, the second dose produced a lesser extent of phosphaturia in both intact and PTX rats. The phosphaturic response was accompanied by an increase in sodium and potassium clearances in PTX rats and by an increase in potassium clearance in intact rats. A fall in the apparent clearance values for calcium and magnesium occurred and was maintained throughout the infusion period of hormone in both intact and PTX rats. In conclusion, PTX rats respond to the intravenous administration of salmon calcitonin with a transient phosphaturic response which is accompanied by parallel diuresis of sodium and potassium along with sustained retention of calcium and magnesium by the kidney.


Subunit structure of 27 S thyroid iodoprotein.

The dissociation of thyroid 27 S iodoprotein by sodium dodecyl sulfate (SDS) and by succinic anhydride was investigated by means of ultracentrifugation and polyacrylamide gel electrophoresis. The iodoprotein obtained from either a human or hog was dissociated into three kinds of subunits (S-19, S-17 and S-12) by SDS treatment. At increased concentrations of SDS, the S-12 subunit was predominant among the dissociation products. The succinylation of 27 S iodoprotein showed essentially the same dissociation pattern as in the case of SDS treatment. The dissociation products of the protein preparations of different animals were qualitatively the same as those of thyroglobulin of the respective animals, confirming the hypothesis that 27 S iodoprotein was composed of two molecules of thyroglobulin. However, the extent of dissociation of 27 S iodoprotein measured by S-12 formation showed higher resistancy of the protein to the dissociating agents than that of thyroglobulin. The contents of sialic acid and hexose as well as iodoamino acids of 27 S iodoprotein were found to be the same as, or not far from, those of thyroglobulin. The dissociability and chemical composition of 27 S iodoprotein was discussed with reference to the subunit structure of the protein.


Occurrence of permanent changes in vaginal and uterine epithelia in mice treated neonatally with progestin, estrogen and aromatizable or non-aromatizable androgens.

Female mice of the C57 Black/Tw strain were injected daily with 100 microgram testosterone, 50 microgram testosterone propionate (TP), 100 microgram 5alpha-dihydrotestosterone (DHT) or 50 microgram 5alpha-dihydrotestosterone propionate (DHTP), for 10 days from the day of birth. Two other groups of female mice were given neonatal injections with 20 microgram estradiol-17beta and 100 microgram progesterone for 10 days, respectively. All mice were ovariectomized at 60 days of age and killed at 90 days. In 100% of neonatally estrogenized or androgenized, ovariectomized mice, the cranial part of the vagina was lined with stratified epithelium with either cornification or parakeratosis or mucification. Stratification only or stratification with superficial squamous metaplasia or cornification took place in the uterine epithelia of 18% of the TP-treated, 75% of the DHT-treated and 50% of the DHTP-treated, ovariectomized mice. In contrast, neonatally estrogenized, ovariectomized mice did not show the estrogen-independent, persistent uterine changes. Neonatal progesterone treatment failed to induce the permanent changes in the vaginal and uterine epithelia.


The effects of light deprivation/blindness on testicular function of gerbil (Meriones hurrianae Jerdon).

1. Light deprivation either by enucleation or darkness resulted in a wide-spread testicular damage. The changes consisted of loss of type A spermatogonia, spermatocytes, spermatids and spermatozoa. 2. The atrophic testes of eyeless gerbils regenerated after 20 weeks and were indistinguishable from those of untreated, continuous light exposed animals. The reversible effects were not seen in continuous dark exposure. 3. Light deprivation (enucleation/continuous darkness) inhibits the synthesis of RNA, protein and sialic acid in the testes, epididymides and seminal vesicles. The testicular cholesterol and alkaline phosphatase activity was increased. 4. Haemoglobulin, haematrocrit and serum-transaminase levels were all the time within normal limits. Histological preparations of the liver showed normal architecture. 5. Reduced androgen production following a long term light deprivation was reflected in low levels of RNA and sialic acid in the testes and epididymides and shrunken Leydig cell nuclei. 6. In conclusion, light deprivation caused damage to the male genital tract of gerbils.


Action of testosterone in melanin metabolism in liver of toad (Bufo melanostictus).

The melanin content of liver of male toad was altered by testosterone injection. A single injection of testosterone at a dose of 1 microgram/g or 2 microgram/g of body weight caused an increase in melanin content of liver of male toad on the 3rd and 5th day after injection. With lower doses (0.1 microgram/g and 0.5 microgram/g), however, there was no alteration of melanin content of liver. Compared to the results obtained with 1 microgram of testosterone per g of body weight, the degree of response with respect to the melanin content with 2 microgram/g tended to be higher, but the difference was not statistically significant. The female toads remained unaffected with respect to melanin content of liver with these doses of testosterone used.


[Effect of oxytocin on regional 3H-orotic acid uptake in rat brain].

The uptake of the RNA precursor [3H] orotic acid by 18 brain regions of male rats was measured after intracarotid injection and a survival time of 15 s. Ocytocin added to the injected solutions (final concentrations: 1 to 1000 mU/ml) caused a dose-dependent enhancement of tracer uptake by 11 areas. Some of these regions (e.g. hippocampus) are thought to be involved in the behavioral effects of vasopressin and other peptide hormones (Van Wimersma Greidanus et al., 1975 a). Results of experiments in which the net uptake of tritiated water was used as a measure of relative blood flow led us to the conclusion that the blood-brain barrier permeability to [3H] orotic acid rather than the cerebral blood flow is changed by ocytocin. The present results support the assumption that the enhanced precursor supply caused by ocytocin might contribute to the influence of this peptide hormone on memory consolidation.


[Effect of degree of experimentally induced hypothyroidism on changes in serum albumin spectra in rats].

