The effects of fluorescent and incandescent illumination upon repetitive behaviors in autistic children. Repetitive behaviors of six autistic children were observed under two conditions of background illumination. During two sessions, the room was illuminated by fluorescent light and during two other sessions, by equal intensity incandescent light. Subjects spent significantly more time engaged in repetitive behavior under fluorescent light. Previous research suggested that these findings were related to the flickering nature of fluorescent ilumination. Practical and theoretical implications were discussed. Further experimentation was suggested to assess relationships between flickering illumination and arousal.


The use of BRIAC for evaluating therapeutic effectiveness. Forty-six children in eight different psychotherapeutic settings were evaluated at the beginning and at the end of a 12-month period by means of the Behavior Rating Instrument for Autistic Children (BRIAC). The younger children (3 to 6 years of age) were initially more severely disturbed and improved significantly more than the older children (7 to 9 years of age). The large, bleak, custodial residential center produced significantly less improvement in the children than did the other settings. However, among good programs--i.e., those which were sensitive to the behaviors and needs of the children and which were skillfully implemented by a dedicated and attentive staff--there was little evidence of differences in therapeutic effectiveness regardless of whether the therapy was behavior modification, education, psychoanalytically oriented relationship therapy, or activity therapy.


HL-A8 and the immune response to various antigens. The possession of the histocompatibility antigen HL-A8 has been correlated with serum levels of antibodies to gluten and a variety of other dietary, viral, and bacterial antigens and autoantigens. The only significant correlation with HL-A8 was of raised levels of gluten antibody. Thus it seems that HL-A8 may be associated with an enhanced immune response specifically to gluten, and not with a generally enhanced immunological responsiveness as has been suggested.


Infection control in small hospitals. Prevalence surveys in 18 institutions. In prevalance surveys of 18 small hospitals in the intermountain region, 20.4% of the patients had community-acquired infections and 7.2% had infections acquired in the hospital. The types of nosocomial infections and patterns of antibiotic usage were similar to those encountered in large hospitals. In the small hospitals, 49% of the suspected bacterial infection were cultured, whereas at a nearby large hospital 77% were cultured. Seventeen of these small hospitals had an infection-control committee but these committees were unable to assess adequately the extent of their nosocomial infection problems. Monitoring of the environment with bacterial cultures was a frequent practice; overall, a ratio of one environmental culture was performed to each three diagnostic cultures. These results indicate the need to develop and evaluate nosocomial infection control programs in small hospitals.


Angiosarcoma of the liver in a rural population. Four cases diagnosed in a 29-month period. Angiosarcoma of the liver has recently been publicized because of its association with polyvinyl chloride (PVC) polymerization workers. Four cases of this rare tumor have been observed at the Marshfield Clinic within a 29-month period. There are no factories that manufacture PVC products in the immediate area, nor were any of the victims ever involved in such manufacturing work. Thus, it is possible that other factors may be related to this cluster of the disease.


Intracranial surgery for cerebral artery aneurysms. Five years' experience. During the previous five years, there were 133 cases of intracranial surgery for cerebral artery aneurysms. For patients with aneurysms in the anterior circulation and in good preoperative condition, the surgical morbidity was 28% and the mortality was 19%. A depressed sensorium preoperatively, an age of 50 years or above, and an interval of less than 15 days from rupture to surgery were associated with markedly increased mortality. The results of this series, which do not compare favorably with those from foreign referral centers, are partially the result of disproportionate numbers of patients in those poor-risk groups. The possible advantages of regionalization are, nevertheless, apparent. Further comparative studies should be conducted on an interinstitutional basis.


Tricyclic antidepressants. Prolonged plasma levels after overdose. Twenty-four patients hospitalized for overdose of a tricyclic antidepressant were monitored clinically, and serial plasma-drug measurements were taken for up to 144 hours. Six of 24 patients had maximum antidepressant plasma levels greater than or equal to 1,000 ng/ml, and their plasma levels at 96 hours ranged from 170 to 1,280 ng/ml. Patients ingesting substantial tricyclic overdoses may remain medically unstable for days. When high tricyclic levels persist, accurate psychiatric assessment is often impossible.


Reaching out to the depressed physician. Many of the character traits that contribute to physician success can become risk factors to depression when amplified. Only reluctantly do some physicians attend to and express personal needs. The preemptory desire to satisfy the demands of his patients and colleagues may further subvert self-awareness and appropriate self-indulgence. Ultimately, frank depression emerges. Too often, depression remains unrecognized or untreated until the physician's self-destructive pattern compromises his capacity to care for his patients. The author discusses clues to the early recognition of depression as well as strategies in the prevention and treatment of the depressed physician.


Dissecting aortic aneurysm manifested as fever of unknown origin. A patient with a dissecting aneurysm of the ascending aorta had fever of unknown origin. Although his clinical picture included a number of classical features of his disorder, these were initially misinterpreted, largely because fever was the patient's chief complaint. Polymorphonuclear leukocytes sequestered within the aortic hemagen as they disintegrated. This case emphasizes the protean nature of the dissecting aortic aneurysm, adding yet another distinct clinical manifestation, fever of unknown origin, with which it may be associated.


Cholelithiasis in persons under 25 years old. Clinicopathologic review of 96 cases. Ninety-six of 683 patients undergoing cholecystectomy at the Naval Regional Medical Center, Long Beach, Calif, from 1967 to 1974 were between 7 and 25 years old. Although females predominated in ratio of 4:1, the sex incidence was equal when nulliparous females were compared with males. Signs and symptoms were nonspecific in 70%, leading to delay in proper diagnosis in 26%. Only two patients had an underlying blood dyscrasia. Oral cholecystography proved to be the most reliable diagnostic test. Moreover, the incidence of choledocholithiasis was 4.1%, approximately one third less than in older age groups.


Carbon tetrachloride toxicity potentiated by isopropyl alcohol. Investigation of an industrial outbreak. Fourteen workers in an isopropyl alcohol packaging plant became ill after accidental exposure to carbon tetrachloride. In four, renal failure or hepatitis developed. Isopropyl alcohol potentiation of carbon tetrachloride toxicity has been shown previously only in rats. Acetone, a product of isopropyl alcohol metabolism, is a major potentiator of carbon tetrachloride toxicity. Workers had elevated levels of acetone in samples of expired alveolar gas and thus were metabolically predisposed to carbon tetrachloride injury. Stricter limits for industrial carbon tetrachloride exposure should be established where concomitant isopropyl alcohol use occurs.


Resistance to nalidixic acid. A misconception due to underdosage. The clinical impression of inordinate selection of resistant mutants to nalidixic acid cannot be substantiated on close scrutiny when sensitive infections are treated at a full dosage of 4 gm/day. When 27 consecutive patients were treated with 4 gm of nalidixic acid per day, resistance developed in the bacteriuric population in only 7%. Moreover, resistance in the fecal reservoir was surprisingly minimal and much less than that reported for sulfonamides, tetracyclines, and ampicillin. The observation is important because multiply-resistant Enterobacteriaceae maintain their sensitivity to nalidixic acid since extrachromosomal R-factor resistance to nalidixic acid has never been demonstrated and cannot be transferred from one organism to another. In vitro data on 100 sensitive strains of Enterobacteriaceae show that the developmental of resistance to nalidixic acid is inversely proportional to the concentration of nalidixic acid regardless of whether the inoculum size is 10(5) or 10(8) bacteria per milliliter. Underdosage (less than 4 gm/day) with nalidixic acid is the probable cause of excessive resistance.


The clinical course of diabetic nephropathy. A retrospective record analysis of 112 juvenile-onset diabetics with nephropathy was conducted in order to determine their clinical course. The mean duration of diabetes at the onset of proteinuria was 17.3+/-6.0 years. Early renal failure appeared two years after the onset of protein-uria, and severe renal failure (mean serum creatinine level, 8.5+/-3.9 mg/100 ml) four years after the onset of proteinuria. The mean duration of life after the onset of severe renal failure was six months. The mortality was 53%, with 59% of the deaths attributable to renal failure and 36% to cardiovascular disease. All patients experienced progressive deterioration of renal function as well as the other complications of diabetes, the rate of progression being accelerated toward the end of the course. Juvenile onset diabetics should be considered for renal transplantation before the serum creatinine level reaches 8.5 mg/100 ml.


Surgeons in the United States. Activities, output and income. In a national surgical manpower questionnaire survey, 76% of those MD and DO surgeons who were contactable returned questionnaires that included a log diary reporting details of their daily activities. Comparisons were made of allocation of professional time, number of operations performed, and net income of respondents by physician classification (including certification), specialty, practice arrangement, age, and census division. The mean professional workweek was estimated at 46 hours for all respondents. More than two thirds of the total professional time was spent in direct patient care; about half the surgeon's time was spent in the hospital, with nearly 20% in the operating room. The median annual work load of respondents was 170 operations. Their median annual net income was $45,700.


Fatal massive hepatic necrosis following acetaminophen overdose. A young woman ingested approximately 13 gm of an over-the-counter acetaminophen preparation and died seven days later in profound coma. Postmortem findings included massive centrilobular hepatic necrosis and renal tubular necrosis. Although hepatotoxicity secondary to acetaminophen overdose is well recognized in Britain, this entity has received little emphasis in the United States. Recognition of the potentially severe consequences is important because early treatment with sulfhydryl compounds may prevent serious liver injury.


Serum levels of immunoglobulin and complement in giant-cell arteritis. The levels of IgG, total complement, and complement factors C3 and C4 were elevated in serum from patients with giant-cell arteritis as compared to a control group of patients in the same range of age. No increase of the IgM concentration was found. The concentration of IgA was higher in men with giant-cell arteritis as compared to men in a control group. This increase of IgA was not seen in women. There were no statistically significant differences in any of the studied variables between those with a histologically verified arteritis on temporal biopsy specimens and those without.


Disseminated Mycobacterium kansasii infection complicating hairy cell leukemia. Mycobacterium kansasii was isolated from the spleen of a patient with ""hairy cell leukemia'' (HCL) who had caseating necrosis in the spleen and in the liver. The disseminated infection in this patient suggests a cellular immunity deficit. Despite intensive investigations, the nature of the cell of origin in HCL remains unknown.


