Opposite effects of dexamethasone on serum concentrations of 3,3',5'-triiodothyronine (reverse T3) and 3,3'5-triiodothyronine (T3). Dexamethasone, 2 mg every 6 hours for 4 doses, was given to 4 hypothyroid patients receiving treatment with synthetic thyroxine (T4) and to 8 untreated hyperthyroid patients with Graves' disease, and serum concentrations of thyroid hormones were measured by radioimmunoassays. Serum concentration of 3,3'5'-triiodothyronine (reverse T3, rT3) increased appreciably within 8 hours after the first dose of dexamethasone, was maximum at 24-32 hours after beginning dexamethasone, and remained elevated for about 24 hours after discontinuing the steroid. The mean baseline serum rT3 was 58 ng/per 100 ml in treated hypothyroid patients and 119 ng per 100 ml in patients with Graves' disease; the corresponding maximal post-dexamethasone serum rT3 values were 87 and 170 serum concentration of 3,3',5-triiodothyronine (T3) decreased. The decrease in serum T3 was significant at about 24 hours after beginning dexamethasone and was maximal at about 30 hours in both groups of cases under study. The decrease in serum T3 persisted in treated hypothyroid cases for about 24-48 hours and in Graves' disease cases as long as studied, at least 5 days after discontinuing hexamethasone. The changes in serum rT3 and T3 could not be attributed to the effect of dexamethasone on serum protein binding of the iodothyronines because the dialyzable fractions of rT3 and T3 following steroid administration were not different from those before it. Serum T4 did not change appreciably in treated hypothyroid cases, but decreased in Graves' disease cases from a mean baseline value of 23.5 mug per 100 ml to 18.4 mug per 100 ml 3 days after beginning dexamethasone. In addition, 3 hyperthyroid cases were studied before, during, and after administration of dexamethasone, 2 mg every 6 h for 5 days. Serum rT3 increased again as noted above and the increase persisted until about 24 hours after the last dose of the steroid. Serum T3 decreased considerably and remained decreased as long as studied, at least 4 days after discontinuing the steroid. Serum T4 decreased appreciably in 2 of the 3 cases studied. The data suggest that 1) conversion of T4 to T3 and to rT3 may occur via two distinct pathways in the metabolism of T4; 2) the changes in serum rT3 and T3 observed in our study may be due in part at least to a steroid-induced 'shift' in the metabolism of T4 whereby conversion of T4 to T3 is diminished and that to rT3 is enhanced; 3) in addition to the effect on peripheral metabolism of T4, steroids appear to reduce the circulating thyroid hormones in Graves' disease by another mechanism, probably by reduction in thyroid secretion.


Determinations of nonprotein nitrogen content of cheese whey. Nonprotein nitrogen in pooled sweet (Cheddar and Dagano) and acid (cottage) wheys was estimated by currently proposed dialysis and chemical precipitation methods. Kjeldahl nitrogen analyses of (a) membrane retentates after water dialysis, and (b) 12% trichloroacetic acid plus .2% phosphotungstic acid filtrates indicated that nonprotein nitrogen values vary significantly with the method of sample preparation. Membrane porosity influence nonprotein nitrogen values for molecular weight cut-offs of 3500, 6000 to 8000 and 12,000 to 14,000. Dialyzable nitrogen values with all membranes were lower than 12% trichloroacetic acid soluble nitrogen for both wheys and higher than the 12% trichloroacetic acid + .2% phosphotungstic acid soluble nitrogen for all but the 3500 molecular weight cut-off membrane. The dialyzable nonprotein nitrogen fraction was heterogeneous but more that 80% was less than 3500 in molecular weight.


Role of the blood-brain barrier in the anticholinergic differential effects on LH and prolactin release in proestrous rats. The effects of homatropine and atropine on plasma LH and prolactin (PRL) levels during the afternoon of pro-oestrus were investigated. Homatropine methylbromide was unable to block the spontaneous increase of LH but prevented the prolactin surge in pro-oestrous rats at doses of 450 and 700 mg/kg s.c. Atropine sulphate blocked both LH and PRL at doses of 450 and 700 mg/kg s.c. These two anticholinergics when injected into the 3rd ventricle (250 mug/rat) blocked the pro-oestrus increase of LH and inhibited PRL. Pharmacological experiments were performed in parallel and the injection of either homatropine or atropine (450 mg/kg s.c.) resulted in the abolishment of peripheral toxic signs induced by pilocarpine (50 mg/kg s.c.) whereas its central toxic signs were prevented by atropine but not by homatropine. Our findings suggest that the difference in action of systemic injections of atropine and homatropine on LH and PRL release is explained by a relatively low permeability of homatropine to the brain. Therefore, cholinergic LH-controlling mechanisms may be situated above the median eminence and those related to PRL placed outside the blood-brain barrier.


Defective phagocytosis due to deficiencies involving the tetrapeptide tuftsin. A description of the symptoms and causes of tuftsin deficiency is presented. Two major causes which give rise to a deficiency of the tetrapeptide (thr-lys-pro-arg) are discussed. One is familial tuftsin deficiency syndrome that results from an inherited mutation involving the tetrapeptide. All patients give a history of repeated infection with variable severity. One parent, father or mother, is deficient and occasionally other siblings may have the disease. The other type of deficiency is the result of loss of splenic function whether it is due to surgical removal of the spleen and to infarction or infiltration of the organ. A method for the assay of tuftsin activity is described.


Effect of parenterally injected benzimidazole compounds on Echinococcus multilocularis and Taenia crassiceps metacestodes in laboratory animals. In mice infected with metacestodes of Taenia crassiceps, the following compounds were at least partially effective when injected intraperitoneally at the dosage indicated: cambendazole (500 mg/kg), mebendazole (6.25 mg/kg), oxibendazole (500 mg/kg), 5-benzamido-2(4-thiazolyl)benzimidazole (500 mg/kg), 2-carboethoxyamino benzimidazole (125 mg/kg), and 2-carbomethoxyamino benzimidazole (500 mg/kg). The following were inactive at the dosage indicated: parbendazole (500 mg/kg), thiabendazole (1,000 mg/kg), and fenbendazole (1,000 mg/kg). Mebendazole, which showed some activity at 6.25 mg/kg, was highly active as a single intraperitoneal dose at 25 mg/kg. When injected subcutaneously, mebendazole was much less active than when given intraperitoneally. In mice infected with metacestodes of Echinococcus multilocularis, intraperitoneal injection of mebendazole at 75 to 150 mg/kg, daily for 3 days, was highly effective (95 to 100% reduction in cyst mass). In contrast, oral administration at 1,000 mg/kg, daily for 3 days, was only partially effective. The drug was also effective when given intraperitoneally to infected cotton rats. A water-soluble benzimidazole, carboxymethyleneamino cambendazole, was approximately 50% effective in mice when injected daily for 3 days at a dosage of 75 or 150 mg/kg. The results suggest that, in metacestode infections of medical importance, it may be possible to kill the parasite by delivering a drug to its immediate vicinity, and so to reduce the required dosage with respect to the host.


Natural antibodies directed against murine lymphosarcoma cells. Natural antibodies reacting in a test of complement-dependent cytotoxicity with untreated murine lymphosarcoma cells of thymic origin were found in murine sera. Normal thymus cells were unaffected and unable to absorb the serum activity. The natural antibodies were IgM-like and stable at 56 degrees C. They were not uniformly distributed in the studied strains, and high (C3H/He and C3Hf), intermediate (AKR and CBA/J), and low level strains (BALB/c, DBA/2, C57BL, and C57BL/6J) were found. Hybrids between a high (C3Hf) and a low level strain (C57BL) had the same response as the parental C3Hf mice. An inverse relationship was demonstrated between cytotoxicity of, and susceptibility to, serum of lymphoma cells in a given strain, which suggested that an immunologic modulation was at work. Embryonic cells absorbed the cytotoxic activity of the normal serum.


Intrathyroidal parathyroid adenoma or hyperplasia. An occasionally overlooked cause of surgical failure in primary hyperparathyroidism. In six surgically proved intrathyroidal parathyroid tumors, neither thyroid scan nor gross appearance of the thyroid at surgery allowed reliable detection of parathyroid glands wholly within the thyroid. Preoperative selective catheterization of thyroid veins with radioimmunoassay for parathyroid hormone facilitated successful removal of hyperfunctioning intrathyroidal parathyroid tissue in all five cases in which it was performed.


Therapeutic balloon occlusion of the inferior vena cava. Thirty-five patients with venous thromboembolism and indication for inferior vena cava (IVC) interruption were treated by experimental balloon occlusion. Experience with this group resulted in the development of a method and equipment to allow transjugular obstruction of the IVC in the awake patient receiving anticoagulants. The study showed that the new method is atraumatic even when applied to sick patients, that it permits simultaneous treatment with anticoagulants and venous occlusion, and that long-term results (to more than four years) are excellent.


Transient atrioventricular standstill. Etiology and management. Four patients with different clinical conditions had transient cardiac standstill for periods of up to 22.5 seconds. All patients showed signs of cerebral ischemia and required cardiac resuscitation. In one patient, the standstill was thought to be the result of a transient increase in the vagal tone, and no long-term therapy was required. In the second patient, cardiac standstill occurred during hospitalization for impending myocardial infarction. Coronary arteriography followed by coronary artery surgery was performed, and there was no further episodes of standstill. In the third patient, standstill was probably related to long-term ingestion of propranolol hydrochloride, and was not observed after this medication was discontinued. In the fourth patient, standstill was the result of the sick sinus syndrome, and a permanent pacemaker was inserted. Standstill of both atria and ventricles may occur under different clinical settings, and management of arrhythmia should be guided by thf etiology of the arrhythmia.