Extreme rat hypothyreosis of identical degree was induced by radiothyroidectomy (group R-HT) and feeding of thyreostatics (groups MTU-HT and MMI-HT). External signs, growth kinetics, serum cholesterol, thyroid weight, and the iodothyrosine pattern of the thyroid glands served as references for the quality of the hypothyreotic state. Determinations of following changes (all changes significant for p less than 0.001): 1. Higher total serum protein levels in hypothyreotic rats 4 and 7 weeks after beginning the experiemnts as compared to the controls (KT). 2. After 4 weeks the relative albumin content was diminished, the relative gamma-globulin content was elevated as compared to the KT. The absolute values of albumines did not change, alpha-1-globuline and gamma-globuline contents were increased in all hypothyreotic groups. 3. After 7 weeks normal albumine values, increase of the relative and absolute alpha-1-globuline content, and decrease of the relative beta-globuline concentrations were measured. Elevated gamma-globulins were found in MMI-HT and R-HT only, and an increased absolute albumine content in MTU-HT alone. The results confirm both hyperproteinemia and dysproteinemia as characteristics of the rat hypothyreotic state. Dynamic changes of absolute and relative contents of different serum protein fractions are demonstrated in relation to the duration of hypothyreosis. This fact can possibly explain contradictory findings on type of dysproteinemia by several authors.


The conversion of delta 5-steriods to testosterone and androstenedione in human amniotic epithelium in vitro.

3 beta-Hydroxysteroid dehydrogenase / delta 5-4 isomerase activity was demonstrated in the human amniotic epithelium from the first trimester of pregnancy. The evidence was based on the in vitro formation of [4-14C] testosterone and [4-14C] androstenedione from [4-14C] 5-androstenediol and [4-14CA1 DEHYDROEPIANDROSTERONE, RESPECTIVELY. The activity of the enzyme studied in age dependent, reaching a maximum in the 8th-9th week of pregnancy and decreasing to negligible values at the end of the second trimester of gestation.


Thyroid activity and TSH levels in pituitary gland and blood serum in response to clomid, sexovid and prostaglandins treatment in Heteropneustes fossilis (Bloch).

Thyroid activity, pituitary and serum thyrotrophic potency in response to the administration of clomid, sexovid, PGE1 and PGF2alpha, were studied in H. fossilis. Hightened thyroidal activity and CR (conversion ratio of PB 131I in blood serum in relation to total serum 131I uptake) were noticed a week after clomid (150 microgram/fish/day) and sexovid (150 microgram/fish/day) treatment. Clomid and sexovid also elevated the serum thyrotrophic potency although pituitary TSH level was unaffected. It is evident from the results that clomid and sexovid either act via hypothalamus or directly over pituitary to increase TSH secretion followed by increased thyroid activity. PGE1 and PGF2alpha (100 microgram/fish/day, each) administration increased thyroidal 131I uptake but failed to stimulate hormone output from thyroid gland. Increased TSH level in blood and decreased level of TSH in pituitary was observed in response to the above prostaglandins. It seems that PGE1 and PGF2alpha  inhibit thyroid hormone secretion like anti-thyroid drugs triggering the release of TSH into blood.


Sex-specific testosterone and FSH concentrations in amniotic fluids of mid-pregnancy.

TG and unconjugated testosterone levels were found to be significantly increased but FSH levels significantly decreased in amniotic fluids of male foetuses as compared to those of female foestuses between week 16 and 26 of pregnancy.


In vitro incorporation of progesterone-1,2-3H in Fallopian tube and uterus of rat during pregnancy and postpartum period.

In vitro incorporation of 3H-progesterone into rat Fallopian tube and uterus during pregnancy and postpartum period is studied. The uptake of progesterone in oviduct and uterus falls sharply during mid-pregnancy (day 8-12 postcoitum) followed by a significantly high uptake prior to parturition. At the time of parturition, the tubal incorporation of radioactivity declines but resumes a rising profile towards day 5 postpartum. Similar pattern of uptake is observed in the uterus.


The increase of the active form of hepatic glycogen phosphorylase in stressed rats.

In rats exposed to 400 revolutions (during 6 min and 40 sec) in rotating Noble-Collip drums essentially the same increase of the active form of hepatic glycogen phosphorylase as in animals studied 6 min and 40 sec after epinephrine (50 microgram/kg) or glucagon (100 microgram/kg), both i.v., was observed. However, in rats injured daily for 6 days, on day 7 this enzyme response was substantially blunted.


Radiological protection in equine radiography and radiotherapy.

The principles of radiological protection are summarised and consideration is then given to problems, which may confront the equine practitioner, in the fulfillment of these principles during diagnostic radiography of the limbs, head, and spine of the horse. The place of anaesthesia in such procedures is discussed and the special problems associated with therapeutic radiography of the horse are considered.


Cardiological problems in equine medicine.

This paper outlines the major problems in evaluating and assessing prognosis in horses with minor cardiac abnormalities. It emphasises that progress will only be made if adequate data on the "natural history" of equine cardiac disease can be collected. This will necessitate a long-term study of suitable cases and will require the collaboration of specialist institutions and general practitioners if it is to be successful.


The clinician's approach to equine cardiology.

The author considers some of the difficulties the clinician may be faced with when giving an opinion on a horse with a cardiac abnormality. The 3 types of cardiological cases presented to the practitioner are described. The first 2 categories both exhibit a reduction in performance either with loss of bodily conduction or without it. The third group, which is the most troublesome for the clinician, involves the horse which shows a cardiological abnormality but is otherwise apparently normal.


Pacing techniques in assessing cardiac function in the horse.

The problem of transitory cardiac arrhythmias in equidae is discussed particularly with regard to the referral of suspect cases to specialist institutions for second opinion. Recently developed electro-stimulation techniques designed to uncover problem arrythmias, are briefly described and their potential in the analysis of cardiac electrical function under varying conditions is reviewed. The author cautions on the too rapid evaluation of the techniques for this purpose while remaining optimistic of the potential of electro-stimulation in the objective analysis of cardiac electric parameters.


The legal responsibilities of the veterinary surgeon arising from advances in equine cardiology and in the prescription of drugs for racehorses.

The paper examines the responsibilities of the veterinary surgeon in relation to the advances more recently made in the field of equine cardiology. Notwithstanding such advances it is stated that the normal established legal principles apply, in particular in relation to the preparation of certificates, namely that the veterinary surgeon must be sufficiently expert to give the opinion sought, that he must make himself fully aware of the purpose for which the certificate is required and that he must make clear the nature and limitations of any examination carried out.


Chronic tenosynovitis of the extensor tendons and tendon sheaths of the carpal region in the horse.

