[Affinity of polar digoxin and digitoxin metabolites for digoxin and digitoxin antibodies].

The affinities of some polar and non-polar digoxin and digitoxin metabolites to the related antibodies are largely dependent on the structure of their genin parts. Metabolites with unchanged genins show high cross reactivities towards their related antibodies when compared to the original immunogenic cardenolides. Towards the digoxin antibody the following cross reactivities were found: digoxin-16'-glucuronide 50%, digoxigenin 89.5%, and digoxigenin-3-glucuronide 85%. Values of the same order of magnitude were found with the corresponding digitoxin metabolites and the digitoxin antibody. In contrast, there is a marked decrease in cross reactivity caused by only minor changes in the genin part. With the digitoxin antibody the following cross reactivities are found: digoxin (i.e. 12-OH-digitoxin) 9.1%, 3-epi-digitoxigenin 5.6% and 3-epi-digitoxigenin-3-sulphate 1%. Bcause 12-hydroxylation has been reported to be one of several possible ways of digitoxin metabolisation in man, from a theoretical point of view erroneous results in the clinical digitoxin estimation by radioimmuno-assay are possible. In the case of all of the other metabolites the alterations in positive inotropic activity and cross reactivity run largely parallel.


The influence of polar and non-polar digoxin and digitoxin metabolites on the 86Rb-uptake of human erythrocytes and the contractility of guinea pig papillary muscles.

The potency of various digoxigenin and digitoxigenin derivatives with different polarity was tested in two biological systems: First, in an 86-Rb-erythrocyte assay which allows to determine the influence on active cation transport (measured as the glycoside concentration exerting half maximal inhibition of 86-Rb-uptake of human erythrocytes = IC50). Second, with isolated guinea pig papillary muscle, which allows to determine glycoside effects on contractile force (measured as the glycoside concentration exerting 100% increase of contractile force = C+100%). The IC50 of the substances covered a range from 3.2 to 4800 X 10(-9) M, the C+100% from 0.7 to 978 X 10(-6) M. In both assay systems the glucuronides of glycosides and genins were between 1.4 and 11 times less potent than the original substances. A highly significant correlation (p less then 0.0001) was found between IC50 and C+100% (r = 0.9996) and between log IC50 and log C+100% (r = 0.9819), the slope for the latter correlation being nearly unite (= 0.9912). The results support the hypothesis that inhibition of active cation transport is and important step in glycoside incuced posite-inotropic effect.


[Fate of orally administered beta-acetyldigoxin in man (author's transl)].

After oral administration of 3H-beta-acetyldigoxin to four patients aspirates of gastric and duodenal contents were obtained with intestinal tubes. Concentration of label in the aspirates was measured. Radiochromatographic analysis of the aspirates showed that 90% of the beta-acetyldigoxin was unchanged during the period  it was in the stomach. In the duodenum a small part of the administered dose was transformed to 3H-alpha-acetyldigoxin. When given 3H-beta acetyl-digoxin intraduodenally to three subjects in the portal vein blood 93% of the labelled compunds was 3H-digoxin. According to these data the absorption of beta-acetyldigoxin can be described as follows: After oral ingestion beta-acetyl-digoxin rapidly passes the stomach with a half-life of 10 min. Most of the glycoside is absorbed unchanged in the duodenum. On passage through the intestinal wall the acetyl group is removed and digoxin is the active drug reaching the heart.


[Studies on the pharmacokinetic equivalence of pivampicillin base and hydrochloride in capsules and tablets (author's transl)].

Absorption and urinary excretion of pivampicillin as hydrochloride and as base were studied following administration of four different formulations to 12 healthy volunteers in a cross-over study. A fluorimetric assay of ampicillin was adapted to be used with an Auto Analyzer system. The plasma concentrations observed are comparable to those reported in the literature. The amount of drug absorbed is the same for all four medications whereas absorption is more rapid from tablets than from capsules. Base and hydrochloride of pivampicillin are equivalent with respect to pharmacokinetic behaviour. So, the formulation itself seems to be more important for biological equivalence than the ionisation of the drug used in the formulation.


[Biopharmaceutic investigations with D-norpseudoephedrine (author's transl)].

The concentrations of D-norpseudoephedrine in the plasma of 6 healthy persons were measured after the oral administration of 60 mg D-norpseudoephedrinehydrochloride in a hard gelatin capsule. One-compartment open-model parameters were derived from the blood levels. No gastric absorption was observed. The intestinal absorption started after a lag time of 0.31 h with an absorption constant of 1.75 h-1. The maximum of plasma concentration with 200 ng D-norpseudoephedrine/ml plasma was reached after 1.3 h. The following monoexponential decay of the plasma concentration curve had a half-life of 3 h. 24 h after ingestion no remaining D-norpseudoephedrine could be detected in the plasma. In vitro absorption constants were measured with the Sartorius-Resorptionsmodell. The in vitro results agreed with the in vivo results. The dissociation constant of D-norpseudoephedrine was determined (pKa = 8.92) with a non-logarithmic titration method.


Some laboratory aspects of hepatic tolerability of diftalone.

The hepatic tolerability of phthalazine-(2,2-b)-phthalazin-5,12-(7H,14H)-dione (diftalone--administered at the dosage of 750 mg/day p.o. for a mean period of 23 days--has been studied in 40 patients by means of: total plasma protein, albumin, fibrinogen, serum glutamin-oxalacetic transaminase, serum glutamic-pyruvic transaminase, lactic dehydrogenase, creatine phosphokinase, alkaline phosphatase, glycemic curve after glucagon and plasmatic elimination of bromosulphalein. A statistically but not clinically significant increase of the SGPT level is the only change observed.


Effect of pyritinol-GCl on blood flow and oxidative metabolism of the brain in patients with dementia.

In order to test whether and in what way pyritinon-HCl affects cerebral blood flow and oxidative metabolism in patients with organic brain disorders, the following parameters were measured in a group of 87 patients: cerebral blood flow using the Kety and Schmidt method, cerebral consumption of oxygen and glucose, and also CO2 and lactate ouptut. 45 out of the 87 patients were given pyritinol in a dose of 900 or 1000 mg/day, 42 out of 87 patients formed a control group and were given 500 mgof 5% laevulose i.v. daily for the average duration of the study of approximately 3 weeks. The results can be summarised as follows: 1. Cerebral blood flow and oxidative metabolism are changed in patients with organic brain disorders in different ways voth as regards quality and quanitity. Findings from earlier investigations could thus be confirmed. 2. When laevulose only was used, the parameters measured did not alter on average. In addition to deteriorations in the findings, spontaneous improvements or normalisationof previously disturbed cerebral blood flow and cerebral metabolism values were also abserved. 3. Pyritinol-HCl usually improved previously disturbed cerebral glucose metabolism significantly. An effect on disturbed cerebral blood flow or pathologically changed cerebral oxygen consumption was not found.


[On the clinical evaluation of therapy with nifedipine in association with various anithypertensive drugs (author's transl)].

During a double-blind cross-over study of 3 weeks duration 42 hypertensive outpatients with prevailingly mild angina pectoris received 30 mg daily of 4-(2'-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarbonic acid dimethylester (nifedipine, Bay a 1040, Adalat) daily or placebo, respectively. 30 patients (mean age: 47 +/- 10 years, mean weight: 79 +/- 13 kg, mean height: 169 +/- 7 cm) completed the whole study period. The mean recumbent blood pressure was 158 +/- 26 mmHg syst. and 101 +/- 16 mmHg diast., the heart rate averaged 74 +/- 12 beats/min. Under these criteria the two cross-over groups of 14 and 16 patients are well comparable. 6 patients dropped out because of side effects under nifedipind (compared to 2 patients under placebo). With one exception mean blood pressures were reduced by less than 10 mmHg during the application of nifedipine as compared to controls, this being true for systolic and diastolic pressures as well as for different positions during measurements. This result is also independent of the corresponding pre-values measured. The differences between the treatment phases did not reach statistical significance. Clinically a blood pressure reduction of this degree is rarely of consequence. But 3 patients reported hypotensive symptoms about 30 min after nifedipine. Nifedipine did not seem to influence the heart rate.


Effect of pirenzepine, a new gastric acid-inhibiting agent, on exocrine pancreatic secretion in man.

The effect of orally ingested 5,1-dihydroxy-11- (4-methyl-1-piperazinyl)-acetyl-6H-pyrido(2,3-b)-I, 4-benzodiazepin-6-one dihydrochloride (LS 519, pirenzepine), a newly developed compound with gastric secretion-inhibitory action but without central-nervous sedation, on the secretion of fluid into the duodenum and on pancreatic enzyme output was studied by a marker perfusion technique in 10 human subjects. A short-lasting increase in duodenal volume was observed, while output of trypsin and lipase remained unchanged. Central and autonomic nervous actions seem unlikely, a possible release of endogenous secretion was discussed.tin was discussed.


Oral antipyretic therapy. Evaluation of mefenamic acid (short communication).

The capacity of N-(2,3-xylyl)anthranilic acid (mefenamic acid) to reduce fever in children was compared with that of acetylsalicylic acid, paracetamol and amino-phenazone. The series of cases consisted of 71 patients in the age range from 3 months to 15 years and with rectal temperatures above 38.5 degrees C. Temperatures were recorded at 15 and 30 min, and 1, 2, 4 and 6 h after challenge with the drug. The antipyretic effect of mefenamic acid in a dose of 4 mg/kg was optimal: it was 2.5 times that of acetyl-salicylic acid or paracetamol and nearly similar to that of aminophenazone. It seems possible that the antipyretic effect of mefenamic acid is stronger than its anti-inflammatory and analgetic properties.


[Basic physiological requirements for therapy of coronary insufficiency (author's transl)].

The determining factors of coronary blood supply are described. The dependence of the coronary vascular resistance and the coronary extra-vascular resistance on the oxygen requirement and metabolism products of the heart muscles on one hand, and the various haemodynamic parameters on the other, are delineated. Based on this conception the principles for a therapy of coronary insufficiency are deduced. The difficulties, however, which limit this therapeutic procedure are also mentioned.


[Prophylaxis of myocardial infarction and follow-up treatment (author's transl)].

There is no specifique prophylaxis of myocardial infarction; it is identical to prophylaxis of coronary artery disease, that is elimination of risk factors and treatment of ischemic heart disease, if diagnosed in the preinfarction stage. Treatment in the postinfarction stage is dependent on symptoms. Of special importance is the diagnosis of life-threatening arrhythmias, which might necessitate prophylactic antiarrhythmic treatment. The value of "clinical" (hospitalised) rehabilitation is still debated, especially with regard to physiological and prognostic aspects. Surgery will be of increasing importance, especially aneurysmectomy (infarctectomy) and revascularization.


