Primary osteoarthrosis of the knee or hip. Prevalence of Heberden nodes in relation to age and sex.

One hundred twenty probands with primary osteoarthrosis of the hip or knee were examined prospectively; there were 194 controls. In addition, 193 patients with hip or knee arthrosis were examined retrospectively. Restriction of rotation on physical examination accurately differentiated arthrotic hips from normal ones. Among women, 38% of the controls and 49% of the probands had Heberden nodes (P more than .1). Their prevalence increased with age. Individuals with multiple arthrosis joints were not older than those with single joint involvement, and they has a similar prevalence of nodes. Of the probands, 14% had arthrosis of both the knee and hip. Of those with bilateral hip arthrosis, 33% had knee arthrosis as well. Heberden nodes are unrelated to osteoarthrosis of the knee or hip. Knee and hip arthroses frequently occur together and remain confined to the initially affected joints. They may have a common cause.


Detection of hypertension. Blood pressure determination in outpatient clinics of medical school-affiliated training programs.

We evaluated past medical records and conducted a hypertension screening program in the outpatient clinic of a university hospital, a community hospital, and a city hospital, with the aid of specially trained high school students under the direction of a cardiovascular nurse. Fifty-one percent of the adult black outpatients had elevations of arterial blood pressure; one half of these patients were aware of a history of hypertension. Analysis of the clinic records showed that many patients who had made multiple visits to the clinic had never had a blood pressure recorded in their charts. If progress is to be made in the detection of hypertension, blood pressures must be routinely determined. This should be incorporated into all clinic routines, particularly in clinics staffed by physicians-in-training.


Human disease caused by Brucella canis. A clinical and epidemiologic study of two cases.

Nonlaboratory-associated human illness caused by Brucella canis occurred in two persons. Fever, chills, malaise, and weight loss were prominent symptoms in both patients. Epidemiologic investigation identified a household dog as the likely source of one patient's infection, and serologic studies and blood cultures on neighborhood dogs showed that approximately 30% were positive for B canis. Persons exposed to infected dogs appeared to have a low risk of disease. Although routine Brucella agglutinin tests do not detect antibodies to B canis, available methods for diagnosis include a specific B canis serologic test and culture techniques.


Hypertensive crisis and death associated with phencyclidine poisoning.

Phencyclidine hydrochloride is a dangerous drug. Its incidence as the causative agent in childhood poisoning is increasing. A pressor effect of phencyclidine has been noted in studies both in man and in experimental animals. We summarize seven cases of poisoning with this drug, including one in which death occurred following a hypertensive crisis. Patients who have ingested this drug should have continuous monitoring of blood pressure in an intensive care unit.


Minibike and motorcycle accidents in adolescents. A new epidemic.

Twenty-one adolescents, ranging in age from 9 to 16 years, sustained accidental injuries while operating a minibike, motorcycle, or go-cart. Their injuries ranged from lacerations and contusions to paraplegia and amputation. This study suggests that this new pattern of injury is reaching epidemic levels in this age group.


Diagnosis of acute myocardial infarction. Relative efficiency of serum enzyme and isoenzyme measurements.

Total serum enzyme activity for creatine phosphokinase (CPK), alpha-hydroxybutyric dehydrogenase (HBDH), lactic dehydrogenase (LDH), and serum glutamic oxaloacetic transaminase (SGOT), as well as the isoenzymes of CPK and LDH, were measured on admission and for ten subsequent days in 100 patients admitted consecutively to a coronary care unit. On discharge, patients were classified by a cardiologist as either having or not having suffered an acute myocardial infarction (MI) on the basis of clinical and electrocardiographic criteria--without knowledge of the enzyme studies. The combined use of CPK and LDH isoenzyme levels provided the greatest laboratory discrimination between the two clinical groups (MI vs non-MI). The routine use of HBDH and SGOT levels can be abandoned in the setting of a coronary care unit if CPK and LDH isoenzyme assays are available.


Feasibility of open heart surgery in a community hospital.

A program for open heart surgery in one community hospital was formulated and put into practice. Experience gained indicates that such services are a necessity in hospitals that fulfill certain criteria. The program is safe and inexpensive. A house staff is not a prerequisite. Finally, the analysis of data obtained from the first 100 cases compares very favorably with results in large medical centers, indicating that the patient's recovery is not compromised.


Osteoarthritis beginning with inflammation. Definitions and correlations.

A syndrome of acute onset of inflammation over interphalangeal joints heralding deforming osteoarthritis may be intermediate between degenerative and rheumatoid joint diseases. The syndrome appears predominantly in women of menopausal age and is remarkably symmetrical. In a prospective study of 170 propositi, later changes more characteristic of rheumatoid arthritis than of generalized or erosive osteoarthritis developed in 15.3%.


LH and its subunits in human pituitary, serum and urine.

Human postmenopausal serum and urine, and saline extracts of human pituitaries were gel-filtered on Sephadex G-100. The eluted fractions were radioimmunoassayed using 3 specific assays for native hLh, hLHalpha and hLHbeta. The elution profile of immunoreactive components in postmenopausal urine exhibited 2 peaks of activity corresponding to those demonstrated for 125I-labeled hLH and hLHalpha. No LHbeta was demonstrated. The immunoreactive components of post-menopausal serum eluted identically to 125I-LH, LHalpha and LHbeta. In addition, a peak of immunoreactive LH material was observed in the pre-LH region of the elution profile, distinctly separate from the void volume. The percent of the total immunoassayable serum LH contained in this peak varied. In elution profiles of all pituitary extracts, LH, LHalpha and LHbeta elution peaks corresponding to the respective labeled preparations were observed. An apparent excess of free alpha subunit was noted. All three antisera demonstrated immunoassayable LH material in the void volume. This large species contained a higher proportion of material reacting in the anti-hLHalpha system than did native hLH. Examination of the void volume material by electron microscopy indicated membrane material, but no ribosomes. Chemical assay failed to detect RNA. When void volume material was subjected to conditions which are known to (a) disrupt membrane continuity and (b) dissociate the noncovalently bonded subunits of native LH, this large species of LH failed to dissociate into smaller molecular species. These studies reveal: (1) an excess of free alpha subunit in the pituitary, serum and urine; (2) a large species of LH in the pituitary which upon analysis does not appear to be simple aggregation of LH, MEMBRANE ENTRAPPED NATIVE LH, OR RIBOSOMAL BOUND LH.


Thyroid imaging in lymphocytic throiditis.

The thyroid radionuclide images of 51 adult patients with a histological diagnosis of either Hashimoto's thyroiditis (HT) or chronic lymphocytic thyroiditis (CLT) were reviewed. The findings were variable but similar in the two groups, the most common being a multinodular pattern and the presence of hypofunctional nodules. Thyroid carcinoma was found in 2 of 41 patients with CLT and in 4 of 10 with HT. In a patient with clinical or laboratory evidence of HT and the radionuclide image finding of a cold nodule, thyroid carcinoma should be excluded by surgical biopsy.


Pattle's bubble-stability method in the rat.

The following report deals with Pattle's alveolar bubble-stability method for surfactant studies in rats. There was no difference in stability ratio of bubbles obtained from separate lung lobes without gross pathological lesions. Bubble stability was not influenced by microscopic illumination (used only briefly for photographing) and by 1-day storage at plus 4degrees C. The stability ratio was significantly lower in distilled water in comparison with the value obtained in isotonic saline. If the time interval passing from squeezing of the bubbles to the time of the first measurement is strictly retained, the reliability of the method is satisfactory. The use of cummulative distribution curves of individual stability ratios' values and non-parametric testing of such results is recommended.


Protein-losing enteropathy in lymphoma of the small intestine.

A patient with crampy abdominal pain was found to have involvement of the jejunum and ileum with innumerable small polypoid filling defects. At laparotomy, dilated serosal lymphatics were seen, and a diagnosis of lymphoma was established on the basis of intestinal and lymph node biopsy. Later, he was determined to have protein-losing enteropathy, and this parameter was used to assess his response to chemotherapy directed at the lymphoma.


Technical advances in resection and graft replacement of thoracic, abdominal, peripheral aneurysms.

Condition we now term aneurysm, deriving from the Greek word for "a sidening," has been recognized since the earliest days of medical history. The predilection of such lesions to rupture, with resultant hemorrhage, thrombosis, and distal ischemia, has led to constant attempts at surgical management, including ligation and incision, wrapping, wiring, plasticizing, packing, obliterative and reconstructive endoaneurysmorrhaphy, and a wide variety of procedures both ingenious and ingenuous. Modern treatment depends on minimal dissection, to obtain proximal and distal control, incision of only the anterior wall, and every attempt to maintain the integrity of the major portion of the involved vessel. A technique of intrasaccular interpolative anastomosis is used, taking deep and generous. The posterior wall of the aneurysm supports the suture lines and splints the graft firmly. Coverage of the graft with the residual sac protects the surrounding organs, minimizing possible complications. The method is applicable to aneurysms of a variety of anatomic sites, even in the presence of dissection, except those aneurysms involving the transverse aortic arch and thoracoabdominal aneurysms involving major visceral branches. Finally, the described techniques lend themselves easily to any sizable peripheral aneurysm and are simpler and safer than other surgical modalities such as total extirpation and bypass procedures.


Corticosteroids and bioavailability.

This presentation has attempted to provide a brief view of the importance of bioavailability and bioequivalence to those physicians who use corticosteroids. In particular it emphasizes that in vitro tests may not be reliable for predicting variability between formulations and, more importantly, cannot take the place of a bioavailability study. The implication would seen clear: namely, that a manufacturer who wishes to market a formulation similar to that already available and found to be acceptable clinically cannot rely on merely matching the standard formulation with in vitro tests but should substantiate that his formulation is, indeed, bioequivalent to the standard. In addition, data have been presented that clearly suggest the importance of bioavailability methodology as a new and useful pharmacological tool. In conclusion, as far as the bioavailability of corticosteroids in the marketplace is concerned, an old adage may be paraphrased: "If you don't know your bioavailability, know your manufacturer."


Trends in radiologic technology education.

Allied health person-power education has for the past ten years shifted significantly from the hospital to college-based degree programs.  Academically strong co-sponsored (college-hospital) programs offer considerable advantage for the health professional.  Radiologic technology education generally has not kept pace with this trend.  The need in radiologic technology education is not for additional training programs, but for better ones, and for continuing education for in-service personnel.  Radiologic technologists should challenge their local institutions of higher education to provide for their needs and aspirations.