Seven cases of chronic tenosynovitis affecting the extensor carpi radialis or lateral digital extensor tendon and their sheaths are described. All cases were chronic and in 4 of the cases previous treatment by drainage and local corticosteroid injection had been ineffective. Surgical exploration of 6 cases demonstrated a distinct lesion and specific surgical treatment was carried out.


Osteochondrosis dissecans of the head of the humerus in two foals.

Two cases of osteochondrosis dissecans of the head of the humerus in foals are described. The lesions were gross compared with those seen in dogs. Arthrotomy and curettage of the affected area resulted in marked clinical improvement.


Coxofemoral luxation complicated by upward fixation of the patella in the pony.

Two cases of coxofemoral luxation complicated by upward fixation of the patella are described in the pony. Clinical signs included outward rotation of the stifle and foot and inward rotation of the hock with the stifle and hock joints fixed in extension. One case was treated by performing a medial patellar desmotomy with a resultant significant improvement in locomotion. Other cases of hip luxation reported in the literature, some complicated by upward patellar fixation, are reviewed. Hip luxation is principally seen in ponies and it is suggested that upward fixation of the patella occurring in some of these cases is a result of rotation of the limb produced by dislocation of the hip, which alters the normal anatomy and mechanics of the femoro-patellar joint and/or interferes with the normal leverage of the rectus femoris muscle.


Syringomyelia in a thoroughbred foal.

The report describes a case of myelodysplasia involing spinal cord segments C7 to T8 of a 5 month old part-Thoroughbred foal. There was a single extensive syringomyelic and hydromyelic cavity which extended from the seventh cervical segment (C7), to the seventh thoracic segment (T7), abnormal size and shape of central canal, and disorderly differentiation of the grey and white matter. The cause of the defect is unknown.


Familial methaemoglobinaemia and haemolytic anaemia in the horse associated with decreased erythrocytic glutathione reductase and glutathione.

A trotter mare with a history of poor performance was found to have methaemoglobinaemia and haemolytic anaemia associated with decreased erythrocyte glutathione reductase and glutathione levels. The mare's dam, which also had a history of poor performance, was subsequently found to be similarly affected.


The value of arterial blood pressure measurement in assessing the prognosis in equine colic.

Indirect arterial blood pressure was determined on 33 horses prior to surgical intervention for the diagnosis and/or correction of acute abdominal disorders and a relationship between low systolic blood pressure and non-survival was established. It is suggested that blood pressure determination should be used to augment other methods of clinical and laboratory examination in cases of equine colic.


A case of primary lymphoid leukaemia in a horse.

Progressive leukaemic changes and a persistent anaemia were demonstrated in the blood of a 7 year old gelding, which had shown early signs of lowered performance and unthriftiness, and later developed dependent oedema and became dull and listless. The total leucocyte count, initially within the normal range although reflecting an absolute lymphocytosis, increased fourfold in 6 days from excessive lymphoid production involving predominantly the more immature cell types; lymphoblasts, prolymphocytes and large lymphocytes. The severity of the condition was confirmed by bone marrow biopsy.


A correlation of the endoscopic and pathological changes in subclinical pathology of the horse's larynx.

The larynges of 6 horses were examined endoscopically and the findings correlated with the gross and histological appearance of the intrinsic laryngeal muscles and their nerve supply. In all cases it appeared that the balance between abductor and adductor muscle groups had been lost due to preferential atrophy of individual muscles or groups of muscles. The laryngeal abnormalities recorded were asymmetry of the larynx with asynchronous left sided abduction and fluttering or trembling of the left vocal cord and arytenoid cartilage. It is suggested that these changes represent the early signs of a progressive lesion which may result in left sided laryngeal hemiplegia.


Effect of training on some metabolic changes associated with submaximal endurance exercise in the horse.

The effects of prolonged cantering before and after a 10 week training programme were studied in 6 horses. Determinations were carried on on venous blood for packed cell volume, glucose, glycerol, free fatty acids, beta-hydroxybutyrate, 11-hydroxycorticosteroids, pH and pCO2. Exercise caused a slight increase in glucose, lactate and pH, a moderate rise in PCV, glycerol and free fatty acids, and a marked rise in 11-hydroxycorticosteroids. A decrease in venous pCO2 occurred and a slight but not significant decrease in beta-hydroxybutyrate. Training was found to cause no significant difference in the changes seen. However, there was a tendency for exercise to result in higher 11-hydroxycorticosteroid levels after training.


An experimental study of autologous digital tendon transplants in the horse.

Four autologous tendon grafting techniques, bipedicle, pedicle and free grafts of the deep digital flexor tendon and free grafts from the lateral digital extensor tendon were described. The vascularization and remodelling of the transplant and the reactions in the donor, as well as the recipient tendon, were studied by means of microangiographic and histochemical methods. The results indicated that regardless of the technique used the grafts were revascularized and replaced by a highly orientated and organized tendon. The use of free grafts may therefore be worthwhile in treatment of severe tendon lesions in valuable racehorses.


Acidic phosphoproteins of the 60-S ribosomal subunits from HeLa cells.

Two-dimensional analysis of the ribosomal proteins from 60-S subunits of HeLa cells revealed a triplet of acidic proteins, L40a, L40b and L40c, of identical molecular weight (13,700), which can be separated only on the basis of their charge differences. Two of the spots, L40b and L40c, become labeled after incubation of the cells with inorganic [32P]phosphate. The electrophoretic behavior and molecular weights of these proteins support the notion that the proteins L40b and L40c, are phosphorylated forms of the protein L40a. The same proteins can be phosphorylated also in vitro by a HeLa protein kinase on 60-S subunits but not on 80-S ribosomes. The inaccessibility of L40 proteins to the phosphorylation in vitro on 80-S ribosomes suggests that they are located in the interface between the 40-S and 60-S subunits.


Negatively charged reactants as probes in the study of the essential mercaptide-imidazolium ion-pair of thiolenzymes.

The reactive mercaptide-imidazolium ion-pair at the active site of papain and thiolsubtilisin was alkylated with negatively charged reactants. The reactivities of the two thiolenzymes differ considerably. The iodoacetate reaction is faster by more than 1000 times with papain than with thiolsubtilisin. On the other hand, towards 3-iodopropionate thiolsubtilisin is more reactive than papain by about a factor of 7. These findings, which are interpreted in terms of the different geometries of the two ion-pairs, offer an explanation of the basic difference between the catalytic abilities of papain and thiolsubtilisin.