[Therapy with coronary dilators].

The pathophysiological basis of antianginal therapy with vasodilating agents is critically reviewed. The concept of specific coronary vasodilation should not be pursued in the search for new antianginal agents. Although controlled clinical trials with coronary vasodilators in patients have been successful, no inferences can be drawn as to the concept of coronary vasodilation since most of these compounds vasodilate only the coronaires of experimental animals after i.v. administration but not those of humans after oral ingestion. The stimulating influence of coronary vasodilators on coronary collaterals is an interesting but so far unproven claim. Nitroglycerine dilates the large epicardial coronary vessels. This effect can be of significance in excentric stenoses where the arterial wall is to a small part intact.


[Combined therapy with glycosides and Ca++-antagonistic agents (author's transl)].

Ca-antagonistic drugs increase cardiac oxygen supply by a coronary vasodilator action whilst they simultaneously lower myocardial oxygen demand. The latter drug effect is due to a decrease in cardiac contractile energy expenditure both directly (restriction of myocardial contractility) and indirectly (reduction of arterial blood pressure resulting from systemic vasodilation). In coronary disease all these factors can contribute to an improvement of the disturbed myocardial energy balance. As to the coronary vasodilator action of Ca-antagonistic drugs in particular, it is important to note that they readily relax the smooth musculature of the major extramural stem arteries where most of the occlusive atherosclerotic intima processes (about 95%) are located. In contrast, other coronary vasodilators such as adenosine, dipyridamole, chromonar, lidoflazine, theophylline, which lack Ca-antagonistic properties, are primarily acting on the small intramural resistance vessels of the heart whereas vascular smooth musculature originating from the major extramural arteries is less affected. Therefore, in elderly atherosclerotic patients the possible risk of glycoside-induced vasoconstriction in extramural coronary stem arteries (and also in arteries of systemic circulation) can be sufficiently eliminated only with the help of Ca-antagonists.


[Investigations of the reaction kinetics in the formation of 7-chloro-2N-nitrosomethylamino-5-phenyl-3H-1,4-benzodiazepine-4-oxide (author's transl)].

The influence of alcohol, ascorbic acid, phenol and thiocyanic acid on the formation of N-nitrosochlordiazepoxide from chlordiazepoxide and nitrous acid was investigated by means of high-performance liquid chromatography.


Synthesis, structure and antibacterial activity of some alkyltriazenopyrazoles.

A series of bis-beta-chlorethyl-, dimethyl- and diethyltriazenopyrazoles (I-IV) were synthesized. By the method of IR spectroscopy the most probable transformation form of I was shown. The compounds were tested as antibacterial agents on a series of bacterial species. It was established that only one of them (VI) possessed a low inhibitory effect. All the rest inhibited strongly the growth of Staphylococcus aureaus 209 and E. coli 387.


Effects of chloroquine on the adrenocortical function. III. Sex differences in concentrations of cholesterol and ascorbic acid in the suprarenal gland after a single administration of chloroquine in the rat.

Effects of single doses of 4-(4-diethylamino-1-methylbutylamino)-7-chloroquinoline (chloroquine diphosphate, Delagil Egyt) given orally (40, 80, 160 and 320 mg of base/kg) or s.c. (40, 80 and 120 mg of base/kg) upon cholesterol and ascorbic acid concentrations in the white rat suprarenal glands were followed up. The occurrence of signs of adrenocortical activation was found to be dependent on the route of application and sex of animals. Chloroquine given s.c. caused a decrease in ascorbic acid level only in doses close to LD50. The oral administration of chloroquine in doses of 80 mg/kg and more produced a significant decrease in cholesterol and ascorbic acid concentrations in the suprarenal glands of female rats, while in males chloroquine in any of the dose levels tested was without effect.


[Involvement of both H1- and H2-receptors in the depressor responses of blood pressure to histamine in the rat (author's transl)].

Histamine caused a dose-dependent fall in blood pressure. This dose-response curve could be shifted to the right by administration of dimethylaminoethyl-N-p-methoxybenzyl-N-alpha-aminopyridine (mepyramine; H1-antagonist). 1-Methyl-([(5-methyl-4-imidazolyl)-2-methylthio]-3-ethyl)-2-thiourea (metiamide; H2-antagonist) alone had no effect on the histamine dose-response curve. The combination of both antagonists caused a further dose-dependent shift to the right. These results found in anaesthetized rats indicate the presence of both histamine receptors in the circulatory system of the rat.


A new cephalosporin derivative (ST-21) orally administered in laboratory animals.

The pivaloxymethyl ester of 7-(D-2-amino-2-phenylacetamido)-desacetoxicephalosporanic acid hydrochloride (ST-21) and cephalexin possess the same bacteridal activity. In fact, in the animal body ST-21 releases cephalexin. The acute toxicity study shows the good tolerance of both substances, whereas the tissue distribution is different, both after oral and i.v. administration. Cephalexin concentrations in some tissues of rats and rabbits, particularly in the lungs and kidneys, are higher and longer-lasting in the animals treated with ST-21 than in those receiving cephalexin, thus showing a different pattern of distribution in the body. For this reason ST-21 might be more suited for the treatment of lung and kidney infections.


Steroidal influence on the resynthesis of adrenomedullary hormones. Short communication.

The role of glucocorticoid on the resynthesis of catecholamines was studied in the pigeon. Hydrocortisone was administered to the reserpinized pigeons. The steroid treated birds were autopsied along with the reserpinized controls. It was found that epinephrine production was considerably increased in the steroid treated group, which indicated that hydrocortisone had effectively triggered the methyl transferase activity during the restitution phase of catecholamines.


In vitro metabolism of lidoflazine by rat and dog liver fractions.

Lidoflazine was metabolized very rapidly by 16000 g supernatant fractions of rat and dog liver. The rate and the extent of metabolism were considerably superior for rat liver. Lidoflazine metabolites were purified by extraction and thin-layer chromatography and identified by mass spectrometry. The main pathways of the in vitro metabolism by rat and dog liver fractions were the same. Oxidative N-dealkylation was the most important. An incubation of major metabolite 1-[4,4-bis(4-fluorophenyl)-butyl]piperazine, with rat liver fraction was performed. A hydroxylated metabolite and a ketopiperazine metabolite were detected only in the dog experiments.


Pharmacokinetics and metabolism of 14C-glipentide, a new antidiabetic, after oral and intravenous administration.

The pharmacokinetic study of 14C-glipentide in male Wistar rats shows, at 0.2 mg/kg doses, that blood radioactivity drops quickly. The metabolization is effected in the liver and leads to four labelled metabolites which are eliminated mainly by the bile. The physiological disposition of unchanged glipentide can be described by a two-compartment open model. Autoradiography and quantitative studies have shown that the liver presents the highest concentration of radioactivity, that diminishes to a very low value 96 h after the administration. In the other tissues the radioactivity is never large, even following repeated administrations. The plasma protein binding does not change with the time, and it can be presumed that binding forces of glipentide and its metabolites to plasma proteins are similar. Glipentide is very well absorbed. The urinary and fecal elimination of radioactivity is similar after oral and i.v. administration.


[The value of radiographical examination for the evaluation adjuvant disease in the rat (author's transl)].

Radiographical examinations of the rat with adjuvant disease reveal characteristic changes in the joints and soft tissues which are useful for the evaluation of this experimental arthritis model. Sequential radiographical analysis with estimation of radiological joint score allows a close follow-up of the disease, which parallels some clinical parameters. Being objective and easy to be documented this method shows several advantages over the conventional evaluation methods. Furthermore, it enables an insight into the paraarticular and spine involvement, which otherwise remains uncovered. The radiographical evaluations might provide some additional and eventually essential information in the study of some drug effect in this disease. Our data should encourage the use of this method for the evaluation of the adjuvant disease in the rat.


Further evidence for the induction of proteolysis by coumarin in rats with various high-protein oedemas.

It has been shown that coumarin can induce lysis of tracer protein injected into animals with normal limbs as well as such with various high-protein oedemas. Although this experiment greatly underestimates protein lysis, burn treated groups showed significant increases in protein fragments of both the body and limb. Although the reverse was the case for the group with lymphoedema and for the group with lymphoedema in combination with burn, the results could be explained by incorporation of the fragments into protein not precipitable with trichloroacetic acid (TCA) in the maturing phagocytes of the lesion. Coumarin alone cannot induce this proteolysis, it needs the tissues and the cells within them.


[Long-term infusion technique via tail vein in unrestrained rat. Technical short communication (author's transl)].

A technique is described that allows tail vein infusion in the rat up to several weeks without the risk of pressure necrosis of the tail. By the aid of a simple metallic device the catheter is protected against damage by the animal. Since this armament is well tolerated and the mobility of the rat remains unimpaired, psychic stress is minimized.


Absorption studies with the anti-diarrhoeal agent ethacridine lactate in laboratory animals and man.

Tritiated 2-ethoxy-6,9-diaminoacridine (ethacridine lactate, Rivanol) has been orally administered to rat, dog, rabbit and man, and the distribution of radioactivity between urine and faeces determined. Complete recoveries of radioactivity were obtained from rat, rabbit and man. From direct measurement of levels of radioactivity, the maximum percentage of the dose excreted via the urine varied from 1.7% (man) to 6.1% (dog). Tritiated water accounted for nearly 50% of this amount. The low levels of radioactivity in plasma of dog and man and in the bile of rats following administration of 3H-ethacridine lactate suggested that there was only a low degree of oral absorption and substantiated previous reports that the drug is essentially unabsorbed in man. From fluorimetric measurements and the determination of levels of radioactivity in ether extracts of urine, it could be concluded that for all species less than 0.1% of the dose appeared in the urine as acridine-like material.


Haemodynamic effects of a new anti-anginal drug, diltiazem hydrochloride.

The haemodynamic effects of a new anti-anginal drug, dilitazem HCl, were studied in 20 patients with angina pectoris. The 131I-dilution method was used. In two patients, one with atrial septal defect and the other with pulmonic regurgitation, heart catheterization was carried out. The drug exerted significant decrease in stroke volume, cardiac output, cardiac work, stroke work and cardiac output/circulating blood volume ratio. The patients who underwent direct cardiac catheterization disclosed no changes in Vmax and ejection fraction, but there were decreases in stroke volume. The decrease in cardiac work and stroke work after after diltiazem Hcl therapy was apparently due to diminution of venous return and prolongation of systemic circulation time. It is postulated that such a decrease leads to inhibition of myocardial oxygen consumption, which in turn has beneficial effects on angina pectoris.