Effect of television violence on children and youth. One hundred forty-six articles in behavioral science journals, representing 50 studies involving 10,000 children and adolescents from every conceivable background, all showed that violence viewing produces increased aggressive behavior in the young and that immediate remedial action in terms of television programming is warranted. Four major issues are covered: effects on learning, emotional effects, the question of catharsis, and effects on aggressive behavior. The research findings regarding each of these issues are summarized, as well as the controversial 1972 Surgeon General's report, Television and Social Behavior. The time is long past due for a major, organized cry of protest from the medical profession in relation to what, in political terms, I consider a national scandal.


Do volunteer donors decrease posttranfusion hepattis? A change from a paid to a volunteer blood donor system was instituted as recommended by the American Association of Blood Banks "Statement on the National Blood Policy." The incidence of counterelectrophoresis HBSAg positive units from each donor group was determined. Of 2,785 purchased units, 3 (0.10%) were HBSAg positive, while 34 (0.94%) of 3,609 units from volunteers were HBSAg positive. This 840% increase suggests that careful selection of donor population rather than blind reliance on volunteers should be emphasized in providing the safest blood for transfusion.


Glucorrhea revisited. Prolonged promulgation of another plastic pearl. Glucose oxidase test strips were used to evaluate the presence of glucose in nasal secretions and tears in a group of normal children. Substantial amounts of glucose were present in 15 of 17 samples of nasal discharge and 10 of 15 samples of tears. The use of glucose oxidase test strips for diagnosis of cerebrospinal fluid rhinorrhea, therefore, is without merit.


High-dose bolus urography. A superior technique in advanced renal failure. High-dose bolus urography was evaluated in 38 patients with severe renal failure. Iothalamate meglumine (Conray 60) (2 ml/kg of body weight) was injected within one minute and nephrotomograms were taken for 30 minutes, with delayed films until 24 hours. Immediate nephrograms were obtained in all cases. The collecting systems, seen in 29 cases, were dilated in three. In the rest, obstruction could be ruled out by a combination of roentgenographic criteria. No untoward reactions occurred, and all the required information was obtained within 30 minutes. The results were superior to plain nephrotomography or infusion pyelography. We conclude that bolus nephrotomography is the procedure of choice in the investigation of severe renal failure.


Knee stability and knee ligament injuries. Controversy exists on the relationship of knee ligament stability to knee injuries. Subjective evaluation of joint tightness or looseness has been proposed as a criterion for prescribing selective corrective strengthening or stretching exercises. Biomechanical studies of knee ligament stability were performed on 401 college football players from 1969 to 1971. Forty-three knee ligament injuries occurred during this period of time, 19 (44.2%) in "loose-jointed" players and 24 (55.8%) in "tight-jointed" players. Joint laxity tests were performed on 72 college football players; the distribution of college football players failing to perform each of the tests was quite different from that reported for professional football players. There was no relationship between the subjective joint laxity tests and the objective biomechanical tests of knee ligament stability. We conclude that it is not possible to predict knee injuries by subjective evaluations of joint laxity or by objective biomechanical knee ligament evaluations and that exercise programs based on subjective studies are therefore not sound.


Hopelessness and suicidal behavior. An overview. The relation of hopelessness to levels of depression and suicidal intent was explored both psychometrically and clinically. The results of an investigation of 384 suicide attempters support previous reports that hopelessness is the key variable linking depression to suicidal behavior. This finding has direct implications for the therapy of suicidal individuals. By focusing on reducing the sources of a patient's hopelessness, the professional may be able to alleviate suicidal crises more effectively than in the past.


Transtracheal ventilation.

Transtracheal ventilation. Effective percutaneous oxygenation and ventilation can be achieved through the use of transtracheal catheters. A graphic study of pressure-flow requirements through different-sized catheters can serve as a guide for the caliber and driving pressure requirement to obtain optimal oxygen flow.


Pulmonary embolism with factor XI deficiency. A patient with factor XI deficiency had pulmonary embolism, although his factor XI assay was less than 1% of normal and his postoperative course was complicated by prolonged bleeding. Programs designed to prevent postoperative venous thrombosis should be carried out in factor XI-deficient patients, since the deficient state offers no protection from a pulmonary embolus. All surgical patients who are to receive low-dose heparin therapy as a part of such a program should be screened by means of preoperative determination of the partial thromboplastin time, to identify previously unsuspected bleeding disorders.


Thrombosis of the renal veins and vena cava. Occurrence in morbid obesity. Renal vein thrombosis caused the nephrotic syndrome in a patient with morbid obesity. Pulmonary embolism occurred initially, but not after anticoagulants were administered. Surviving for three years, the patient died of profound uremia and hyperosmolar coma. At autopsy, membranous glomerular changes were found. Conclusive exclusion of renal vein thrombosis in the morbidly obese patient with nephrotic syndrome appears advisable.


Hormone treatment of breast cancer.

Hormone treatment of breast cancer. Alteration of the hormonal milieu is still one of the major and most successful methods for treating advanced breast cancer. With the exception of the use of thyroid hormone in conjunction with corticosteroids, we are not aware of any proved advantageous combination of hormonal agents that improves the objective regression rates in advanced breast cancer.


Appraisal of the double two-step exercise test. A long-term follow-up study of 3,325 men. We made an evaulation of the double two-step exercise test in the diagnosis and prognosis of coronary artery disease, on the basis of the findings among 3,325 male applicants for life insurance who were given the test and observed for an average of nine years. The results suggest that (1) ischemic ST segment depression of any amount after exercise is pathognomonic of coronary insufficiency, for all practical purposes; (2) the amount of ischemic depression is related to the severity of the coronary insufficiency and the prognosis; (3) ischemic depression in multiple leads denotes widespread coronary insufficiency; (4) a nonischemic response practically excludes coronary disease of a type that will cause premature death; and (5) the exercise test is more reliable than the medical history in the diagnosis of silent coronary disease.


New drug introduction 1973-1974.

New drug introduction 1973-1974. A review of the number of newly synthesized drugs introduced in the United States during the years 1973 and 1974 reveals that there has been an encouraging improvement in comparison with the previous two-year period. The number for 1971 to 1972 was 25, and for 1973 to 1974, thirty-seven. These drugs can be grouped into nine major therapeutic classifications. Some represent real advances in therapy; others enable the physician to vary his therapeutic regimen. In 1974, of all new and refill prescriptions, 68% were filled with 200 drugs. Of these, 126 contain one active ingredient, and 76 products contain more than one. The number of prescriptions written for each group is in close relationship to the number of drug products in each class.


Control of methadone dosage by patients. Patients in a methadone clinic were given knowledge and control of their own dosages. Dosages could be changed by 5 mg/week, but if more than 50 mg was used, no take-home privileges were allowed. The maximum dosage permitted was 120 mg. Plasma methadone levels were determined for some patients. The result of the study was that there was little dosage change, with the median dosage increasing from 40 to 50 mg at the end of six months. A small group of patients did raise their dosages systematically, and these patients tended to decrease illicit opiate use. There was no indication that these patients had abnormally low plasma methadone levels. At the end of six months, patients and staff overwhelmingly preferred an open-dose self-adjustment system over the usual procedure of dosage management by professional staff and dosage changes achieved by negotiation.


Geophagia. A cause of life-threatening hyperkalemia in patients with chronic renal failure. Geophagia has been associated with life-threatening hyperkalemia in five patients with chronic renal failure. All five patients were black and had been born in the southeastern United States. Four had had frequent hyperkalemia requiring at least one hospitalization, and two had had hyperkalemia with serum potassium concentration as high as 9.8 mEq/liter, resulting in cardiac arrest in one and paralysis, disorientation, and cardiac arrythmia in the other. Since riverbed clay contains as much as 100 mEq of potassium in 100 gm of clay, much of which is exchangeable at acid pH, the mechanism of geophagia-induced hyperkalemia appears to be the absorption of potassium released from clay after ingestion. After discontinuing geophagia, no new hyperkalemic episodes occurred in these patients.


The management of cerebral metastasis.

The management of cerebral metastasis. Central nervous system (CNS) metastases are a common clinical problem, and management spans the three major therapeutic disciplines in oncology. Surgery, radiotherapy, and chemotherapy are employed alone, in combination, or sequentially and are based on four local factors--the number, size, site, and depth of the lesions; and three tumor factors--the natural or biologic history of the primary tumor, the quantitative host tumor burden, and the tumor responsiveness to individual therapeutic modalities. The median survival of patients with CNS metastasis is 3 to 12 months and is not necessarily compromised by the CNS lesions, if the diagnosis is established and therapy promptly instituted.


Acute heat stroke. Epidemiologic, biochemical, renal, and coagulation studies. Fifteen Marine recruits with acute heat stroke were examined for (1) predisposing factors, (2) blood coagulation disturbances, (3) renal function abnormalities, and (4) blood composition alterations. Epidemiologic data identified the following risk factors; previous residence in a temperate climate, first phase of training, fatigue, and strenuous exercise in hot, humid conditions. Results of blood coagulation studies disclosed an increase in prothrombin and partial thromboplastin times, with a decrease in platelet count, probably indicating a transient, low-grade consumptive process. Blood urea nitrogen and creatinine levels and creatinine clearance were normal. Only mild elevations of SGOT, SGPT, and lactic dehydrogenase levels were noted, and in combination with clinical observations, they argued against significant muscle damage. No deaths or instances of renal failure occurred.