Baseline results of therapy for burned patients. Baseline results of therapy for burned patients have been determined. The data (21,000 cases) from the National Burn Information Exchange have been analyzed by probit analysis to determine survival as it is influenced by the size and death of the burn, age and sex of patients, topical agents, and the institution providing treatment. The results demonstrate that survival is influenced by the size and depth of the burn; that there is increased survival of males, compared to that of females; that five differnent age categories can be identified that influence survival; that the topical agent used has little effect on survival; and that there is a significant difference in survival when the institution providing the treatment is considered.


Independence of serum lipid levels and dietary habits. The Tecumseh study. Serum cholesterol and triglyceride levels were correlated with dietary habits of 4,057 adult participants in a prospective epidemiologic survey of cardiovascular disease in Tecumseh, Mich. Frequency of consumption of 110 different food items was determined for each participant and average weekly consumption rates of foods high in fat, sugar, starch, and alcohol content were calculated. Frequency of consumption of these nutrients was then correlated with serum cholesterol and triglyceride levels of individual subjects. Serum cholesterol and triglyceride values were not positively correlated with selection of dietary constituents. Positive correlations between serum lipid levels and adiposity were statistically significant. These findings suggest that serum cholesterol and triglyceride levels among Americans are more dependent on degree of adiposity than on frequency of consumption of fat, sugar, starch, or alcohol.


New, poorly recognized echocardiographic findings. Occurrence in patients with pericardial effusion. New, poorly recognized echocardiographic findings were recorded in six patients with pericardial effusion. These findings were apparent prolapse of mitral and tricuspid valves, apparent systolic anterior motion of mitral valve, and midsystolic notching of pulmonic valve. Beat-to-beat variation of the dimensions of right and left ventricle and in the diastolic opening amplitude of the anterior mitral valve were present in cardiac tamponade. Substantial decrease or resolution of effusion resulted in disappearance of the observed abnormalities. Serial echographic studies before and after fluid resolution may prevent misleading echographic and clinical diagnoses.


Productivity of women physicians.

Productivity of women physicians. Personal interview data obtained from 87 randomly selected women physicians in metropolitan Detroit indicates that productivity of women physicians has increased over that shown in previous studies. Eighty-four percent were engaged in medical work at the time of survey, 90% full-time. Only 7% were not working for reasons related to being a woman. Fifty-nine percent had worked continuously full-time since medical school graduation. Nearly half do not plan to retire from medical work. Fifty-eight percent are in private practice and 51% in primary care specialities; 54% are board certified. Direct patient care was listed as their main task by 86% of the women. Sixty-seven percent are married (43% to physicians). Although the 87 women physicians have responsibilities for households containing a total of nearly 300 people, almost one third of whom are children under 18 years old, their productivity is high.


Influenza vaccination in patients with multiple sclerosis. Vaccination was well tolerated by 93 patients with multiple sclerosis who received a total of 209 doses of influenza vaccine. In one patient, evidence of a new lesion developed after vaccination; the relapse rate was less than would be expected in the natural course of the illness. Toxic and allergic reactions appeared with 7% and 0.5% of the vaccinations, respectively--a rate no higher than that observed in the general population.


Mollaret meningitis. A report of three cases. Three cases of benign, recurrent meningitis of Mollaret demonstrated unusual aspects of this disease. Postpartum pituitary necrosis was an antecedent event in one case. A second case occurred in an otherwise healthy 82-year-old woman, and a third patient was thought to have Histoplasma meningitis. The pathophysiology of Mollaret meningitis remains an enigma, and the therapy consists of supportive care.


Beclomethasone dipropionate use in chronic asthmatic patients. Effect on adrenal function after substitution for oral glucocorticosteroids. The clinical effectiveness of beclomethasone dipropionate (BDP) aerosol and adrenal function after withdrawal of oral corticosteroid therapy were evaluated in 32 severely steroid-dependent asthmatic patients. Twenty-four of 28 patients were able to discontinue oral glucocorticosteroid therapy, while four failed to do so. Ventilatory studies showed no substantial changes at the end of six months' BDP treatment. In 24 patients, adrenal insufficiency was present before BDP therapy was started. In 20 of those patients, the response of cosyntropin returned to normal two months after discontinuation of systemic steroid treatment and administration of BDP.


Carcinoembryonic antigen assay in hepatic metastases detection. An adjunct to liver scanning. In a double-blind study involving 377 patients, we assessed the value of the serum carcinoembryonic antigen (CEA) assay as an adjunct to the radionuclide liver scan for detection of liver metastases. Fifty-seven patients studied by both methods were ultimately proved to have liver metastases. In 28 instances in which the results of both tests were in agreement, these results were diagnostic with regard to presence or absence of hepatic involvement. The CEA assay suggested the presence of metastatic tumor in eight of the 12 patients with false-negative liver scans, thus proving to be a very useful adjunct to liver scanning in the detection of hepatic metastasis.


Fallibility of urine drug screens in monitoring methadone programs. Urine specimens containing five different drugs, each at three levels of concentration with zero to five drugs in a specimen, were sent to two "approved" laboratories. In only 46.9% and 13.8%, respectively, were all drugs present correctly identified and no false-positive results reported. With some allowances, the results improved to 53.8% and 49.4%. If these tests are to be continued then (1) the fallibility of these tests should be known by all treatment personnel, (2) laboratories should be licensed rather than merely approved, and (3) maintenance of the license should be made contingent on passing "blind" proficiency tests.


Benign desoxycorticosterone-producing adrenal tumor. A woman with a benign tumor of the left adrenal cortex had a six-year history of hypertension. Serum potassium level and plasma renin activity were low. Plasma aldosterone and cortisol levels were low normal, and plasma desoxycorticosterone (DOC) level was extremely high. Iodine 131-labeled cholesterol accumulated in the tumor in the left upper quadrant of the abdomen. At laparotomy, a benign adrenal tumor was excised; thereafter, the blood pressure and plasma DOC levels returned to normal. We believe that this is the first case of a benign DOC-producing adrenal tumor.


[Radiologic approaches to gastric cancer (author's transl)]. Radiologic study of patients continues to be of major importance in the detection of gastric malignant neoplasms and often provides the stimulus for further diagnostic procedures. The conventional roentgenographic procedure for this disease comprises a careful fluoroscopic examination of gastric peristalsis and distensibility, and views obtained with graded compression, mucosal relief, double-contrast technique, and barium filling. No single method has the ability to disclose all pathognomonic signs of a gastric tumor. Pharmacologic motor inhibitors or stimulators may be used to aid study of peristalsis. The usefulness of peritoneography, parietography and arteriography in the diagnosis of gastric carcinoma is also examined. Diagnosis of early gastric carcinoma remains a radiologic challenge and the Japanese classification system is recommended. Perhaps the disease could be detected earlier, in countries with low or moderate incidence and without the benefit of regional screeing centers, if subtile roentgenographic techniques were applied to patients with conditions known to be associated with high risk of gastric carcinoma. The differential diagnosis of lesions which simulate gastric carcinoma is extensive and is briefly reviewed.


The effect of blood, meconium, and temperature on the rapid surfactant test. Amniotic fluid samples for physiologic maturity tests are frequently (15 to 20%) contaminated with blood and/or meconium. The effects of this contamination on the lecithin/sphingomyelin ratio is well known. However, less is known about the effect of blood and meconium on the rapid surfactant test. Additionally, because the RST may be performed in the office or at bedside, there is the possibility of temperature affecting the result. Therefore, the effects of blood, meconium, and temperature on the rapid surfactant test have been investigated. Contamination with blood or meconium may result in a false indication of fetal maturity. However, the test may still provide useful information concerning pulmonary status of the fetus, if the rapid surfactant test is intermediate or immature despite contamination. Temperature also affects the reliability of the rapid surfactant test. The test is found to be most reliable in the range of 20 to 30 C (with higher temperatures the bubbles dissipate more rapidly; with lower temperatures the foam is more stable).


Possible enzyme deficiency in bovine lymphosarcoma cells grown in vitro. A culture of bovine lymphosarcoma cells was unable to grow in HAT medium, suggesting that the cells were unable to use either exogenous hypoxanthine or exogenous thymidine. Further work showed that they were able to incorporate tritiated thymidine but not tritiated guanine. This indicated that failure to grow in HAT medium was due to the cells being deficient in the enzyme hypoxanthine guanine phosphoribosyl transferase which is responsible for incorporation of the bases hypoxanthine and guanine. This finding may have application in the therapy of bovine lymphosarcoma.


Effect of distension on release of surfactant in excised dogs' lungs. The freshly excised lower lobes of lungs of dogs were washed by filling and emptying the lobe with isotonic saline. The wash fluid was then discarded and the procedure was repeated 9 times. The 9th wash was collected and used for measurements of surface tension and lecithin content. The lobe was then constantly inflated for 3 hr; washed again with isotonic saline (10th wash) and surgace tension and lecithin content of wash fluid measured. When the lobe was inflated with air, at room temperature, the surface activity and the lecithin content of the 10th wash were increased in comparison to the 9th wash. This increase waoom temperature, or with air at 6 degrees C. Increase in the surface activity of the 10th wash was directly related to the inflating pressures used. This study suggests that distension of the lung enhances the release of surfactant and that this release is a metabolically active process. It appears also that 100% O2 has an inhibitory effect on this process.


Effect of ventilation on movement of surfactant in airways. The effect of ventilation on movement of surfactant in airways was studied in rat lungs. Male albino rats were anesthetized and sacrificed by exsanguination. The trachea was cannulated and the diaphragm opened to allow the lungs to collapse. The lungs were left in chest and kept at minimal volume, or at constant inflation with air, or were ventilated with air, nitrogen or oxygen. At the end of 3 hr the extrapulmonary airways (EPA), i.e. trachea and bronchi, were separated from the lungs and flushed with 40 ml isotonic saline. The surface tension and lecithin content of the saline wash was then measured. The surface activity and lecithin content of the EPA wash did not change if the lungs were kept at minimal volume or at constant inflation, but increased following ventilation. This increase was directly related to the duration of ventilation and to the tidal volume and inversely related to the end-expiratory pressure. It was independent of O2 concentration of the gas used for ventilation. The results suggest that ventilation enhances the movement of surfactant in airways and that positive end-expiratory pressure prevents this effect of ventilation.