Biological properties and clinical application of propolis. I. Some physico-chemical properties of propolis.

The presence of 19 elements has been shown in the ethanol extracts of propolis (EEP). Three fractions have been obtained by filtration through a structural gel that did not show an initial antibacterial activity when investigated separately. Fractions 2 and 3 joined together have regained this activity. EEP solutions maintain their anitbacterial activity in acidic or neutral pH. Insensitivity of EEP solutions on temperautre of 75 degrees C for 30 min has been found.


Effect of prolactin and bromocriptine on growth of transplanted hormone-dependent mouse mammary tumours.

Administration of ovine prolactin alone supported growth of hormone-dependent GR mouse mammary tumours. Growth of hormone-independent tumours was not stimulated. Furthermore, administration of bromocriptine, a compound that inhibits release of prolactin from the pituitary gland, was shown to inhibit the growth of hormone-dependent tumours in animals receiving treatment with progesterone + oestrone. Administration of prolactin or bromocriptine to mice bearing tumours that grew independently of progesterone + oestrone treatment had no influence on tumour growth. We conclude that direct as well as indirect evidence has been found for the involvement of prolactin in the growth of transplanted, hormone-dependent GR mouse mammary tumours.


How often is genital yeast infection sexually transmitted?

We analysed data from a computer-based bank of clinical records of patients seen in a clinic for sexually transmitted diseases over a three-year period to investigate the association between genital yeast infections and sexually transmitted diseases (STDs). We classified STDs as primary and secondary syphilis; gonorrhoea; lymphogranuloma venereum; trichomoniasis; scabies; pediculosis; genital herpes; warts; and molluscum contagiosum. Of a total of 2984 disease episodes among women, 1054 (35-3%) included yeast infections, whereas only 382 (6-9%) of 5501 episodes in heterosexual men were associated with yeast infections, We found a significant association between yeast infection and STD and non-specific genital infection (non-specific urethritis (NSU) and procitis in men, and female contacts of men with NSU), which suggested that yeast infection was sexually acquired in 414 out of 1054 disease episodes in women (39%) and 110 out of 382 episodes in heterosexual men (29%). We conclude that sexually active patients with genital yeast infections should be screened for other STDs particularly non-specific genital infection.


Growth hormone, insulin, and prolactin secretion in anorexia nervosa and obesity during bromocriptine treatment.

We studied secretion of growth hormone (GH), insulin, and prolactin in eight women with anorexia nervosa and nine women with refractory obesity before and during treatment with bromocriptine, 10 mg/day. In the anorexic patients the raised plasma GH concentrations occurring during an oral glucose tolerance test fell significantly while on bromocriptine treatment, but there was no change in plasma insulin or blood glucose concentrations. In the obese patients, however, plasma GH concentrations remained low during the oral glucose tolerance test, and were not modified by bromocriptine. Blood glucose and plasma insulin concentrations were also unchanged. Plasma GH and plasma 11-hydroxycorticosteroid responses to insulin-induced hypoglycaemia were unaffected. Serum prolactin concentrations which were raised in five anorexic patients and marginally raised in two obese subjects, fell significantly in both groups during treatment. We observed no consistent weight changes in either groups.


[Scintillography using tensio-active pulmonary iodine-131 (surfactant I-131)].

Using 200 microCuries of surfactant iodine 131, for the first time in the world, we took surfactant scan in 2 patient with hyaline membranes and compared with normal images. No intolerance, or radiotoxicity was found 3 months of clinical follow-up of the subjects. The results are very encouraging; a great variety of clinical situations, including hyaline membrane, can be now examinated with this new technic and radiocompound and given new perspectives in its study and diagnoses and through knowledge of its pathophysiology.


Caustic ingestions: a rational look at diluents.

Treatment of lye ingestions by antidotes recommended on product labels includes the use of acid neutralizers. The possibility that heat produced by this exothermic reaction increased tissue damage was examined in vitro. Although Drano produced heat with all diluents including water and milk, acid antidotes prolonged the duration of high temperature. Clinitest tablets neutralized with milk produced no temperatures above 40 degrees C. The ready availability of milk or water, their acceptance by the child, and lack of toxic side effects make them diluents of choice for alkaline corrosive agents.


Tolamolol in the treatment of hypertension: an open evaluation study.

The effect of tolamolol 50-300 mg three times daily in the treatment of 30 patients with mild-severe hypertension was studied. The duration of therapy in the majority of cases was 3-6 months. There was a highly significant reduction of mean blood pressure (p less than 0.001) for the group as a whole. Overall, 61% of patients became normotensive or showed a reduction in severity of hypertension, In the majority of cases, this improvement occurred within the first four weeks of therapy. There was not postural hypertension. Apart from one patient with Prurigo Besnier who developed asthma, another patient who developed severe headache and a third patient who stopped treatment without giving a reason, treatment was well tolerated and there were no other serious side or toxic effects.


More evidence for the recessive inheritance of selective adult type lactose malabsorption.

Selective adult type lactose malabsorption appears in childhood or adolescence because of the great decline in jejunal lactase activity. There is strong evidence that this is a genetically determined disorder. Specifically, selective adult type lactose malabsorptions seem to be inherited by a single autosomal recessive gene. In the present prospective study the transition from the state of lactose absorption to that of lactose malabsorption was documented for the first time in two Finnish boys who were at risk for selective adult type lactose malabsorption because the parents of both boys had the disorder. At the age of 14 and 9 years, respectively, the boys had normal lactose absorption. Three years and 7 months and 4 years and 5 months later, respectively, the boys were shown to have lactose malabsorption. The period of documented transition averaged less than 4 years. These manifestations clearly strengthen the genetic model proposed.


[Needle biopsies of sarcomas of the breast: cytomorphology and DNA cytophotometry (author's transl)].

When needle biopsies are done on all palpable changes in the breasts, some sarcomas of the breast can be found. The cytomorphology of this mesenchymal tumor is described and the differential cytology is discussed. In some of our cases the relative content of DNS of the cell nuclei in the smear was determined by quantitative cytophotometry in a Feulgen Stain. It was found that the DNS  values of lymphosarcoma and spindle cell stromal sarcoma were within the norm of class 2C to 4C. The DNS content of angiosarcoma and polymorphous stromal sarcomas showed wide variations up to class 8 C. The result is discussed in view of automated cytological diagnosis.


Sex counseling of the elderly.

A sympathetic, nonjudgmental approach may reveal sexual dissatisfactions to be the basis of vague complaints about health, opening the way to counseling, changes in drug regimens, and referrals that can greatly improve quality of life.


A syntactic investigation of verbal autistic, mentally retarded, and normal children.

The syndrome of childhood autism is typified by major abnormalities in language development, yet there are few systematic descriptions of autistic children's linguistic systems. We have, therefore, begun a comprehensive investigation of the language of verbal autistic children and concentrate in this paper on comparing the syntax used by 10 verbal autistic children matched for nonlinguistic mental age with a group of mentally retarded subjects and normal controls. Two different means of assessing syntactic development were utilized: Lee's Developmental Sentence analysis and Chomsky's Transformational analysis. The autistic group was found to rank significantly lower than either the mentally retarded or the normal groups in terms of Developmental Sentence Scores. When a transformational grammar was used to describe the language samples of our subjects the autistic children were typified by a higher error rate and lower level of complexity compared to the other two groups. However, the results also indicate that the grammatical system of autistic children is rule-governed and probably not unlike that of young normal or retarded children. In conclusion, it appears that the syntactic abnormalities characteristic of autism are attributable to an extreme delay in language development as well as to an impaired ability to make use of linguistic rules.


Communication training in mute autistic adolescents using the written work.

The expressive and receptive use of three written words was taught to three mute autistic adolescents using a procedure based on Terrace's errorless discrimination model and Premack's language training with chimps. Expressive language was measured by the subject's selection of the appropriate word card from among the available alternatives when the corresponding object was presented. Receptive language was measured by the subject's selection of the appropriate object from among the available alternatives when the corresponding word card was presented. The sequence of the presentations and the order of placement of the available alternatives were randomized. The three subjects required 979, 1,791, and 1,644 trails, respectively, to master both the expressive and receptive use of the three words. The correct response rates for the three subjects over the entire training program were 92, 92, and 90%, respectively. It was concluded that, as concrete visual symbols, written words may provide a viable communication system for the mute autistic. The implications for treatment are discussed and suggestions for future research are made.


Hand preference in autistic children and their parents.

Hand preference was tested in groups of between 40 and 50 autistic children and in sex-, age-, and ability-matched controls. Results were also compared with existing findings on normal children. Small differences occurred between the groups in the directions which would be predicted on the assumption that mental subnormality is associated with delayed development of normal patterns of handedness, and on the hypothesis that autistic children as a group will show a persistent slightly increased tendency to use the left hand. Parents of the autistic group were also assessed for handedness. Contrary to the prediction of slightly increased sinistrality in this group of subjects, some indication of increased dextrality occurred. Results were discussed in relation to possible genetic factors in the etiology of autism.


Thyroxine toxicosis in patients with iodine induced thyrotoxicosis.

Serum concentrations of thyroxine (T4) and triiodothyronine (T3) were measured in 74 untreated hyperthyroid patients. Of these, 47 had Graves' disease, 12 had toxic nodular goiter and 15 had iodine induced thyrotoxicosis (IIT). The average serum T4 concentrations were, respectively, 13.5 microgram/100 ml and 13.3 microgram/100 ml (normal 4.5-10.3 microgram/100 ml). The average serum T3 concentrations were in the same order 732 ng/100 ml, 505 ng/100 ml and 378 ng/100 ml )normal 116-288 ng/100 ml). Of the 15 patients with IIT 5 had a pattern of T4-toxicosis (T4 larger than or equal to 10.5 microgram/100 ml; T3 less than 290 ng/100 ml). This pattern was not found in any of the patients from the other two groups. In IIT the ratio between the serum concentrations of serum T4 and T3 is similar to the one observed in normal individuals from non endemic areas. In patients with Graves' disease and toxic nodular goiter the increase in serum T3 is twice as high as the increase in serum T4. It is concluded that in IIT the serum concentrations of T3 and T4 increase in parallel while in the other two groups there is a preferential secretion of T3. As a consequence, a pattern of T4 toxicosis is a likely event in IIT and, when present, may constitute a biochemical characteristic of the condition.