Photoperiodic control of LH release in the ram. I. Influence of increasing and decreasing light photoperiods.

The influence of variations in the duration of light photoperiod on LH release has been studied in intact and castrated rams submitted to a 6 months "annual" light rhythm. Blood was collected once a month and the plasma LH levels were determined by radioimmunoassay. In intact rams, the LH level is decreased when the light photoperiod is increased, but as soon as this photoperiod begins to decrease, a sharp increase (about 80%) in the LH level is observed. Thereafter a slow decline in plasma LH occurs until the photoperiod reaches a minimum. In the castrated animals, the plasma LH level is three to four times higher than in the intact animals but the pattern of the variations with regard to the light photoperiod duration, is essentially the same. Thus an increase of 59 and 43% in plasma LH occurs in the two breeds used when the light photoperiod begins to decrease. These results indicate that hypothalamo-hypophyseal activity is modulated by gradual changes in the duration of light photoperiods either in the presence or absence of androgens.


Photoperiodic control of LH release in the ram. II. Light-androgens interaction.

The intensity of negative feedback of androgens on hypothalamo-hypophyseal activity was compared in two groups of castrated rams under 8.00 or 16.00 h of daily illumination respectively following a conditioning period. In experiment I, two groups of 15 rams under each light photoperiod were slaughtered at different times after a 200 mg testosterone propionate (TP) intramuscular injection. Animals receiving the vehicle only acted as controls. The hypophyseal LH concentration, which increases when there is temporary inhibition of the release into the blood, was taken as a criterion of the inhibition due to TP. In both groups of rams the LH concentration increased in the pituitary following TP treatment. A return to the pre-injection level was observed 48 h later only in animals under a 8.00 h light photoperiod, indicating a shorter negative effect of the injection than in the case of rams under 16.00 h light photoperiod. In experiment II, the inhibitory effect of TP was assessed at two doses, i. e. 300 and 600 mg, by the decrease in the plasma LH level following an intramuscularly injection. In both cases the decrease in LH release was more pronounced in rams under 16.00 h of daily illumination than in those under 8.00 h (mean decrease in LH release: 21.2 and 33.2% respectively in 300 and 600 mg treated rams under 16.00 h daylight as against 9.2 and 14.8% in rams under 8.00 h). Thus it appears that to the intrinsic action of the photoperiod is superposed on a modulatory effect of steroid action on the hypothalamo-hypophyseal activity. The hypothesis is therefore presented that, in rams a decreasing light photoperiod acts in two ways: 1) by stimulating the activity of the hypothalamo-hypophyseal system, 2) by decreasing the intensity of the negative feedback effect of steroids.


Effect of the exposure to cold on the extrathyroidal conversion of L-thyroxine to triiodo-L-thyronine, and on intramitochondrial alpha-glycerophosphate dehydrogenase activity in thyroidectomized rats on L-thyroxine.

Thyroidectomized rats have been injected daily with 125-I labelled L-thyroxine (T4) and, once isotopic equilibrium was attained, divided into cold-exposed (4-10 degrees C) and control (21-24 degrees C) groups, the daily T4 administration being continued till the end of the experiment. Fourteen days after onset of cold exposure, the total I of different organs and of the carcass was determined and the tissues submitted to extraction and paper chromatography for the separation of T4 and T4-derived I-containing compounds. The Activity of intramitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) was measured in kidneys and liver. It was found that the total amount of I was intensely decreased in all samples from cold-exposed animals. The proportion of this Iwhich was non-extractable was the same, in all tissues, for cold-exposed and control rats. The % of extractable tissue radioactivity in the form of T4 was decreased, and that found as T4-derived T3 was increased, in all samples from cold-exposed animals. The T3/T4 ratio was increased more than two-fold in all tissues studied. The concentration of T4 decreased significantly in all tissues, whereas the concentration of T3 in tissues of cold-exposed rats did not decrease. It actually increased in kidneys and lungs, and remained the same in liver and carcass. Despite the decrease in the concentration of T4 in the kidneys, alpha-GPD activity was increased in this tissue, where the concentration of T3 was increased. No change in the alpha-GPD activity was found for the liver, where the concentration of T3 was the same for cold-exposed and control rats. Thus, it appears likely that the conversion of T4 AND T3 is increased by the exposure to cold of thyroidectomized rats on a constant dose of T4.alpha-GPD activity in a given tissue appears to be more closely related to the concentration of T3, than to that of T4.


The diagnostic value of a radioimmunoassay for parathyroid hormone in human serum.

A radioimmunoassay for the measurement of immunoreactive parathyroid hormone (PTH) in human serum is described. The assay is based on the ability of human parathyroid hormone (h-PTH) to compete with 125I-labelled bovine parathyroid hormone (b-PTH) for binding to a guinea-pig antiserum directed against b-PTH. The linear part of the standard curve was parallel with dose response curves for anti-b-PTH serum reacting with dilutions of sera from patients with primary hyperparathyroidism and from h-PTH purified from human parathyroid adenomas, indicating that levels of immunoreactive PTH could be expressed as b-PTH equivalents. The range in 62 healthy blood donors was 1.1-2.5 ng b-PTH Eg./ml. The reproducibility was satisfactory, and the sensitivity permitted the measurement of PTH concentrations down to 0.8 ng b-PTH Eg./ml. No crossreaction with h-CT, h-STH or h-ACTH was observed. The clinical value of the assay has been considered in a number of patients with various disorders of calcium metabolism, diagnosed and treated conventionally. About 80 per cent of patients with primary hyperparathyroidism had elevated PTH levels on one or more occasions before surgery. In patients with chronic renal failure of other aetiology than primary hyperparathyroidism the levels were usually far higher. Patients with primary hyperparathyroidism and increased S-creatinine had higher PTH levels than those with normal S-creatinine. After parathyroidectomy all previously increased PTH levels became normal or low. High PTH concentrations were found in 3 patients with normocalcaemic hyperparathyroidism who at operation were shown to have parathyroid adenomas. However, in normocalcaemic patients there were also some falsely elevated PTH values which limit the diagnostic value of the assay in this group of patients. Low PTH values were observed in patients with hypercalcaemia due to malignant disorders, indicating that PTH determination may be of some value in the diagnosis of patients with hypercalcaemia of unknown origin.


Complete inhibition of adrenocortical responses following sciatic nerve stimulation in rats with hypothalamic islands.

Previous studies from this laboratory have demonstrated that in rats with hypothalamic islands the adrenocortical response to photic and acoustic stimulation was partially inhibited indicating that they were at least to a certain degree neurally mediated, though ether stress produced normal adrenocortical responses. With the purpose of determining to what extent afferent somatosensory connections to the hypothalamus participate in the activation of adrenocortical responses following sciatic nerve stimulation, the effects of this stimulus applied through chronically implanted electrodes were studied on the plasma corticosterone levels in pentobarbital anaesthetized intact animals and in rats with hypothalamic islands. Ether stress or sciatic nerve stimulation for 2 min in intact rats produced a rise of plasma corticosterone to 32.1 plus or minus 1.2 and 32.1 plus or minus 1.8 mug/100 ml, respectively. However, in animals with hypothalamic islands the corresponding values were 29.2 plus or minus 1.8 and 12.4 plus or minus 0.8 mug/100 ml, respectively. The latter value was not significantly different from the basal corticosterone levels (13.0 plus or minus 1.2 mug/100 ml) found in rats 15 min after pentobarbital anaesthesia, the time when the sciatic stimulus was applied. The present data indicate that the adrenocortical discharge following sciatic nerve stimulation is completely inhibited by hypothalamic deafferentation and therefore depends entirely on the activation of the afferent neural pathways to the hypothalamus.


Influence of prolactin on the metabolism of steroid hormones in rat liver and adrenals.

The influence of prolactin treatment on the hepatic metabolism of 4-(4-14C) androstene-3, 17-doine (in the microsomal and 105 000 times g supernatant fractions) and 5alpha-(4-14C) androstane-3alpha, 17beta-diol (in the microsomal fraction) and on the adrenal metabolism of 4-(4-14C) androstene-3, 17-dione was studied in intact and castrated male and female rats with and without concomitant treatment with testosterone propionate. Whereas prolactin gave a significant and specific decrease in the activity of adrenal 5alpha-reductase by about 20-30% in both male and female rats no specific effects were noted in the metabolism of steroids in the liver. Neither did prolactin compensate for the relative androgen unresponsiveness characteristic of neonatally castrated male rats. These results suggest that prolactin does not play any significant role in mediating the recently discovered hypophyseal control of sexual differentiation of hepatic steroid metabolism in the rat whereas it may have a function in maintaining sexual differences in alrenal 5alpha-reductase activity.


Blood plasma levels of progesterone and oestradiol in the dog during the oestrous cycle and pregnancy.

Plasma oestradiol and progesterone levels were studied in German Shepherd and Greyhound bitches during the normal oestrous cycle, pregnancy and at parturition. The mean oestradiol level increased from approximately 7 to 13 pg/ml during the fifth week before onset of oestrus. Oestradiol stayed at this level until pro oestrus which was characterized by a steady increase to a mean peak level of about 30 pg/ml 5-6 days before oestrus. At the start of oestrus the level was approximately 12 pg/ml. A level between 10-15 pg/ml was kept during the following 10 weeks whether or not the bitch was pregnant and no change occurred at parturition. The mean progesterone level was found to be very low, around or under 1 ng/ml, until 1-4 days after the oestradiol peak after which the level gradually increased to around 10 ng/ml at the start of oestrus. During oestrus and metoestrus or pregnancy the pattern was inconsistent. In some bitches the level gradually increased during 3-4 weeks and reached a peak value of 30-50 ng/ml. The level then gradually decreased during 5-6 weeks. During the first 5 weeks of the same period progesterone in other bitches fluctuated between similar maximum levels and extremely low levels. After the fifth week the pattern was the same for all bitches. In the pregnant bitches there was a significant drop of the progesterone level at parturition. The data suggest that the dog is not an ideal test animal for steroids synthetized for use in man.


Simultaneous determinations of oestradiol-17 beta, progesterone and luteinizing hormone in the plasma during the ovulatory cycle of the hen.