"Caring" as part of health care quality. The subjective aspects of "caring" are an important part of health care quality and should be understood in the context of the illness-recovery process and the physician-patient relationship. "Caring" requires sensitivity on the part of the physician to the role of illness in our society and to the emotional component of illness in every patient. The patient's emotional response to the health care he or she receives should be respected as a valid aspect of health care quality. It is a continuing challenge to the medical profession to include some means of assessing this aspect of health care as part of professional standards review. As Dr Peabody noted, "The secret of the care of the patient is in caring for the patient."


Ethyl alcohol sniffing by patients undergoing hemodialysis. Seven uremic patients undergoing long-term hemodialysis became addicted to vapors of denaturated ethyl alcohol. Sniffing produced relaxation, euphoria, and a sense of well-being. In all but one patient, this was the the only form of deviance. Two patients who tried stopping this practice while under psychiatric help were unsuccessful because of acute abstinence symptoms. Denaturated ethyl alcohol does not seem to be toxic per se. In these patients, results of hematological and liver function tests were within normal limits. Anemia supervened in one patient after two years of dialysis, and peripheral neuropathy developed in another.


Hepatitis B in Nuremberg, Germany. Epidemiology of a drug-associated epidemic. Among US Army soldiers. Beginning in 1971, acute viral hepatitis was epidemic among US soldiers stationed in Europe, with a total of over 8,700 cases reported between 1971 and 1974. Hepatitis B surface antigen (HBsAg) determinations suggest a predominance of hepatitis B. In the Nuremberg area, primary association was with the illicit use of drugs. This association was demonstrated by a chronologic relationship between measurable community drug use and the number of hepatitis admissions three to six months later and by a case-control study. Parenteral drug use and, to a lesser degree, cannabis smoking appeared to be factors in disease transmission. Sharing of illicit drugs with a hepatitis contact, whether parenterally or orally, was associated with increased risk of contracting the disease.


Migration of plasticizer from hemodialysis blood tubing. Preliminary report. Di-2-ethylhexyl phthalate was found to be migrating from polyvinyl chloride blood tubing into human blood during hemodialysis in 16 patients with end-stage renal failure. Although toxic effects have not yet been observed, we believe plastic tubing that does not contain extractable materials should be developed.


Left atrial myxoma: diagnosis, treatment, and cytological observations. A patient first seen with cardiac cachexia was found to have a large left atrial myxoma. The diagnosis was first suggested by echocardiographic examination. Cure was achieved by surgery. Light and electron microscopic studies indicate a multipotential mesenchymal cell origin of myxomata.


Haemobartonella canis infection in research dogs. During 1970-1972 haemobartonellosis occurred in research canines at 2 widely separated institutions. Clinical anemia occurred in a splenectomized dog at a Maryland facility, and subsequent screening disclosed an infection rate of 65% in a group of 20 splenectomized subjects. Treatment was successful, and the animals were used in research. A research institution in Texas encountered a number of dogs with fever (to 106 degrees F) and eosinophilia (to 42%) following minor surgery. Blood from affected animals was injected iv into splenectomized dogs, and 3 of 6 recipients developed haemobartonellosis. Further study was conducted, with some success, to establish a relationship between fever and eosinophilia and Haemobartonella canis infection in nonsplenectomized subjects. Our experiences suggest that haemobartonellosis is a widespread, latent disease of dogs and that significant potential exists for the infection to adversely affect research results.


Histopathological study on six cases of calf leukosis. A pathological study was carried out on six calves 4 to 10 months of age affected with lymphoid tumors. Most of the lymph nodes enlarged in consequence of leukotic changes in all the calves. These changes occurred also in other various organs. When the leukotic lesions were investigated to clarify the distribution and histological manifestation, three pathological patterns were discriminated among them. One of the patterns was seen in four cases, in which leukotic lesions were present constantly in bone marrow, thymus, liver and kidney. In the lymph nodes, tonsils, and intestinal lymphatic apparatus, neoplastic cellular proliferation took place in paracortical or interfollicular areas and medullary cords obliterating the lymph follicles. Leukotic involvement was observed in the interstitial and the vascular connective tissue in the thymus, as well as in liver and kidney. A second pattern of lesion was revealed in one of the other two cases. Besides lymph nodes in which neoplastic proliferation was seen in the paracortical area, only the thymus manifested intralobular neoplastic involvement in this case. In the remaining case, the leukotic lesion was characterized by the presence of neoplastic cellular masses resembling large lymph follicles in appearance in the lymphatic tissues. It was manifested distinctly in the spleen. Severe thymic atrophy and granulocytic hyperplasia in bone marrow were present in this case.


Telencephalic leucoencephalopathy in premature infants dying after prolonged artificial respiration. Report on 6 cases. This study reports clinical and neuropathological findings in six premature infants dying after prolonged assisted ventilation (IPPB and CPPB) due to pulmonary insufficiency (gestational age: 26.--32. week; birth weight 820--1400 Gm; respirator therapy 41--143 days; survival 104--263 days). During the rspirator therapy the children developed marked extensor rigidity of the trunc and spasticity of the extremities. Postmortem examination revealed cor pulmonale and right ventricular failure. Signs of marked perinatal brain damage were missed. The slightly atrophic brains showed predominant damage to the telencephalic white matter of varying intensity ranging from focal necroses to gliosis and retarded myelination. Constant findings were increased vascularisation and transformation of the premyelinating glia into astrocytes in the deep and subcortical white matter. This form of telencephalic leucoencephalopathy indicates the particular vulnerability of the developing white matter in conditions with chronic hypoxia, hypercapnia, acidosis and vascular congestion. The varying intensity of the lesions suggests that, in principle, minor lesions are either reversible or may be compensated in surviving children.


Spectral analysis of the abnormal theta rhythm in the EEG of young children. The abnormal theta rhythm of the EEG of early childhood was investigated by spectral analysis. The pattern in the power spectrum is characterized by a peak in the thetaband. The relative peak intensity (peak ratio = ratio of peak intensity and average intensity of the spectrum within the frequency range of 0--10 Hz) as well as the right-left coherence proved to be good criteria for the description of the abnormal theta rhythms. When the ratio q greater than or equal to 2.0 and the coherence Coh greater than or equal to 0.7 an abnormal theta rhythm can be considered to be present. When this definition is applied, a high correspondence between the mathematical and visual evaluation of the EEG is present. The abnormal theta rhythm must be regarded as a symptom of a functional anomaly which is -- under electroencephalographic aspects -- characterized by generators acting in abnormal synchronism and monofrequency.


[The relationship between age and the cerebrospinal fluid protein profile profile of normal children. Cellulose acetate and agarose gel electrophoretic studies]. Neuropädiatrie 6: 383--397 (1975). CSF samples of 63 normal children 2 days to 14 years of age were concentrated (ultrafiltration in "Kollodiumhülsen") and examined by electrophoresis on cellulose acetate and agarose gel. In the CSF of all children 7 protein fractions were found by cellulose acetate electrophoresis. Analysing the pherograms by the means of an analog computer 15 fractions could be separated by agarose gel electrophoresis. Compared with the children of school age the newborn showed low prealbumin, beta1-globulin and tau-globulin fractions besides high albumin and gamma-globulin concentrations owing to an increased permeability of the blood-CSF barrier. During the following weeks a low prealbumin and a high albumin fraction still was found. Children from 3 month to 2 years of age showed a moderate increase of the relative prealbumin and beta1-globulin concentration in comparison with older children. The gamma-globulin fraction was lowest beyond the third month of life and increased again in the group of the 2--14 years old children. The variation of the protein profile with age could not only be demonstrated by the more difficult agarose gel electrophoresis but also by a simple technique of cellulose acetate electrophoresis.


[A dysplasia-epilepsy syndrome in a patient with ring chromosome 21]. We report a 10 year old girl with psychomotor retardation, myoclonic syndrome and extreme photosensitivity. Clinical symptomatology and EEG-findings were not compatible with any of the known myoclonic syndromes. The patient's remarkable phenotype with short stature, dystrophy, facial dysmorphia characterized by antimongoloid palpebral fissures, broad root of the nose, coarse nose, inner epicanthic folds, dysplasia of the external ears, higharched palate, syndactylism between 2nd and 3rd toes on both sides, small narrow hands is suggested of a chromosomal disorder. A ring-shaped chromosome of the G-group (21--22) could be found. After using the Giemsa- and C-banding technique this chromosome could be identified as number 21. Patients with ring chromosome 21 or 22 are phenotypically not distinguishable. This is due to duplication-deficiency-variability of ring chromosomes in growing somatic tissues. The cellular genotype of ring chromosomes varies between monosomy, trisomy and polysomie.


[Oculocerebrovertebral syndrome].

[Oculocerebrovertebral syndrome]. After description of the oculovertebral syndrome Weyers-Thier a personal observation is reported. It was characterized by severe cerebral malformations (agenesis of the olfactory lobes, incomplete agenesis of corpus callosum with large sagittal arachnoidal cyst) associated with polycystic brain damage. The relationship of this "oculovertebral syndrome" to the "oculoauriculovertebral syndrome" is discussed. The combination of various malformations in our observation indicates an embryonic lesion between the 4th and 11th week. Additional polycystic brain damage was due to perinatal anoxy. The causal factor of the malformative syndrome remains unknown, but similar lesions were experimentally induced by fetal hypoxia.