Imaging of spontaneous canine tumours with ammonia and L-glutamine labeled with N-13.

Ammonia and 6-glutamine, labeled with N-13, were tested as imaging agents for a variety of spontaneous canine tumors. The imaging capabilities of these compounds were compared with each other, with other scanning agents, and with radiologic and pathologic procedures. Good agreement between positive gamma images and postmortem findings occurred in 11 of 15 cases with [13N] ammonia as the localizing agent. Eight of the nine scans using [13N] glutamine as the imaging agent showed positive correlation with postmortem findings. In cases where both ammonia and glutamine were used to image the same lesion, no qualitative differences in tumor uptake were found between the two.


Immunologic aspects of human colostrum and milk. III. Fate and absorption of cellular and soluble components in the gastrointestinal tract of the newborn.

A group of formula-fed infants were administered a single feed of poliovirus IgA antibody-rich human colostrum 18 to 72 hr after birth. Subsequently, the presence of IgG, IgA, and IgM immunoglobulin and poliovirus antibody activity was determined in serial serum and fecal samples of the neonates. Absorption of IgA immunoglobulin from the colostrum to the circulation was observed in three infants who were fed with colostrum between 18 and 24 hr after birth. Another group of infants of tuberculin-positive mothers who were being breast fed by their own mothers were followed for the development of in vitro correlates of cell-mediated immunity against tuberculin after prolonged breast feeding. Tuberculin-specific proliferative response was observed in the peripheral blood lymphocytes of two neonates after 5 weeks of breast feeding. The responses were undetectable after 12 weeks, although the infants continued to breast feed. No tuberculin reactivity was observed in the cord lymphocytes. These observations  suggest uptake of IgA immunoglobulin and components of cellular immunity in the intestine during the immediate neonatal period.


Toxicity kinetics and clinical potential of subarachnoid lymphocyte infusions.

The feasibility of intrathecal lymphocyte infusions was examined since patients with gliomas are known to have circulating, tumor-specific, cytotoxic lymphocytes. Human (xenogenic) and syngenic lymphocytes were infused intrathecally into rabbits, and the toxicity and kinetics of the infused cells evaluated. Cerebrospinal fluid cell counts rose to as high as 70,000 lymphocytes/cu mm 12 hours after infusion and then dropped logarithmically over several days. No infiltration of host cells into the subarachnoid space in response to the lymphocyte infusions was detected. Evidence is presented that intrathecally infused lymphocytes may escape into the systemic circulation. Toxicity was minimal, especially following syngenic intrathecal lymphocyte infusions. A systemic allergic response, characterized by choroid plexitis and pulmonary edema was noted following a second xenogenic but not after a second or even a third syngenic lymphocyte infusion.


Iron absorption in infants: high bioavailability of breast milk iron as indicated by the extrinsic tag method of iron absorption and by the concentration of serum ferritin.

Breast feeding is thought to result in a lower incidence of iron deficiency than does the use of unfortified cow milk forumalas, but there is scant documentation for this belief. The relationship of breast and cow milk feeding to absorption of iron and to iron status was investigated in a total of 45 term infants at about six months of age. Iron absorption was measured by total body counting. Laboratory assessment of iron status was based on the serum ferritin, hemoglobin, mean corpuscular volume, and transferrin saturation. The results indicated that infants fed breast milk during the entire first six to seven months of life attained greater iron stores than did those fed a cow milk formula. Breast-fed infants absorbed an average of 49% of a trace dose of extrinsic iron administered during a breast feeding in contrast to about 10% reported to be absorbed from cow milk under similar conditions. The data indicate that term infants who are breast fed may not require routine administration of supplemental iron.


Pharmacokinetics of methsuximide and a major metabolite in dogs.

The pharmacokinetics of methsuximide and its major metabolite 2-methyl-2-phenylsuccinimide were studied in dogs after single intravenous doses. Plasma methsuximide levels were described by a two-compartment open model, and those of the metabolite were described by a one-compartment open model. An expression was derived that describes both methsuximide and metabolite plasma levels after methsuximide administration. Excellent fits were obtained between observed data and those predicted from the model. The metabolite accounted for 40% of the overall elimination of methsuximide, and the half-life of the metabolite (15 hr) was much greater than that of the parent drug (1--3.5 hr). The results suggest that pharmacological effects after methsuximide administration may be due primarily to the metabolite, which may accumulate in the body during repeated doses.


Plasma isosorbide dinitrate concentrations in human subjects after administration of standard and sustained-release formulations.

After sublingual administration of 5 mg of isosorbide dinitrate, mean plasma concentrations (+/-SD) peaked (8.9+/-3.1 ng/ml) at 15 min after dosing and declined with a half-life of 30 min. After oral administration of 5 mg, mean concentrations peaked (3.1+/-0.7 ng/ml) at 30 min and declined with a half-life of 40 min. After oral administration of 20 mg in a sustained-release tablet, mean concentrations initially peaked (1.4+/-1.2 ng/ml) at 40 min, declining to 0.9+/-0.5 ng/ml after 8 hr. Mean concentrations were maintained above half the mean peak level during 10 hr. Because of probable rapid first-pass metabolism, the bioavailability of isosorbide dinitrate after administration of the oral dose of the standard tablet was 58% of that from the sublingual dose, and the bioavailability from the sustained-release tablet was 47% of that from the sublingual dose of the standard tablet. The time course of mean plasma concentration data could be described by a one-compartment model; but a more complex model, taking the pass effect into account, probably is needed for a better description of the pharmacokinetics of isosorbide dinitrate.


Nature and rate of neoplasia found in captive wild mammals, birds, and reptiles at necropsy.

The nature and rate of neoplasia found at necropsy of captive wild animals of the Zoological Society of San Diego collection were studied. Neoplasia was present at necropsy in 2.75% of 3,127 mammals, 1.89% of 5,957 birds, and 2.19% of 1,233 reptiles. Neoplasms were not detected during 198 necropsies of amphibians. Gross and histologic examinations were performed on the 92 mammalian, 111 avian, and 28 reptilian neoplasms. The lesions were diagnosed. The findings findings included a high frequency of lymphosarcomas in birds and reptiles, multiple lung adenomas in mammals, multiple endocrine tumors in 2 European mouflons (Ovis musimon), and proliferative lesions of the biliary and pancreatic ductal systems in several species.


Chlamydia and non-specific urethritis.

Chlamydia organisms were found in 42 per cent of patients with non-specific urethritis and these organisms probably were the cause of the urethritis. Contact is by venereal means. The drug of choice is 500 mg. tetracycline every 6 hours for 10 days.


Purified duck embryo rabies vaccine. An accelerated schedule for preexposure immunization against rabies.

Seroconversion and adverse reaction rates were studied in 92 persons given four or five doses in a two-week period of duck embryo rabies vaccine (DEV) or duck embryo rabies vaccine purified by ultracentrifugation (P-DEV). Mouse-neutralizing antibodies developed in 78 of 92 (84.8%) persons in these accelerated schedules. There were no significant differences in the frequency of antibody conversion or in geometric mean titers of antibody between persons given either vaccine. However, local and systemic adverse reactions were substantially less common with P-DEV. These data suggest that four of five doses of DEV or P-DEV given in a two-week course can be used for preexposure prophylaxis in situations where the more drawn-out regimens would result in continuation of a high-risk of rabies exposure. The antibody response of persons given this more accelerated regimen must be determined.


Ultrasound. A new diagnostic approach to the jaundiced patient.

Evaluation of the jaundiced patient's condition frequently can be difficult. Clinical history, physical examination, liver function tests, and other laboratory data are often inconclusive in differentiating extrahepatic obstruction (surgical jaundice) form intrahepatic cholestasis (medical laundice). During a 14-month period, we have evaluated 40 cases of jaundice of unknown causes. Ultrasound was able to correctly diagnose pathologically proved extrahepatic obstruction in 23 of 24 patients and intrahepatic cholestasis in 15 of 16 patients. There was one false-positive and one false-negative result in this series.


Causes of perinatal mortality in the US Collaborative Perinatal Project.

The underlying causes of 80% of perinatal deaths were identified in a study of 53,518 pregnacies in the United States: 17% of the deaths were due to amniotic fluid infections, 11% to abruptio placentae, 10% to premature rupture of the membranes, 9% to congenital anomalies, 6% to large placental infarcts, and the rest to more than 20 other specific disorders.


Dieting and peroneal nerve palsy.

In seven patients, peroneal nerve palsies developed while they were on weight-reduction diets. Five palsies were unilateral; two, bilateral. All patients recovered following diet modification. Therapeutic weight loss, of itself, can cause foot-drop. The prognosis is uniformly good.


Hyperthyroidism after propranolol withdrawal.

Classic features of thyrotoxicosis developed in three patients with no prior history of thyroid disease shortly after the discontinuation of therapy with or decrease in doseage of propranolol hydrochloride. Graves' disease probably developed fortuitously after propranolol therapy was instituted, but the beta-adrenergic blockade masked the clinical features of hyperthyroidism. On discontinuation of propranolol therapy or decrease in propranolol dosage, previously latent thyrotoxicosis became manifest. If hyperthyroidism masked by beta-blockade is not recognized before withdrawal of propranolol therapy in patients with ischemic heart disease, the sudden appearance of thyrotoxicosis may lead to symptoms of increased myocardial ischemia.


Guillain-Barré syndrome in Greater New York-New Jersey.

Epidemiologic data on 176 patients with acute Guillain-Barré syndrome observed over a nine-year period in the New York-New Jersey metropolitan area are presented. A striking predilection for patients aged 16 to 25 years, with a second lesser peak between ages 45 to 60, was found. Seasonal clustering of patients occurred, with nearly half the patients afflicted during the four-month period of late summer and fall. The distribution between men and women was equal. In this series 23% of the patients required tracheostomy, and 5% had a fatal course.


Essential hypertension in childhood.

Fifteen patients, aged 8 to 17 years, were found to have hpertension and were studied from February 1974 to Decemober 1975. Hypertension was defined as supine diastolic blood pressure repeatedly above 90 mm Hg. Five patients had a family history of hypertension. Extensive diagnostic evaluation performed in all cases failed to show an underlying cause for the hypertension. Patients with target-organ involvement were treated with hydrochlorothiazide; five of them are currently normotensive. Of the remaining nine untreated patients, four became spontaneously normotensive within eight to 14 months of the initial evaluation. These results suggest that extensive studies in children with hypertension may not be necessary in every case if clinical findings meet the critiera for the diagnosis of essential hypertension. These studies might be desirable, however, if target-organ involvement is present.