Morphological and physical basis for lung surfactant action. An abhesive or 'anti-glue' function for lung surfactant is proposed which is reconcilable with the known unfolding of alveolar walls at low lung volumes. The theory is developed based upon the fact that the work required to part wetted surfaces is directly proportional to the surface tension. Application of the concept of the spreading coefficient from surface physical chemistry S = gammata-(gamma lla + gamma lle), where the gamma's refer to the surface (interfacial) tensions among the tissue (t), air (a) and lining layer (ll) surface, is shown to explain qualitatively physiological data in lungs subjected to maneuvers with working fluids varying widely in surface tension and spreading properties.


[Use of enzyme preparations in wine production (author's transl)]. The Author after having examined the present acquirements of the native enzymes of the grapes, summarizes the enologic uses of the enzyme preparations at various degrees of purity with the point of view of the influence on the organoleptic (color, aromatic composition) ad rheologic (yield, filtrability) characteristics of the musts and wines besides some microbiological implications. Subsequently the Author exposes the original results extrapolated from the pilot and industrial trials on the use of different hydrolases (pectinase, cellulase, hemicellulase, acid protease, xylanase) on the wine-making processes (traditional red wine-making, heating red-wine-making, white wine-making). From the comparison of the last data with those of the reference are drawed conclusive considerations on some aspects of the subject.


[Fish as proteic food: its preservation technology and new methods of utilization (author's transl)]. This review analyses the possibility to increase fishery production in order to satisfy the always increasing requirement of protein food. The most important chemical and nutritional chracteristics of fish and its by-products, as well as the preservation and elaboration technologies are reported. Some new or unusual fish utilization processes, as protein concentrates, extracts and spread pastes productions, are proposed as human food new sources.


[Endocrine ophthalmopathy. Clinical symptoms, classification, diagnostic classification, indications for treatment (author's transl)]. The clinical aspects and classification of "endocrine ophthalmopathy" were described. The clinical picture is of importance for the physician in nuclear medicine who is involved with the diagnosis and therapy of hyperthyroidism. In vivo and in vitro investigations in nuclear medicine regarding the classification of ophthalmic findings are derived from disturbances in control of the regulatory systems of the hypothalmas-pituitary-thyroid which are parallel to the ophthalmic processes. The clinical forms of endocrine ophthalmopathy and the thyroid findings which accompany it were systematized and an appropriate therapeutic procedure for the respective anomaly was described.


[Effects of reversing the feeding cycle and the light period on the spontaneous activity of the rat (author's transl)]. The amount and the circadian distribution of spontaneous activity in the rat are influenced by a number of factors, whose importance and interrelationships are still deeply discussed. In order to check the reliability of previous studies about the effects of meal-eating on the spontaneous activity (wheel running) of rats of our Sprague-Dawley strain, the adjustment to the modifications of the normal day-night cycle and of the normal nocturnal feeding rhythm have been controlled. Reversing the normal light and dark periods caused the rats, after a 24 hours period, to lower and to irregularly distribute their spontaneous activity. Rats shifted their pattern of maximal activity by 12 hours in the new period of darkness in about five days, and showed to have completely fixed the new reversed running habit. Also feeding habits changed in a similar way, but more slowly. The levels of mean daily activity did not change. In a second experiment, rats, received food during light hours, and were deprived during dark hours. Their activity increased considerably and irregularly during dark hours, while a very slight rise of wheel running was shown during light hours. Body weight gain and food consumption were similar to those of the control group. These results slightly differ from those obtained using other rat strains, and are an interesting example of reinforcement of a spontaneous behavior resulting more from the light-dark cycle than from cues provided by food deprivation.


[Preliminary investigations on carbohydrates changes during fruit and leaf growth of three peach cultivar (author's transl)]. Changes in sugars and polyols content of fruits and leaves of three cultivar of peach, from fruit set to over maturity, have been studied. Sucrose, glucose, fructose and sorbitol were found both in leaves and in fruits. In fruits, inositol and galactose were also found but only in traces. Redhaven fruits show the greatest total sugars content (sorbitol included) (866 mg/g.d.m.)followed in order by Favorita and Prodigiosa ones (771 and 694 mg/g.d.m.) For Redhaven and Favorita fruits, at harvest matuity, the sugar present in greatest amount was sucrose followed in order by glucose, fructose and sorbitol. On the contrary, in Prodigiosa fruits the order was sucrose, sorbitol, fructose and glucose. In the leaves of three cultivar, the compound present in the greatest amount was sorbitol followed by sucrose, glucose and fructose. The sucrose decrease in leaves during fruit growth could confirm that the disaccharide is the main sugar transported from the leaves to the fruits.


Immunotherapy of cancer with antibody.

Immunotherapy of cancer with antibody. A long-term suppression of a transplanted solid tumor that has been growing in a syngeneic animal can be achieved by the administration of antibody against the tumor. The susceptibility of such growing tumor cells to antibody treatment is similar to that of a comparable number of freshly injected tumor cells.


[Differentiation of natural red wines from white wines blended with oenocyanine (author's transl)]. A method is proposed for the differentiation of natural red wines from those obtained by addition of oenocyanine to white wines. The procedure is based on the determination of tannin phenolics and nontannin phenolics by selective precipitation with methyl cellulose and subsequent estimation of the intensity of absorption at 450 nm and 520 nm. The sum of ratio: mg/1 non tannin phenolics/absorption at 450 nm X 1000 and mg/1 tannin phenolics/absorption at 520 nm X 1000, furnishes values which are in correlation with the origin of two wines and such as to consent their differentiation.


[Optimization of Milk sterilization apparatus (author's transl)]. Referring to a typical plant for milk sterilization fixed and variable costs are evaluated at different heat recovery levels. The results of the analysis indicate that the transformation cost significantly decreases increasing heat recovery, and reaches a minimum at 90% heat regeneration. Milk sterilization apparatuses now on the market are characterized by a heat recovery between 40 and 85%.


Pure red cell aplasia.

Pure red cell aplasia. The presentation and clinical course of pure red cell aplasia in 5 patients are described. In 3 of them no concomitant diseases were present, in 1 the condition was associated with the presence of a thymoma, and the remaining patient was suffering from a lymphocytic lymphoma. Pregnancy led to a recurrence of the disorder in 2 patients. The fact that 4 of the patients exhibited unequivocal evidence of other auto-immune disturbances adds further support to the concept that pure red cell aplasia itself has an auto-immune basis.


The estimation of the number of binding sites for antibody on antigen molecules with reference to factor VIII and its antibody. The theoretical basis for determining the number of antibody sites on antigen molecules is examined. The theoretical considerations are applied to factor VIII molecules. Examples based on data available at the Oxford Haemophilia Centre are calculated to illustrate the approach. It is concluded that there are few sites on each factor VIII molecule for human antibody. The three antibodies for which reasonable data were available suggest 1-3 sites for human antibody. The data for rabbit antibody suggest 5-6 sites per factor VIII molecule.


Molecular variant of factor VII.

Molecular variant of factor VII. Two patients with severe factor VII deficiency appeared to be different with respect to the presence of inactive factor VII-like material in their plasma. The inactive material, demonstrated in one patient's plasma and adsorbable onto BaSO4, inhibits the thrombotest-system and is capable of neutralizing a heterologous antibody against factor VII in a fluid phase system.


Fibrinogen and its derivatives: cofactors in the intrinsic generation of thrombin. The simultaneous additon of suboptimal concentrations of factor VIII and intact or plasmin-lysed fibrinogen into mixtures of the vitamin K dependent factors, phospholipids, adsorbed bovine serum (supplier to factor V) and calcium, increased the amount of thrombin which was generated three to twenty times over the sum of the amounts which were generated when factor VIII, or fibrinogen, or its derivatives were added separately into the thrombin generating mixture. When factor VIII was added together with both fibrinogen and its derivatives, the amount of thrombin generated was even greater, about 130% larger than the amount which was generated in the presence of equal concentrations of only intact fibrinogen plus factor VIII. Addition of albumin instead of fibrinogen or its derivatives has a similar but significantly lower effect on thrombin generation. It appears, therefore, that both intact fibrinogen and its plasminolytic derivatives, singly or in combination, and to a lesser extent albumin, act as cofactors in the reaction which is regulated by factor VIII.


The clotting of a snake (Crotalus viridis Helleri) plasma and its interaction with various snake venoms. The clotting of C. V. Helleri plasma is not accelerated by the factor X activator or thrombin-like enzymes from its own venom. Clotting of the plasma is accelerated by the factor Xactivator from Russell's viper venom, but not by the thrombin-like enzyme from Agkistrodon Rhodostoma venom ("Arvin"). The prothrombin activator from the Taipan venom clots C.V. Helleri plasma equally well as human plasma, but the thrombin which is produced has a marked specificity for its own fibrinogen, and clots bovine fibrinogen more slowly. C.V. Helleri plasma contains an inhibitor which progressively inactivates bovine factor Xa and thrombin, but the inhibitor is not potentiated by heparin. The slow, protracted clotting of the snake plasma either alone or when mixed with human plasma or bovine fibrinogen suggests that this inhibitor may interfere with the polymerisation of fibrin monomer.


Studies on chemically modified fibrinogen. Treatment of fibrinogen with maleic acid anhydride renders fibrinogen unclottable depending on the degree of modification of the molecule. According to radioactive studies the release of fibrinopeptides by thrombin or reptilase is undisturbed. The incoagulability is due to inhibition of the polymerization process of fibrinmonomers derived from modified fibronogen, mainly caused by the increase of electronegative charges upon the fibrogen molecule. According to discelectrophoretic analysis modified fibrinogen fails to produce fragments D and E following plasmic digestion, however, may be degraded to high molecular weight products. Modified fibrinogen reveals some similarities to abnormal fibrinogens in congenital dysfibrinogenemia with regard to its functional properties.