Transcriptional and post-transcriptional defects in beta0-thalassaemia.

Complementary DNA enriched in sequences hybridizing to beta-globin mRNA was prepared with viral RNA-dependent DNA polymerase and used as a probe for the presence of beta-globin mRNA in nuclear and cytoplasmic RNA from two Italian patients with beta0-thalassaemia. In both cases the beta-globin gene was present and cytoplasmic mRNAbeta was absent; however, one case appeared to transcribe mRNAbeta and to fail to process it, while the other appeared transcriptionally defective. Evidence is also presented that the low levels of hybridization usually found at high RNA/cDNAbeta ratios in beta0-thalassaemia are due to  delta-globin mRNA; the melting profile of the hybrid formed has been determined and a low melting temperature relative to mRNAbeta - cDNAbeta demonstrated.


The low-spin/high-spin transition equilibrium of camphor-bound cytochrome P-450. Effects of medium and temperature on equilibrium data.

The spin state of camphor-bound cytochrome P-450 is shown to depend largely on medium and temperature in aqueous as well as in mixed organic buffer. At sub-zero temperatures a variation of paH, ionic strength or camphor concentration modifies the spin equilibrium from nearly pure high-spin form to nearly pure low-spin form. Since the apparent pKa of transition is a linear function of log I, the spin state seems to be controlled by the electrostatic potential in the heme proximity. K+ is found to have a specific effect on the spin state. The change of enthalpy, deltaH, of the spin transition depends on the same parameters as the equilibrium constant, in the organic cosolvent as well as in aqueous buffer. As the cosolvent effect is reflected by higher deltaH values, and KCl and pH tend to lower deltaH, the cosolvent effect can easily be compensated. Therefore kinetic studies of the spin conversion might well be undertaken at sub-zero temperature in this solvent.


Structure of the cell wall of Bacillus species C.I.P. 76-111.

An unusual type of bacterial cell wall was encountered in a Bacillus strain referred to as Bacillus sp. C.I.P. 76-111. The major constituent of this cell wall is a high-molecular-weight anionic protein non-covalently associated to a peptidoglycan-polysaccharide complex. The cell wall appeared as a multilayered structure when sections of whole cells or of isolated cell walls fixed with glutaraldehyde and postfixed with osmium tetroxide were examined by electron microscopy. The correlation  between the observed morphological features and the biochemical data suggested that a thin central electron-dense layer identifiable with the peptidoglycan-polysaccharide complex is located between two similar thick layers of protein. Furthermore, negative staining of isolated cell walls revealed that the outer protein layer has a regular surface array of subunits with hexagonal symmetry. Several structural properties of the cell wall peptidoglycan were investigated and were found to resemble those of other bacilli. Further characterization of the autolytic system showed that an N-acetylmuramyl-L-alanine amidase and a glycosidase, presumably a N-acetylmuramidase, were associated with the peptidoglycan-polysaccharide complex. It was also established that this strain is devoid of membrane teichoic acid.


Differences in the modulations of the soluble of plasma-membrane-bound 5'-nucleotidase.

The treatment of plasma membranes by a French pressure cell in sucrose medium devoid of detergents solubilized 20% of the total protein and 95--100% of 5'-nucleotidase activity. The soluble enzyme was 40--90-fold purified by centrifugation in a sucrose gradient with a 10--20% yield with respect to the orginal lysate. The purified fraction retained the same high specificity for 5'-AMP (Km = 20 micron) as in the plasma membranes and was enriched in sphingomyelin. Whereas 5'-AMP at high concentration inhibited the membrane-bound enzyme, it had no effect on the solubilized form. The soluble enzyme was stimulated by 2 X 10(-13)-2 X 10(-15) g concanavalin A without any inhibition with higher doses of lectin. The plasma-membrane bound stimulated and inhibited 5'-nucleotidase was modulated by concanavalin A concentrations higher than 0.1 microgram. Inhibition of the activity of the soluble enzyme by antiphosphorylcholine antibodies was not observed with membranes. The regulation of 5'-nucleotidase acitvity in plasma membranes might be associated with a supramolecular organization.


Properties of human erythrocyte catalases after crosslinking with bifunctional reagents. Symmetry of the quaternary structure.

Normal erythrocyte catalase, the enzyme present in the blood of Swiss acatalasemic heterozygotes, and their hybrid produced in vitro, were studied after crosslinking with bifunctional reagents. On theoretical grounds [cf. Hajdu, J., Bartha, F. & Friedrich, P. (1976) Eur. J. Biochem. 68, 373--383] it is inferred from the dodecylsulphate gel electrophoretic patterns obtained after treating catalase with diimidates of various chain lengths that the enzyme is an isologous tetramer (D2 symmetry). The minimal distances between crosslinkable primary amino groups across the three domains of bonding are different. Reaction with diimidates causes a moderate loss of enzyme activity  in all three enzyme types due to amidination rather than crosslink formation. On the other hand, crosslinking stabilizes the enzyme against urea and heat inactivation. This is most prominent with heterozygote acatalasemic catalase. Crosslinking markedly prevents the development of peroxidase activity that can be elicited in catalases by urea treatment. The role of the quaternary structure of the protein in the relationship between catalase and peroxidase activities is discussed.


Adsorption equilibria of thyroid hormones in the liver cell.

The adsorptive distribution of L-thyroxine and L-triiodothyronine at 0.04--25nM concentrations was determined in suspensions of mitochondria in soluble cytoplasmic proteins from rat livers, at protein  concentrations of 0.5--4.7 mg total protein/ml suspension. In the concentration ranges measured no saturation of both mitochondria and soluble proteins with thyroid hormones could be observed. The distribution of the hormones between the liquid phase of cytoplasmic proteins and the solid phase of the mitochondria depended mainly on the ratio of the amounts of proteins in both phases. Certain drugs such as chlorpromazine and phenobarbital in concentrations used therapeutically can interfere with the processes of adsorptive transport in vitro. Chlorpromazine, in the presence of desorptively functioning cytoplasmic proteins or serum proteins, promotes the adsorption of thyroxine and triiodothyronine onto the mitochondria. In contrast, phenobarbital weakens the binding of the hormones to the mitochondria. The processes of adsorptive binding of thyroid hormones to cell proteins in vitro are suggested as possible links in a transport chain between different compartments in vivo. The new model may also explain the effect of drugs on the distribution of thyroid hormones within the cell.