High elevations of creatine phosphokinase in hypothyroidism. An isoenzyme analysis.

In hypothyroidism, slight elevations of serum creatine phosphokinase (CPK) levels are common. In contrast, we describe six hypothyroid patients with extreme elevations (17- to 160-fold) of CPK levels. Enzyme analysis showed only MM isoenzyme in four cases and MM plus trace MB isoenzyme in two patients. Hypothyroidism should, therefore, be considered when elevated CPK levels, even extreme, are found. Isoenzyme analysis in such a case will show primarily an MM pattern, although trace MB fraction can also be seen. This isoenzyme pattern suggests that the sources of the CPK elevations is skeletal muscle.


Malignant mesenchymoma and birth defects. Prenatal exposure to phenytoin.

Malignant mesenchymoma developed in an 18-year-old patient with phenytoin-associated cleft lip and palate. Although these conditions may be related by chance, the possibility of transplacental carcinogenesis by phenytoin should be considered, especially since neuroblastoma was reported recently in two children with phenytoin-induced malformations. Following combination chemotherapy for metastases, the patient experienced a 7-year disease-free interval, which is consistent with recent improvement in the treatment of soft-tissue sarcomas.


Common cardiac prosthetic valves. Radiologic identification and associated complications.

The development of prosthetic heart valves has been an important advance in the treatment of patients with serious valvular cardiac disease. Because there are many types of prosthetic valves, we have prepared a diagram of the valves currently or previously used and list their potential complications. Prosthetic valves were identified according to photographic and radiologic features, valve replacement location, and reported associated complications. Data have been compiled in tabular form for quick reference; valves have been identified according to valve base, cage, and poppet. They may be categorized as caged-ball or low-profile valves. Such information helps to provide recognition of the valve that has been inserted and permits the clinician or radiologist to be alert to possible complications with the various prosthetic devices.


Thyroid uptake of radioactive iodine in hyperthyroidism.

We compared the 24-hour uptake of radioactive iodine (RAIU) in hyperthyroid patients diagnosed from 1970 to 1972 (Group A) and from 1975 to 1976 (Group B). Mean RAIU values in Group B decreased from those in Group A. In 1969 we lowered the normal range for the RAIU test to 0% to 24%, and used the new range for the diagnosis of hyperthyroidism in both groups of patients. The RAIU in Group B is within normal limits in 14% of the patients with Graves' disease and 80% of the patients with toxic nodular goiter (TNG). This study demonstrates that in our geographic area, the 24-hour RAIU has become a poor test for the diagnosis of hyperthyroidism, particularly TNG. However, the test should be performed before radioactive iodine therapy because it is necessary in calculating the therapeutic dose.


Factor VII deficiency and surgery. Is preoperative replacement therapy necessary?

A patient with congenital factor VII deficiency (factor VII was 12%) had gynecologic surgery performed without prophylactic blood-product replacement therapy. Blood loss was not excessive. A review of 12 additional patients with factor VII deficiency who underwent surgery without replacement therapy showed that surgical bleeding was uncommon and that there was no relationship between factor VII levels and hemorrhage. It is proposed that patients who bleed may be those who also have a prolonged bleeding time or who have ingested aspirin shortly before surgery. It is all proposed that replacement therapy be available for use if required, but that its routine preoperative use is probably unnecessary in this disorder.


The mechanism of hypophosphatemia in acute heat stroke.

Severe heat stroke may be associated with hypophosphatemia and hypocalcemia. Hypophosphatemia is generally observed within hours after onset, but hypocalcemia usually occurs on the second or third day, and after hypophosphatemia has undergone spontaneous correction. A young man displayed respiratory alkalosis during the course of severe heat stroke. The hypophosphatemia abated spontaneously as metabolic acidosis and acute renal failure supervened. Hypocalcemia became prominent and was more severe than that ascribable to uremia. Hypocalcemia was probably the result of calcium phosphate and calcium carbonate deposition in injured skeletal muscle.


Safe transfer of civilian burn casualties.

The advisability of transporting severely burned civilian patients to a definitive burn-care facility during the first hours following injury is discussed and methods providing safe transport for 353 civilian burn patients are described. Feasibility of and methods for transporting patients over various distances are outlined and the problems of jet transportation presented. Adequate communication between referring and receiving physicians is imperative, as are adequate preparation before evacuation and maintenance of intravenous fluid resuscitation, intake and output records, and sterile technique during transport.


Predicting coronary heart disease in middle-aged and older persons. The Framington study.

Of 1,025 men and 1,445 women, aged 49 to 82 years, who were free of coronary heart disease (CHD), 79 men and 63 women subsequently had CHD. Using a risk function based on cholesterol in the high density and low density lipoproteins, systolic blood pressure, left ventricular hypertrophy, and diabetes, less than 2% of the subsequent CHD cases were found in the lowest decile of risk, whereas 25% of the cases for men and 37% for women were found in the highest decile. Predictability held for each specific age group. This predictability was at least as good as that obtained by the usual CHD risk profile at younger ages.


Liver toxicity after acetaminophen ingestion. Inadequacy of the dose estimate as an index of risk.

With increasing frequency, the physician is confronted with the problem of determining the risk of liver toxicity in a person who may have ingested an overdose of acetaminophen. To be effective, antidotal therapy must be given early after acetaminophen ingestion when the patient, despite the toxic injury occurring in his liver, may appear quite well. We have reviewed the cases of the first five persons who came to our institution with a history of having ingested a large overdose of acetaminophen. In each case plasma or serum acetaminophen levels were low and substantial liver injury did not occur. Measurement of acetaminophen levels, indicating the amount of drug absorbed, were a more reliable index of the risk of toxic liver injury and the need for antidotal therapy than the estimate of the dose ingested.


Maternal primary hyperparathyroidism of pregnancy. Successful treatment by parathyroidectomy.

Primary hyperparathyroidism of pregnancy may result in spontaneous abortion, neonatal hypocalcemia, or neonatal tetany if appropriate treatment is not instituted. Of great importance in prevention of these complications is an awareness by physicians that this disease exists and is of clinical importance. Parathyroidectomy performed during the second trimester of pregnancy offers the best chance for fetal and neonatal survival. This operation results in little risk to either the mother or the fetus. Normal calcium homeostasis is restored to the fetus and the risk of hypocalcemia in the neonatal period is virtually eliminated.


Bile acid deconjugation in intestinal obstruction studied by breath test.

Bile acid deconjugation was assessed by measuring specific activity of expired 14CO2 after the oral administration of cholyl-glycine-1-14C in 17 cases of intestinal obstruction, i.e. 15 mechanical and two paralytic. In the former, nine cases were operated and the remaining six cases were managed by the conservative treatment. Cumulative output of 14CO2 in breath for six hours before the treatment was 40.20=11.30 (mean+/-SEM) (control 2.96+/-1.16) but decreased to 6.86+/-3.64 after the treatment. Enteric bacteria capable of splitting amino moiety of the conjugated bile acid were found to be present more than 10(5)/ml. in the obstructed bowel content. Cumulative output of 14CO2 in breath for six hours in two paralytic ileus was lower than in controls. Deconjugated bile acid reported to inhibited water and electrolytes absorption in the small intestine may play an important role in fluid retention in intestinal obstruction.


The prophylactic treatment of retrolental fibroplasia.

10 premature infants with stage 3 retinopathy of prematurity have had photocoagulation and/or cryocoagulation therapy to one eye and have been followed for a period of 1-6 years. Although the long-term results of this therapy are not known, particularly in the prevention of retinal detachment, early observations suggest that treatment is neither harmful nor particularly beneficial. Macular dragging does not seem to be influenced by treatment. The refractive error, as one would expect, does not appear to be altered by this form of therapy. Marked amelioration of the vascular dilatation and tortuosity at the posterior pole is apparent shortly after treatment. It is stressed that this is a trial project and until more definite beneficial results are obtained, treatment of stage 3 retinopathy should be deferred. Retinal detachments (stage 4) may be quite amenable to a buckling procedure.


EEG and visual evoked responses in children with learning disorders.

A study was made of 58 children with learning disorders, in all of whom a spontaneous EEG as well as a Visual Evoked Response (VER) was registered. The latencies in the secondary complex of the VER were increased and the amplitudes of waves II and III were increased as compared with normal subjects. Two subgroups--children with a good and children with a poor clinical test score--did not differ in VER parameters. A spontaneous EEG evaluated as abnormal was present in 45% of the children. These children showed more absence of peaks in both VER complexes and more increased latencies in the primary complex than children with a normal EEG. The findings show that the VER is a valuable supplement to EEG in demonstrating organic changes in children with learning disorders.


Cisternography with isotopes following posterior fossa surgery in children.

Surgery of posterior fossa tumors is afflicted with some important problems. One of these is the postoperative communicating hydrocephalus. According to the literature this form of hydrocephalus is found in 10-30% of all children operated on; but a permanent shunt is necessary in only 8-18%. Aim of the present investigation was to find out disturbances of cerebrospinal fluid (CSF)--circulation and--reabsorption after posterior fossa surgery. Therefore 25 children ranging in the age from 3 to 12 years were examined on the basis of isotope cisternographic studies 8 to 21 after the operation. In 4 cases all parameters of pathological CSF-dynamics were found which required a permanent ventriculo-atrial shunt. 21 children showed a minimal or significant accumulation of the isotope in the posterior fossa but a normal circulation and a sufficient clearance on later scans. In these cases neither a temporary nor a permanent shunt was necessary. These findings are confirmed by follow-up examinations between 2 and 3 years.


Fucosidosis. II. Ultrastructure.

The ultrastructural changes of a sural nerve biopsy, liver biopsy and the autopsy of a case (I) of fucosidosis are described. Light microscopy revealed the presence of foam cells in various organs. The contents of the vacuoles stained positive with P.A.S. and Sudan. Electron microscopical examination showed inclusions in hepatocytes, Schwann cells and neurons. These inclusions had a single limiting membrane and contained heterogeneous structures, vesicular, multivesicular and membrane like structures, forming concentric lamellae. In another patient (case III) with a different clinical presentation and a different enzyme pattern (a reduced alpha-L-fucosidase activity, in combination with a reduced arylsulfatase A activity) similar abnormalities as in case I were found in a sural nerve and liver biopsy. It is suggested that the combined reduction of enzyme activity is responsible for the disease.


Basic rest activity cycle and stereotyped behavior of a mentally defective child.