Simultaneous determinations of plasma levels of oestradiol-17beta, progesterone and luteinizing hormone (LH) during the ovulatory cycles of hens were performed using radioimmunoassay techniques without chromatography. Blood samples were collected from the wing vein of 7 hens with regular ovulatory cycle at intervals of 1, 2 or 4 h throughout 36 h starting 24-25 h before the second egg (C-2) ovulation of the clutch and ending 11-12 h after C-2 ovulation. The oestradiol-17 beta level of the plasma during the ovulatory cycle varied from 50 pg/ml to 250 pg/ml. The value was high 24 h before ovulation and decreased until 10 h before ovulation, then increased and reached a peak 4-5 h before ovulation, when it started to decrease again until 12 h after ovulation. The plasma levels of progesterone varied from 1 ng/ml to 6 ng/ml, and reached a peak 4-6 h before ovulation. The plasma LH value varied from 1 ng/ml to 4 ng/ml, and the changes in the levels corresponded well with that of progesterone, also showing a coincident peak.


The hypercalcaemic syndrome in rats bearing the Walker carcinosarcoma 256.

The strain of Walker carcinosarcoma 256 described induces hypercalcaemia, hyperphosphataemia and hyperuraemia in tumour bearing rats. Changes in calcium and phosphorus excretion are observed as well as accompanying calcification of soft tissue organs and loss of bone calcium. These changes in calcium metabolism disappear after removal of the tumour, so that long-range action of the tumour can be stated. The results are discussed in comparison with three other animal models of tumour dependent hypercalcaemia.


Risk of respiratory distress syndrome as determined by amniotic fluid lecithin concentration.

Lecithin concentration has been determined in 476 samples of amniotic fluid collected within 72 hours of delivery. If delivery is associated with a level of lecithin of 0.100 mg/100 ml. of lecithin phosphorus or greater, the risk of RDS in the neonate is minimal, if any. If delivery is associated with a level of lecithin less than 0.100 mg/100 ml. of lecithin phosphorus, a definite risk of RDS is present. This "risk factor" is a function of the lecithin concentraion and may be expressed in terms of a simple mathematical equation. The equation, log y equals minus 1.0187 minus 0.0101 chi, expresses the relationship in a highly significant manner (r equals 0.99) where y equals lecithin concentration and chi equals risk of RDS. In managing individual high-risk patients, our general policy is to weigh the chemically determined "risk factor" of RDS if delivery is done against the clinically determined "risk factors" involved if delivery is delayed. By comparing the various risks involved, appropriate management is decided upon.


Amniotic fluid phospholipids and fetal lung maturity. I. Assessment of various methods of determining lecithin and sphingomyelin.

The measurement of the lecithin/sphingomyelin ratio in amniotic fluid as an index of fetal lung maturity has been a controversial and much-discussed topic since the initial report of this procedure appeared in the literature in 1971. Our laboratory has investigated several methods of measuring phospholipid components of amniotic fluid and compared relative reproducibility and accuracy. Correlation of these phospholipid determinations with the clinical presence or absence and relative severity of neonatal respiratory distress syndrome forms the basis of this report. Our findings indicate that careful attention to the biochemical basis of this test results in the ability to predict with great accuracy developmental respiratory distress syndrome. This presentation describes our method of determining lecithin/sphingomyelin ratios in amniotic fluid, compares our results with other tests for determining fetal maturity, and assesses the value of this procedure in clinical situations.


Benign lymphoepithelial lesions of the salivary glands.

The benign lymphoepithelial lesion of the salivary glands has been labeled with multiple, confusing terms. We recommend the abandonment of the vague term of Mikulicz disease. The histopathologic findings of lymphoid infiltration, intraductal proliferation, epimyoepithelial islands, and acinar atrophy are presented. The relationship between this lesion and autoimmune diseases, including Sjögren syndrome, is noted. Difficulty of histopathologic differentiation between this lesion and malignant lymphoma can occur. The association of the benign lymphoepithelial lesion with the simultaneous presence or future development of lymphoma is discussed.


In vitro inhibition of aggregation of human erythrocytes by synthetic fibrinolytic compounds.

It has been shown that a variety of synthetic organic anions which induce fibrinolytic activity in human plasma in vitro and which in addition inhibit collagen-induced aggregation of human platelets, also exert to various degrees an inhibition of dextran, fibrinogen and gelatin induced aggregation of human erythrocytes and of the pathologically accelerated erythrocyte sedimentation rate.  Since increased erythrocyte aggregation is contributing to thrombogenesis, ability to prevent erythrocyte aggregation is a desirable feature for synthetic antithrombotic compounds.  They should exert three actions: induce fibrinolytic activity, prevent platelet aggregation, and inhibit erythrocyte aggregation.  This communication refers to prototypes of such compounds.


[Sense and applicability of means.  Various critical considerations].

The range of application and account of the arithmetic and geometric mean, the mode and the median set different standards to the frequency distribution of the original data.  The quite frequently inadequate use of the geometric mean in serological dilution series will be demonstrated in a practical example.  The interview of 66 physicians and 31 graduate and postgraduate engineers was made to give an impression of the participants' knowledge of the above mentioned statistical mean values and their practical application. The arithmetic mean proved to be the best known and most popular method in use, closely followed by the geometric mean and far of by the median and the mode.  Other questions were to find out, why the arithmetic mean was the favourite.  The result was as astonishing as it was simple:  The arithmetic mean seemed to be used most because it was known best at school and university.  Therefore in a great number of cases statistical means were chosen from a formalistic point of view and not, as it would be much more appreciated, according to the specific nature of the data or to pertinent accounts.


[Pyrogen testing in vitro using the Limulus test].

The applicability of the Limulus test for the pyrogen test was checked in comparison to the pyrogen test in rabbits.  In 6 out of 24 lots of raw materials and drugs pyrogens could be detected by means of the pyrogen test in rabbits. 2 of these 6 lots showed positive reaction in the Limulus test, there were no false positive results.  Testing 7 bacterial strains in modified quantity of germs the Limulus test turned out to be more sensitive than the pyrogen test in rabbits.  The application of this in vitro test as a complement to the pyrogen test in rabbits for a certain kind of problems is discussed.


[Pharmacology of D-penicillamine].

In acute pharmacological experiments, D-betta,betta-dimethylcysteine (D-penicillamine, Metalcaptase) stands out for its good oral and intravenous tolerance.  In case of high dosage, slight analgesic and anti-inflammatory effects can be found.  The influence on newly formed connective tissue is not uniform.  While the wet and dry weights of granulomata are not influenced, D-penicillamine causes a retardation of the healing process in standardised burns.  Mechanical properties of connective tissue such as the resistance of cut wounds, the tearing strength of excised dorsal skin strips or of the capsule of the knee-joint show after long-term treatment with D-penicillamine a dose-dependent change in the sense of a decrease of the data obtained.  After discontinuation of the test substance, the data reach standard values within a few days.


[The antihepatotoxic effect of silymarine on lipid metabolism in the rat disturbed by phalloidine intoxication].

Single application of 600-750 mug phalloidine/kg body weight produces within 4-6 h a decrease of serum cholesterol esters and a rising concentration of free fatty acids and lysophosphatidyl choline in liver homogenate.  Analysis of fatty acids compounds in liver lipid fractions indicates an increase of shorter-chain fatty acids and a percentage diminution of highly unsaturated longer-chain fatty acids.  In the prophylactic test, and also when giving silymarine-N-methylglucamine-salt simultaneously with the toxic agent, most analysed parameters show a variance according to those of the nonintoxicated control group.  Correlation analysis of paramenters points out typical variations between normal, control and experimental animals.


Pharmacokinetic study of maleate acid of 2-(N,N-dimethylaminoethanol-14C1)-cyclohexylpropionate (cyprodenate) and of N,N-dimethylaminoethanol-14C1 in animals.

The localization, distribution, and elimination of maleate acid 2-(N,N-dimethylaminoethanol-14C1)-cyclohexylpropionate (14C-cyprodenate, Actebral) was studied in rats and pigs.  Beside this, dimethylaminoethanol-14C (DMAE) was also administered to rats enabling a comparison of the pharmacokinetics of the two 14C-labelled molecules to be made.  The study of the localization by autoradiography and the study of the quantitative distribution of the radioactivity showed that cyprodenate, a psychotonic drug, diffused more rapidly than DMAE through the hemo-encephalic barrier.  However, it was also observed that the radioactivity found in the brain rises continually as a function of time, regardless of the product administered.  The two labelled products were primarily excreted in the urine (30-35 per cent of the dose in 72 h in rats and 6 per cent of the dose in 48 h in pigs) following oral administration of cyprodenate.  Radioactivity found in the feces was practically nil and in rats the biliary elimination of the drug was very weak.  Thus, whichever animal is used, it was found that 14C-cyprodenate is totally absorbed. Radioactivity expired as 14CO2 was negligible (around 1 per cent of the administered dose in 8 h), however, this value increases as a function of time, becoming 4 per cent in 24 h.  In rats the maximum radioactivity in the blood was found at 45 min to 1 h after oral administration of 14C-cyprodenate.  These values decrease slowly until 3 h when they begin to increase again.  The rising of the blood level values is practically the same for pigs, the maximum being attained at 1 h.  Therefore, whatever route of administration, whichever dose or animal, we always found a progressive elevation of the protein binding to the plasma proteins for these two labelled products in vivo.


The study of the biotransformation of 2-(N,N-dimethylaminoethanol)-cyclohexylpropionate-meleate acid (cyprodenate, Actebral), a psychotonic brain stimulant, was carried out on two species of animals (rats and pigs) with the aid of 14C-labelled molecules. Following i.v. administration in rats it was found that 14C-cyprodenate diffuses very rapidly to the principal organs (liver, brain, kidneys) preceding a hydrolysis which gives 14C-dimethylaminoethanol (DMAE). The latter undergoes N-oxidation but the major portion of DMAE goes directly into the metabolic cycle of the phospholipids up to the formation of 14C-choline, as shown in the metabolic scheme proposed by the authors that identifies the principal labelled intermediaries: 14C-phosphoryl-DMAE (P-DMAE), 14C-glycerophosphatidyl-N,N-dimethylethanolamine (GP-DMAE), 14C-glycerophosphatidyl-choline (GP-choline). Similar results were found with the oral administration of 14C-cyprodenate in pigs, thus showing a more intense participation of the product at the level of the intermediary metabolism of phospholipids, precursors of choline.


Pharmacological action of FD-008, a new dopamine-beta-hydroxylase inhibitor.