Amino acid sequences of neurotoxins I and III of the elapidae snake Naja mossambica massambica.

The amino acid sequences of two neurotoxins of the African cobra Naja mossambica mossambica have been determined using almost uniquely phenylisothiocyanate degradation in a liquid protein sequencer programmed alternatively with 'protein' and 'peptide' programs. When compared to known sequences of so-called 'short' neurotoxins belonging to other Elapidae snakes, neurotoxins I and III of Naja mossambica mossambica are very similar to the cobrotoxin, a neurotoxin isolated from the formosan cobra Naja atra atra.


Purification and properties of citrate lyase ligase from Streptococcus diacetilactis.

Citrate lyase ligase (acetate: SH--[acyl-carrier protein] enzyme ligase (AMP) from Streptococcus diacetilactis was purified 920-fold with a yield of 6.3%. The molecular weight of the enzyme was estimated to be 41000; the ligase consisted of one polypeptide chain. The acetylation of 1 mol of deacetyl-citrate lyase to enzymatically active citrate lyase required 6 mol ATP. The formation of AMP and pyrophosphate in the acetylation reaction was demonstrated. Citrate lyase ligase was specific for the lyase from S. diacetilacitis and did not acetylate lyases from Rhodopseudomonas gelatinosa and Enterobacter aerogenes. The substract acetate and ATP could be replaced by propionate and dATP, repectively. The reaction rates for ATP, acetate and deacetyl-citrate lyase followed Michaelis-Menten kinetics (Km values: 26 micron for ATP, 25 mM for acetate and 38 nM for deacetyl-citrate lyase).


Studies by small-angle X-ray scattering of the quaternary structure of the beta-haemocyanin of Helix pomatia.

Helix pomatia beta-haemocyanin was studied in solution by small-angle X-ray scattering. The following molecular parameters were determined: molecular weight = 9.02 X 10(6), volume = 14000 nm3, radius of gyration = 18.4 nm, radius of the spherical subunits = 2.5 +/- 0.2 nm. With these data, and with information of dissociation products described in a former paper, a model of the molecule was built whose theoretical scattering curve showed good agreement with the experimental one. The model consists of 160 spherical subunits of a radius of 2.5 nm; 12 rings each built up of 10 spheres form the outer wall of a hollow cylinder; 20 subunits are situated at the inner side of each end.


The Protein Data Bank. A computer-based archival file for macromolecular structures.

The Protein Data Bank is a computer-based archival file for macromolecular structures. The Bank stores in a uniform format atomic co-ordinates and partial bond connectivities, as derived from crystallographic studies. Text included in each data entry gives pertinent information for the structure at hand (e.g. species from which the molecule has been obtained, resolution of diffraction data, literature citations and specifications of secondary structure). In addition to atomic co-ordinates and connectivities, the Protein Data Bank stores structure factors and phases, although these latter data are not placed in any uniform format. Input of data to the Bank and general maintenance functions are carried out at Brookhaven National Laboratory. All data stored in the Bank are available on magnetic tape for public distribution, from Brookhaven (to laboratories in the Americas), Tokyo (Japan), and Cambridge (Europe and worldwide). A master file is maintained at Brookhaven and duplicate copies are stored in Cambridge and Tokyo. In the future, it is hoped to expand the scope of the Protein Data Bank to make available co-ordinates for standard structural types (e.g. alpha-helix, RNA double-stranded helix) and representative computer programs of utility in the study and interpretation of macromolecular structures.


An analysis of the contracted sheath structure of bacteriophage Mu.

Polymers of contracted sheath particles of bacteriophage Mu were imaged by the negative-staining technique and the electron images were analyzed by optical and digital methods. By means of the three-dimensional reconstruction technique of DeRosier and Klug [Nature (Lond.) 217, 130--134 (1968)] an averaged density map of the sheath structure at a resolution of about 2.0 nm was derived. The sheath is known to consist of one type of protein with a molecular weight of about 52000 [Admiraal and Mellema, J. Ultrastr. Res. 56, 48--64 (1976)]. The interpretation of the map has given information about packing and shape of the protein subunits. One way to describe the structure is by a set of annular rings with 6-fold symmetry. The height of these rings is about 1.8 nm and successive rings in the structure change by about 33 degrees in azimuth. The protein subunit which occupies more than one ring in the polymer, is elongated. The long axis of the protein subunit is at an angle of about 20 degrees with the plane normal to the polymer axis. These data are discussed in relation to changes in the sheath molecules upon contraction.


Structure and function of ornithine carbamoyltransferases.

The reaction catalyzed by ornithine carbamoyltransferase can participate in either the anabolism or the catabolism of arginine. The carbamoylation of ornithine, yielding citrulline, is involved in the biosynthetic sequence; the reverse reaction, the phosphorolysis of citrulline, is the second step of the arginine deiminase pathway. The ornithine carbamoyltransferases of a number of microorganisms which can fulfil both of these functions have been studied in this work. This group of organisms was found to possess two distinct ornithine carbamoyltransferases. The functions of these enzymes were surmised by determining the type of genetic regulation to which they were subjected. The kinetic properties of these various enzymes have been determined. All of them, regardless of the role they play in the cell, catalyze both the synthesis and arsenolysis of citrulline. The anabolic transferase of Pseudomonas is the only enzyme which displays functional irreversibility. A comparison of the quaternary structure of these transferases was performed and reveals interesting features in relation to the metabolic function of these enzymes. All well-characterized anabolic enzymes have low molecular weights (from 150000--105000) and are likely to be trimers. Catabolic enzymes, with the exception of those of Bacillus licheniformis and Halobacterium salinarium, display much higher molecular weights and more elaborate quaternary structure. The properties of these two groups of transferases are discussed in relation to their metabolic role in the cells.


Development of a microassay for estradiol receptors.

The calculation of equilibrium binding constants for a specific receptor-hormone interaction requires the exact determination of the unbound ligand concentration and the specifically bound concentration at equilibrium. These determinations usually require corrections for the contribution of non-specific binding. We introduce several parameters allowing equilibrium concentrations to be calculated from experimental concentration values; these parameters can be measured for the particular receptor assay procedure used. These parameters are used in a microassay of estradiol-receptor complex by selective retention on DE-81 cellulose paper.