Stereotyped acts of a mentally defective girl, 6 1/2 years old, were observed from 6 a.m. til 8 p.m. during 16 days. Alternating phases of more or less frequent hand waving showed intervals of about 1 1/2 hours. Sleep stages were also determined by polygraphic recordings during 10 nights. As statistically proved the mean peak-to-peak interval of stereotyped activity at days corresponded with the mean REM-to-REM period of consecutive nights. This suggests, that the stereotyped hand waving of this child was driven by the BASIC REST ACTIVITY CYCLE (BRAC) already described by Kleitman. The mean periodicity of sleep cycles was represented by model rhythms adapted to the scored sleep stages. If the model rhythms of all 10 nights were extended backward to the preceding days, they paralleled the stereotyped activity. Thereby half periods found in phase with REM-stages approximatly corresponded to maxima of stereotyped activity. It will be discussed that the BRAC triggers motor and sensory mechanisms characterizing both the phases of enhanced stereotyped activity at day and REM stages at night.


Intoxication with primidone: continuous monitoring of serum primidone and its metabolites during forced diuresis.

An 18 year old girl is reported, who ingested 15 g of primidone (Liskantin), 330 mg/kg, to commit suicide. Continuous monitoring of the serum levels of primidone, PEMA, and phenobarbital revealed increased elimination of primidone by forced diuresis (6000 ml/24 hours). It is concluded that forced diuresis inhibits the otherwise mandatory increase in primidone metabolites, PEMA and phenobarbital. It is suggested that even after improvement of the clinical symptoms forced diuresis should be continued for at least 48 hours. In epileptic patients the reinstitution of primidone therapy should be considered only on the third day after accidental ingestion, if the clinical symptoms have improved, and if there is no possibility of immediate determination of primidone serum levels.


Periodic lateralised epileptiform discharges in a case of diffuse cerebral cysticercosis.

A case of diffuse cerebral cysticercosis is described. The case is of interest because the involvement of brain was extensive and bilateral but electro-encephalographically unilateral periodic epileptiform complexes were recorded on 3 different occasions. Possible mechanisms of these lateralised periodic epileptiform discharges are discussed.


[Preliminary results of treatment of hormone-dependent metastatic carcinoma of the breast with the bromocriptin-medroxyprogesterone acetate combination].

A brief account of the concept of hormone dependence in breast neoplasia is followed by the presentation of results obtained with an association of medroxyprogesterone acetate (MAP) and 2-bromo-alpha-ergocriptine (CB 154) in 14 women with metastatic cancer of the breast, hormone dependent due to the presence of the cytoplasmic receptor for 17-beta-oestradiol. All patients, in fertile or premenopausal stage, were subjected to prior surgical ovariectomy. MAP was given i.m. at a dose of 1 g/day for 30 days and then 150 mg/day. In the same time 2.5 mg CB 154 were administered every 6 hr per os. Evaluation in accordance with the criteria proposed by the Coop Breast Cancer Group showed that rapid improvement was obtained in all cases, persisting (at the time of writing) for a minimum of 6 months to a maximum of 2 yr of observation. In addition, rapid disappearance of pain was noted, particularly in subjects with secondary bone lesions. Side-effects were in all cases of slight consequence and suspension of the treatment was never necessary. The mechanism of the two drugs and the advantages of their association are discussed.


Visual abnormalities in a pregnancy following bromocriptin medication.

A patient with hyperprolactinemia, amenorrhea, and an enlarged sella turcica, but without galactorrhea, was treated with Bromocriptin to effect restoration of ovarian function. The subsequent pregnancy was without problems from an obstetric point of view, but visual field abnormalities developed progressively, leading to termination of the pregnancy in the 39th week. However, within 1 week after delivery, the field defects disappeared and the visual acuity returned to normal.


Rapid prediction of pulmonary maturity by amniotic fluid lipid globule formation.

Utilizing the surface tension (ST) lowering properties of an amniotic fluid lipid extract, it was noted that the amniotic fluid lipid layer formed a subsurface globule when the ST reached 36.9 dynes/cm +/- 0.1877 (SEM). The amount of required extract to achieve globule formation varied with the degree of fetal pulmonary maturity and the volume required could be used to differentiate pulmonary maturity (less than or equal to 320 microliter), transitional status (340 to 440 microliter), and pulmonary immaturity (greater than 460 microliter), as related to fetal outcome (amniotic fluid obtained within 48 hours of delivery). Of the 70 patients studied, the 7 (100%) who developed respiratory distress syndrome (RDS) were predicted correctly. Nine of 70 (12.1%) gave false negative results (predicted pulmonary immaturity, no RDS developed); there were no false positives. Globule measurements of a separate series of 74 samples were compared with their L/S ratios. Twenty-two of 24 (91.7%) samples termed mature had an L/S greater than 2.0, while 32 of 42 with a value termed immature had an L/S less than or equal to 1.9. The physical events in the establishment of the monolayer and subsequent globule formation are discussed. This method now provides a rapid and reliable screening indicator of fetal pulmonary maturity.


Pulmonary surfactant and amniotic fluid insulin.

Immunoreactive insulin was measured in 66 amniotic fluid samples and the level compared to two indices of pulmonary surfactant activity, namely, lecithin sphingomyelin ratio and lecithin palmitic acid. An apparent inverse relation between lecithin and insulin was demonstrated after 34-35 weeks' gestation. These results tend to support the hypothesis that insulin can inhibit lecithin synthesis.


Coeliac disease and goitre.

Two cases of coeliac disease associated with thyroid enlargement are presented. One had a large simple adenomatous goitre which was removed surgically and the other had histological confirmation of lymphadenoma (Hashimoto's disease).


Metrizamide computed tomography cisternography: pediatric applications.

The methodology and clinical use of metrizamide (Amipaque) computed tomography (CT) cisternography are described as applied in the cases of 22 children with morphologic and physiologic abnormalities affecting the cranial portion portion of the central nervous system. In contrast to pneumoencephalography, CT cisternography affords equivalent or superior visualization of the basal cranal subarachnoid spaces with simpler technique and low morbidity. Intrathecal metrizamide enchancement in children causes a very low incidence of side effects.


Mycotic aneurysm of the hepatic artery. Case diagnosed with radionuclide imaging and ultrasound.

The authors report a case of hepatic mycotic aneurysm following Staphylococcus aureus septicemia and subsequent bacterial endocarditis. The diagnosis was made preoperatively using serial radionuclide imaging and ultrasound and confirmed by angiography and surgery.


The chromosomes of the transmissible venereal tumour of dogs in Ibadan, Nigeria.

Cytogenetic studies on 11 transmissible venereal tumours in seven dogs in Ibadan, Nigeria, are reported. The number and the morphology of the chromosomes, as shown by the metaphase cells, revealed that the tumour cells have similar cytogenetic features to those reported in other parts of the world. The suggestion of common sources of infection for the animals in the different geographical locations of the world was supported.


Use of brom-ergocryptine in treating amenorrhea/galactorrhea.

Seven women with amenorrhea and galactorrhea, and no evidence of pituitary adenoma, were treated with brom-ergocryptine for two to 24 weeks. All seven patients had the resumption of regular menses within eight weeks, but six patients required 24 weeks of therapy to completely cease lacting. Two of the five women attempting to conceive became pregnant. Four of the five nonpregnant patients had a total recurrence of their symptoms after discontinuing the drug. Brom-ergocryptine appears to be very effective in inhibiting prolactin secretion and thus reestablishing normal ovulatory menstrual cycles and fertility.


Evaluation of a new anti-fibrinogen-coated latex particle agglutination test in the measurement of serum fibrin degradation products.

A new latex particle agglutination test (FIBROTEX) has been compared with the Thrombo-Wellcotest and the tanned red cell hemagglutination inhibition immunoassay (TRCHII) for sensitivity to purified fibrinogen and plasmic degradation products and for reactivity with 31 normal sera and 170 sera from patients with thrombotic disorders. The latex particles in the FIBROTEX are coated with antibodies against fibrinogen and fragment E (anti-FE), in contrast with the anti-fragment D and anti-fragment E antibodies which coat the latex particles of the Thrombo-Wellcotest (anti-DE). The relative sensitivities of the TRCHII and the anti-FE and anti-DE latex tests were, respectively, 0.5, 2.5 and 7.5 microgram/ml for fibrinogen; 0.5, 0.5 and 4.0 microgram/ml for fragment X; and 1.25, greater than 30 and 8.0 microgram/ml for fragment D. Compared with anti-DE, the anti-FE particles demonstrated fewer false-positive results with sera and urines of normals and higher titers, fewer false negatives and better overall correlation with the TRCHII results (r = 0.89 vs. 0.75) on pathologic sera. The FIBROTEX is simple and rapid (5 minutes) and provides a more sensitive and accurate determination of serum fibrin degradation products than the Thrombo-Wellcotest.


Soluble fibrin complexes in early fibrin digests.

Early fibrin digests were analyzed in the ultracentrifuge and were found to contain compounds with molecular weights up to 3 X 10(6); these compounds are considered to be soluble fibrin complexes. Their similarity with intermediate polymers in inhibited clotting systems has been stressed. Their viscosity at low shear rates is extremely high; therefore, a rapid method to establish their presence in plasma would be the measurement of plasma and serum viscosity at low shear rates, moreover, they shorten the clotting time (thrombin time) of fibrinogen considerably.


The half-life of plasmic degradation products of human fibrinogen in rabbits.

Human fibrinogen and purified plasmic degradation fragments X (stages 1 and 2), D and E were labelled with 125-I using the lactoperoxidase method. The chromatographic, electrophoretic and immunologic properties of the labelled proteins were found to be similar to those of non-labelled fragments. All the degradation products diffused rapidly (T 1/2 0.27-0.75 hours) from the intravascular space of rabbits, as compared with fibrinogen (4.26 hours). In addition, the metabolic half-life was found to be 49.3 hours for fibrinogen, as compared with only 5.6, 6.1, 2.3 and 1.4 for fragments X (stage 1), X (stage 2), D and E, respectively. The metabolic half-life roughly reflects the molecular size of the degradation products.


A new method for the determination of plasma activators fibrinolysis.

The term "effective activator" of plasminogen is proposed, to denote the resultant of activator-antiactivator interaction, and a method for the determination of the level of these activators is described. By adding axcess plasminogen to the euglobulin fraction of plasma the influence of the level of endogenous plasminogen and of the antiplasmin is eliminated. It is shown that the level of fibrinogen has very little bearing on the results. An effective activator unit is defined as equal to 1 CTA unit of urokinase activity on a fibrinogen-plasminogen substrate.