The effects of 5-(4'-chlorobutyl)-picolinic acid (FD-008), a new dopamine beta-hydroxylase inhibitor of fusaric acid derivatives, on the central nervous system in mice and rats were investigated. FD-008 and fusaric acid did not show marked effects on spontaneous movement, convulsion, sleeping time, tremor and conditioned avoidance response but lowered the body temperature of rats at 100 mg/kg p.o. FD-008 potentiated the depressive action of ethanol on conditioned avoidance response in spite of the lack of aldehyde dehydrogenase inhibition. FD-008 markedly depressed the performance on a shuttle box and lowered the body temperature in rats after reserpine treatment at a dose at which FD-008 per se had no effect.


[Effect of the antrum and vagus nerve on the stimulation of the rat stomach by betazol in the perfusion test].

In the perfusion model on Wistar rats the action of a single s. c. injection of betazol (Histalog) in a dose of 50 mg/kg b. w. in dependence on various types of stomach operations was studied.  The following effects were observed: 1. the vagotomy shortly before the perfusion test did not reduce the effect of betazol. 2. If the vagotomy dated back at least 4 weeks, a reduction of the stimulated maximum secretion to half of the controls was seen. 3. The combination of the vagotomy with a pyloroplasty led to a reduction of the stimulated maximum acid secretion to half the amount.  Futhermore, the betazol effect was shortened considerably and was demonstrable for no more than 2 h after the injection. 4. The antrectomy without vagotomy, however, casued a retardation of the answer to betazol with a maximum of the stimulated secretion in the 4th hour after s.c. injection. The dissociation of the effect of betazol caused by vagotomy or antrectomy leads to the conclusion that betazol has a direct site of action in the parietal cell and a second one in the cholinergic stimulation of the vagal system.


Bilogical and toxicological properties of econazole, a broad-spectrum antimycotic.

The spectrum of activity of 1-(2,4-dichloro-beta-[(p-chlorobenzoyl)oxy]phenethyl)imidazole-nitrate (econazole, R 14827) was tested in vitro on various pathogenic fungi and bacteria, and also in vivo in guinea-pigs and rats experimentally infected with dermatophytes and C. albicans. The in vitro activity spectrum is very broad: the dermatophytes, the yeasts, the dimorphic fungi, the aspergilli, the mycetoma causing agents and the Gram-positive bacteria being most sensitive. Guinea-pigs infected with T. mentagrophytes, M. canis or C. albicans and treated topically or orally with econazole, were cured. In each of these tests the activity of econazole was compared with that of different reference drugs. Vaginal candidiasis in rats was cured after oral administration of econazole. Toxicity and teratogenicity studies in different laboratory animals indicate that econazole is well tolerated.


Anti-inflammatory action of an s-triazine derivative in rats.

Anti-inflammatory action of an s-triazine derivate (M 1704, 2-amino-4-(p-fluoroanilino)-6-n-propyl-1,3,5-triazine) was studied in rats. M 1704 inhibited carrageenan edema, cotton-pellet granuloma and adjuvant arthritis in intact rats. M 1704 was not effective on carrageenan edema in adrenalectomized rats, but effective when administered with cortisol. The drug appeared to potentiate the anti-inflammatory effects of cortisol on cotton-pellet granuloma. The results obtained in this and a previous study suggest that M 1704 exerts the anti-inflammatory action mainly by potentiating the peripheral anti-inflammatory action of endogenous steroid and partly by stimulating the secretion of corticosteroids.


Absorption of morphine, butylscopolamine, mecamylamine and phenobarbitone from the small intestine of the triparanol-treated rat in situ.

The absorption of three basic drugs (morphine, butylscopolamine and mecamylamine) and an acidic drug (phenobarbitone) from the rat small intestine in situ was investigated by using a single perfusion technique.  The effect of intestinal damage on absorption was studied by treating rats with triparanol 25-50 mg/kg every 24 h for three weeks.  Treatment with triparanol decreased the cholesterol concentration in the intestinal wall.  The absorption of morphine and mecamylamine was increased by treatment with triparanol, whereas the absorption of butylscopolamine was decreased and that of phenobarbitone remained unaltered.  Treatment with triparanol decreased the concentration of mecamylamine in the intestinal wall, but the concentrations of other drugs were unchanged.  When comparing the present in situ and previous in vitro results the decreased absorption of butylscopolamine after triparanol in situ was opposite to the finding in vitro.  The increased absorption of morphine and unaltered absorption of phenobarbitone were in accordance with the finding in vitro.  In situ the absorption of mecamylamine was increased, although in vitro it was unchanged.  The structural damage, differences in composition of the intestinal wall and intestinal blood flow are supposed to be the reasons for changes in absorption.


[Structure-activity relationships in the diuretic xipamide (4-chloro-5-sulfamoyl-2', 6' -salicyloxylidide)].

The synthesis of various derivatives of 4-chlorosalicylic acid substituted in position 5 is described.  The evaluation of their diuretic potency on the rat showed 4-chloro-5-sulfamoyl-2,6-salicyloxylidide (BE 1293, xipamide, Aquaphor) as the most effective one.  The normal urinary volume is increased tenfold by a oral dose of 100 mg/kg body weight.  All changes in the molecular structure of xipamide, even acetylation, the introduction of a second sulfamoyl group or the exchange of the sulfonic group for the carbonyl group, lead to a decrease in activity.


[Nicotinic acid blood levels after application of xanthinolnicotinate in a new galenic retard preparation].

Nicotinic acid blood level determinations were carried out in 30 male test subjects following application of xantinol-nicotinate in a new galenic retard preparation.  The investigations showed that there is a continuous absorption of the agent--lasting for a longer period--with a maximum of blood level values between the 5th and 7th hour.  In comparative studies with non-retarded xantinol-nicotinate the peak of concentration is already reached 1 h after application.  The use of pharmacokinetic methods showed that by the retardation of xantinol-nicotinate there are no losses of absorption of nicotinic acid--as compared with the non-retarded forms.  By the special galenic properties of the new retard form therapeutically effective nicotinic acid blood levels lasting for more than 8 h with an ascertained biological availability are attained.


[Pharmacological and toxicological properties of the saluretic xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide)].

Xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide, Aquaphor), a new compound is a derivate of salicylic acid with marked sodium and water excreting potency.  Its effect is dosage dependent.  Dosages as low as 0.001 mg/kg p.o. in rats and 0.04 mg/kg p.o. in dogs lead to a statistically significant increase of sodium and water excretion.  Potassium excretion was less affected and showed to be rather constant in a dosage range between 0.01 and 10.0 mg/kg.  In rats a maximum of sodium and water excretion could be reached by a dose of 200 mg/kg duration of action in rats was approximately 10 h.  In dogs a statistically significant sodium and chloride excretion could be detected after oral application of 0.04 mg/kg.  Xipamide increased diuresis started with an oral dose of 0.1 mg/kg.  Intravenous application of xipamide in a dose of 0.2 mg/kg in dogs accompanied by permanent infusion of 5 per cent mannit solution clearly showed the diuretic profile of the substance: increased diuresis started within 40 min.  A peak was reached within 40-60 min post injectionem.  Then excretion decreased slowly.  Even 120 min post injectionem a diuretic action could be detected.  Diuresis and sodium excretion could be demonstrated in rats with experimentally predamaged kidneys and with steroid dependent sodium retention.  As could be demonstrated in hypertensive rats xipamide had a hypotensive effect, normotensive rats were not affected.  In animal studies xipamide was excellently tolerated.  The therapeutic range of the substance was high in single doses as well as when the drug administered over 6 weeks.


[The saluretic effect of xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylilide) in normal subjects].

The diuretic and saluretic effectiveness of xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide, Aquaphor) is determined and compared to those of chlortalidone and furosemid in normal subjects. The substance is revealed as a potent diuretic agent. In the range of 0.035--0.750 mg/kg body weight the dose-response curve of orally administered xipamide for the increase of excretion of urine, sodium and potassium ion and chloride during 24 h is described. Observing the renal activity over a period of 3 days after a single administration the duration of action is found to be up to 24 h with its maximum within the first 12 h. In the following 2 days the degree of the physiological rebound effect depends on the preceding saluretic effect and thus on the given dose. The pattern of ion-excretion (Na


[Inhibition of carbonic anhydrase by xipamide (4-chloro-sulfamoyl-2',6'-salicyloxylidide) in the modified Philpot test].

The inhibition  of carbonic anhydrase by xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide, Aquaphor), a poorly watersoluble saluretic agent, is determined with the Philpot method in the presence of 5 per cent N,N-dimethyl-formamide.  The addition of the amide does not affect the enzyme.  For xipamide 1.1 times 10-5 M is found as the 50 per cent inhibitory concentration.


[Effect of 1-desamino-8-D-arginine-vasopressin in limited renal function].

U-Deamino-8-D-arginine-vasopressin (DDAVP) is a new synthetic antidiuretic hormone with prolonged action. 0.02 mg given intranasally to 38 patients with far advanced chronic renal failure effected an instantaneous decrease in urine volume as well as an augmentation of U/P-inulin ratio, fraction of filtered sodium and chloride excreted and of the absolute elimination of these ions. These findings suggest an improvement of permeability at the descending limb of Henle, too, the latter and a diminution of circulation in the renal medulla being responsible for the increase in renal salt loss after DDAVP. A rise of blood pressure or other side effects could not be observed.


[Methodological problems in studying psychotropic drugs with special reference of the AMP system].

There are several methodical problems that have to be coped with when testing psychotropic drugs in psychiatric clinics. In this paper some relevant problems have been discussed which are encountered during that part of a clinical trial, starting with the assessment of the initial psychopathological state of the patients and ending with the statistical analysis. Especially the AMP-System was considered. Particularly the following points have been dealt with: comparison of different methods for the assessment of psychotropic effects, special problems of rating scales, studies on the AMP-system concerning psychopathological and methodical aspects, conversion and processing of AMP-data, general considerations on the statistical analysis of drug trials.


Tests of the carrier model for ion transport by nonactin and trinactin.

The fluxes of K+ and NH+4 carried by nonactin and trinactin across thin lipid membranes have been measured as functions of ion activity, electric potential and time. In agreement with the predictions of a version of the carrier model in common use, the shape of the initial current-voltage relation is independent of the activity of the electrolyte, alpha-i, while the ratio of the initial conductance, G-o, to the steady-state conductance, G infinity, increases according to G-o/G infinity equals const1+const2 times alpha-i. For trinactin the data presented allow the estimation of the rate constants of the carrier process (in the limit of zero potential) in a manner which does not assume any particular variation with potential for the constants. Using empirically determined functions of potential, a complete set of values is also available for nonactin. The curve fitting which is necessary is described in the following paper. The data presently available for valinomycin are sufficient neither to test the model nor to determine a complete set of constants.