[Why are some cases of Hashimoto's thyroiditis operated on? Apropos of a series of cases]. Hashimoto's thyroiditis is a polymorphous condition. Its clinical diagnosis depends on the presence of a moderately large goitre of recent onset (2-3 yr) that is usually symmetrical and node-free, and particularly hard and rubbery. In addition, a high level of antithyroid antibodies is observed. A search for these antibodies should certainly be made more often. Histological confirmation is required as soon as the level of antibodies is low, or when the goitre is nodular with cold scintiscan areas. Furthermore, development of the intrathyroid lymphoid system is of uncertain import, especially since there is no relation between the number of cells that could theoretically be secreting antibodies (i.e. intrathyroid plasma cells) and the incidence or level of the various antithyroid antibodies.


[Value and limits of different method in diagnosis and differential diagnosis of retroperitoneal tumors within the lymphatic systems (author's transl)]. The demonstration of retroperitoneal intralymphatic primary or secondary tumors requires a progressive radiological investigation beginning with simple methods and advancing to more complicated ones. Radiological lymphography is a method which is superior due to its ability to demonstrate small structures in lymphatic vessels and lymphnodes. However, the usefulness of lymphography is limited partially to the retroperitoneal lymphatic system and to gross changes. To improve diagnostic accuracy further diagnostic measures are needed, namely intravenous urography, venocavography, lumbar venography of catheter, sonotomography of the upper abdomen and lymphatic scintigraphy. Exstirpation of lymphnodes- possibly by explorative laparotomy- and histopathological examination enables an extact assessment of lymphnodes of microscopical dimension as determination of the tumor type. The value and limits of complementary methods and the criteria for the diagnosis and differential diagnosis of metastatic lymphnodes and lymphoreticular systemic diseases are discussed. The significance of lymphography for evaluation of topographic expansion of pathological lymphnode changes, the further course of the disease and the effect of therapy according to the authors' experience are presented. It is stressed that the value of lymphography in diagnosing the type of disease is limited.


Diffuse osteosclerosis with lymphocytic lymphoma. A case report. A unique case of diffuse osteosclerosis of the hemopoietic skeleton in a patient with lymphocytic lymphoma is described. Biopsy findings excluded a concurrent myeloproliferative disorder.


[Multiple intracranial arterial aneurysm of mycotic appearance. Repeated vascular embolic accidents. Myxoma of the left atrium]. The authors describe a case of myxoma of the left auricle disclosed by repeated cerebral embolism and multiple aneuryms of mycotic appearance of the cerebral arteries in a woman exhibiting no cardiac symptoms. The immediate post-operative results were excellent. In the light of 7 similar cases in the literature, diagnostic and prognostic points are analysed.


Medium-long incubation posttransfusional hepatitis (a possible immunological implication). Icteric hepatitis which developed in the first 6 months after blood transfusion was studied in 159 cases. One fourth of these (39) occurred within a period of only 15 days: between the 30th and 45th day after transfusion. So, their incubation period was longer than that of short incubation hepatitis (type A), and shorter than that of long incubation hepatitis (type B). In these cases the incidence of HBs antibodies was more than 10 times greater than in hepatitis with long incubation, and the incidence of HBs antigen was approximately the same as in the healthy control group. This fact suggests the involvement of a special factor in their appearance, probably an immunologic (or of other nature) process giving rise to antigen-antibody complexes in the HB ag-ab system.


Primary evolution of chronic hepatitis estimated 3 to 14 years after the liver biopuncture. From over 800 patients with chronic hepatic diseases admitted to the Institute of Internal Medicine between 1960-1969 and in whom diagnosis was assessed by hepatic biopuncture, 180 were reexamined 3-14 years later to estimate the clinical evolution and the prognostic value of the bioptic findings. The evolution was favourable in most of the cases of persistent chronic hepatitis (70%) and of moderate aggressive chronic hepatitis (59%). Severe aggressive chronic hepatitis evaluated favourably in 34% of the cases and was aggravated in 42% of the cases (26% exits). In the patients with cirrhosis the percentage of deaths reached 65 but 30% were still in a stationary form; a single exceptional case was improved 7 years after the hepatic biopuncture. The prognostic value of hepatic biopuncture is much increased if, in addition to the common histological features, other histochemical and morphological criteria such as: structural stability of collagen fibers, importance of cellular infiltrates and presence of plasma cells, nuclear changes, degree of steatosis, amount of glycogen storage, siderosis and cholestasis are also taken into consideration.


Enzymatic equipment of lymphocyte lysosomes in the premature or term infants and in the adults. The activity of some lymphocyte lysosomal enzymes such as: acid phosphatase, beta-glucuronidase and beta-glucosaminidase was studied comparatively in 29 prematures, 20 term infants and 20 adults. The activity of lysosomal enzymes was found to increase gradually in the course of fetal maturation and later on after birth. The percentage of lymphocytes exhibiting strong intracellular acid phosphatase and beta-glucuronidase activity was highest in adults. Differences between lymphocyte beta-glucuronidase activity in the term infants and that in adults were less evident. The results of the study seem to confirm the previous assumption of certain authors that B lymphocytes, generally characterized by a low activity of lysosomal enzymes, are more numerous in the premature and term infants than in the adults.


Biogenesis of erythropoietin: evidence for pro-erythropoietin in a subcellular fraction of kidney. The light mitochondrial fraction of hypoxic rodent kidneys, called the renal erythropoietic factor, contains erythropoietin in a pro, or active form. Erythropoietin is released from this inactive form when the renal erythropoietic factor is incubated with normal serum. The biogenesis of erythropoietin possibly involves a system in kidney reminiscent of the proinsulin-insulin system in pancreas.


Human placental lactogen and plasma total oestriol values in the third trimester of pregnancy. The value of serial human placental lactogen and plasma total oestriol measurements in assessing fetoplacental function early in the third trimester, is discussed. In particular, the use of the two measurements simultaneously may provide an indication of impending fetal death, of growth retardation, or of gross fetal malformation.


Endoscopy in patients with malignant conditions of the gastrointestinal tract. Two hundred and fifteen consecutive upper gastrointestinal endoscopies were performed. It is evident that the patient population in our setting is quite different when compared with that of a general hospital. The incidence of both gastrointestinal hemorrhage and unknown primary malignant tumor is high. In this group of patients, malignant lesions of the stomach were the most common problem encountered. Primary malignant tumors of the stomach account for the diagnoses in approximately 20 per cent of our patients. Fifty per cent of the patients with cancer of the stomach demonstrated invasion of the lower part of the esophagus or esophagogastric junctional area. The accuracy of endoscopic biopsy was correct in 83 per cent of the patients with malignant tumors of the stomach detected by scopic examination. Thirteen per cent false-negative biopsies occurred from infiltrating diffuse lesions. Endoscopy established the diagnosis of carcinoma of the stomach in one-third of the patients with adenocarcinoma of unknown primary source.


[Peridural anesthesia in obstetrics (author's transl)]. In German speaking countries peridural anesthesia in obstetrics has been introduced 25 years ago by Anselmino. Because of the increase of operative delivery and the--however rare--serious complications in the mother the technique has been employed less and less. Now, with the introduction of the catheter technique, which renders lower doses of the anesthetic effective and with improved treatment of complications due to it, the technique has become safer for the mother. Anomalies of the position of the fetal head are not more common than in deliveries without peridural anesthesia. But the more frequent need for low forceps delivery remains, since the strain-reflex is abolished, although motorfunction of lower limbs and abdomen are intact. The safe use of peridural anesthesia requires a considerably increased personnel, since the doctor conducting the delivery is only rarely sufficiently qualified in anesthetics and even then should not have to take the responsibility for both delivery and anesthesia. Since we can consider the technique safe for the mother, its effect on the child is predominant interest. Examination of the acid-base metabolism in the fetal blood from the scalp and umbilical cord post-partum has shown favorable results. The effect of complete painlessness on respiration and blood-gases of the mother is of interest (Strasser, Huch, Huch). Further investigations of the effects on fetal heart frequency and its assessment in supine or constant lateral positioning and of the maternal circulation with modern cardiologic techniques have not yet been concluded. On their results will depend, at least in part, the indication for peridural anesthesia in pregnancies and deliveries at risk. Clinical observations and comparison with deliveries under general anesthesia indicate that catheter peridural anesthesia may be advantageous for the child with diabetes, EPH gestosis and prematurity.


Ferrous and hemoglobin-59Fe absorption from supplemented cow milk in infants with normal and depleted iron stores. Small amounts of milk do inhibit ferrous iron absorption from a 5 mg 59Fe2+ dose in 1- to 18-month-old infants. Only 50 ml of 2/3 cow milk reduced the absorption from 18+/-3% (Xa +/- S.E.) to 3.8 +/- 1.2% in infants with normal iron stores (inhibition index 0.21) and from 26 +/- 3% to 8.5 +/- 1.4% in infants with depleted iron stores (inhibition index 0.33%). Milk does not inhibit the bioavailability of hemoglobin iron. From a 5 mg dose of hemoglobin-59Fe added to 50 ml of 2/3 cow milk 4.8 +/- 1.0% were absorbed by infants with normal iron stores and 8.3 +/- 0.8% by infants with depleted iron stores. The low iron content of milk (50 mug Fe/100 ml) and its poor bioavailability (approximately5% in infants with normal iron stores) would require a dialy consumption of 32 1 of unfortified milk to cover infants daily iron requirement of 0.8 mg/day. The supplementation of 2--3 milk meals per day with 5 mg hemoglobin iron each meets the whole iron requirements of infants with depleted and normal iron stores respectively and can be used for iron prophylaxis in infancy during the first and second year. Prophylaxis with inorganic iron requires an empty stomach and duodenum for optimal bioavailability. A daily dose of only 5 mg ferrous sulfate iron is enough to cover the total iron requirement of infants.