Controlled trial of the sequential use of streptokinase and ancrod in the treatment of deep vein thrombosis of lower limb.

Treatment with streptokinase ('Kabikinase') was given to 26 patients with venographically confirmed deep vein thrombosis extending into the popliteal vein or above. Treatment was continued for 4 days and the patients were allocated randomly to oral anticoagulant therapy or a course of treatment with ancrod ('Arvin') for 6 days followed by oral anticoagulant therapy. The degree of thrombolysis as judged by further venographic examination at 10 days was not significantly different between the 2 groups. The majority of patients showed clinical improvement but there was no appreciable difference between the groups at 3 and 6 months. Haemorrhagic complications were a more serious problem during the period of treatment with ancrod than during the equivalent period in the control group.


Some factors influencing metabolism and distribution of fibrinogen in man and rabbits.

To shed some light on the homeostatic regulation of plasma fibrinogen, metabolic studies were made in healthy females, and in normal, thyroidectomized, and thyroxine-treated rabbits. In females, compared with normal males, plasma fibrinogen concentration, plasma and interstitial fibrinogen decreased consequent to an increased fractional catabolic rate and a normal fibrinogen synthesis rate. The interstitial/plasma fibrinogen ratio remained unchanged. In normal rabbits, with increasing body weight fractional catabolic rate and catabolic rate decreased, while fibrinogen concentration and plasma fibrinogen remained constant owing to a simultaneous decrease in fibrinogen synthesis. In addition, fractional transcapillary transfer rate and transcapillary flux also decreased resulting in a shrinkage of interstitial fibrinogen. Thyroidectomy and thyroxine-injection markedly altered fibrinogen metabolism: thyroid hormone accelerated fibrinogen catabolism but also stimulated synthesis. The net result was an increase in plasma fibrinogen and fibrinogen concentration. The interstitial/plasma fibrinogen ratio decreased in thyroxine-treated, and increased in thyroidectomized animals. This study defines the variations of the fibrinogen system parameters in these physiologic and pathologic conditions, and illustrates some patterns of alterations in fibrinogen metabolism.


The stability of glutardialdehyde-stabilized 35-heparinized surfaces in contact with blood.

Heparin can be bound to polymer surfaces by precipitation of an ionic heparin-amine complex which can be stabilized against dissolution by treatment with glutardialdehyde. The aim of this investigation was to study the degree and course of desorption of heparin from such a heparinized surface on contact with blood. This desorption must be considered when analysing the interaction between the heparinized surface and blood. Different heparinized surfaces were prepared by using 35S-labelled heparin, and the desorption of heparin on exposure in vitro to citrated plasma or heparinized blood as well as during exposure at in vivo conditions was quantified. During in vitro experiments, the glutardialdehyde stabilized surface became stable with no further desorption of heparin after an initial loss of about 3% of the initial surface-bound heparin. Under in vivo conditions, there was an initial loss of about 12%. There was no further loss from surfaces inserted into the circulation of the dog for seven days as compared to those inserted for one hour.


Prevention of platelet adhesion and aggregation by a glutardialdehyde-stabilized heparin surface.

A stable heparinized surface was prepared by sequential treatment of polyethylene with water solutions of hexadecylamine hydrochloride, heparin and glutardialdehyde. In order to explain the "non-thrombogenic" properties of this surface, it was evaluated with regard to prevention of platelet adhesion and aggregation. Human heparinized blood (2 and 10 IU/ml) with 51Cr-labelled autologous platelets was rotated for 60 minutes in untreated and heparin-treated circular tubings. The surface area/blood volume ratio was varied and an air-blood interface was present. In untreated tubings, platelet adhesion and aggregation increased in proportion to the size of the surface area/blood volume ratio, irrespective of the heparin concentrations of the blood. In the heparin-treated tubings, there was no measurable platelet adhesion to the surface and no platelet aggregation in the blood. The difference between the heparinized and the untreated surfaces with regard to platelet adhesion was discernible even after 10 minutes storage of stagnant blood. It is concluded that platelet adhesion and aggregation induced by exposure of blood to a foreign surface in an in vitro experimental model can be prevented by a stable heparin coating of the surface.


Kinetic parameters of platelet aggregation as an expression of platelet responsiveness.

The kinetics of platelet aggregation induced by collagen and by ADP were studied. The maximum aggregation (deltaLTmax) and the ADP and collagen concentrations required to produce half-maximum aggregation (Kd) were determined using platelets obtained from normal individuals, individuals who ingested aspirin and individuals whose platelet-rich plasma (PRP) demonstrated spontaneous aggregation. The Kd and deltaLTmax for ADP-induced platelet aggregation were variable and markedly affected by the citrate concentration. Conversely, kinetic parameters of collagen-induced aggregation were more reproducible and less affected by citrate. The Kd for collagen in platelet aggregation was increased following aspirin ingestion and decreased in samples of PRP that demonstrated spontaneous aggregation. These results suggest that kinetic parameters of platelet aggregation may be useful to express the responsiveness of platelets.


Cyanide insensitive oxidase in platelets of newborn infant.

The authors studied the behaviour of neonate platelet O2 consumption after the addition of pyridine nucleotide compared to adult controls. O2 consumption of neonate platelets after NADH addition was 103,2 millimicronmol O2/10(9)/hr (SE = 24,74) and in adult controls 188,8 millimicronmol O2/10(9)/hr (SE = 36,46). After the addition of NADPH O2 consumption was, respectively, 233,5 millimicronmol (SE = 46,29) and 218,3 millimicronmol (SE = 30,01).


Ethanol-induced microaggregate formation in pig and rabbit blood. An in vitro study.

Increased microaggregate formation was found after mixing ethanol with blood from pig and rabbit in vitro, measured with Swank's Screen Filtration pressure method. Final ethanol concentrations were in the range found in ethanol-intoxication in man. No rise in SFP was noticed when plasma with 10,000 platelets/microliter was used. It is therefore doubtful that altered plasma proteins caused the rise in SFP. It is suggested that if a direct effect of ethanol upon platelet aggregation exists in vivo, it may be of importance in acute ethanol intoxication and in chronic alcoholism.


[Regarding the effect of bromhexine metabolite VII on lecithin synthesis in fetal lungs (author's transl)].

With the help of incorporated amounts of radioactively labeled choline, it was shown that bromhexine metabolite VIII in vivo (10 mg, 5 mg, 1 mg/kg body weight) and in vitro (100 microgram to 0,01 microgram/g fetal lung tissue) does not stimulate lecithin synthesis in fetal lungs of rats.


[Effect of storage on the vitamin B6 activity of foods (author's transl)].

In a study of the effect of storage on the vitamin B6 activity of foods, the vitamin B6 content of different foods of plant and animal origin and also of a mixed feed with added pyridoxine were analyzed microbiologically using Saccharomyces carlsbergensis as test organism. Vitamin B6 activity was determined initially, in some of the specimens after storage for 10 months and again in all foods after 40 months. The storage period of 10 months caused a loss of the natural vitamin B6 content of about 25--30%. This loss increased to more than 50% after 40 months storage. The diet containing the high level of synthetic pyridoxine lost 85% of its vitamin B6 content.


Analysis of rabbit and guinea pig complement efficiency in cytotoxicity tests against fibrosarcoma and lymphosarcoma cells.

In a complement-dependent 51Cr cytotoxicity assay, using as target murine fibrosarcoma or lymphosarcoma cells, the rabbit complement (RC) was more efficient than guinea pig complement (GPC) when tested either with strong antisera, such as antihistocompatibility sera, or with weak sera, such as wera from normal mice shown previously to posses a natural antitumor response. The high efficiency of RC was not due to activation by antibodies of a different class or specificity than those activating GPC. In fact, both 2-mercaptoethanol (2-Me)-sensitive or-resistant immunoglobulins could activate both RC and GPC, and the results of absorption tests indicated that the antibodies detected using either of the 2 complements were directed against the same specificities. In addition, the results of tests searching for cooperative antibodies excluded that a cooperative effect might be responsible for the high efficiency of RC. With weak antisera, sera of different rabbits were found to have different complement activity.


[New strategies for prevention in adolescents and young adults].

For various reasons, it is justified to revise the classical strategies of intervention concerning medical and social action to help young people. New behaviours such as drug addiction, for instance, have emphasized the inadequacies of the conventional means of treatment. Since 1970, Youth Advisory Services have appeared in Europe. Their aims may be various: information, counselling, lodging, social and educative help, medical assistance. These services which were created by the community have such ethical and organizational features that it is easy to discern them among the conventional administrative services. Their users are mainly teenagers and young adults whose reasons for consultation are due to various causes. The originality of the methods, facilities and principles of these innovating services may be considered as a decisive contribution to the research of new prevention strategies to help young people.


Lactose malabsorption in preschool black children.

One hundred sixteen healthy black children ages 13 to 59 months, representing high and low socioeconomic deciles, were studied for lactose malabsorption. A fasting lactose tolerance test using 2 g of lactose/kg of body weight was carried out. Glucose was determined at 0, 15, 30, and 60 min. Of the 116 preschoolers 34 (29%) evidenced lactose malabsorption as determined by a blood glucose rise of less than 26 mg/100 ml. Clinical signs of diarrhea, gas, and cramps were noted singly or in combination in 18% of the 34 lactose-malabsorbing children. Of the 82 lactose absorbers, 12% demonstrated similar signs. The nature and length of the initial infant milk feeding failed to show any relationship to the onset of malabsorption. Current milk drinking patterns were reported as being similar. Eight-seven percent of the malabsorbers and 92% of the absorbers report drinking 240 ml or more of milk/day. Socioeconomic status, education, marital status, and medical assistance of the parent is similarly distributed between lactose absorbers and malabsorbers.


Selected beverage consumption patterns among Mormon and non-Mormon populations from the same geographic location.

This study presents data from a mail questionnaire survey designed to determine the daily beverage consumption patterns of Mormon and non-Mormon households in Utah and southern Idaho. Mormons differed significantly from their non-Mormon counterparts in both their low intake of coffee, tea, and beer, and increased daily consumption of milk and water. A high percentage of Mormons adhere to Church doctrin in their beverage intake habits and the results would appear to substantiate previous preliminary studies of the dietary habits in this religious group.


Amniotic fluid analysis in assessment of fetal maturity.