Steady-state ion transport by nonactin and trinactin.

The steady-state fluxes of Na+, K+, and NH4+ carried by nonactin and trinactin across thin lipid membranes have been measured as functions of ion activity, carrier concentration, and the applied potential. In agreement with earlier studies the conductance, G(O), is found to be proportional to the carrier concentration and, for low activities, to the ion activity. The determination of the dependence of G(O) on activity at high activities is, however, apparently obscured by changes in the concentration of carrier in the membrane. Using the values for the rate constants at zero potential which were determined in the preceding paper, it is possible to adjust the potential dependence of the constants so as to achieve a reasonable fit to the current-voltage relations. The data presented provide further evidence that a single molecule of nonactin or trinactin acts cyclicly as a carrier of univalent cations.


Nutritional effects on precursor uptake and compartmentalization of intracellular pools in relation to RNA synthesis.

The effects of nutritional variables on the processing of exogenous precursors into RNA was examined. General nutritional deprivation, or asparagine depletion, led to significant changes in the absolute pool sizes, especially of ATP, UTP and CTP. Fluctuations were found depending on the elapsed time after the nutritional perturbations occurred, and the cell density of the cultures. Depletion of the medium by 28 h of growth, or 1 h of guinea pig asparaginase action, led to considerable inhibition of the conversion of exogenous uridine to CTP by the cells. A series of experiments indicated that in 6C3HED lymphoma cells the uridine nucleotide pool which provided the immediate precursors to RNA (denoted UTP-NA) behaves as a small compartment in rapid equilibrium with exogenously supplied nucleosides. The resemblance to the compartmentation model described by Plagemann (Plagemann, P.G.W. (1972) J. Cell Biol. 52, 131-146 and (1971) J. Cell. Physiol. 77, 241-258) for rat hepatoma cells was close. The UTP-NA pool of the 6C3HED cells constitutes no more than 5% of the cellular UTP pool and is relatively slow in equilibrating with the general cell pool. Correction of the rates of incorporation of isotope into RNA by using some function of the whole cell UTP specific activity to normalize the pool effects, was shown to be invalid.


Replication of mitochondrial DNA. Selective inhibition of the H-strand synthesis in isolated mitochondria by sibiromycin.

Sibiromycin, an antitumour antibiotic forming a stable complex with the double-stranded DNA selectively inhibits the incorporation of [3H]thymidine into the H-strand of mtDNA during the incubation of isolated rat liver mitochondria in vitro. A model accounting for this result is presented. It is concluded that the H-strand is a leading strand throughout mtDNA replication adn consequently the replication of rat liver monomer mtDNA is unidirectional.


Hemolysis and iodination of erythrocyte components by a myeloperoxidase-mediated system.

Erythrocytes are hemolyzed by myeloperoxidase, an H2O2-generating system (glucose + glucose oxidase; hypoxanthine + xanthine oxidase) and an oxidizable cofactor (chloride, iodide, thyroxine, triiodothyronine). The combined effect of chloride and either iodide or the thyroid hormones is greater than additive. Myeloperoxidase can be replaced by lactoperoxidase in the iodide-, thyroxine and triiodothyronine-dependent, but not in the chloride-dependent, systems. Hemolysis is is inhibited by the peroxidase inhibitors, azide and cyanide, and by catalase and is stimulated by superoxide dismutase when the xanthine oxidase system is employed as the source of H2O2. Hemolysis by the iodide-dependent system is associated with the iodination of erythrocyte components.


Thyroid cancer: twenty years' experience in a general hospital.

Twenty year's experience of thyroid cancer in a district general hospital has been reviewed. Its incidence, prognosis and natural history have been studied. Particular attention has been focused on the relationship of malignant to benign goitre. The relevance of this to the treatment of 'apparently benign goitre' is discussed. Clinical evidence is presented supporting the hypothesis that differentiated thyroid carcinoma evolves from a solitary focus through a multinodular form before presenting the picture of a frankly malignant locally invasive cancer. An increase in the incidence of papillary carcinoma is confirmed.


Malignant lymphoma of the thyroid following irradiation.

A case of primary lymphocytic lymphoma of the thyroid is presented occurring in a 19-year-old woman. The young age of this patient, as well as the possibility of thymic radiation therapy as an infant, being a predisposing factor makes this case unique. The association with Hashimoto's thyroiditis has been previously reported.


Poly (A) polymerase of bovine lymphosarcoma.

Poly(A) polymerase has been extensively purified from low-salt extracts of bovine lymphosarcoma. The enzyme is Mn2+ dependent, requires an oligonucleotide or RNA primer, incorporates only adenosine triphosphate, and is inhibited by other ribonucleotides or deoxynucleotides. Oligoadenylate and ribosomal RNA are good primers for the enzyme; transfer RNA and poly(A) are poor. RNA transcribed in vitro by homologous RNA polymerase is an efficient primer. The properties of the enzyme are similar to the properties of the Mn2+ -activated poly(A) polymerase of calf thymus. Approximately the same amount of enzyme appears to be present in lymphosarcoma and calf thymus.


Ultrastructural study of the uptake of peroxidase by the rat median eminence.

An active role of the ependymal cells (tanycytes) of the median eminence in the transport of hypothalamic hormones has been recently suggested. In order to investigate the fate of material present in the cerebrospinal fluid, a protein tracer, horse-radish peroxidase (HRP) was injected into the left lateral ventricle of rats. Two minutes after the injection, HRP had largely diffused between tanycytes and hypendymal cells. As soon as 5 min after the injection, HRP had completely penetrated all the layers of the median eminence. A few labelled vesicles and lysosomes were occasionally seen in ependymal and glial cells. At longer time intervals (20 min, 1 and 4 hrs), a reaction was observed in the lumen of fenestrated capillaries of the pituitary portal plexus. In many nerve endings of the external zone, vesicles and lysosomes were seen to contain HRP. An interesting observation was the localization of HRP between nerve endings and cells in both the pars nervosa and the pars intermedia of the pituitary gland. No reaction was recorded in the anterior pituitary and the kidney. Seventeen hours after the injection, the extracellular space was free of reaction but a few positive intracellular structure were still found. These results clearly indicate that some material from the third ventricle can rapidly diffuse between cells and axons of the median eminence to reach the fenestrated capillaries of the pituitary portal plexus and the posterior pituitary without involving an active transport by tanycytes.


A comparative cytological study between hepatocytes of insecticide-resistant and susceptible mosquitofish (Gambusia affinis).

The livers from a naturally occurring insecticide-resistant mosquitofish population were examined cytologically and compared to liver preparations from a susceptible population. There was a marked increase in cell size and lipid inclusions in the hepatocytes of resistant mosquitofish as compared to susceptible mosquitofish. The pronounced lipid inclusions in the liver preparations of resistant mosquitofish remained essentially unchanged in mosquitofish starved for up to 2 weeks. No observable differences were noted in any cellular organelles.


Clincal pharmacology of O2,2'-cyclocytidine.

Two metabolites of 2-14C-cyclocytidine (cyclo-C) were found in the plasma and urine and a hydrolytic product, arabinosylcytosine (ara-C), and its deaminated product, arabinosyluracil (ara-U), were found in patients with cancer; 80% of the dose was found in urine in 24 hr, 70% as cyclo-C and 10% as ara-C and ara-U. The plasma disappearance curve of ara-C curvilinear; the half-life of ara-C estimated from the terminal phase is 8 hr. By 6 hr, the ara-C level is 0.35 mug/ml and falls exponentially to 0.006 mug/ml by 24 hr. Plasma concentration ratios of ara-U to ara-C are 0.1 to 0.3, 0.3 to 0.4, and 1.1 to 1.3 at 10 min, 1 hr, and 4 hr following intravenous injection of cyclo-C at 200 mg/m2. Five min after an equal dose of ara-C, this ratio is approximately 2, and by 4 hr, plasma ara-C levels are immeasurable. After intramuscular and subcutaneous administration, cyclo-C is rapidly absorbed. The plasma disappearance curves of the cyclo-C hydrolytic product, ara-C, are similar to those of the intravenous route. Intramuscularly, subcutaneously, and intravenously cyclo-C should be equally effective. Intrathecal injections of cyclo-C (50 mg/m2) result in an effective ara-C level (0.1 mug/ml) in cerebrospinal fluid (CSF) at 24 hr. When cyclo-C is given orally to fasting patients, less than 15% of the dose is excreted in urine in 24 hr and none can be detected in the plasma.


Effect of tolamolol and propranolol on exercise heart rate and angina.

Fifteen patients with angina pectoris participated in a double-blind study evaluating the effect of intravenous saline, 10 mg of intravenous tolamolol, 20 mg of intravenous tolamolol, and 10 mg of intravenous propranolol on resting and exercise heart rate and on exercise time until angina. Twenty mg of tolamolol and 10 mg of propranolol caused a similar decrease in mean resting heart rate, heart rate after a similar amount of exercise, heart rate at angina, resting product of systolic blood pressure times heart rate, and product of systolic blood pressure times heart rate at angina and were, therefore, judged equipotent. Tolamolol, 10 and 20 mg, and propranolol, 10 mg. were not followed by a significant change in mean exercise duration until angina, but there was a 25 percent increase in exercise time until angina in 4 of 15 patients (27 percent) after 10 mg of propranolol and in 3 of 15 patients (20 percent) after 20 mg of tolamolol.


Propranolol-induced urticaria: successful therapy with tolamolol.

Urticaria with systemic effects occurred in a patient being treated with propranolol and was reproducible upon rechallenge with the drug; Successful beta-adrenergic blocking therapy was achieved using a new agent, tolamolol, with no evidence of any adverse effects.


An attempt to eliminate platelet antibodies from antilymphocyte serum (ALS) by absorption with unwashed human erythrocytes.

After repeated, 10-20 absorptions of ALS with one-half of its volume of unwashed human erythrocytes, performed each time for 30 min. at room temperature, the titres of the undesired thrombo-agglutinins and thrombolysins can be reduced or these antibodies can be eliminated from ALS. After absorption anticomplementarity of ALS increases and the lymphocytotoxin titre declines. The optimal number of absorptions which would not reduce markedly the immunosuppressive activity of ALS remains to be determined.


Mycotic aneurysm of the internal carotid artery in an unusual intra-cranial location.