Maintenance of the ratio of alpha and beta globin synthesis in rabbit reticulocytes.

The synthesis of rabbit alpha and beta globins under various conditions was studied using intact reticulocytes and reticulocyte cell-free systems. Raising salt concentration of media in which reticulocytes were incubated with radioactive amino acids reduced the total protein synthesis but did not affect the ratio of alpha to beta globins produced. Using a reticulocyte lysate which had been incubated with micrococcal nuclease to remove the endogenous globin messenger RNA activity, it was found that unlike the intact cell or the untreated lysate very little alpha globin was synthesised on adding purified globin mRNA. These results are discussed in terms of their compatibility with some proposed models of coordination of alpha and beta globin production.


Adenosylhomocysteinase from yellow lupin seeds. Purification and properties.

Adenosylhomocysteinase from yellow lupin seeds (Lupinus luteus) has been purified to homogeneity. Active enzyme, Mr = 110000, consists of two probably identical subunits with Mr = 55000 as judged by gel filtration and dodecyl sulphage/polyacrylamide gel electrophoresis in the presence of 2-mercaptoethanol. The isoelectric point of the enzyme was shown to be 4.9 +/- 0.1. It was demonstrated by disc and pore gradient electrophoresis that the most purified fraction formed multimers. The enzyme shows optimum activity at pH 8.5-9.0. Km values are 2.3 micrometer, 4.6 mM and 12 micrometer for adenosine, DL-homocysteine and S-adenosyl-L-homocysteine, respectively. The energy of activation for S-adenosylhomocysteine synthesis was estimated as 14.4 kcal/mol (60.2 kJ/mol) and temperature coefficient as 2.4. The equilibrium constant for the hydrolysis of S-adenosylhomocysteine amounts to 5 X 10(-7) M. Anti-sulfhydryl reagents such as p-hydroxymercuribenzoate and N-ethylmaleimide acted as irreversible inhibitors. The enzyme exhibits high specificity for homocysteine whereas some of the rare nucleosides tested could substitute for adenosine.


Human alpha-n-acetylglucosaminidase. 2. Activity towards natural substrates and multiple recognition forms.

Purified urinary alpha-N-acetylglucosaminidase acts as an exoglycosidase. The enzyme removes from heparan sulfate exclusively alpha-glycosidically linked N-acetylglucosamine residues. The pH optimum of around 4.4 towards heparan sulfate and heparin is similar to that towards synthetic arylglycosides. Urinary alpha-N-acetylglucosaminidase can be separated by isoelectric focusing into multiple forms with pI values between 3.3 and 6.0. The multiple forms differ in their recognition and endocytosis by cultivated skin fibroblasts. Forms with pI values of 4.8 +/- 0.3 respond best to endcytosis. From these forms up to 0.8 X 10(6) molecules may be recognized and taken up in an hour by a single cell. Sodium periodate treatment reduces the alpha-N-acetylglucosaminidase recognition by fibroblasts and suggests that the recognition sites on the enzyme are associated with its carbohydrate moiety. Attempts to modify the recognition of alpha-N-acetylglucosaminidase by pretreatment with purified glycosidases failed.


Thyrotropin stimulation of a thyroid contractile protein phosphorylation.

Contractile proteins were isolated from preincubated dog thyroid slices by a procedure identical to the one used for the preparation of muscle actomyosin. At least two of these proteins (molecular weight = 26000 and 15000) were phosphorylated in the intact cell system. After one hour of incubation of the slices with thrytropin (10 mU/ml) and [32P]phosphate, the specific activity of the 26000-Mr protein was increased by a factor of three while no significant change in specific activity was observed in the 1500-Mr contractile protein. This effect of thyrotropin was already observed after 30 min of action, was elicited at hormone concentrations of the same order as those required to induce secretion and has been reproduced by dibutyryl adenosine 3':5'-monophosphate. Cycloheximide (0.35 mM) which almost totally inhibited protein synthesis in thyroid slices, did not affect the thyrotropin stimulation of the phosphorylation of the 26000-Mr protein. The phosphorylation of serine residue(s) has been demonstrated in this protein but the presence of radioactive phosphothreonine could not be detected. On the basis of its molecular weight, the 26000-Mr protein could be similar to the inhibitory component of muscle troponin complex (TN-I).


The hyphal wall of Mucor mucedo. 1. Polyanionic polymers.

Treatment of isolated hyphal walls of Mucor mucedo with nitrous acid resulted in the release of two water-soluble polyanions: (a) a glycuronan, containing all the neutral sugars and uronic acid present in the hyphal wall and (b) an inorganic polyphosphate. The glycuronan could also be extracted quantitatively with salt solutions of high ionic strength and partially with a solution of potassium hydroxide. This is presented as evidence that the glycuronan is a genuine constituent of the cell wall, non-covalently bound to glucosamine-containing polymers which are susceptible to depolymerization by nitrous acid. By treatment with acid the glycuronan was partly converted to crystalline poly(glucuronic acid) with the properties of mucoric acid. This strongly suggests that mucoric acid, which can be extracted from the walls of M. mucedo by alkali after acid treatment, is not a genuine wall component but arises by partial acid hydrolysis of the heteropolymeric glycuronan.


The hyphal wall of Mucor mucedo. 2. Hexosamine-containing polymers.

Nitrous acid, which specifically depolymerises polymers containing hexosamines with a primary amino group, was used to analyse the hexosamine-containing polymers in the hyphal wall of Mucor mucedo. N-Acetylglucosamine was found to occur in three polymeric fractions. One fraction which was solubilised by HNO2 treatment contained-N-acetylglucosamine interspersed with glucosamine; no homopolymer of glucosamine (chitosan) was detected. Another fraction became HNO2-soluble after treatment with pronase or alkali; this points to the occurrence of a heteropolymer containing N-acetylglucosamine and glucosamine in which some of the glucosamine residues are linked to peptides via their amino groups. The residue remaaining after pronase and HNO* treatment appeared to consist of a homopolymer of N-acetylglucosamine (chitin).