Management of myogenic (myopathic) ptosis. In senile ptosis and late-acquired hereditary ptosis, the Fasanella-Servat procedure is dependable and successful. However, levator resection by the posterior approach is appropriate for the more severe problems. In senile ptosis, a search should be made for signs that might prompt disinsertion repair. The decision for surgery in patients with chronic progressive external ophthalmoplegia or myotonic dystrophy should be made cautiously, and the "optical tarsectomy" should be considerable before conservative levator resection or fascia lata suspension. The patient with myasthenia gravis should be identified, medical evaluation initiated, and except in rare instances, surgery avoided. The more unusual forms of myogenic ptosis should be treated surgically only when the ptosis persists and has stabilized.


Radioimmunoassay of (8-arginine)-vasopressin. I. Methodology. A radioimmunological method for the determination of the human antidiuretic hormone [8-arginine]-vasopressin (AVP), is described in detail. The antiserum has been raised in rabbits injected with AVP adsorbed onto charcoal particles and is used at a final dilution of 1:200,000. It contains antibodies directed specifically against the C-terminal tripeptide and possesses a high association constant of 8.2 x 10(12) 1/mole. AVP is labelled in monoiodinated form (as proven after pronase digestion) at a high specific activity close to the theoretical maximum after purification from unlabelled hormone on Sephadex gel. The standard curves are characterized by a Bo of 55%, a limit of detection ascertained at least at 3 pg (10% displacement) and a 50% displacement achieved with 35.5 pg. The index of precision lambda ranges from 0.033 to 0.042. The conditions of the assay (buffer's composition and pH, timing) were systematically varied and tested. In addition the result of immunization of chicken with AVP is reported. The assay is adequate for the measurement of AVP in urine and plasma and will be described in forthcoming papers.


Radioimmunoassay of (8-arginine)-vasopressin. II. Application to determination of antidiuretic hormone in urine. A radioimmunoassay for [8-arginine]-vasopressin (AVP), previously described (Czernichow et al. 1975) has been used for the determination of antidiuretic hormone in a 4 ml urine sample. AVP is extracted from acidified urine with a cation exchanger (Amberlite CG 50) with an overall recovery of 72%. The blank value measured in extracted samples of urine was 0.29 pg/ml +/- 0.21 (SEM) and calculated by extrapolation of the regression line of the recovery experiment was 0.49 pg/ml. The coefficient of variation within-assay was 13% and between-assay 18%. Addition of the amounts of AVP found in each specimen of urine voided gave results nearly identical to those of the amounts found in 24 h pool of urine, indicating that the assay was not affected by changes in concentration of the other urinary components during the day. The daily urinary excretion of AVP measured in 34 subjects was found to be 34 ng in 17 women and 70 ng in 17 men, a significant difference. Urinary concentration and excretion rate of AVP rose during thirst test and during Carter-Robbins test performed in 13 healthy subjects. In the latter test it was observed that the women displayed a strikingly more pronounced AVP elevation after the osmolar stimulus than the men. In both sexes a significant correlation was found between AVP excretion rate and plasma osmolality as well as free water clearance. Three cases of complete or incomplete diabetes insipidus and potomania could be clearly differentiated according to the total output of AVP during the thirst test. Extremely high values of AVP were found in the urine of 5 subjects with Schwartz-Bartter syndrome associated with bronchogenic tumours.


Synthetic human calcitonin: analysis of antibodies obtained from various animal species and determination of immunoreactive hormone in human sera. Antibodies to synthetic human calcitonin (hCT) were developed in rabbits, goats and mice. The free peptide (32 amino-acid residues, Mwt. 3418) was administered together with adjuvant, and the effect of various immunization procedures, as well as of different dose-levels, was evaluated comparatively. Synthetic hCT was found to be a good immunogen for the three animal species examined. The relative importance of various structural parts of the hCT molecule with regard to immunological specificity was determined by reference to the inhibition of the specific binding of 125I-hCT to antibodies by peptide fragments of hCT. All the antisera studied were directed to structural and/or conformational properties of the 11-28 or 11-32 amino acid sequence of hCT. Six different antisera from rabbits and goats were selected for radioimmunological assay of hCT on the basis of their inhibitory dose50-values and immunological specificity. To improve the sensitivity of the radioimmunoassay (RIA), we studied the preparation of radioiodinated hCT and assessed various parameters determining the sensitivity of the assay. Despite all the efforts, CT in human plasma from healthy subjects could not be determined with certainty. The difficulties encountered in the determination of normal levels of circulating CT are discussed in terms of the sensitivity of RIA and non-specific interference of serum factors with RIA.


Effects of hypothyroidism and thyroxine substitution on the metabolism of L-methionine, L-cystathionine and taurine in developing rat brain. In hypothyroidism induced by radioiodine the activity of cystathionine synthase and the concentration of L-cytathionine in cerebrum and cerebellum of developing rat decreased markedly. The amount of taurine was significantly higher in cerebral and cerebellar tissue of hypothyroid rats than in corresponding parts of normal rat brain. Early substitution therapy with L-thyroxine corrected these changes.


Action of growth-promoting hormones on macromolecular biosynthesis during lobulo-alveolar development of the entire mammary gland in organ culture. The entire 2nd thoracic mammary gland of the immature virgin BALB/c mouse was stimulated to full lobulo-alveolar (LA) growth after 120 h organ culture in hormone supplemented medium. The minimal hormonal combination required was insulin (I) + prolactin (Prl) + aldosterone (A). The corticosteroid was replaceable by oestradiol-17beta (E) + progesterone (P). The combination I alone or I + the steroid hormone(s) failed to induce the LA development and similar results were also evident in presence of Prl + the steroids. Incubation of the glands in medium with I + Prl + A activated a sequential rise of RNA, protein and DNA synthesis. A near maximal increase of RNA synthesis was present at 48 h in the medium with I + Prl, addition of the steroid hormones did not show further stimulatory effect. Supplementation of the medium with I + Prl and the adrenal or the ovarian steroids was needed for maximal activation of protein synthesis at 72 h and DNA replication at 96 h. The medium with I alone did not show a substantial rise of macromolecular biosynthesis in the mammary gland in organ culture. The highest level of DNA polymerase activity was observed at 72 h in glands cultivated in medium with I + Prl and A or E + P. Only a modest increase of DNA polymerase activity was present in glands cultivated with I alone or I + Prl. Prior treatment of the glands (cultivated with I + Prl + A) with actinomycin D or puromycin resulted into 44 and 40% reduction of DNA polymerase activity suggesting hormone-induced synthesis of the enzyme before the rise of DNA synthesis in the mammary cells at 96 h in organ culture. Significance of these results with respect to the action of the "growth-promoting" hormones in the mammary gland in organ culture and in the animal has been discussed.


Aminoglutethimide and glutethimide: effects on 18-hydroxycorticosterone biosynthesis by human and sheep adrenals in vitro. The conversion of [1,2-3H]corticosterone to 18-hydroxycorticosterone in vitro was studied on human and animal adrenal tissue homogenates. Human adrenals were surgically resected from a patient with Cushing's disease. Sheep adrenal homogenates were prepared from the pooled glands of 20 animals. Incubations supplemented with a NADPH generating system were performed in order to evaluate the effect of aminoglutethimide and its closely related compound glutethimide on corticosterone 18-hydroxylation in vitro. Increasing concentrations of the two drugs were assayed on both human and animal adrenal homogenates. Aminoglutethimide was clearly found to inhibit corticosterone 18-hydroxylation in sheep adrenal homogenates as a 72.6% inhibition occurred in the presence of only 0.2 mumole of the drug. Inhibition reached 91.1% in the presence of 0.5 mumole aminoglutethimide. When added to the human incubated adrenal, a 59.4% inhibition occurred in the presence of 0.5 mumole aminoglutethimide. Glutethimide, a sedative of wide clinical usage, was also found to inhibit corticosterone 18-hydroxylation but the inhibitory effect occurred only in the presence of much higher concentrations. In fact, 5.0 mumoles were necessary to obtain a 43.9% inhibition of 18-hydroxycorticosterone synthesis. This study clearly demonstrates the marked inhibitory effect of aminoglutethimide on corticosterone 18-hydroxylation. Glutethimide, to a lesser extent, also inhibits 18-hydroxycorticosterone synthesis.