Enzymatic removal of ADP from plasma: unaltered platelet adhesion but reduced aggregation on subendothelium and collagen fibrils. Subendothelium of rabbit aorta and fibrillar collagen were exposed to citrated human or rabbit blood which was circulated through a perfusion chamber under flow conditions similar to those found in arteries. The resulting platelet adhesion and subsequent formation of platelet microthrombi on the exposed surfaces were measured in 0.8 mum thich sections by a morphometric technique using light microscopy. Removal of plasma ADP by the substrate-enzyme combination  CP-CPK (creatine phosphate-creatine phosphokinase; 3 mM and 90 U/ml blood) did not affect the initial attachment and spreading of platelets on subendothelium, whereas platelet thrombus formation was strongly inhibited. On free collagen fibrils CP-CPK was much less inhibitory on platelet thrombus formation but platelet adhesion again was not affected. It is concluded that platelet aggregation induced by thrombogenic surfaces in the presence of arterial blood flow is at least partially governed by ADP released from adhering platelets. Platelet adhesion to the examined surfaces, however, does not seem to be mediated by plasma ADP.


The young platelet population in children with cyanotic congenital heart disease. Some morphological, biochemical and functional parameters of platelet population in children with cyanotic congenital heart disease (CCHD) were studied by making comparisons of the normal platelet population in both CCHD patients and controls. The mean volume of the platelets from cyanotic patients was greater than from normals. The platelet size distribution curves demonstrated a shift towards larger than normal size in the case of CCHD. The mean protein content, as well as the mean PF3 content of platelets was increased in CCHD. Following addition of kaolin, PF3 release was more rapid and of shorter duration with platelets from CCHD patients as compared to normal platelets. They also released more PF3 than did normal platelets. After addition of ADP, collagen, or adrenalin, platelets of CCHD patients were more responsive than similarly treated platelets from normals. Platelets from CCHD showed an increased initial rate of aggregation and greater maximum aggregation. These data suggested that the platelet population of CCHD  patients consists of larger, younger and functionally more active platelets than does the platelet population of normals.


Increased protein synthesis by human platelets during phagocytosis of latex particles in vitro. A three-fold increase of protein synthesis by human platelets during in vitro phagocytosis of polystyrene latex particles was detected. During the first two hours of incubation, the percentage of phagocytizing platelets and the number of latex particles per platelet increased; by the end of the third hour, the first parameter remained stable, while the number of latex particles per cell had decreased. Vincristine (20 mug/ml of cell suspension) inhibited platelet protein synthesis. This effect was both time- and dose-dependent. The drug also caused a decrease in the number of phagocytizing cells, as well as in their phagocytotic activity.


The effect of halofenate or halofenate free acid on human, rat and guinea pig platelet aggregation. Halofenate free acid (HFA), the major metabolite of the hypolipemic agent halofenate, blocked the secondary phase of human platelet aggregation induced by ADP, epinephrine, or thrombin; higher concentrations of clofibrate free acid (CFA) were required to produce similar inhibitory effects on platelet aggregation. HFA and CFA inhibited collagen-induced aggregation of human, rat, or guinea pig platelets. Halofenate orally administered to rats caused inhibition of collagen-induced aggregation when plasma levels of HFA exceeded 300 mug/ml, a clinically achievable human plasma concentration. The platelet inhibitory effects of clofibrate administration were less than those observed with halofenate administration.


Treatment of amyloidosis associated factor X deficiency. This is the tenth patient in thirteen years to be reported with the findings of an isolated factor X deficiency associated with primary amyloidosis. A favorable response to factor IX concentrate was manifested by temporary clinical and laboratory correction of her diathesis. This mode of treatment, therefore, provides an approach to therapy for bleeding complications in this group of patients who have previously failed to response to fresh frozen plasma.


Changes in human amniotic fluid fibrinolytic inhibitor levels during pregnancy. The amniotic fluid (AF) when incubated with the patient's own plasma diminishes the lytic activity of the plasma. It is suggested that this inhibition is due to the presence of fibrinolytic inhibitors in the AF. The inhibitors rate increases as pregnancy advances. Evaluating these inhibitors in a group of 65 women before and after the 38th week of pregnancy, a higher rate of fibrinolytic inhibitors is found after the 38th week. The said differences are statistically significant. For the moment it does not seem that the increasing of the inhibitors in the last part of pregnancy might be used as a fetal maturity test.


Various prothrombin complex concentrates and their effect on coagulation and fibrinolysis in vivo. Thromboembolic complications occurring in patients treated with factor IX concentrates have been reported. To study the thrombogenicity various types of factor IX concentrates (50 or 100 units F. IX/kg bodyweight) have been infused in dogs. As control albumin was given. The various components of the coagulation and fibrinolytic system have been assayed before the infusion and at various intervals after the end of infusion (0, 1, 4 and 24 hrs). Konyne resulted in marked activation of the coagulation process with decrease of platelets, fibrinogen, F. VIII and appearance of FDP and positive ethanol gelation test. Prothromplex and Preconativ gave no significant changes. Preconativ is prepared without addition of heparin during the procedure.


The effects of therapy with oestriol succinate and ethinyl oestradiol on the haemostatic mechanism in post-menopausal women. The effects on the haemostatic mechanism of oestrogen therapy, given to prevent bone loss in post-menopausal women, have been investigated. Oestriol succinate was given orally to 10 women at a level of 2 mg/day for 1 month and for a further 3 months with incremental increase of 2 mg each month. 6 of the 10 women were subsequently treated with 25 mug/day orally of ethinyl oestradiol. Oestriol succinate therapy resulted in a small increase in the level of factor VII, a decrease in factor VIII concentration and increased sensitivity of platelets to aggregating agents. Ethinyl oestradiol treatment resulted in much more widespread changes with marked increases in coagulation factors VII, VIII, IX and X, decreased levels of antithrombin and dramatic increases in circulating plasminogen levels and euglobulin lysis activity. The data suggested that the nature of oestrogens employed therapeutically is important in determining the qualitative and quantitative effect of oestrogen therapy on components of the haemostatic mechanism.


Blood coagulation and fibrinolysis in thyroid disease. Fibrinolytic activity and factor VIII concentration were studied in 30 patients with moderate to minimal hypothyroidism and in 7 patients with hyperthyroidism. In the hypothyroid group, the results were related to serum thyroxine levels, HL-A phenotypes and thyroid autoantibody titres. As serum thyroxine decreased so did factor VIII concentration, however, euglobulin lysis time was correspondingly prolonged. Factor VIII appears to be the most sensitive among coagulation factors to the deterioration of thyroid function tests. There was a significant correlation between the reciprocal of thyroid antibody titres and fibrinolysis; however, there was no relationship between factor VIII concentration or fibrinolysis and a specific HL-A phenotype although the incidence of HL-A8 was increased in the group as a whole. Euglobulin lysis time was prolonged in 6 out of 7 patients with Graves' hyperthyroidism. Factor VIII was elevated in only 3 of these patients.


Chemorheological studies of the effect of heparin on the course of coagulation. The influence of sodium heparin on viscoelastic change during coagulation was determined in vitro for whole blood samples from ten normal subjects at heparin concentrations ranging from 0 to 1.45 units/(ml whole blood). A four-parameter chemorheological model was used to describe the time course of coagulation as measured by the Weissenberg Rheogoniometer. One parameter compares closely with the whole blood activated partial thromboplastin time, while the other three may be related to the chemical kinetics of clotting. The chemorheological model and experimental techniques were then tested in a dog preparation. It was found that rheological measurements are more self-consistent than either thrombelastography or the activated partial thromboplastin time for the assay of in vivo heparin in two dogs.


Effects of endotoxin in cortisone-treated rabbits with a hereditary deficiency of the sixth component of complement (C6 deficiency). Endotoxin was infused into normal rabbits and C6 deficient rabbits prepared with cortisone for the generalized Shwartzman reaction. Endotoxin produced profound granulocytopenia and moderate thrombocytopenia in both normal and C6 deficient rabbits. In normal rabbits endotoxin consistently produced extensive intravascular clotting. In C6 deficient animals endotoxin resulted in intravascular clotting of variable extent. In one group of eight C6 deficient rabbits mean fibrinogen levels fell 0.67 g per 1 over 6 hrs after endotoxin and four of eight animals developed a generalized Shwartzman reaction. In a second group of seven C6 deficient rabbits mean fibrinogen level fell only 0.17 g per 1 over 6 hrs and one animal developed a generalized Shwartzman reaction. Values for mean fibrinogen consumption, calculated from plasma fibrinogen levels and rate of disappearance of 25I-fibrinogen, were as follows: normal animals infused with saline, 10 mg per kg; C6 deficient animals infused with endotoxin, 58 mg per kg. Fibrinogen consumption after endotoxin was found to be related to granulocyte levels prior to endotoxin, which determined the number of granulocytes disappearing from the blood after endotoxin. The data indicate that C6 deficiency in the rabbit does not prevent intravascular clotting and the generalized Shwartzman reaction.


The association of HLA with autoimmune thyroid disease in Newfoundland. The influence of HLA homozygosity in Graves' disease. Forty-seven patients with Graves' disease, 73 with thyroiditis and 128 controls drawn from the same geographical area of Newfoundland were HLA typed. The frequency of HLA-B8 was significantly increased in the Graves' disease patients when compared to the control group giving a relative risk of 3.9. There were no significant HLA differences between the thyroiditis and control groups. Homozygosity for the HLA haplotype, which is common in this island population, was more common in Graves' disease patients (12.8%) than in controls (5.5%) but did not reach statistical significance in this sample. Homozygosity was due in five of the six cases to either an A1;B8 haplotype or an A2;B8 haplotype. This contrasted with an apparently random assortment of haplotypes in the control and thyroiditis groups. Calculations suggest that homozygosity for a B8 haplotype confers an additional risk over heterozygosity for B8 of about 3.5 fold; however, homozygosity had no observable influence on the severity of the disease. These results strengthen the idea that B8, or an allele in linkage disequilibrium with it, determines in part the susceptibility of an individual to developing Graves' disease.


[Thoughts about the qualification of assessors for sensory testing (authors transl)]. On the occasion of a storage test in order to evaluate the tightness of milk packing materials to permeating flavours by sensory analysis the statistical method for judging the concerned assessors recommended by Römer and Renner was applied. We gained the experience, that this method allows no statement about the assessor's sensory ability at all, but merely fixes his order of precedence in a panel as to his ability to realize sensory differences in the scope of one special problem. The mentioned statistical procedure cannot substitute a selection of assessors aimed at the subject of the following sensory analysis.