A child is reported who developed a mycotic aneurysm of the cavernous portion of the internal carotid artery following staphylococcal cellulitis and septicemia. The unique feature of this case was the conspicuous absence of clinical or arteriographic evidence of carvernous sinus thrombosis. The pathogenesis of mycotic aneurysms is discussed.


Cross-protection among feline caliciviruses.

Each of five groups of specific-pathogen-free and conventionally reared cats was infected with a different strain of feline calicivirus. Two of the strains were pathogenic, producing characteristically fever, depression, loss of appetite, buccal ulceration, and occasionally increased ocular and nasal secretion. Two of the other strains were midly pathogenic and associated with fever or buccal ulceration or both; the fifth strain was nonpathogenic. The two pathogenic strains plus three others shown also to be pathogenic were used 3 months after the initial infection to challenge the cats in rearranged groupings. Of the 28 conventional cats challenged six (21.4%) showed at least a febrile response, although none of the 30 specific-pathogen-free cats showed any clinical signs. After challenge, virus was recovered from throat swabs of 37 or the 58 cats (63.8%) including the six which showed symptoms, but the duration of the excretion of virus was significantly less than that seen with the initial infection. The homologous and heterotypic antibody responses correlated well with the clinical protection, or lack of it, seen on challenge. The results provide further evidence for significant cross-relationships between feline caliciviruses.


Citrate utilization in milk by Leuconostoc cremoris and Streptococcus diacetilactis.

Citrate utilization and diacetyl, acetoin and acetaldehyde production by 2 strains each of Leuconostoc cremoris and Streptococcus diacetilactis in milk were studied. With the leuconostoc bacteria no growth and little citrate utilization occurred unless a stimulant (yeast extract) was present, when complete utilization of citrate without concomitant production of diacetyl or acetoin was obtained. The additon of Mn2+ stimulated growth resulted in diacetyl and acetoin production. Destruction of diacetyl and acetoin occurred when the citric acid level fell to c.1000 and 600 mug/g in the case of Leuc. cremoris FR8-1 and CAF1, respectively. Only strain FR8-1 produced acetaldehyde. In contrast, Str. diacetilactis produced diacetyl, acetoin and acetaldehyde concomitant with citrate utilization.


Pneumatosis cystoides intestinalis. Treatment with oxygen via close-fitting mask.

Four patients with pneumatosis cystoides intestinalis were recently treated with oxygen via a close-fitting mask. They responded initially to this therapy, with cessation of all symptoms and, after seven days of treatment, with return of proctoscopic and barium-contrast roentgenographic findings in the colon to normal. However, the disease recurred in one of the four patients after six months. There is a potential hazard of toxic effects from oxygen, and this may be detected by frequent measurement of pulmonary vital capacity. Our experience corroborates the efficacy of oxygen therapy in the treatment of this disorder but we question its long-term effectiveness in all cases.


Therapeutic regimens in advanced breast cancer.

A retrospective study of the methods of treatment in 98 patients with advanced breast cancer over the past five years showed striking differences in remission rates, duration of remissions, and overall survival according to the method of treatment. Adrenalectomy and oophorectomy produced remissions in 58% of patients, with a median duration of 22 months. Survival curves were impressive and favored the surgically ablated group, who had a median survival of 32 months. Sixty-seven percent of responders continue to survive at four years. Chemotherapy with single agents produced remissions in 30% of patients, having a median duration of nine months. Additive endocrine therapy produced 33% to 36% remission rates, with median durations of 12 to 16 months. Responses were more frequent and longer lasting in older patients. Radiotherapy, when used without supplemental therapy, resulted in good local control, but a short median survival of 7.5 months.


Imipramine-induced heart block. A longitudinal case study.

A 2:1 atrioventricular block developed during treatment with the tricyclic antidepressant imipramine in a 74-year-old man with a three-year history of right bundle-branch block. Serial cardiographic studies and determinations of blood imipramine concentrations showed that the heart block was directly related to the plasma concentration of the drug and occurred below the atrioventricular node in the His-Purkinje system.


Guillan-Barré syndrome in heroin addiction.

In two cases of Guillain-Barré syndrome (acute polyneuritis) as a complication of narcotic abuse, the onset of paralysis began approximately 4 and 12 hours after self-administration of opiates intravenously. Bulbar and respiratory paralysis developed in one patient and required prolonged ventilation therapy; the other patient had peripheral muscular and unilateral facial weakness, with notable pleocytosis was present in both.


Recurrent urinary tract infections. Prevention by prophylactic antibiotics after sexual intercourse.

Fourteen patients with chronic or multiple recurrences of infection of the urinary tract have self-administered a single oral dose of one of five antibiotics after sexual intercourse for periods of 19 to 111 months for a total of 761 months. Infections did not occur among 15 of 22 treatment periods. A total of 19 infections occurred while the patients were taking prophylactic medication, significantly less than the total of 90 infections recorded during the 705 months when these patients did not take prophylactic doses of antibiotics. Patients taking nitrofurantoin, a cephalosporin, or nalidixic acid had a significant reduction in the proportion of specimens of urine containing any Gram-negative bacteria. Serious toxic effects were not encountered.


Physostigmine salicylate in the treatment of tricyclic antidepressant overdosage.

Following intravenous administration of physostigmine salicylate for tricyclic antidepressant poisoning in 21 patients, convulsions occurred in two patients, and severe cholinergic manifestations occurred in two others. Because of these untoward effects and the very short duration of its beneficial action, it is very doubtful that physostigmine has any place in the routine management of tricyclic antidepressant poisoning.


Hypersensitivity alveolitis.

Hypersensitivity alveolitis developed in an 11-year-old girl during heavy exposure to mold spores contaminating the straw filters of an evaporation-type home air cooler. It is likely that the causative organism was Micropolyspora faeni, the mold responsible for farmer's lung.


Sickle cell crisis treated by exchange transfusion. Treatment of two patients with heterozygous sickle cell syndrome.

In two patients with severe painful sickle cell crisis and a deteriorating clinical course, recovery coincided with large-scale exchange transfusions (6 liters). The one patient, with sickle cell beta thalassemia, achieved a 90% exchange, calculated on the sickle cell hemoglobin present before and after transfusion. The other patient, with sickle cell hemoglobin Hb A, S, and (Hb) C disease, also achieved an 80% exchange calculated on the level of HbA.S. AND C in samples before and after transfusion.


Secondary hyperparathyroidism. Conservative management in patients with renal insufficiency.

In three patients with advanced renal disease (inulin clearance, 4.6 to 9.1 ml/min) and systemic manifestations of secondary hyperparathyroidism, concentrations of serum calcium and phosphorus were maintained within our normal limits (9 and 3.5 mg/100 ml, respectively) with phosphate-binding antacids and orally given calcium carbonate. The result was progressive disappearance of symptoms related to secondary hyperparathyroidism, healing of osteitis fibrosa, and normalization of serum concentrations of immunoreactive parathyroid hormone.


Infarction of breast fibroadenomas during pregnancy.

Two cases of infarcted fibroadenomas of the breast during pregnancy represent the total incidence of this entity from a total of 404 fibroadenomas diagnosed during the last five years in our department. Gross and microscopic pathologic findings of these breast tumors must be carefully evaluated, since the relative rarity of this lesion may lead to suspicion of carcinoma.


Hyperlipoproteinemia in occlusive cerebrovascular disease.

The distribution of occlusive atherosclerotic lesions in the aortocranial circulation as determined by arteriography was correlated with results of plasma lipid and lipoprotein determinations of patients with symptoms and signs of cerebrovascular disease. The incidence of hyperlipoproteinemia in the total study population was 31.8%. The frequency of hyperlipoproteinemia was signigicantly higher in patients with atherosclerotic lesions limited to extracranial (51%) and intracranial major vessels (44.2%) when compared to the total number of patients and patients with only intracranial small-vessel disease (P less than .05). Type IV hyperlipoproteinemia was the most common abnormality (extracranial group, 42% type IV, 9% type II; intracranial major-vessel group, 35.8% type IV, 8.4% type II). Patients with intracranial small-vessel disease had the lowest frequency of hyperlipoproteinemia (14.2%). The frequency of hypertension with or without hyperlipoproteinemia was higher in patients with intracranial small-vessel disease (P less than .01).


Penicillin treatment of neurosyphilis. Are recommended dosages sufficient?

A 60-year-old man with symptomatic neurosyphilis was treated with penicillin G procaine in the dosages recommended by the Public Health Service, and a less than spirocheticidal level of penicillin G was found in the cerebrospinal fluid.


Lymphocytic choriomeningitis outbreak associated with pet hamsters. Fifty-seven cases from New York State;.

An outbreak of lymphocytic choriomeningitis (LCM) associated with pet hamsters adquired through nationwide distributor was recognized in New York in February 1974. In upstate a New York, 57 cases occurred in a four-month period. Complete information was obtained on 49 patients ranging in age from 3 to 70 years. Characteristic findings included fever (90%), headache (85%), and severe myalgia (80%). Typically, laboratory findings consisted of a normal blood cell count and cerebrospinal fluid with mononuclear leukocyte pleocytosis and moderate hypoglycorrhacia. Al patients had contact with hamsters from one distributor. Most of the hamsters were acquired in mid to late December 1973, but some as late as March 1974. From each of eight families in which hamsters were available, at least one hamster had detectable complement-fixing antibodies for LCM. Infection rates within families varied with location and type of hamster cage; open cages and cages situated in common living areas were associated with highest infection rates (45% and 52%, respectively). Severity of illness was not associated with direct contact with hamsters. Onset of illness occurred between 8 and 90 days after initial exposure to hamsters.


Library and information services for small hospitals.

The quality of medical care is dependent on effective and expeditious information services for physicians and other health workers. Small hospitals have been at a particular disadvantage in this respect, mainly because unit costs of library services have been quite high when delivered on a small scale with traditional resources and methods. The importance of this problem is suggested by the fact that more than half of the US hospitals have less than 100 beds, and that library services have been primitive or nonexistent in most of these institutions. Certain recent developments will permit most of these smaller hospitals to provide creditable information services at modest cost.


Venereal disease control among homosexuals; An outreach program.

With the support and participation of area homosexual organizations and a local bar, the City Health Department developed an outreach/education/screening program for venereal disease (VD) control. Venereal disease education and blood testing were conducted during four sequential Wednesday evenings in the bar on a volunteer basis, anonymously if requested. Of the 118 sera drawn, ten were reactive on serologic testing. Two of these reactive blood tests led to the discovery of two new cases of primary syphiles. No cultures were positive for Neisseria gonorrhoeae. The subject response rate confirms the value of an anonymous reporting method; the discovery of two cases of primary syphilis lends credence to case finding by field-screening a high-risk population.