Circadian rhythm of plasma corticosteroid in adult female rats: chronological shifts in abnormal lighting regimens and connection with oestrous cycle. The circadian rhythm of plasma corticosteroid (CS) levels in adult female rats was studied chronologically under the following conditions: normal light-dark (LD), inverted light-dark (DL), constant dark (DD) and constant light (LL). Animals were accustomed to LD condition for 7 days before exposure to each abnormal lighting regimen. Normal circadian rhythm established under LD condition was clearly inverted on the third day of DL regimen, and the inverted rhythm persisted thereafter under DL condition. The circadian CS rhythm persisted essentially unchanged throughout DD condition, but lost its regular periodicity showing "free running" and changed day by day under LL condition. The average CS levels over a 24 h period were higher under LL than under DD condition. Plasma CS levels in each lighting regimen exhibited diurnal variations regardless of the vaginal smear patterns of autopsied animals. Exposure of rats to LL for 21 days made the circadian CS rhythm flat, but induced persistent oestrus in only a few animals. The data suggest that (1) an unexpectedly rapid inversion of the circadian CS rhythm occurs if animals are exposed to inverted light-dark environment; (2) constant darkness seems to be a near-natural environment for rats, and changes little of the pre-established circadian CS rhythm; (3) constant light, on the contrary, is assumed to be a stress for rats, and disrupts the circadian CS rhythm and elevates CS levels; (4) the change in circadian CS rhythm in adult female rats is not mediated by a change in gonadal function and the two conditions may not be connected directly with each other.


Variations in the concentration of testosterone in peripheral venous plasma from healthy women. The concentration of testosterone (ng/100 ml; mean +/- SD) has been determined in peripheral venous plasma at 4 hourly intervals for 24 h from 9 non-pregnant women (39.8 +/- 11.8) and 9 during late pregnancy (70 +/- 32). In addition, the level of this hormone has been measured in samples of plasma removed daily (between 08.30 and 10.00 h) throughout 9 ovarian cycles (41.6 +/- 11.8), and weekly from 10 women during gestation (57.6 +/- 14.7). The results show that there is considerable individual variation in both the concentration and pattern in serial samples over the respective time scales. The values of the arithmetic mean from non-pregnant subjects show that there is a tendency for the concentration to be lower between 20.00 and 04.00 h. However, the differences between the values at defined times over a 24 h period are not statistically significant. During the ovarian cycle 3 subjects had peak values during the peri-ovulatory phase, 2 in the luteal, 1 in the follicular and 3 showed no consistent pattern. There was no significant difference in values (40.9 +/- 11.8, 41.9 +/- 11.9 and 41.8 +/- 11.9) for the 3 phases of the cycle. There is a significant rise in the concentration of plasma testosterone during pregnancy (P less than 0.0005), but the pattern of the arithmetic mean is not related to the corresponding values for progesterone or oestradiol. During late pregnancy (34 weeks to term) there is a change in the nycterohemeral pattern, with the highest mean values occurring between 16.00 and 04.00 h. The results are discussed.


Effect of ampicillin administration on the excretion of twelve oestrogens in pregnancy urine. The excretion of twelve oestrogens in urine, pooled daily from a group of pregnant women, was determined before, during and after ampicillin administration (2 g/day, for 3 days). On the second day of ampicillin administration total oestrogen excretion fell to 67% of the mean control value, oestriol excretion to 69% and that of the other eleven individual oestrogens to an average of 62% of the mean control values. In general, on the third day of treatment and on the two post-treatment days this decrease tended to be corrected. The patterns of change in the urinary levels of the individual metabolites provided no clear lead to the basic mechanism of ampicillin impairment of oestrogen excretion. However, as the drug affected all their excretion in more or less the same way as it did that of oestriol, it is possible that ampicillin interferes primarily with their enterohepatic circulation in the mother as has been established with reasonable certainty in the case of oestriol.


Progesterone 20 alpha-dihydroprogesterone and 20 beta-dihydroprogesterone levels in different compartments from the human foeto-placental unit. The endogenous levels of progesterone, 20 alpha-dihydroprogesterone and 20 beta-dihydroprogesterone in different foetal tissues, in placental tissue and in foetal blood during pregnancy (week 9-25) were determined by gas-liquid chromatography or by radioimmunoassay. The identification of these steroids in foetal tissues was based on the behaviour in paper and thin-layer chromatography, the formation of different derivatives, and the retention times in gas-liquid chromatography. For additional identification of progesterone and 20 alpha-dihydroprogesterone a mass spectrum was obtained. The average concentrations of progesterone (P), 20 alpha-dihydroprogesterone (20 alpha-DHP) and 20 beta-dihydroprogesterone (20 beta-DHP) in foetal tissues were as follows (ng/g wet weight tissue): brain, P 119.0 +/- 45.5, 20 alpha-DHP 86.9 +/- 44.7 and 20 beta-DHP 9.7; lungs, P 257.7 +/- 195.7, 20 alpha-DHP 60.3 +/- 26.4 and 20 beta-DHP 7.8; liver, P 103.7 +/- 84.6, 20 alpha-DHP 95.2 +/- 89.8 and 20 beta-DHP 17.8; adrenals, P 295.7 +/- 90.0 20 alpha-DHP 254.5 +/- 194.6; kidneys, P 214.2 +/- 155.3 and 20 alpha-DHP 76.6 +/- 43.0; intestine, P 273.2 +/- 166.7, 20 alpha-DHP 77.9 +/- 51.2 and 20 beta-DHP 8.7; residual tissues, P 246.3 +/- 178.3 and 20 alpha-DHP 54.8 +/- 44.5. The average concentrations in placental tissue and in foetal plasma (week 12-18) were as follows (ng/g wet weight tissue or ng/ml plasma): placenta, P 2619. +/- 2153.6 and 20 alpha-DHP 461.0 +/- 155.9; foetal plasma, P 378.7 +/- 231.8 and 20 alpha-DHP 283.0 +/- 108.9. These results indicate that some foetal organs contain a high 20 alpha-reductase activity at least during the first half of pregnancy.


Progesterone, 20 alpha-dihydroprogesterone and 20 beta-dihydroprogesterone in mother and child at birth. In 14 healthy pregnant women at term progesterone (P) and 20 alpha-dihydroprogesterone (20 alpha-DHP) were determined by radioimmunoassay both in the maternal and foetal compartments. The average concentrations were as follows (ng/ml blood or ng/g wet weight tissue):  peripheral maternal blood P 56 +/- 26, 20 alpha-DHP 16 +/- 8; placental tissue P 2514 +/- 1516, 20 alpha-DHP 429 +/- 412; placental blood P 365 +/- 160, 20 alpha-DHP 35 +/- 18; blood of the umbilical vein P 388 +/- 121, 20 alpha-DHP 33 +/- 15; blood of the umbilical arteries P 162 +/- 62, 20 alpha-DHP 28 +/- 10. In 5 healthy pregnant women at term progesterone (P), 20 alpha-dihydroprogesterone (20 alpha-DHP) and 20 beta-dihydroprogesterone (20 beta-DHP) were also determined by gas-liquid chromatography both in the maternal and foetal compartments. The average concentrations were as follows (ng/ml plasma or ng/g wet weight tissue): peripheral maternal plasma P 129 +/- 49, 20 alpha-DHP 15 +/- 15, 20 beta-DHP 1.7 +/- 0.9; placental tissue P 5060 +/- 1435, 20 alpha-DHP 230 +/- 158, 20 beta-DHP 38 +/- 30; placental plasma P 723 +/- 245, 20 alpha-DHP 24 +/- 13, 20 beta-DHP 1.0 +/- 0.1; plasma of the umbilical vein P 740 +/- 227, 20 alpha-DHP 17 +/- 3, 20 beta-DHP 1.2 +/- 0.3; plasma of the umbilical arteries P 324 +/- 94, 20 alpha-DHP 17 +/- 5, 20 beta-DHP 2.6 +/- 2.1. These results show that, contrary to the progesterone concentrations, no significant difference exists in the concentrations of 20 alpha-DHP and 20 beta-DHP between the blood from the umbilical vein and arteries. Furthermore, no significant difference could be found in the concentrations of P and 20 alpha-DHP between the sexes in either the blood from the umbilical vein or from the umbilical arteries.


Metabolism and mode of action of androgens in target tissues of male rats. V. Uptake and metabolism of cyproterone acetate and its influence on the uptake and metabolism of testosterone and 5alpha-dihydrotestosterone in target organs and peripheral tissues. In order to get more information on the mode of action of anti-androgens, two series with low but biologically active doses of cyproterone acetate were started. In the first experiments 12 mug of [3H]cyproterone acetate was injected intravenously into adult rats castrated 3 days before treatment. Thirty min after injection the radioactivity uptake in the target organs and other tissues was measured. The metabolites were separated by thin layer chromatography. A large pool of radioactivity could be shown in the liver. Thin layer chromatography revealed that in this pool cyproterone acetate had been converted by more than 80% to one metabolite. In blood plasma, too, the metabolite accounted for the major part of radioactivity. When compared to skeletal muscle, the prostate, seminal vesicles, and m. bulbocavernosus and m. levator ani accumulated more radioactivity. Within 30 min unchanged cyproterone acetate was retained selectively thus showing its relative high affinity to target organs. In a second experimental series, adult castrated male rats were given 10 mug of cyproterone acetate intravenously 30 min before the injection of [3H]testosterone or [3H]5alpha-dihydrotestosterone. Under this condition androgen uptake in target tissues was reduced to about 70% of the control values. The data parallel the results of in vivo studies on cytosol receptor displacement of androgens by cyproterone acetate. In agreement with previous investigators no significant influence of the anti-androgen on androgen metabolism was observed. The importance of the findings concerning the mode of anti-androgen action is discussed.