Sulfinpyrazone and postoperative deep vein thrombosis.

Small doses of subcutaneous heparin and infusions of dextran both reduce the incidence of fatal pulmonary embolism after elective general surgery. But both methods have disadvantages. Therefore, the protection against deep vein thrombosis afforded by sulfinpyrazone, a drug which can be taken by mouth as well as by injection, was assessed in a prospective study of 119 patients undergoing elective general or urological surgery. The prophylactic administration of sulfinpyrazone was compared with the effects of small doses of sodium heparin and infusions of dextran-70. The 125I-fibrinogen test was carried out in all patients during their hospitalization. Deep vein thrombosis was diagnosed in 13 of 30 patients (43%) who received sulfinpyrazone, in 9 of 29 (31%) receiving dextran-70 and in 2 of 22 (9%) having subcutaneous heparin. The difference between the sulfinpyrazone and heparin groups was statistically significant (p less than 0.01). Sulfinpyrazone in the dose used in this trial was not effective in reducing the incidence of deep vein thrombosis during elective general surgery.


Effect of dextran and hyaluronic acid on the development of postoperative peritoneal adhesions in experimental animals.

The development of postoperative peritoneal adhesions was studied in rats and rabbits, the frequency of adhesions in the experimental model used being very high. In the development of an adhesion, fibrin seems to be an important contributor to the bridge between different tissues. Dextran, which modifies the fibrin network and makes it more susceptible to lysis, was used as a possible prophylactic agent, but we found no difference between treated and control groups. It is concluded that the stimulus for fibrin formation in the peritoneal adhesions using this atraumatic model was too strong to be overcome by the normal fibrinolytic system. The anti-inflammatory reaction of hyaluronic acid did not diminish the frequency or degree of adhesions.


Repeated arterial embolization of rat livers by degradable microspheres.

A transient arrest of arterial blood flow can be accomplished by intra-arterial injection of a new type of degradable microsphere. The effects of single and multiple injections of these microspheres into rat hepatic arteries were studied by measurements of fractional cardiac output distribution and 133Xe washout from the liver before and after embolization. Injection of these microspheres into the hepatic artery caused a significant but transient reduction of the arterial blood flow to the liver. Repetition of the injection several times over several days produced identical effects on each embolization. No signs of hepatic cell damage were detected after repeated embolization, as suggested by assay of the serum enzymes or the Bromsulphalein retention test.


Blood flow in normal and cholestatic dog liver as measured by intraparenchymal injection of Xenon 133.

Parenchymal liver blood flow as reflected by the wash-out of intraparenchymally injected 133Xe was studied at different stages of total cholestasis in the dog. 248 registrations at 13 laparotomies in 6 mongrel dogs showed that extrahepatic cholestasis had no statistically significant influence on the blood flow as compared to normal. A review of the literature shows little harmony between the results of this and various other studies.


Myocardial radiopaque markers used to quantify minor axis shortening for follow-up studies in experimental surgery. I. Recording and analysis techniques. II. Comparison with contractility indices.

This work further validates the use of radiopaque epicardial marker motion for quantifying myocardial shortening in long duration follow-up studies. Mean velocity and extent of minor axis shortening were determined in 8 dogs filmed daily for 6--10 days postoperative. As an independent measure of contractility, peak dP/dt was also determined. A useful approximation to the mean ejection slope was developed which uses the end diastolic minor axis 50 msec after the Q wave, and end systolic minor axis 150 msec after the Q wave of the ECG.


Transmembrane fluxes of potassium in dog kidney slices. A quantitation of the effect of warm ischemia.

The effect of warm ischemia on the transmembrane transport of potassium in dog kidney slices was studied by measurement of the uptake of 42K. The requirement for steady-state conditions concerning the intracellular potassium concentration was thereby studied. The total potassium content in the slices was found to be constant between 120 and 180 min incubation at both 25 and 37 degrees C. The cell water calculated from the total tissue water and 14C-inulin space in the dog kidney slices amounted to 38 ml-100 g wet weight-1 at 37 degrees C and 45 ml-100 g wet weight-1 at 25 degrees C and was found to remain constant for the incubation interval 120--180 min. The major part of the tissue uptake of 42K could be described by one single mono-exponential function under these conditions. The transmembrane influx at 37 degrees C calculated by using a modified Keynes formula amounted to 1.70 mmol K+-kg wet weight-1-min-1 after no warm ischemia and to 0.89 mmol K+-kg wet weight-1-min-1 after 2 h warm ischemia. The corresponding values for incubation at 25 degrees C were 1.26 and 0.77 mmol K+-kg wet weight-1-min-1, respectively. In the slices incubated at 25 degrees C, the potassium content was higher and the sodium content lower than in slices incubated at 37 degrees C.


Friedreich's disease--a family study.

Friedreich's disease occurring in 4 male siblings in a sibship of seven caused cardiac and neurological abnormalities and one twin of an affected member died in cardiac failure; at autopsy characteristic pathological features of Friedreich's disease were demonstrated in the nervous system and heart. One female sibling had a patent ductus arteriosus which was treated surgically and a continuous murmur was present in another sister but cardiac catheterization in childhood had been normal.


Traumatic myocardial infarction with subsequent normal coronary arteriogram.

A 36-yr-old man suffered from transmural anterior myocardial infarction almost immediately after being hit by a football on the chest. There were neither external signs of injury to the chest wall, nor fractures of the thoracic cage. Coronary angiography 6 wk later revealed no demonstrable obstruction in any vessel; therefore, coronary artery injury with subsequent platelet aggregates or thrombosis followed by lysis and recanalization was suspected. Myocardial contusion or coronary spasm are alternative explanations.


Long-term survival after myocardial infarction as related to early complications.

The material consists of 404 hospitalized patients with their first AMI. After an observation time of 1 and 5 yr, respectively, the mortality was 27% and 45%, against an expected mortality of 3% and 17% in a corresponding normal population. The annual mortality rate was 5.5% from 1 to 3 yr after the acute infarction, against an expected 3.5%. 3-5 yr after occurrence of the infarction, both the observed and expected annual mortality rates were 3.5%. In patients alive 1 mth after the acute attack, congestive heart failure (CHF) or left bundle branch block (LBBB) or secondary ventricular fibrillation (VF) during the acute phase gave a lower long-term survival, as compared to patients without CHF, intraventricular block or VF, respectively. Left anterior hemiblock, complete atrioventricular block following inferior infarction, or primary VF had no influence on the long-term prognosis.