Action of rubratoxin B on mouse liver mitochondria. The effect of rubratoxin B on the electron transport system of mouse liver mitochondria was investigated. Oxygen consumption in mitochondria isolated from male mice was measured polarographically in a Gilson Oxygraph Model K-ICC. Oxygen consumption was depressed 73% at a concentration of 1.13 mM rubratoxin. At concentrations as low as 0.08 mM rubratoxin B, 50% inhibition was observed. Rubratoxin B (0.28 mM) depressed oxygen consumption 67% in ADP-coupled mitochondria and 60% in 2,4-dinitrophenol (DNP)-uncoupled mitochondria using either pyridine-nucleotide linked substrates or succinate. By employing the N,N,N',N''-tetramethyl-p-phenylenediamine (TMPD) shunt, it was shown that inhibition was not between cytochrome b and cytochrome C1 or C. It appears, based on these studies and comparison with known inhibitors of specific sites along the electron transport system that the principal site of action of rubratoxin B is between cytochrome C1 or C and the termination of electron flow.


[Analytical investigations of the delta-endotoxin of Bacillus thuriginiensis (author's transl)]. Biochemical properties of the crystalline delta-endotoxin of Bacillus thuringiensis, such as stability and solubility in different solvents, were investigated. The dissolved compounds were characterized  by gel-electrophoresis and gel-filtration. Covalent and non-covalent bonds are responsible for the crystallisation of the protein molecules. The solubilisation of crystals with non-enzymatic solvents led to high molecular weight products (MW greater than or equal to 800,000) and to components with a molecular weight less than or equal to 10,000. Only the high molecular weight compounds showed toxic activity. The enzymatic degradation of the protein crystals yielded components with molecular weights of greater than or equal to 800,000, 250,000, 100,000, and less than or equal to 10,000. Again, the fraction less than or equal to 10,000 showed no toxic activity. Digestion of the crystals with proteases isolated from the gut juice of Pieris brassicae resulted in a highly toxic fraction with a molecular weight of 100,000. This component, which is resistant to further degradation, appears to be the toxic unit of the protein crystal.


Studies on some nutritional factors influencing the production of gluconic acid. Investigations were carried out to formulate an economical medium that can give maximum yield of gluconic acid by the submerged culture technique, using Aspergillus niger NRRL3. It was found that the highest yield of acid could be secured when a medium of the following ingredients was used: 13.0% glucose syrup, 0.1% NaNO3, 0.025% calcium superphosphate, 0.007% KCl, 0.025% MgSO4-7H20, and 0.5% CaCO3. It was also found that glucose syrup, which represents an available and cheap carbohydrate source for gluconic acid production by fermentation, can replace glucose powder which is more expensive.


Nitrogen fixation by microbial cultures with sodium salt of organic acids as carbon source. The best source of carbon, when used as the sodium salt of organic acids, is sodium salicylate which shows highest nitrogen fixation and also appreciably large amounts of nitrogen fixed per g carbon consumed. Next in order is sodium benzoate, then oxalate. Sodium citrate is followed by sowium acetate in the order of decreasing efficiency.


[Effect of plant residues on the parasitic activity of soilborne pathogens and the saprophytic microflora of the soil. I. Model trials with Rhizoctonia solani Kühn (author's transl)]. 1. In glass-house trials the influence of residues of clover, grass, and mixtures (1:1) of them added to natural and partially sterilized loam soil upon the parasitic activity of Rhizoctonia solani and the soil micro-organisms and their activity was analyzed. 2. Burying of plant residues (1%) increased the content of organic substance in soil for 8 weeks and longer. 3. The soil reaction (pH) was not noteworthy affected by application of clover or grass residues. 4. However, the populations of bacteria and actinomycetes were increased, especially by adding clover dried. In natural soil, the maximum of stimulation was reached later than in soil sterilized. Adding of grass and roots of grass enlarged the spectrum of fungi observed in the soil amended. Roots of grass stimulated the cellulose-decomposing organisms remarkably. 5. The activity of dehydrogenase (AD) was influenced in different manner: in natural soil fresh clover, grass, mixtures of them, and clover dried increased, and fresh roots of clover, grass, and mixtures of them diminished AD; in soil sterilized the most variants stimulated this activity. 6. All plants residues increased the cellulolytic activity of soil for a long time, but in sterilized soil this effect reached its maximum earlier than in natural soil amended and did not last so long, too. 7. The possible explanations for the inhibition of parasitic activity of Rhizoctonia solani caused by burying plant residues are discussed.


Effect of prolactin suppression on gonadotrophic secretion in the puerperium. Serum levels of prolactin (PRL), FSH, LH and oestradiol-17 beta were determined by radioimmunoassay in 57 lactating women and in 20 women in whom lactation was inhibited by ergocryptine (CS-154). Women who breast fed their infants exhibited high PRL levels which abruptly declined within 48 h post-partum, and remained low for the duration of the study. Serum FSH was undetectable during the first week post-partum in lactating as well as in CB-154 treated women. Thereafter, lactating women showed increasing FSH levels which reached a maximum by the third week post-partum. These FSH values were higher in lactating women than in the CBS-154 treated group. In contrast, LH levels were higher in those women receiving CB-154. Serum oestradiol-17 beta remained in low levels throughout the study, and no difference was observed between the two groups of subjects. From these results it seems that: 1) inhibition of PRL secretion leads to a faster recovery of gonadotrophin secretion toward the "menstrual type", and 2) PRL suppression produces no effect on the ovarian oestrogen production.


The serum half-life of somatomedin activity: evidence for growth hormone dependence. The serum half-life of somatomedin (SM) activity has been measured following the intravenous injection of SM activity into hypophysectomized rats. A [3H]thymidine incorporation assay in chick embryo fibroblasts (CEFs) has been utilized to measure SM activity. Cell cycle analysis data obtained with the flow microfluorometer shows that the [3H]thymidine incorporation data reflects actual DNA synthesis. When normal rat serum was injected, a half-life for SM activity of approximately 3 h was determined. In marked contrast, when serum from hypophysectomized (hypox) rats acutely treated with growth hormone (GH) was used as the source of SM actively, the half-life of the SM actively was short, approximately 8 min. However, when serum from hypox rats chronically treated with GH was injected, the half-life was again long, approximately 4 h. SM activity has been separated from its binding proteins by boiling under acid conditions or chromatography on Sephadex G-50 in 1 N acetic acid. The half-life of this partially purified SM activity was short, in the range of 10-30 min finally, recombination of the partially purified sm activity with the large proteins in normal serum extended in half-life of the sm from 10-03 min to about 2 h. These data indicate that the serum half-life of SM activity is GH dependent and suggest that the serum binding protein, like SM itself, is under GH control.


Factors governing the stimulation of embryonic chick cartilage by somatomedin. In these studies of the stimulation of embryonic chick pelvic rudiments by somatomedin (Sm) in serum, we have found that cartilage weight and duration of cartilage exposure to serum determine the stimulation of cartilage by serum and the relative stimulation by Sm and by other non-Sm serum components, respectively. These factors are critical for the use of this system to measure Sm in serum. Initial experiments revealed that incorporation of sulfate (SO4) by cartilage incubated in buffer fell rapidly after 9 h and reached very low levels by 30 h. Incubation in 40% normal human serum (NHS) produced significant stimulation of incorporation of SO4 after 4 h, and maintained at least initial levels of incorporation for 24 h. The greatest % stimulation by NHS over buffer was seen with prolonged incubation (44 h). However, specificity for Sm (iscrimination between NHS and hypophysectomized human serum (HHS)) was greater with shorter incubation times. The potency of HHS was 11, 42 and 92% of the potency of NHS following early, intermediate and late measurement of incorporation of SO4 by cartilage, respectively. The best overall results were obtained with intermediate incubation time and measurement of SO4 incorporation ((35S)-SO4 present for the final 5 h of a 25 h incubation), which allowed good precision (gamma = 0.17) while maintaining satisfactory specificity for Sm. Since prolonged incubation with late measurement of SO4 incorporation allowed the greatest % stimulation by serum with little differentiation between NHS and HHS, stimulation of incorporation of SO4 under these conditions is apparently due to non-Sm factors present in both NHS and HHS. In addition to incubation time, cartilage stimulation by serum was also determined by cartilage weight. Lighter cartilage (from younger embryos) was associated with higher unstimulated incorporation of SO4 (P less than 0.01), lower stimulation by added serum (P less than 0.01), and inadequate assay precision (P less than 0.05): satisfactory assays were generally obtained with cartilage rudiments weighing more than 0.7 mg (dry weight).


Circadian fluctuations of serum hormone levels in prepubertal male and female rats. Diurnal variations in serum hormone levels during 2 different stages of prepubertal development were investigated in male and female rats. Groups of 13 to 18 and 25 to 30 day old male and female rats were decapitated at 4-hour by intervals during a period of 24 h. Their blood was collected and hormones were measured by radio-immunoassay. FSH levels were constantly high in 13 to 18, but low in 25 to 30 day old females. FSH was low in younger males, and significantly higher but without diurnal fluctuations in the older males. Serum LH was low in approximately 40% of the 13 to 18 day old females, while 40% had moderately high levels, and the remaining females extremely high levels of the hormone. Most of the extremely high LH peaks were found at 15.00 h and some at 03.00 h. Older females and males of both age groups had constantly low serum LH levels. Serum oestradiol was high in males and females during days 13 to 18, but it was lower in the 25 to 30 day old animals. In the young females prolactin was slightly elevated between 15.00 h and 19.00 h, while in the males the serum prolactin fluctuations were not significant. Serum testosterone was low in females at all times. The 13 to 18 day old males had higher testosterone levels than the 25 to 30 day old males. Both groups showed slight, but insignificant fluctuations in serum testosterone.