Effects of oestradiol-17 beta benzoate treatment on fracture healing and bone collagen synthesis in female rats. The influence of oestradiol-17 beta benzoate, 70 mug administered intramuscularly twice a week for up to four weeks, on collagen synthesis in fractured bones, was studied in young adult castrated female rats. The specific activity of [14C]hydroxyproline in the fracture region of the treated rats was constantly below that of the normal and the castrated control animals throughout the experimental periods. The percentage of incorporated 14C found as [14C]hydroxyproline was also reduced in the fracture regions of the oestrogen treated rats compared to the percentage observed in normal rats. During the first two weeks after fracture and the start of treatment, there was no differences in tensile strength of the fractures and no significant difference in collagen content of the fractured tibia of the 3 experimental groups. The weights of the unfractured tibiae in oestrogen treated rats were lower than those of the control animals. The findings suggest a "slow down" of collagen metabolism after administration of high doses of oestradiol.


The effect of different doses of oestradiol-17 beta on collagen synthesis in the femur of castrated female rats. The effect of different doses of oestradiol-17beta on collagen metabolism in the femur of castrated young mature female rats was studied. The animals received daily injections of the hormone for 21 days and 25 muCi [14C] proline was injected intraperitoneally 24 h before the rats were sacrificed. The rats receiving 1 mug oestradiol per day had a significantly higher specific activity of hydroxyproline in bone compared to the normal and the castrated control rats. At the same time the bone weights and collagen content per femur was less in the rats receiving oestradiol 1 and 2 mug/day than in the control animals. The higher specific activity of bone hydroxyproline in the rats receiving oestradiol-17beta 1 mug/day did not, however, indicate a higher bone collagen accretion rate. As all rats received the same amount of [14C] proline, and the body weights differed considerably at sacrifice, tha naimals probably had different tissue fluid concentrations of [14C] proline. This possibility was supported by the observation that serum concentrations of radioactivity were inversely correlated to body weights. "Correcting" for differences in body weights, the castrated control rats turned out to be the group with the highest specific activity. On doses of 10 and 20 mug oestradiol-17beta per day, the specific activity of hydroxyproline in bone was lower than in the control rats while bone weights and collagen content of the femur were not different from the corresponding values of the castrated controls. This finding suggests a "slow down" of collagen metabolism - both with regard to the accretion and the resorption.


Adrenocortical responses following sciatic nerve stimulation in rats with partial hypothalamic deafferentations. Studies from this laboratory have demonstrated that the adrenocortical response following sciatic nerve stimulation is completely inhibited in rats with hypothalamic islands, indicating that this response depends entirely on the activation of afferent neural pathways to the hypothalamus. With the purpose of identifying the site of entry of these neural pathways into the mediobasal hypothalamus the effects of partial hypothalamic deafferentations were studied. It was found that in rats with posterior or posterolateral deafferentation the adrenocortical responses were similar to those obtained in intact rats, while anterior and anterolateral deafferentation resulted in a reduction of 62.3 and 53.3%, respectively. These results would indicate that the sciatic impulses which activate the adrenocortical response involve neural afferents which enter the mediobasal hypothalamus by an anterior pathway.


The effects of dexamethasone and starvation on body composition and regional adipose tissue cellularity in the rat. In order to examine regional effects of corticosteroids on the depot fat distribution a dose of dexamethasone that produced changes in fat cell weight (40 mug per kg per day) was administered to rats. Starved rats were included for comparison. Starvation caused a decrease in depot fat and fat cell weight proportional to the characteristic fat cell weight of that region. In comparison with the changes found in the depots of pair-fed rats the effects of dexamethasone in this dose were largely the same. The epididymal adipocytes behaved differently and were emptied more slowly than their weight indicated.


Changes in ovarian and pituitary function in non-pregnant women during the infusion of prostaglandin F2alpha. The concentrations of prostaglandin F2alpha, progesterone, oestradiol, LH and cortisol have been determined in serial samples of peripheral venous plasma, before, during and after, the intravenous administration of prostaglandin F2alpha (50 mug/min, for 5 h) to 8 women in the luteal phase of the ovarian cycle. The results show that the mean concentrations of prostaglandin F2alpha and cortisol increased during the infusion by factors of 8.8 and 2.6 respectively. The highest levels of cortisol occurred after 3 h, and were significantly different (P less than 0.0005, Student's t-test) from those obtained before the infusion. There were progressive decreases in the concentrations of LH and progesterone. After 3 h the values for LH were significantly lower (P less than 0.0025) than those before the administration of prostaglandin F2alpha, and the lowest mean value was 26% of the control. The values for progesterone were significantly lower (P less than 0.025) after 5 h, and the mean value at this time was 38% of the control. The pattern of the mean concentration for oestradiol was similar to that for progesterone. The levels of all 5 compounds had returned to normal within 1 h after completion of the infusion. The findings are discussed.


Progesterone, oestradiol-17 beta and testosterone levels in the follicular fluid of tertiary follicles and Graafian follicles of human ovaries. Radioimmunoassays of testosterone (T), oestradiol-17 beta (Oe2) and progesterone (P) in the fluid of a total of 47 follicles of different degrees of maturity gave the following mean values: T: 49 ng/ml, Oe2: 932 ng/ml, P: 999 ng/ml. In normal, atretic and cystic tertiary follicles not larger than 1 cm and without luteinized theca interna the following mean values were calculated: T: 54 ng/ml, Oe2: 502 ng/ml, P: 368 ng/ml. In six women mature and less mature follicles were compared, the former having significantly higher Oe2 and higher P values but significantly lower T values than the latter. Genuine Graafian follicles were observed four times, once after HMG stimulation; the values observed lay within the following ranges: T: 12-35 ng/ml, Oe2: 1900-4100 ng/ml, P: 156-6000 ng/ml. The difference in concentration compared with cubital-vein blood before ovulation was highest for Oe2, suggesting a particularly marked aromatinzing activity of the follicles of that phase of the cycle. The findings suggest that in the course of accelerated follicular ripening prior to ovulation both the aromatizing enzyme and 3 beta-hydroxysteroid-dehydrogenase are activated, resulting in a sharper rise in Oe2 and P. The profuse production of P causes a transistory lack of precursors for androgen and oestrogen production (T and Oe2 declines). In the course of an overall increase in steroid production during the luteal phase - which probably goes hand in hand with an increased supply of pregnenolone - there is not only a pronounced rise in progesterone but also a moderate increase in oestrogen production. The androgens are transformed more rapidly into oestrogens on account of the marked activity of the aromatizing enzyme in the corpus luteum and thus show a decline in the luteal phase.


Metabolism of oestradiol-17 beta and oestrone in the human uterus. A study of the metabolism of oestradiol in the human endometrium and  myometrium of the proliferative and secretory phases of the cycle showed that the conversion of oestradiol to oestrone by endometrium in the proliferative phase was higher than that in the secretory phase. The decreased metabolic activity of the secretory phase endometrium was attributed to the influence of progesterone on the endometrium. The metabolic conversion of oestradiol to oestrone was enhanced when pyridine nucleotides were added to the system. The conversion of oestradiol to oestrone was maximum in the cytoplasmic and nuclear fractions of the endometrium. Furthermore, the conversion of oestradiol was low in all the subcellular fractions of the myometrium as  compared with the endometrial subcellular fractions. The presence of co-factors increased the metabolic conversion of oestradiol to oestrone in the subcellular fractions of the endometrium. The presence of 17 beta-hydroxysteroid oxidoreductase was indicated in all the subcellular fractions. A correlation was found between the amount of oestradiol and oestrone bound to the receptors in the uterus and the rate of metabolism of oestradiol in the uterus. The physiological significance of metabolism of oestradiol and the hormone action are discussed.


Circannual and circadian rhythms in plasma testosterone in five healthy young Parisian males. Every other month, during the course of 14 months, the circadian rhythm in plasma testosterone (among others variables) of 5 healthy males (26 to 32 years) was documented. Subjects' synchronization: light-on at 7 +/- 1 h; light-off at 23 +/- 1.5 h during the whole year. Blood sampling 4-hourly, at fixed times during 28 h, for radioimmunological testosterone determinations. The cosinor method was used for statistical analyses. An annual rhythm in the testosterone 24-h mean is detected (P less than 0.025) with a peak in October (from 16 July to 26 December, with 95% confidence limits). Annual mean (+/-1 se)= 759 (+/- 26) ng/100 ml. Peaktrough difference=197 ng/100 ml (from 106 to 290 with 95% confidence limits). The timing of the testosterone circadian peak, in the 24-h-scales also varies during the course of the year. The peak is found around 8 h in May and around 14 h in November, this phase-shift being statistically significant (P less than 0.05).


Asymmetrical gonadal differentiation and gonadoblastoma. Clinical, cytogenetic and histological findings. Case report. A 10 10/12 years old virilized girl with the syndrome of asymmetrical gonadal differentiation is reported. The patient had a negative sex chromatin and positive Y chromatin (bright fluorescent body of Y chromosome) in the buccal smear and 45,X/46,XY karyotype in the peripheral blood lymphocytes. An exploratory laparotomy showed a small uterus, two Fallopian tubes, a tumoural testis on the right side and a streak on the left side. Pathological examination revealed the presence of gonadoblastoma in both gonads. The Y chromatin was identified on histological sections only on the side of the testis, and was absent on the streak and its gonadoblastoma's nests. The distribution of the different cell lines and the fluorescence of the Y chromosome is discussed in relation to gonadal differentiation and the occurrence of gonadoblastoma.