Sixty samples of amniotic fluid were analyzed for their surfactant level by measuring the lecithin-spingomyelin ratio and performing the "shake" test. Cytologic examination of the sediment was also performed using Nile blue sulfate staining. The lecithin-sphingomyelin ratio was found to be the best method to predict fetal maturity and assess the probability of subsequent respiratory distress syndrome. The "shake" test proved to be a valuable screening tool in assessment of fetal pulmonary maturity when the fetus is mature, but of little value when the fetus is immature. The estimation fetal fat cells seemed to be of lesser value in predicting fetal maturity.


Early functional closure of the ductus arteriosus associated with decreased severity of respiratory distress syndrome in preterm infants.

It has been shown that a patent ductus arteriosus may complicate the course of the respiratory distress syndrome (RDS) in preterm infants. In this study, an attempt is made to answer the question: Is there any relationship between RDS and patency of the ductus arteriosus in preterm infants, that is, do preterm infants without the RDS have early functional closure of the ductus arteriosus? Clinical observations were made on 144 preterm infants 25 to 34 weeks' gestation. Infants were included in the study if the status of the ductus arteriosus (open or closed) could be established either by clinical examination or retrograde aortography. The ductus arteriosus was closed in 59 infants within 48 hours of birth and open in 85. None of the infants with a closed ductus had severe RDS and only three had mild RDS. In contrast, 50% (43 of 85) of infants with open ductus had severe RDS. These findings suggest that early functional closure of the ductus can occur even in very immature infants, and this early closure appears to be associated with a decreased incidence of RDS.


Molluscum contagiosum venereum in a women's outpatient clinic: a venereally transmitted disease.

Molluscum contagiosum in a venereal distribution (MCV) was identified as an incidental finding in 14 patients in a women's outpatient clinic at a general hospital. The lesions were frequently overlooked both by patients and physicians. The lesions of MCV are frequently asymptomatic. The sexual history of the patients and the genital distribution of the lesions provide circumstantial evidence that MCV is a veneral disease. Management of cases of MCV should include a culture for the gonococcus and a serologic test for syphilis.


Effects of hydrocortisone on lecithin-sphingomyelin ratio.

An intravenous infusion of hydrocortisone succinate was given in four divided doses during a 24 hour period to 17 high-risk pregnant women to accelarate fetal pulmonary maturity. Amniocentesis was performed before and 48 to 72 hours after treatment in all 17 patients. Comparisons were made of lecithin/sphingomyelin (L/S) ratios before and after treatment. The L/S ratio rose in 12 or 17 cases and was not influenced by the type of severity of maternal disease. Neither lenght of rupture of the membranes nor gestational age at the time of treatment affected the change in L/S ratio. Pretreatment L/S ratios (1.21 +/- 0.435 S.D.) were found to have a statistically significant difference from posttreatment values.


Lecithin/sphingomyelin ratio in pregnancies complicated by diabetes mellitus.

The amniotic fluid lecithin/sphingomyelin (L/S) ratio was determined in 182 pregnancies complicated by Classes B and C diabetes and in 28 patients with Classes D, F, and R diabetes. These data were retrospectively correlated with the occurrence of the respiratory distress syndrome (RDS) or hyaline membrane disease (HMD). Only four cases of RDS and two cases of HMD were observed in 200 patients with an L/S ratio of 2.0 or greater prior to delivery. This 3 per cent incidence of complications is no higher than that of the nondiabetic population in our institution. Seven of 10 neonates with an antenatal L/S ratio of 1.5 to 1.9 developed RDS. An L/S ratio of 2.0 or more appears to be reliable predictor of fetal pulmonary maturity even in pregnancies complicated by diabetes mellitus.


Serum immunoglobulin concentrations of cattle in a herd with bovine leukosis.

Consistent relationship was not found between the serum concentrations of immunoglobulin IgM and IgG and the concentration of blood lymphocytes (Bendixen index) in 289 Holstein-Friesian heifers and cows from a dairy herd in which bovine lymphoma had been identified repeatedly. Serum IgM was present in all cattle, and those cows with highest concentrations of blood lymphocytes generally had higher levels of IgM.


Malignant tumors of the intestine: a review of 37 cases.

Malignant tumors of the small bowel are rare but carry a grave prognosis. Thirty-seven cases from the Tumor Registries of Brooke Army Medical Center. Fort Sam Houston, Texas, and Fitzsimons Army Medical Center, Denver, Colorado, were retrospectively studied. Twenty-nine males and eight females ranging from five to 86 years were included in the combined series. Thirteen carcinoid tumors, eight adenocarcinomas, seven lymphosarcomas, five leiomyosarcomas, two reticulum cell sarcomas, one liposarcoma, and one mesenchymal cell sarcoma were found. Symptoms included intermittent crampy abdominal pain, intestinal obstruction, intestinal bleeding with anemia, and weight loss. The diagnosis was made on the basis of the clinical picture in addition to physical findings and pertinent x-ray contrast studies. The overall survival rate was 25%. The treatment of choice is surgical extirpation of the tumor whenever possible followed by appropriate adjunctive modalities.


Association of immunoblastic lymphadenopathy and Hashimoto's thyroiditis.

A 75-year-old white woman with a supraclavicular mass and primary hypothyroidism was found to have immunoblastic lymphadenopathy and Hashimoto's thyroidits. Peripheral blood contained normal percentages of T and B lymphocytes, but there was a markedly decreased response to phytohemagglutinin and to skin testing for delayed hypersensitivity. Since lack of suppressor T cells, B-cell proliferation, and decreased immunosurveillance may be causative factors in these diseases, it was of interest to document this rare association of immunoblastic lymphadenopathy and Hashimoto's thyroiditis.


Single-step gastric aspirate shake test: bedside predictor of neonatal pulmonary morbidity.

A simplified, single-step shake test has been performed on gastric aspirate samples from 85 preterm infants and a control group of 214 term infants. Respiratory symptoms were seen in 25 of 30 preterm infants with a negative or intermediate test, but in only 2 of 55 infants with a positive test (P less than 0-001). No infant with a positive test developed respiratory distress syndrome (RDS) while RDS developed in 66% of those preterm infants with a negative test. False-negative results were not seen in the preterm group. The gastric aspirate shake test had better sensitivity and selectivity in prediction of clinical outcome than did the amniotic fluid lecithin/sphingomyelin ratio in 37 preterm infants in whom both results were available. Serial shake tests were performed on samples from a number of infants with RDS and the results were seen to change in parallel with clinical recovery. This and other observations suggest that the result of the gastric aspirate shake test depends more upon direct swallowing of fetal lung liquid than on swallowing of amniotic fluid.


Unusual events preceding hyperthyroidism with diffuse goiter.

Two unique patients with hyperthyroidism are presented here. A 48-year-old woman with a family history of Graves' disease was first evaluated and treated for a toxic adenoma with radioactive iodine. Three months later, she was again hyperthyroid, was found to have a diffuse thyromegaly, and was treated with radioactive iodine for the second time. This patient represents, to our knowledge, the first reported case of two sequential forms of endogenous hyperthyroidism. The second patient, a 64-year-old woman, had well-documented hypothyroidism that was presumably primary. She was admitted in thyroid storm and subsequently died. The autopsy disclosed characteristic changes in the thyroid of hyperthyroidism and a normal pituitary gland. The timing of the onset of Graves' disease with hyperthyroidism cannot be accurately determined.


Peliosis hepatis. Twelve cases associated with oral androgen therapy.

Peliosis hepatis was encountered in 12 patients treated with high-dose oxymetholone or fluoxymesterone therapy. In three cases liver failure was the primary cause of death. In one case, the diagnosis was established by biopsy, the androgen therapy was discontinued, and the lesion was absent at autopsy two years later. In eight cases peliosis hepatis was an incidental finding at postmortem examination. The clinical and anatomic features of these cases are described, and previously reported cases of peliosis are briefly reviewed. A hypothesis is offered to explain the association of this peculiar lesion with anabolic androgen therapy.


Fatty metamorphosis of the liver associated with jejunoileal bypass. Report of five cases.

Detailed postmortem examination was carried out on five patients who died three months to four years after jejunoileal bypass for obesity. A spectrum of histological changes was observed in the liver, with pericentral fat deposition being a common feature. Evidence of previous and/or ongoing liver cell dropout with accompanying polymorphonuclear and mononuclear infiltration was seen in all cases, but Mallory hyalin was not detected. Liver function abnormalities included decreased plasma protein levels, decreased prothrombin activity, increased serum alkaline phosphatase levels, and variable elevations of the serum transaminases, bilirubin, and ammonia concentrations. The pattern of the hepatic disease does not resemble protein deficiency. An uncharacterized hepatotoxin or toxic effect of hepatic fat accumulation may play a significant role in the changes observed in these patients.


Congenital extrahepatic biliary atresia.

Ten cases of congenital extrahepatic biliary atresia were studied ultrastructurally. Samples of liver were obtained from each and in six of the cases, fibrous tracts, which we hoped would contain extrahepatic bile ducts, were also secured. The observed extrahepatic biliary structures were real, but hypoplastic, bile ducts. In places, necrosed epithelial cells, without obvious inflammatory processes, could be observed. The ductular cell cytoplasmic changes and the inflammatory reaction are different according to whether extrahepatic or intrahepatic sites are considered. These differences, as well as the cytoplasmic modifications of liver parenchymal cells, seem to be the result of impaired bile flow. On the contrary, extrahepatic bile duct hypoplasia and necrosis seem to be directly related to the unknown origin of this disease. Whether the nuclear changes of hepatocytes are the expression of direct injury of the liver is another important question. If there is direct injury, it is possible that the disease might evolve as an independent liver disease despite a correctly performed and uncomplicated surgical intervention.


Ultrastructure of chronically inflamed human submandibular glands.

The structure of chronically inflamed submandibular glands from four patients was examined by electron microscopy. The patients were free of the sicca syndrome and lacked other symptoms of Sjögren's syndrome or related autoimmune diseases. The affected glands were characterized by a reduction in acinar elements, by ductular proliferation and hyperplasia, and by large numbers of inflammatory cells in the stroma. This study indicates that many of the ultrastructural changes in salivary glands previously attributed to autoimmune diseases may also occur in patients who are free of such afflictions but whose salivary glands have undergone intermittent obstruction or infection.


Extraskeletal Ewing sarcoma. An ultrastructural study.

Soft tissue tumors with the characteristics of Ewing sarcoma of bone have thus far only been studied by light microscopy. A pelvic tumor of this type in a 13-year-old girl was examined by electron microscopy. Comparison of its ultrastructural features with those of reported cases of bony Ewing sarcoma reveal much similarity. It is believed that they are probably identical and that the tumor cells are of immature mesenchymal type. However, their site of origin and the direction of their potential differentiation remain obscure.