Factors influencing triiodothyronine binding properties of liver nuclear receptors. Triiodothyronine (T3) may bind directly to receptors present in liver cell nuclei, or may be transported into nuclei by receptor protein(s) present in the cytosol. To evaluate these possibilities, T3 binding was studied in vitro using liver cell nuclei isolated from rats exposed in vivo to very low (H), normal (N),or high levels of T3 (H + T3), and using nuclei incubated in vitro with added cytosol proteins. Ka for T3 was 0.075 +/- 0.05 x 10(10) M-1 in N, 0.1 + 0.04 in H, and 0.094 + 0.04 in H + T3, and pg T3 bound/100 mug DNA were 47 +/- 17, 31 +/- 14, and 29 +/- 8 in the three groups. The data indicate no difference in binding capacity between the groups related to prior in vivo exposure to T3, and that T3 may bind directly to empty nuclear receptor sites. Rat liver cytosol proteins added to the in vitro incubation medium always depressed T3 uptake by nuclei. Bovine serum albumin had a similar effect. Large amounts of rat serum proteins depressed uptake, but low levels augmented T3 binding through an unknown mechanism. It is probable that free T3 in serum is in equilibrium with free T3 in the cytosol and nucleus, and binds directly to nuclear receptor proteins without mediation by a cytosol receptor protein.


Concentration of thyroid hormone in skeletal muscle. 1. A modified method for the determination of thyroid hormone levels in muscle is described. 2. The levels of T4 and T3 in skeletal muscle tissue of rats lie in the same range. 3. The level of T4 in plasma is about a hundred times higher than that of T3. 4. To remove plasma hormones from the tissue in which hormone levels are to be determined, the animals should be perfused with saline before tissue samples are taken.


Anti-insulin-antibodies and late diabetic complications. Two hundred and seventy-four insulin-dependent juvenile diabetics were examined. One hundred and sixty-six patients were without late diabetic complications, while 108 patients had one or more complications. At the time of the investigation patients with and without complications were found to have the same insulin requirement. Retrospectively it was observed, that after treatment for 10 years the insulin requirement was significantly higher among patients who had developed complications after treatment for 19 years as compared to patients who after 19 years of treatment had not developed complications. One hundred and eighty-four patients, of which 110 were without and 74 with late diabetic omplications were examined for anti-insulin-antibodies. Patients with complications, especially those with early onset of proliferative retinopathy or nephropathy had a slightly although insignificantly elevated plasma insulin-binding capacity. The frequency of high titres was significantly greater among patients with complications as compared to the frequency in patients without complications. The observations support the assumption, that insulin-anti-insulin-antibody complexes may aggravate the vascular complications.


The liver as a source of somatomedin.

The liver as a source of somatomedin. Somatomedin (Sm) activity (measured by [35S] utake in chick embryo cartilage) was determined in serum samples simultaneously drawn from the hepatic vein, portal vein, femoral artery and demoral vein of seventeen anaesthezied normal adult dogs). A pool of human serum was taken as reference (Sm = 1 U/ml). Sm levels in the peripheral vein of dogs were 0.38 +/- 0.03 U/ml). Mean +/- SEM). Sm activity was greater in the hepatic vein (0.48 U/ml) than in the other vessels (0.36, 0.39, 0.38 U/ml), and the paired differences were significant (P less than 0.002 to P less than 0.05). In three dogs which received b-GH (20 IU/day), the Sm levels were significantly increased after nine days in the femoural vein (P less than 0.05) and in the hepatic vein (P less than 0.05). The validity of the assay is discussed; a possible interference of NEFA in the assay is eliminated. The difference of Sm levels between hepatic and portal veins, related to hepatic flow measured in seven of these dogs, indicate an important production of Sm by the liver.


The influence of norethisterone oenanthate on ovarian function. Two-hundred mg norethisterone oenanthate was injected im into five women on the fifth or sixth day after the onset of the menstrual bleeding. The plasma levels of oestradiol and progesterone were measured during one control cycle before the injection and then for three months or until ovulation occurred. According to the plasma progesterone pattern the five women ovulated during the control cycle. After the injection ovulation was delayed in all the subjects. In two of the participants the first ovulation occurred around 55 days after the injection, while in two others ovulation was delayed about 80 days. The fifth woman did not ovulate until 16 weeks after the injection. The treatment did not suppress the plasma levels of oestradiol below the levels seen in untreated women during the follicular phase. It is concluded that the treatment with 200 mg of norethisterone oenanthate im can inhibit ovulation for an unpredictable time, but that the ovulatory pattern is restored within 12 weeks in most of the women.


The source of ovarian oestradiol and androstenedione in the sheep during the luteal phase. The secretion of oestradiol and androstenedione was investigated in sheep by cannulating both ovarian veins in situ. The mean ovarian blood flow (ml/min +/- SE) was significantly higher on the side containing the corpus luteum (7.67 +/- 1.36) than on the contralateral side (4.93 +/- 0.85). The mean secretion (ng/min +/- SE) of oestradiol (1.09 +/- 0.36) and androstenedione (1.52 +/- 0.16) was higher on the side containing at least one large follicle (diameter greater than 4 mm) than on the contralateral side (0.19 +/- 0.05 and 0.62 +/- 0.21, respectively). The secretion of oestradiol was unchanged following enucleation of the corpus luteum but fell to very low levels (0.062 +/- 0.022 ng/min) after enucleation of follicles diameter greater than 4 mm. The secretion of androstenedione fell significantly after enucleation of both corpus luteum and largefollicles. These results suggest that during the luteal phase in the sheep oestradiol is secreted virtually exclusively by the largest non-atretic Graafian follicle. Androstenedione in contrast arises from both follicle, corpus luteum and possibly stroma.


Oestrogen in human pregnancy faeces.

Oestrogen in human pregnancy faeces. The oestrogen content  of two 24 h pools of pregnancy faeces, obtained from 2 normal women in the 33rd-37th week og gestation, was studied. The qualitative analyses were made by gas chromatography - mass spectrometry and the quantitative analyses by mass fragmentography. The presence of the following oestrogens in pregnancy faeces was established: Oestriol, oestrone, oestradiol-17 beta, 16-epioestriol, 17-epioestriol, 16 alpha-hydroxyoestrone, 16-oxo-oestradiol-17 beta, 15 alpha-hydroxyoestrone and 15 alpha-hydroxyoestradiol-17 beta. In addition, mass fragmentographic evidence was obtained for the presence of 16 beta-hydroxyoestrone, 2-methoxyoestrone and oestradiol-17 alpha. The total oestrogen excretion determined in the two pools was 786 and 1300 mug per 24 h. Unconjugated oestrogens accounted for 97.8 and 98.6% of these amounts, respectively. Oestriol, oestradiol-17 beta, 15 alpha-hydroxyoestradiol-17 beta, 16-epioestriol and oestrone, in that order, were quantitatively the most significant of the oestrogens determined. The remarkably high levels of oestradiol-17 beta fround in faeces show, that in pregnancy, this mode of excretion is as important as urine for the elimination of this biologically active steroid. It is suggested that some of the oestradiol may have b-en formed through bacterial enzyme action from other oestrogens or neutral steroids. Only trace amounts of ring D alpha-ketolic oestrogens were found in faeces. This is in marked contrast to the considerable amounts of these steroids found in pregnancy bile and urine.


Effects of sex steroids on serotonin uptake in blood platelets. Blood platelets have been suggested as amodel for serotonin uptake and storage in the brain. To examine possible effects of se- steroids, platelets from human volunteers were incugated for 15 min with oestradiol, testosterone, and dihydrotestosterone, and then incubated fro 1 min with radioactive serotonin. The effects of the various steroids on serotonin uptake were measured. At 10(-3) M, oestradiol decreased serotonin uptake by 70%, testosterone by 49%, and dihydrotestosterone by 25%. Both oestradiol and testosterone showed maximal enhancement of uptake at 10(-6) M; oestradiol increased serotonin uptake by 41%, and testosterone by 60%. Dihydrotestosterone maximally facilitated uptake by 40% at a concentration of 10(-4) M. No sex differences were found in either direction or in magnitude of change in uptake due to any hormone. It is suggested that the effects of oestradiol are of physiological significance and that the site of action of the sterioid effect on serotonin uptake is the cell membrane of the platelets.


Oligomeric oestradiol esters: a new class of long-acting oestrogens. Dimeric and trimeric oestradiol derivatives were administered as single subcutaneous injections into ovariectomized rats and the duration of oestrogenic effect was determined by means of daily vaginal smears. It could be shown that these preparations have a very protracted oestrogenic effect, and their threshold dose is considerably higher as compared to monomeric oestradiol diacetate. A dimeric compound containing one free hydroxy group caused a relatively even response in all animals with a linear relationship between the logarithm of dose and the duration of action. The effect was even more protracted when fully esterified dimeric or trimeric oestradiol succinates were used, but occurred in a more scattering manner. The duration of effect of 40 mug of the trimeric compound exceeded that of the equivalent dose of oestradiol undecylate. It is conceivable that the depot-effect of these oestradiol derivatives is due to delayed elimination.


Autoimmunity in patients with Pemphigus foliaceus. The presence of conventional autoantibodies in the sera from 28 patients with Pemphigus foliaceus (South American pemphigus) was investigated. Gastric parietal cell antibody was found in six patients (21.4 per cent); and in two of them mitochondrial antibody was also detected. Antibody to smooth muscle was found in one patient. Based on the above results, the role of autoimmunity in Pemphigus foliaceus was discussed. Nuclear and rheumatoid factors were not detected, and antibodies against glomerular components, salivary duct and thyreoglobulin were not found.


[Bronchial antigen provocation tests with the use of whole body plethysmography]. Bronchial provocation tests are performed in order to reproduce the symptoms of extrinsic bronchial asthma. The bronchial obstruction induced hereby can be demonstrated by plethysmographic measurement of specific airway resistance, which is superior to spirometric parameters with regard to sensitivity and effort independence. A rise of specific airway resistance above 20 cmH2O X sec ("dyspnoea threshhold") can be used as the criterium of a positive result. In contrast to forced expiratory manoeuvres no spirometry induced asthma can occur. Automatic evaluation by electronic data processing is possible.