Medullary cystic disease vs nephronophthisis. A valid distinction?

It has been proposed that medullary cystic disease and nephronophthisis are distinguishable by the mode of inheritance and the age of onset. The former is inherited as an autosomal dominant, the latter as an autosomal recessive, with the onset at the average age of 26.7 years and 10.5 years, respectively. The present kindred would appear to have a dominant inheritance and onset at 10.1 years of age. This emphasizes the importance of examining those families in whom medullary cystic disease is suspected, prior to genetic consultation.


Brucellosis linked to Mexican cheese.

Three cases of brucellosis occurred, two acute cases and one chronic, all of which likely resulted from the ingestion of fresh cheese containing Brucella melitensis. A history of patients with illness suggestive of brucellosis should include details about food ingested recently in addition to the usual questions about travel and occupation. As the US domestic-animal disease comes under better control, and travel to Mexico, Spain, and Italy increases, it seems likely that human disease caused by B melitensis will become relatively more common.


Hepatitis B and the HB-SAg carrier. An outbreak related to sexual contact.

Within six months, acute viral hepatitis, type B, developed in three individuals associated with a nursing home in Denver. This attack rate, 1.4 cases per 100 patients and employees, was apparently higher than the reported incidence of hepatitis B in Denver during the same period. Parenteral inoculations could not be implicated as the means of acquiring hepatitis B. However, two of the hepatitis patients had had sexual contact within six months before their illness with an employee who was an insulin-dependent diabetic and a symptomatic carrier of HB-Sg. In addition, anti-HB-S antibodies were detected in his homosexual roommate. Although the chronic carrier was a food-handler, a seroepidemiologic survey of the employee population showed no spread of HB-Sag by means of food or casual contact. Only 1 (4.6%) of 22 employees tested had anti-HB-S antibodies. These results suggest that household and, in particular, sexual contact with a symptomatic HB-SAg carrier may be an effective nonparenteral or inapparent parenteral mode of transmitting HB-SAg.


A computerized national Blood Donor Deferral Register.

With blood given exclusively by volunteer donors, the American National Red Cross (ANRC) Blood Program aims to supply patients needing transfusion with blood products of the highest quality. The use of blood from volunteers, with its established greater safety, combined with laboratory testing to detect carriers of hepatitis B surface antigen (HB-SAg) and modern computer technology, creates an effective system to reduce the risk of post-transfusion hepatitis. The ANRC has devised a national Donor Deferral System, which is designed to minimize the transmission of hepatitis by blood and blood products.


The mentally ill physician as practitioner.

Mentally ill physicians may hurt patients through direct involvement of physicians' symptoms. Not all mentally ill physicians are disqualified by their illness from practicing medicine. Some may be disqualified for some time or permanently; some may be able to continue to function effectively. Certain characteristics of the physician-patient relationship and physicians' beliefs about their own and their colleagues' work make it difficult to discern harm done to patients.


Childhood idiopathic thrombocytopenic purpura. Aggressive management of life-threatening complications.

Idiopathic thrombocytopenic purpura (ITP) in childhood is usually a benign, self-limited illness. Life-threatening complications, such as central nervous system (CNS) hemorrhage, occur in less than 1% of cases. We report a case in which the patient failed to respond to splenectomy and high-dose corticosteroid therapy. Immunosuppressive therapy with cyclophosphamide, vincristine sulfate, and corticosteroids in conjunction with frequent transfusions of platelets was associated with a complete remission that persisted after therapy was discontinued.


Serum alkaline phosphatase isoenzymes in sickle cell anemia.

Alkaline phosphatase isoenzymes in sera from patients with sickle cell anemia were separated by electrophoresis on starch gel. Physical and biochemical criteria identified bone alkaline phosphatase as the principal, although not necessarily the sole, enzyme fraction that increases during symptomatic sickle cell crises. Moreover, there appeared to be concordance between crisis severity, serum levels of alkaline phosphatase, and isoenzyme patterns; electrophoretic and biochemical abnormalities could be detected even when the patients were asymptomatic. The present data suggest that the serum alkaline phosphatase level may be an additional indicator of the degree, frequency, and persistence of tissue injuries that occur in sickle cell anemia.


Anicteric carbenicillin hepatitis. Eight episodes in four patients.

Carbenicillin disodium was temporally associated with eight episodes of a mild reversible anicteric hepatitis characterized by nausea, vomiting, and a tender, somewhat enlarged liver. Serum glutamic and oxaloacetic transaminase as well as alkaline phosphatase levels rose, but serum bilirubin values remained normal. There usually were no signs of concomitant allergy to penicillin, and other penicillins could be given subsequently without ill effects. Biopsy specimens of the liver showed spotty liver cell necrosis with no cholestasis.


Surgical treatment of diverticulitis. Experience at a large Municipal Hospital.

In the past 5 1/2 years, 71 patients with diverticulitis were operated on--20.8% of all cases of diverticulitis admitted to the Bronx Municipal Hospital Center. Operative mortality was 22%, primarily because of delayed diagnosis, inadequate surgery, and a high incidence of associated disease. Only 20% of patients operated on had a previous history of diverticular disease. Hemorrhage was the indication for surgery in 16 cases; in this situation, a subtotal colectomy in one stage is the operation of choice. Perforation was the indication in 47 cases, eight of these being acute and with free air under the diaphragm. In cases with peritoneal contamination, a two-stage procedure (removing the diseased portion of colon at stage one) is advocated. Colostomy without drainage, or closure of a free perforation, is condemned.


The type II epithelial cells of the lung. II. Chemical composition and phospholipid synthesis.

A method to isolate 93 per cent viable (trypan blue), 95 plus or minus 2 per cent pure type II alveolar epithelial cells (Kikkawa, Y., and Yoneda, K. Lab. Invest. 30: 76, 1974) was slightly modified and was used to isolate type II cells of similar purity and viability from New Zealand White male rabbits. The modification as described in this report now permits the regular harvest of 20 to 30 times 10-6 cells from a rabbit weighing 2 to 4 kg. Lipid composition of type II cell pools thus collected was compared with that of macrophages collected by alveolar washing. Per milligram of protein, type II cells contained 19 mug. of lipid phosphorus, compared with 11 mug. for macrophages. Per 1 times 10-8 cells, type II cells contained 110 mug. of lipid phosphorus compared with 155 mug. for macrophages; Phosphatidylcholine comprised 48 per cent of total phospholipid in type II cells and 34 per cent in macrophages. Forty-nine per cent of the phosphatidylcholine in type II cells was disaturated, compared with 29 per cent in macrophages. These data indicate that, per cell, type II cells contain almost twice as much disaturated phosphatidycholine as do alveolar macrophages. Radiolabeled precursor studies suggest that isolated type II cells synthesize disaturated lecithin predominantly through the cytidine diphosphocholine pathway. -14C-choline incorporation into disaturated lecithin was 3 times as active in type II cells as in macrophages. No evidence was found for a significant contribution to synthesis of disaturated lecithin by the transmethylation pathway in isolated type II cell preparations. These results offer the most direct evidence to date of the significant role of the type II alveolar epithelial cell in the synthesis of disaturated lecithin, a major constituent of pulmonary surfactant.


Lactose and milk intolerance: clinical implications.

We studied 166 hospitalized male patients to determine the clinical importance of tolerance-test-determined "lactose intolerance," assumed to affect most of the world's adults. Abnormal lactose tolerance tests were found in 81% of 98 blacks, 12% of 59 whites of Scandinavian or Northwestern European extraction, and three of nine non-European whites. Seventy-two per cent of the "lactose-intolerant" subjects had previously realized that milk drinking could induce abdominal and bowel symptoms. Two hundred and forty milliliters of low-fat milk produced gaseousness or cramps in 59% of 44 "lactose-intolerant" men, and 68% were symptomatic with the equivalent amount of lactose. None of 18 "lactose-tolerant" men noted symptoms with milk or lactose. Refusal to drink 240 ml of low-fat milk served with meals correlated significantly with "lactose-intolerance": 31.4% versus 12.9% among "lactose-tolerant" patients. "Lactose intolerance" is common in adults and is a clinically relevant problem.


Eye signs of Graves' disease.

Graves' disease can affect the eyes and orbits in many ways, some seemingly trivial, others obviously devastating to vision. Because of the relative simplicity of diagnosing Graves' disease in the majority of cases, and now with the addition of B-scan ultrasonography, much expense and needless risk is avoidable in most patients with ophthalmopathic Graves' disease. Those patients whose diagnosis cannot be confirmed by noninvasive techniques may not have Graves' disease and deserve more in-depth study.


[Angiography and pharmacoangiography of tumors and inflammatory lesions of the lower extremities].

Pharmacoangiography has not yet become a routine method to differentiate inflammatory and tumorous processes of the lower extremities. Noradrenalin and Vasoxin was compared in its effect on the peripheral blood vessels in inflammatory and tumourous disease.


[Clinical and experimental contribution concerning the pathogenesis of acute life-threatening complications during neck anaesthesia].

Apart from the usual hazards of local anesthesia (toxic reaction due to overdose or intravasal administration, allergic reaction, reaction to the vasoconstrictor), a further risk which should be borne in mind in local anesthesia of the neck region is inadvertent epidural or intrathecal administration of the local anesthetic agent. Depression of respiration or total respiratory failure may occur due to blockade of the superficially located medullary chemoreceptors in the form of a high or total spinal block. The pathogenesis of these incidents is investigated. Respiratory failure is usually reversible and requires immediate and effective therapy (artificial respiration, oxygen administration). The indications for neck anesthesia and their relativity within the entire therapeutic program should be given careful consideration. If (radicular) pain occurs during the injection, or if cerebrospinal fluid is aspirated, the procedure should be interrupted immediately and some time allowed to elapse. In fatal cases the injection channel must be dissected layer-wise in local anemia down to the dural sac. The possible pathway of toxic administration (epidural, subdural, intravasal) must be demonstrated chemically.


Availability of phendimetrazine from sustained and non-sustained action formulations.

Two tablet formulations of d-phendimetrazine bitartrate, Obex (35 mg non-sustained action) and Obex-LA (105 my sustained action), were compared in terms of biological availability in 9 volunteers on the basis of serum level findings. The ratio of the areas under the absorption and elimination curves was 1:2,2 (Obex:Oves-LA), indicating that the biological availability of phendimetrazine from Obex-LA was plus or minus 70% of that from Obex. The elimination half-life of phendimetrazine was found to be 9,1 hours. An evaluation of appetite suppression revealed that the two formulations were equally effective at breakfast and at dinner, with Obex-LA significantly superior to Obex at lunch.