The influence of allopurinol and size of dose on the metabolism of phenylbutazone in patients with gout.

Administration of allopurinol 300 mg/day produced minimal changes in the disappearance of phenylbutazone in each of five subjects following single doses (6 mg/kg) in clinical range and caused some prolongation (21%, 52%) of drug half-lives in two of six subjects after single small doses (0.5 mg/kg); mean half-life was not significantly altered by allopurinol at either dose level (means of 52 versus 48 at 0.5 mg/kg and 68 versus 70 h at 6 mg/kg). Size of dose altered half-life when phenylbutazone was used alone; three subjects showed considerably longer half-lives at the higher dose (86 versus 47, 91 versus 41, 65 versus 38 h). Allopurinol caused a greater than 50% prolongation of half-lives in two of five subjects who received single 0.5 g doses of probenecid. These preliminary data do not indicate a need to change the dose of phenylbutazone when subjects are receiving allopurinol.


Effect of indomethacin on pulmonary vasomotor response in patients with mitral stenosis.

In 10 patients with mitral stenosis, ingestion of 125 mg indomethacin over a 24-h period had no effect on the elevated pressure in pulmonary artery. It did, however, in all patients, slightly potentiate a fall in pulmonary pressure induced by breathing of 100% oxygen. The results do not suggest that a prostaglandin mechanism is involved in chronic pulmonary vasoconstriction or that this mechanism is responsible for acute vasodilatation of the pulmonary bed induced by oxygen inhalation.


The conduction system in corrected transposition with situs inversus.

The location and course of the conduction system were investigated by serial section in two hearts with corrected transposition of the great arteries in situs inversus. In the first case, characterized by dextrocardia, the interventricular septum was intact, while in the second case with levocardia, a high ventricular septal defect was associated with pulmonary atresia. In both hearts, a regular posterior connecting AV node was present, left-sided in one case and right-sided in the other. The bundle branches were distributed in the morphologically appropriate ventricles. Extensive hemorrhage and coagulation necrosis of the common bundle and bundle branches were observed in the first case, being consequent upon surgical replacement of the right-sided tricuspid valve. The common bundle ran below the membranous septum in this case. In the heart with ventricular septal defect it was related to the postero-inferior rim of the defect. In both cases, an accessory AV node was located anteriorly in the interatrial septum but did not connect with the ventricular musculature. The different position of the atrioventricular conducting tissue in corrected transposition, between cases in situs solitus and situs inversus, is emphasized.


Serum zinc and serum copper and indices of drug metabolism in alcoholics.

Serum zinc and copper levels were studied in relation to in vitro and in vivo drug metabolism in 25 alcoholics, in whom various diseases of the liver had been diagnosed by histology. Serum zinc was elevated in alcoholics with normal or fatty liver and was low in those with alcoholic hepatitis or cirrhosis. There was a significant positive correlation between serum zinc and cytochrome P-450 content of liver biopsies. The relationship between zinc and antipyrine half-life was significant and non-linear. Serum copper level was elevated in all the alcoholics and no significant relationship could be found between copper and drug metabolism in alcoholics. The findings suggest parallelism between changes in serum zinc and indices of drug metabolism in alcoholics.


A sensitive radioimmunoassay for fentanyl. Plasma level in dogs and man.

Antiserum to fentanyl was obtained in rabbits repeatedly injected with carboxyfentanyl conjugated to bovine serum albumin. Using the antiserum, a highly sensitive radioimmunoassay has been developed, based on the dextran-coated charcoal method. It proved possible to assay the drug directly in plasma, in amounts as small as 30 picogram in 0.5 ml. The antibody was highly specific for fentanyl and no cross-reaction was observed with its major metabolites. This sensitive and specific radioimmunoassay method was employed to determine fentanyl in plasma from six volunteers after an intravenous bolus of 0.2 mg, and in plasma from dogs treated both intravenously and subcutaneously with 0.02 mg/kg. The plasma level of fentanyl could be followed for up to 6 h after a therapeutic dose in dogs and man.


Plasma renin concentration in essential hypertension during beta-adrenergic blockade and vasodilator therapy.

Plasma renin concentration (PRC) was measured in 46 patients with essential hypertension before and after treatment for 4 weeks with alprenolol 600-1200 mg daily. In 27 of these patients PRC was measured after 4 weeks of combined treatment with alprenolol and hydralizine. During alprenolol treatment PRC and blood pressure were reduced, but the changes were not correlated. Alprenolol treatment caused similar blood pressure reductions in patients with high and low PRC, and the antihypertensive efficacy of beta-adrenergic blocking agents could not be predicted from the pretreatment PRC. When beta-adrenergic blockade was supplemented with hydralazine, blood pressure was further reduced, but PRC remained unchanged. Although a causal relationship between blood pressure reduction and suppression of renin, production might exist at low doses of beta-adrenergic blocking agents, the present study did not indicate such a relationship when higher doses were used. It was shown that alprenolol inhibited the increase in PRC usually induced by hydralazine, but it is not known whether this was important for the effectiveness of the fall in blood pressure produced by hydralazine.


Suppression of anti-hapten antibody response in vitro by hapten-carrier conjugates.

Production of antibodies was stimulated or suppressed arbitrarily by antigen treatment in vitro of spleens cultured at various time intervals after in vivo immunization. Spleens of mice immunized to the 2,4-dinitrophenyl or (4-hydroxy-3-iodo-5-nitrophenyl)acetyl haptenic determinants produced antibodies in culture when no antigen was applied in vitro. When a conjugate of the hapten to the same carrier employed for priming was given in vitro, an initial reduction of the response was observed, the level of which was dependent on antigen dose. Subsequently, increased amounts of antibodies were measured. In contrast, in vitro exposure to the hapten conjugated to an unrelated carrier resulted in significant reduction of the response for the entire period of the test. This suppressive effect manifested with various carrier proteins (ovalbumin, bovin IgG, bovine and rabbit serum albumin and keyhole limpet hemocyanin), when when applied to cultures in doses which were potentially immunogenic.