Relationship between antigen and antibody-induced suppression of IgE antibody formation in the rat. Formation of specific IgE antibodies as elicited in Sprague-Dawley rats against Ascaris antigen could be suppressed by intravenous administration both of antigen and of specific antiserum. The suppressive agent in the antiserum was shown to be antibodies of the IgG class, whereas a suppressive effect of cytophilic activity and of IgE antibodies could be outruled. Suppression of IgE response lasted the longer the more antibodies were transferred. An antibody-induced suppression was achieved when antibodies were transferred during an early period (day -3 to day +8), whereas an antigen-induced suppression took place when the antigen was intravenously administered following the antibody-sensitive period (day +8 until day +14). This is consistent with the fact that an antigen-induced suppression of IgE formation requires the presence of a certain amount of antibodies. A strictly peripheric suppression could be outruled, since with elapse of time a decreasing dose of antigen was required to induce a suppression. The results are discussed on the basis of an antigen-antibody complex-induced suppression in the IgE system and its possible central site of action.


Densitometric evaluation of lung aeration in chest films. Lung aeration can be evaluated densitometrically from chest films, using a microscope with one eyepiece replaced by a photocell, and the attenuation of the pulmonary parenchyma can be assessed numberically, as a "radiologic expansion index". In premature rabbit neonates, this index was significantly increased among animals receiving a pharyngeal deposit of homologous lung surfactant before the first breath, as compared with untreated controls. This technique could in modified form be used for clinical purposes, such as the evaluation of lung aeration in newborn infants with respiratory distress.


Ossicle of the meniscus.

Ossicle of the meniscus. Two patients with an ossicle of the meniscus are described. Radiologic differentiation from osteochondral loose body or chondrocalcinosis can be made by its ossified appearance and its location within the meniscus. Correct diagnosis is important so that unnecessary surgery is avoided and a protracted search for a free fragment is not carried out.


Tuberculous aortitis: a rare cause of mycotic aneurysm of the aorta. A case of a true mycotic aneurysm of the aortic arch secondary to mediastinal lymph node tuberculosis is presented. This was promptly recognized by aortography, treated by surgery, diagnosed by pathology, and followed by antituberculous therapy. The early diagnosis is emphasized as a prerequisite to successful treatment.


[The influence of methoxyflurane (penthrane) on surface activity of the lung (author's transl)]. Methoxyflurane, at the moment the most potent inhalation anaesthetic, was examined in respect of its surfactant irritating properties in the rabbit. After a five hour anaesthesia with this compound there was, compared with a control group of animals which underwent only mechanical ventilation with room air for the same period, a significant decline of the compliance quotient from 2.99 to 2.55, indicating a relevant impairment of alveolar lining surfactant. A concomitant fall of arterial PaO2 from 84.8 to 71.3 mm Hg showed the resulting deterioration of respiratory function. Postanaesthetic preparations of these lungs examined using the Wilhelmy balance exhibited a significant fall of the stability index from 1.73 to 1.25, though hysteresis remained unaffected. Lung histology showed interstitial edema and patchy atelectasis, features which are found also in the early stages of post-traumatic pulmonary insufficiency. On this basis we recommend that methoxyflurane is not used in patients with impaired surfactant activity as such is found after severe traumatisation, head injury or in special preexisting pulmonary diseases. If this anesthetic is given to healthy individuals, the ventilatory pattern should include periodic sighs and prophylactic PEEP.


Effect of wool dust on respiratory function. A group of 252 workers (176 women and 76 men) employed in two wool mills was studied. The mean age of 36 years; mean exposure, 11 years. All women were nonsmokers, and 47 per cent of the men were regular smokers. Ventilatory function was measured by recording maximal expiratory flow-volume curves and forced expiratory volume in 1 sec on the first working day of the week (Monday) before and after the work shift. On maximal expiratory flow-volume curves the flow rates at 50 per cent of the control vital capacity were read. Workers exposed to wool dust for more than 10 years had a higher prevalence of chronic respiratory symptoms than did those with less than 10 years' exposure, but the difference was not significant. Significant reductions during the work shift were found in maximal expiratory flow rates at 50 per cent of the control vital capapity and 1-sec forced expiratory volume, the first test being considerably more sensitive. Workers exposed to wool dust for more than 10 years had signficantly lower than predicted pre-shift values for maximal expiratory flow rates at 50 per cent of the control vital capapcity. Inhalation of wool dust extract caused a significant decrease of maximal expiratory flow rates at 40 per cent of the control vital capacity on partial expiratory flow-volume curves during the 100 min after exposure. Comparison with the same concentration of cotton dust extract revealed a similar effect during the first 40 min after exposure but a significantly larger effect of the cotton dust extract after 40 min. The data suggest that preventive measures, especially medical supervision, are necessary in wool-processing mills to protect workers sensitive to dust.


Effect of medical care review on the use of injections: a study of the New Mexico Experimental Medical Care Review Organization. Evaluation of peer review activities in the New Mexico Medicaid program (1971 to 1973) showed that it can affect aspects of quality, that is, the appropriateness of the use of injections as judged by medical criteria. Use of injections, nearly 50% of which were antibiotics, declined by more than 60%, from 41 to 16 per 100 ambulatory visits. Still, at the end of the study, 40% of the injections given were considered medically unnecessary. Analyses showed that [1] groups used injections more appropriately; [2] for solo physicians, being board-certified, being a doctor of medicine, and being a pediatrician were all associated with more proper use of injections; [3] 6% of the physicians gave 40% of the medically unnecessary injections, but even their behavior changed dramatically for the better as a result of the peer review system.


Clinical and roentgenographic findings in splenic abscess. A splenic abscess developed in a 16-year-old boy following a supposed viral illness and left lower thoracic trauma. Preoperative diagnosis was at first obscured, but a spleen scan suggested fractured spleen and a splenic arteriogram showed a "subcapsular hematoma" and an aneurysm of the left hepatic artery. A 1,800-gm spleen containing one large abscess and one small one was removed. Splenic abscess is rare and, before modern methods of spleen scan and arteriography, rarely diagnosed.


On the mechanism of lanthanide-induced liver toxicity. The intravenous injection of the lighter lanthanide ions Pr(III), Nd(III), and Sm(III) in doses of 35 mumoles/kg inhibits, and isoosmolar doses of the heavier lanthanide ions Gd(III), Dy(III), and Er(III) stimulate rat liver nuclear in vitro RNA synthesis catalyzed by RNA polymerase B 24 h after their application, while nuclear RNA synthesis, catalyzed by RNA polymerase A, was inhibited by the same isoosmolar doses of Pr(III), Nd(III) and not influenced by Sm(III), Gd(III), Dy(III), or Er(III). The effect of in vivo applied Pr(III) and Nd(III) on rat liver in vitro nuclear RNA synthesis shows a similar time and dose-dependent pattern. The decreased rat liver nuclear in vitro RNA synthesis 24 h after intravenous injection of Pr(III) as well as after Nd(III) was accompanied by a decreased nuclear in vitro 3H-acetate uptake by the chromatin-bound histone fractions, F 2a2, F 3, and F 2al. At the same time after the Pr(III) injection, the capacity and number of initiation sites of the rat liver nuclear template for homologous nuclear RNA polymerases, prepared from control rat liver nuclei, was lower than the corresponding control template. A decreased activity of endogenous free nuclear RNA polymerases, as determined with the aim of the synthetic poly(dA-dT) template 24 h after Pr(III), may further contribute to the decreased nuclear RNA synthesis. The results indicate a primary ionic size-correlated interference of lanthanides with the nuclear control mechanisms of RNA synthesis.


[Effect of silymarin on the total dry mass of hepatocytes inacute poisoning by phalloidin and alpha-amanitine (author's transl)]. The effects of silymarin on the total dry mass and class pattern of rat hepatocytes have been studied during acute poisoning by phalloidin and alpha-amanitine. Phalloidin (2/5 of the LD50) after 3 h causes a marked change in the hepatocyte class pattern due to a displacement of a high percentage of cells in the intervals among classes, while the cell dry mass increases slightly. alpha-Amanitine (1/4 or 1/2 of the LD50) after 3 h causes a decrease in the number of classes of hepatocytes due to a disappearance of the heavier ones, a displacement of cells in the intervals among classes, an appearance of very light cells, and a decrease by about 25% in the mean dry mass of the hepatocytes. Silymarin, administered 30 min before poisoning, prevents all the changes due to 2/5 of the LD50 of phalloidin and to 1/4 of the LD50 of alpha-amanitine, and strongly reduces the effects of 1/2 of the LD50 of alpha-amanitine. The effects of alpha-amanitine and phalloidin and the protective action of silymarin on the dry mass and class pattern of hepatocytes are discussed.


Efficacy of gut lavage, hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication. Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents. Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1-2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1-2 ppm, the clearance values for hemoperfusion were some 5-7 times higher than those for hemodialysis. In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquats less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.


The interaction between cadmium, mercury and zinc--administered subcutaneously in a single injection. The interaction between three heavy metals, cadmium, mercury and zinc was investigated. The metals were injected subcutaneously into the hind leg of male rats of approximately 200 g body weight in a volume of 0.2 ml either alone or in combination with another metal. It has been shown that interaction started at the site of injection, at which the retention of one metal was increased by the presence of the other over a 48 h period. Besides this local interaction, probably based on competition for a carrier compound, there were differences in distribution. Analysis of the data indicates that metals injected simultaneously can influence the distribution of each other and, although each of the studied metal is able to induce thionein, the observed interactions cannot be explained by a single mechanism.


Differences in distribution and excretion of selenium and cadmium or mercury after their simultaneous administration subcutaneously in equimolar doses. Forty-eight hours after the simultaneous administration of either 1.8 mumoles Se (as Na2SeO3) to 200 g male rats with equivalent doses of Cd (as CdCl2) or 0.5 mumoles Se with equivalent doses of Hg (as HgCl2) the retention of selenium at the subcutaneous injection site was affected only when it was given in a single injection with the heavy metal. The retention of cadmium was increased only if selenium was injected separately and the retention of mercury was increased both in single and separate injections. When there was an increase in retention at the site of injection, this made up less than 8% of the dose for selenium and mercury and 3% for cadmium and thus could not explain either changes in distribution or the reported protective effects by one metal against the other. The shift in the distributionpattern of one metal caused by the other metal was similar, and independent of whether they were injected in single or separate injections. However the shift in the distribution of interacting metals showed some differences indicating that interaction could not be mediated through the formation of a stable complex between selenium on the one hand and mercury or cadmium on the other.