Importance of multiple episodes of hypoxia or cold stress on the development of enterocolitis in an animal model.

Necrotizing enterocolitis, a highly lethal disease in the newborn infant characterized by ischemic necrosis of the gastrointestinal tract frequently leading to perforation, is seen primarily in low birth weight infants who have undergone stress, such as hypoxia. In an animal model it was demonstrated that cold stress was as effective as hypoxia in producing the disease in formula-fed newborn rats. Breast milk was completely protective in both cold- and hypoxic-stressed animals. Presumably cold stress produces the same selective circulatory ischemia as does hypoxia. The experiment further supports the concept that any insult or stress which decreases mesenteric blood flow may initiate the changes leading to necrotizing enterocolitis. It was shown also that the incidence of the disease in formula-fed rats was related directly to the number of episodes of either cold or hypoxic stress. These results suggest that a critical amount of ischemia is necessary to initiate these changes and may help to explain the fact that not all infants exposed to hypoxia or cold stress developthe disease.


Fatal combined anileridine-pethidine poisoning. A gas chromatography, thin layer chromatography and mass spectrometry investigation.

Anileridine and pethidine were established by gas and thin layer chromatography and mass spectroscopy. In the mass spectrum the main peak of anileridine is found at m/e 246 and that of pethidine at m/e 71. The determination was made by gas chromatography from the blood, urine, liver, muscle and stomach contents.


Fine needle and open biopsy in thyroid disorders.

The diagnostic value of cytological, serological and scintigraphical examination was evaluated in 20 histologically verified cases of thyroid disorder. The predictive values of specificity as to malignancy, thyroiditis and thyroid autoantibodies were respectively 0 percent (0-71), 80 percent (28-99) and 75 percent (19-99), and the predictive values of sensitivity were 88 percent (64-99), 100 percent (78-100) and 94 percent (70-100). Cold nodules were malignant in 40 percent. Fine needle biopsy can be used as a supplementary test without any risks and is a valuable aid in the diagnosis of Hashimoto's thyroiditis, but not in the diagnosis of malignant lesions. If any clinical or scintigraphical (cold nodule) suspicion of malignancy exists, a surgical biopsy must be done.


Scanning electron microscopic observations of the human respiratory tract.

As viewed by scanning electron microscopy, the luminal surface of the human trachea at 12 weeks' gestation shows a predominance of microvillous-covered, nonciliated cells, in contrast to the heavily ciliated tracheobronchial surface seen at 34 weeks' gestation. Hyaline membrane disease produces a confluent lining material in the lung periphery that obscures the bronchiolar and alveolar surface architecture. Large saucer-shaped alveoli, numerous alveolar pores, and an abundance of in situ alveolar macrophages are observed in chronic bronchitis and in emphysematous lungs; The scanning electron microscope offers an additional tool for the study of developmental and pathological processes in the human respiratory tract.


Multiple food allergy.

This paper is devoted to a study of multiple food allergy, here defined as sensitivity to three or more foods. The purpose of the study is to report findings obtained from a study of 250 private patients and to show what type of persons develop this condition, how it affects them, and what their common allergens are. It was found that multiple food allergy occurs in both sexes and at all ages but is more common in boys than in girls and more common in women then in men. The clinical manifestations were much like those caused by the more familiar inhalant allergy but with a much more widespread constitutional disturbance. The great majority of patients (86%) also reacted to such air-borne allergens as molds, pollens, house dust, and animal epithelials. This indicates that food allergy and inhalant allergy are fundamentally the same phenomenon. The common food allergens were such everyday foods as milk, chocolate, corn, egg, tomato, peanut, and citrus fruits.


Dudenal ulceration in allergic children.

Forty-three children were studied. All had allergies and peptic ulceration. Twenty-five of them had a demonstrated niche on roentgenological examination. The "functional" stomach ache, often observed in allergic children, might be explained by the organic changes. It is postulated that these changes are influenced by the action of the chemical mediators, liberated during allergic reactions and by multiple accompanying allergies of childhood.


Bovine venereal vibriosis: activity of inflammatory cells in protective immunity.

The capability of bovine polymorphonuclear (PMN) and mononuclear phagocytes to kill Campylobacter (Vibrio) fetus venerealis was tested under various conditions in order to judge their roles in protective immunity. Bovine PMN killed C fetus in the presence of immunoglobulin G (IgG) but not immunoglobulin A (IgA) antibodies. Some phagocytosis occurred in the absence of antibody in glass-adherent cultures, but not in suspension cultures--indicating that surface phagocytosis by the neutrophils normally present during estrus could account for natural protection at this time. Mononuclear phagocytes also killed C fetus in the presence of opsonins, making this a likely factor in protection during the later stages of inflammation when mononuclear cells predominate. The presence of numerous lymphocytes in this mononuclear infiltration and the capability of C fetus antigens to induce delayed hypersensitivity (DH) are consistent with the possibility that cell-mediated immunity (CMI) also may be involved in protective immunity.


Detection of activity for various anthelmintics against in vitro-produced Cooperia punctata.

The in vitro-grown parasitic stages of Cooperia punctata were used to evaluate 28 compounds with different kinds and degrees of in vivo activity. Using presumptive and confirmatory tests, it was possible to establish a group order of in vitro potency that compared favorably with an order based on established in vivo use of these compounds. The procedure lends itself to evaluating activity against a given parasitic growth stage and gives a quantitative estimate (range) of the concentration that produces 50% nematode kill. The system was most successful in detecting compounds with in vivo activity for C punctata, followed in order by compounds active against Cooperia spp, other gastrointestinal nematodes of ruminants, and other nematodes of non-bovine hosts. The procedure showed some differentiation between activity against nematodes versus that against cestodes, trematodes, and arthropods. The system permits considerable flexibility in experimental design, thus making possible the acquisition of the particular information desired. In addition to establishing lethal effects on the nematode, the procedure detected compounds with nematode-anesthetizing effects. The results indicate this in vitro system can be used with some expediency as a preliminary screening method in the search for new anthelmintic compounds.


[Pharmacokinetics of C14-olivomycin in the body of mice with lymphosarcoma (L10-1 strain)].

The pharmacokinetics of C14-olivomycin after its single intravenous administration to mice with lymphosarcome (LIO-I) was studied. It was shown that according to the specific radioactivity the organs may be placed in the following order: I hour after the antibiotic administration-the blood, liver, spleen, thymus, tumor, muscle; 3 hour after the administration-the liver, spleen, thymus, blood, tumor, muscle. Accumulation of olivomycin in the mouse organs was mainly in direct dependence on the dose of the antibiotic administered. Chromatography of the substances extraceted with ethylacetate from the urine collected at various periods after C14-olivomycin administration showed the presence of a new radioactive product (Rf 0.35-0.37) in addition to the unchanged antibiotic (Rf 0.53). Bioautographic analysis of the chromatograms showed that the product of C14-olivomycin conversion preserved its biological activity. The analysis of the substances extracted with ethylacetate from the liver, spleen and tumors 3 hours after the antibiotic administration reveiled (except of the liver) the presence of a spot with Rf corresponding to that of the initial drug.


[Use of prodigioza in the overall treatment of chronic osteomyelitis].

Treatment of 188 patients suffering from chronic osteomyelitis of various etiology and localization with prodigiosan, a bacterial lipopolysaccharide favoured an increase in the nonspecific immunobiological reactivity: the phagocytic activity and leucocytic intensity increased, the average titers of iso- and heteroagglutinins, as well as the complementary activity of the serum became higher. The results of the clinico-laboratory studies are indicative of advisable use of prodigiosan in complex therapy of cases with chronic osteomyelitis.


Psychotherapy in hospitalized research patients.

Operations at the clinical-research interface exert a signal influence on the therapy of patients being treated on investigative units. The effect on the treatment milieu has been described but the impact of a research climate on individual psychotheraphy of hospitalized patients has not. We observed research-therapy interaction in 25 acutely schizophrenic patients. Analytically oriented psychotherapy was carried out on a National Institutes of Health clinical research unit where drugs are only occasionally used, and patients are subjects in psychobiological investigation. The subtle, and often neglected, interplay between therapy and research is examined, with emphasis on the shifting meanings of the patient's participation or refusal to participate in therapy, research, or both. A research transference and countertransference are defined, and some special behavioral patterns of research patients receiving dynamic therapy are considered in this framework.


Oscillation phenomena in black lipid membranes induced by a single alamethicin pore.

In this paper we  show how alamethicin (a small cyclic peptide of molecular weight 1691) can produce voltage oscillations in black lipid membranes and how a nonactin-alamethicin oscillator can be constructed. Alamethicin alone induces oscillations only with an applied bias current, but with nonactin and appropriate salt solutions oscillations occur with no bias current. Both kinds of oscillations can be quantitatively understood in terms of the known properties of alamethicin and nonactin and both depend on the statistical nature of the formation opores in the membrane by alamethicin.


Psychological morbidity in a clinic for sexually transmitted disease.

100 first attenders at a clinic for sexually-transmitted diseases were interviewed using a semistructured schedule. 20 per cent. were regarded as probable psychiatric cases and a considerable amount of psychosocial morbidity was observed. Whilst the majority reported anxiety about their possible illness, in a quarter the anxiety and distress appeared to be of long standing, having arisen before the genital symptoms or risk of infection and being related to chronic social and psychological difficulties. There were no significant differences between those diagnosed as having or not having STD in such characteristics as psychological symptoms, mean psychiatric score, and delya in consulting. Whilst those without a sexually-transmitted infection were less likely to be female, and more likely to feel guilty, to have had a casual sexual partner, and not to complain of specific genital symptoms, there was no evidence to support the concept of a syndrome of 'venereophobia'.


Streptococcal pyoderma of the penis following fellatio.

Gonococcal pharyngitis has been correlated with fellatio in both heterosexual females and homosexual males. This report describes another complication of fellatio, group A beta-eaemolytic streptococcal pyroderma on the penis after exposure to a male who probably had pharyngitis. the erythematous, purulent lesions should be cultured. After the organism has been identified, adequate treatment with either a long-acting parenteral penicillin or a 10-day course of oral penicillin is important in order to prevent the possible life-threatening complication of post-streptococcal glomerulonephritis.