Therapeutic effects of HS-3, HS-6, benactyzine, and atropine in soman poisoning of dogs. Investigations into the therapeutic properties of various combinations of the bispyridinium salts HS-3 and HS-6 and the cholinolytics atropine and benactyzine against soman poisoning in unanesthetized male beagles were performed. In our investigations we observed that: 1. The most effective protection against soman poisoning was attained if both oximes were applied early i.m. 6 min after intoxication together with the cholinolytics. 2. On the basis of clinical symptoms HS-6 proved to have a more intensive therapeutic effect than HS-3 upon early application. 3. If HS-3 was applied early after s.c. intoxication with low concentrations of soman (up to 3 LD50), a significant protection or reactivation effect on serium cholinesterase was measured. 4. When HS-3 was applied at the beginning of convulsions--generally 28 min after s.c. intoxication--it also raised the rate of surviving animals. 5. The maximal blood levels for HS-3 and HS-6 were measured 20-30 min after i.m. injection; the half-life values of HS-3 and HS-6 in plasma were 45-60 min.


Certain oxidative and hydrolytic enzymes in the middle ear effusion in serous otitis media. Activities of various oxidative (LDH, MDH) and hydrolytic (LAP, alkaline- and acid phosphatase, and lysozyme) enzymes in serous middle ear effusions (MEE) and serum from patients with serous otitis media were studied. The ratio of enzyme activity between MEE and serum (MEE/serum) was greater than one for all enzymes studied indicating a higher activity of these enzymes in MEE than in serum. These findings are consistent with a hypothesis suggesting the release of enzymes from inflammatory processes in the middle ear cavity. These enzymes presumably originate from 1) enzymes normally present in blood, 2) release of enzymes from inflamed middle ear mucosa, 3) release of enzymes from inflammatory cells present in the effusions.


Automatic recording and evaluation of neuronography. The introduction in the 60' s of the Nerve Excitability Test (NET) by Laumans and Jongkees for the diagnosis of Bell's palsy stimulated an interest of quantitative testing of the facial nerve. In 1970 Yanagihara reported the Evoced Myography (EMG; i.e. NET is combined with EMG). Starting with electrophysiological basis of the impulse spread of peripheral nerves May, in 1971, extended this concept by including supraliminal stimuli, i.e. Maximal Stimulation Test (MST), for diagnostic purposes. This method eventually developed into what is known as neuronography (Esslen, Huffmann, Ehrenberger, Satoh). It is undoubtedly a refinement in the question of prognosis of Bell's palsy. Continuing the original concept of May we have developed an electronic device with which to carry out automatically the neuronography that demonstrates an evaluation on a numeric display. We use the conventional bipolar negative square wave for a 1 ms stimulation. We stimulate the angle of the mandible, where the ramus marginalis can be readily found in all patients. Neuronography and Evoked Myography provide earlier a more precise prognosis of facial palsy than Nerve Excitability Test (NET). We developed an electronic device for the Maximal Stimulation Test (MST) of May, M., that is automatic. The device counts the spikes of the evoked myogram. A time window is related to the stimulus to exclude stimulus noise and background muscle noise from the counter. Only spikes seen in this window are processed. The number of spikes generated per stimulus is the measurement of the live axons in a stimulated nerve.


Distribution and possible function of lysosomal enzymes in the inner ear under normal and pathophysiological conditions. The normal distribution of several lysosomal enzymes was studied in 20 guinea pigs. In the outer hair cells lysosomal enzymes are mainly localized at the apical cell pole, while in inner hair cells the distribution was uniform. Nonlysosomal enzymes like alcaline phosphatase are of predominantly basal localization. The concentration of some lysosomal enzymes like N-acetyl-beta-glucosaminidase was higher in outer than in inner hair cells while others like acid phosphatase, beta-glucuronidase and sulfatase showed a stronger reaction in the inner hair cells. After 10 days of sound overstimulation with 120 dB for 1 h a day, there was an increase of lysosomal enzyme content namely in the outer hair cells. There was no change of non-lysosomal enzymes. Under these conditions there might be a partial destruction of cellular organelles eliminated by lysosomal activity without loss of a total cell. In addition the distribution and possible function of lysosomal enzymes in other labyrinthine tissues was discussed.


Intensity and rate functions of cochlear and brainstem evoked responses to click stimuli in man. The complex of five waves, which are the responses to click stimuli of the auditory nerve and the brainstem auditory nuclei, were recorded in ten human subjects by means of earlobe and scalp electrodes. The rate of the stimuli was varied from 5/s to 80/s and their intensity was varied over a 70 dB intensity range in order to study the rate and intensity functions of each of the response components. With increasing click intensity, the amplitude of the first wave (generated by the auditory nerve) increased proportionally while the amplitudes of the later waves (generated by the brainstem auditory nuclei) reached their maximum amplitudes at intermediate click levels (saturation), and at high intensities occasionally even decreased in amplitude. The latency of each of the waves decreased by similar amounts as the intensity was increased. With increasing click rates, the amplitude of the first wave decreased the most, while there were smaller effects on the amplitude of the later waves. There was no effect of click rate on the latency of the first wave, but the latency of the later waves increased with click rate, the effect being greater on the later waves. In the rate functions, the latency change of a wave was greater than that of the waves preceding it (accumulative effect). These results are explained by overlapping convergence and divergence in the ascending auditory pathway. These results support the notion that the principal component of each wave is activated by the principal component of the previous wave. These results may explain the relative ease with which several workers record the fourth wave of the complex, and their preference for this response.


Role of the levator veli palatini muscle in movement of the lateral pharyngeal wall. In order to examine both the site and the muscle responsible for inward movement of the lateral pharyngeal wall, the following 3 observations were made. 1. Radiographic observation of the lateral wall by pasting a lead marker to the torus tubarius. 2. Cinematographic analysis of the lateral wall movement in relation to the velar elevation. 3. Anatomical observation of the levator muscle and the torus. Our conclusion was that the lateral wall movement was an inward displacement of the torus tubarius caused by contraction of the levator veli palatini muscle.


[Experimental demonstration of an identic antigenicity of the inner ear and kidney (author's transl)]. An allergic glomerunephritis was produced in rats by injection of an anti-basement-membrane-serum (IgG-fraction), taken from rabbits which were sensitized against a basement membrane fraction of rat-glomerula. Tissues from heart, liver, brain, lung and inner ear were compared with the well known alterations of the glomerula. Exclusively in stria vascularis and renal glomerula heavy changements of the basement membranes and endothelial cells could be shown by electronmicroscopic examination and by immunohistological methods.


A defensive role of IgE mediated reaction in the nose. Immunoglobulins of different classes are known to play a role in humoral defense mechanism, and Immunoglobulin E, without any actual evidence, is also expected to perform the same function. From the point of the defensive role the present study was undertaken in nasal allergy by observing the way in which powdered carbon particles previously insufflated in the nasal cavities are rapidly removed by nasal provocation with a causative allergen extract. The ratio of disapperance time of the carbon powder after/before provocation decreased markedly in good proportion with the intensity of the provocative reaction. Both sneezing and nasal secretion provocated contributed to this removal of the powder. When the nasal cavity on one side only was provocated, the non-provoked side also showed a rapid disappearance of the powder. In conclusion, Immunoglobulin E serves as a gate keeper by removing allergens from the surface of the nasal mucous membrane and by inhibiting the penetration of allergens into the nasal mucous membrane.


Morphological and physiological findings on hair cells with impaired metabolism (nitrogen, monoiodoacetate) in Caiman crocodilus with reference to sudden deafness. Morphological and physiological studies were carried out on Caiman crocodilus under experimentally produced metabolic changes. During N2-respiration the cochlear potentials responded differently. The negative component (CM-) of the cochlear microphonics decreased continuously, whereas the CM+ component showed only a little change. The summation action potential (AP) exhibited a similar behaviour to that of CM-. These alterations were reversible up to periods of 30 min N2-respiration. The morphological findings, after N2-respiration, showed an intracellular oedema of the hair cells. The afferent synaptic contacts are always recognizable. Different degrees of disintegration within the presynaptic structures were seen. Efferent axosomal and axodendritic synapses were unchanged. MIA-perfusion led to an irreversible decrease of the cochlear potentials (CM+; CM-; AP) and morphologically to a total destruction of the papilla basilaris. The changes in the presynaptic structures during anaerobic metabolism offer the possibility of a new explanation for the reversibility of sudden deafness.


[High frequency cinematographic investigations of the mode of operation of common drilling instruments on bone and cartilage (author's transl)]. High frequency cinematographic films were made of the mode of operation of common oto-surgical drilling instruments on bone and cartilage. Rose bits and surgical fraises of different sizes were used at 5,000-80,000 R.P.M. The evaluation of the slow motion pictures was performed on the running films and by review of single frames. In detail: The preparation of the drilling head on the bone without simultaneous flushing leads to a filling of the cutting channel and decreased cutting. Drop flushing only prevents the increasing soiling of the drilling head if the drop sequence is rapid and which must be markedly increased with increasing R.P.M. of the drilling instrument. Flushing with a stream of water, which definitely prevents soiling, is preferable. Both drop flushing as well as the water stream must continuously wet the drilling head, i.e. must be absolutely centric in every case. Safest is the automatic spray flusing which is mounted on the handpiece, but which has so far not been used in oto-surgery. During the preparation, the air space of the working area is always filled with drilling dust or haze. Cutting is always performed tangenitally. The cutting speed lies between 2,9 m/s to 16 m/s. It depends on the R.P.M. of the drilling instrument. A drill head running out of true, even with a gently percussing shaft, touches the bone only with a part of its cutting surface which strikes more vigorously than desired and easily gets soiled, despite flushing. Cutting is therefore less and uncontrolled. An increased feeding energy (pressure on the support) in order to speed up cutting leads to heavy wear of the drilling instrument and unsafety in handling due to jumping of the drilling head. During each contact of a cutter with the bone, coarse fraises with low R.P.M. (5,000 R.P.M. = 83 R/s) show a short stopping of the rotation which results in a jerk and vibration of the whole preparation and can thus lead to a damage of the inner ear.