RNA, protein and DNA synthesis stimulated by testosterone, insulin and prolactin in the rat ventral prostate cultured in chemically defined medium. In an organ type tissue culture of the rat ventral prostate in a chemically defined medium insulin (0.08 IU/ml) stimulated the synthesis of RNA  within 6-12 h, the synthesis of protein within 6-12 h and the synthesis of DNA within 2-4 days. Testosterone (10(-8)m) stimulated these synthetic processes somewhat more slowly: the synthesis of RNA within 12-24 h, protein within 12-24 h and DNA at 4 days. Rather high concentrations of insulin were needed while testosterone was effective at a physiological concentration. Prolactin (1000 ng/ml) stimulated the synthesis of RNA and protein, but not DNA, when added together with either testosterone or insulin, but was completely ineffective when added alone. The response times resembled those of insulin. The lower concentrations of prolactin were ineffective. Growth hormone, luteinizing hormone and follicle stimulating hormone did not stimulate the synthesis of RNA, protein or DNA even when added with testosterone. The results confirm the findings of the numerous in vivo experiments that the hypophyseal hormone prolactin has a direct effect on the ventral prostate.


In vitro studies on collagen metabolism in metaphyseal rat bone. A. The effect of pre-treatment with oestradiol-17 beta. The effect of oestradiol-17 beta treatment on bone collagen metabolism in vitro was studied in metaphyseal rat bone. Rats were oophorectomized and subsequently treated for 3 weeks with different doses of oestradiol-17 beta. Bone pieces were incubated in a modified Krebs-Ringer bicarbonate medium for 6 h. Synthesis of (14c)hydroxyproline from (14C)proline and the incorporation of this amino acid into the bone samples was determined and the collagen synthesis and accretion rates calculated from these data. Collagen resorption rates were calculated from measured release of non-radioactive hydroxyproline to the medium. Castration resulted in an increased rate of accretion and resorption of collagen. All doses of oestradiol tested in this study (1 to 20 mug per animal per day for 3 weeks) decreased both accretion and resorption rates to levels insignificantly different from those of the non-castrated control rats. Only the 2 mug treated group had significantly better collagen balance than the castrated untreated rats.


In vitro studies on collagen metabolism in metaphyseal rat bone. B. The early effects of oestradiol-17 beta. In vitro collagen metabolism in metaphyseal bone has been studied during the first few hours and days after the start of in vivo treatment of castrated female rats with various doses of oestradiol-17 beta. Already during the first 2 h after the start of treatment with oestradiol-17 beta 2 mug/day and within the first 24 h in the rats receiving 20 mug/day, a reduction of the collagen incorporation rate was demonstreated. The incorporation rates remained at approximately the same reduced level during the following 3 weeks. In rats receiving oestradiol-17 beta 1 mug/day no such reduced incorporation rate could be demonstrated during the first 36 h after the start of treatment. The bone collagen resorption rate was significantly elevated during the first 3 days of treatment in the animals receiving oestradiol-17 beta both 1 and 20 mug/day. After this time the resorption rates gradually fell to levels significantly below controls at 3 weeks after start of treatment.


In vitro studies on collagen metabolism in metaphyseal rat bone. C. The effect of oestradiol-17 beta in hypophysectomized and in thyro-parathyroidectomized animals. Oestradiol-17 beta has been administered to hypophysectomized/castrated and to thyro-parathyroidectomized/castrated young mature female rats. Treatment with oestradiol-17 beta 5 mug/day per animal, was continued for 3 weeks. Bone pieces from tibia/femur metaphyses were incubated in vitro for 3 h in order to establish the bone collagen synthesis and resorption rates. The results were compared to results from a previous study on castrated female rats with intact hypophysis, thyroid and parathyroid glands. Bone from the thyro-parathyroidectomized/castrated rats treated with oestradiol-17 beta had a significantly reduced collagen resorption rate in vitro as compared to their paired controls. This is a result consistent with that of castrated female rats with intact thyroid and parathyroid glands treated with oestradiol. Oestradiol-17 beta had no detectable effect upon collagen metabolism in the hypophysectomized/castrated rats. It is concluded that the effect of oestradiol on bone resorption is not exerted via the parathyroid glands or parathyroid hormone. The possibility that oestrogens may act on bone via the hypophysis is discussed.


In vitro studies on peroxidase movement in the epithelium of prostaglandin-treated rabbit ciliary bodies. The movement of horseradish peroxidase (HRP) in the epithelium of isolated rabbit iris/ciliary body preparations, has been studied with the electron microscope. HRP was applied at the stromal side of the epithelium, and was left for 60 and 120 min. The distribution pattern of HRP found in the epithelium of the iridial and ciliary processes is consistent with in vivo studies, i.e. the progression of HRP is blocked at the site of the zonula occludens of the superficial epithelium. The HRP distribution pattern found in the iris epithelium indicates that also the superficial epithelial cells of this epithelium are girdled by zonulae occludentes. Specimens treated with prostaglandins E1, E2, and F2alpha, showed no change in the epithelial distribution pattern of HRP, and the occluding zonules were found to be intact.


Electron microscopic studies on the blood-aqueous barrier of prostaglandin-treated rabbit eyes. I. Iridial and ciliary processes. Prostaglandins E1 and E2 were applied topically to rabbit eyes. Structures related to the blood-aqueous barrier in the iridial and ciliary processes, as well as the permeability of the ciliary epithelium to the protein tracer horseradish peroxidase, were studied with the electron microscope. Marked morphological changes, including dilations of the intercellular spaces and separation of the two epithelial cell layers, were found in the epithelium of the iridial processes. Only minor structural changes were found in the epithelium of the ciliary processes. Leakage of peroxidase through the intercellular spaces of the epithelium was demonstrated in the iridial processes and in the anterior parts of the ciliary processes. In the ciliary vessels of the same regions, opening of interendothelial gaps, platelet aggregations, microthrombi, and haemorrhages were found. In a previous in vitro study on the effects of prostaglandins on the movement of peroxidase in the ciliary epithelium, no structural changes of the epithelium were found, and the epithelial diffusion barrier to peroxidase was found to be intact. It is assumed that the breakdown of this barrier in vivo is secondary to vascular changes.


Electron microscopic studies on the blood-aqueous barrier of prostaglandin-treated rabbit eyes. II. Iris. The distribution of intravenously injected horseradish peroxidase in the iris of prostaglandin (E1 and E2)-treated rabbit eyes, has been studied with the electron microscope. Peroxidase was demonstrated in the stroma of all parts of the iris. The tracer was found throughout interendothelial clefts of iris vessels, indicating that these vessels had become permeable to peroxidase. The distribution of peroxidase in the iris epithelium indicates that the posteroir epithelial cells are girdled by zonulae occludentes.


Effects of ethyl alcohol on the directly recorded standing potential of the human eye. The effects of ethanol on the human standing potential (SP) were studied with a recently developed method, which allows direct SP recordings by means of a suction contact lens, temperature stabilized calomel electrodes and d.c. amplification. It is well known that the human SP oscillates with a frequency of about 2/hour in response to a sudden change in illumination. In the present paper marked cyclic variations of the SP, resembling damped oscillations, were provoked by a small oral dose of ethyl alcohol. A first maximum was reached after about 10 min. The difference in amplitude between the peak and the trough of the first oscillation was of the order of 4 mV. The oscillatory frequency was about 2/hour. The length of a cycle varied between 25 and 34 min in different volunteers, being fairly constant in the same subject on different occasions. The SP response to ethanol was similar both under scotopic and photopic conditions. The results correlate well with earlier findings of 2/hour oscillations in c-wave amplitude in response to ethanol, as may be expected considering the partly common origin of the c-wave and the SP.


Covariation of the simultaneously recorded c-wave and standing potential of the human eye. The c-wave and the directly recorded standing potential (SP) of the human eye were studied with the aid of a recently developed method including matched temperature stabilized calomel electrodes, d.c. amplifiers and a suction contact lens. This technique, which does not require general anaesthesia, permits simultaneous direct d.c. recordings of the SP and the c-wave in human volunteers during long-term experiments. Upon repetitive light flashes (stimulus duration 1 sec, interval 20 sec and flash intensity 4.5 rel. log units above b-wave threshold) both variables responded with slow amplitude oscillations with a frequency of about 2/hour. The oscillations were similar as to phases and frequencies. Both the potentials are held to be generated mainly in the pigment epithelium. Considering this partly common origin the observed covariation was an interesting finding.


Management of traumatic retinal detachment with pars plana vitrectomy, scleral buckling, and gas injection. Vitreous involvement as a result of penetrating trauma complicates and worsens the prognosis in retinal detachment repair. Seven patients in whom poor visualization of the fundus seemed to preclude success by routine procedures underwent combined vitrectomy, scleral buckling, release of subretinal fluid, and intravitreal gas injection. The retina was successfully reattached in five of the seven patients, although postoperative visual acuity was limited - possible on account of the duration of retinal detachment prior to repair or because of the degree of macular involvement.


Evolution of descending optic atrophy. A case report. Fundus changes following severe trauma to the intracranial optic nerve were followed by means of serial fundus photography. The eye was completely blind. Little change was seen during the first 4 weeks. The retinal nerve fibre layer disappeared gradually during weeks 4 to 8. At the same time the retinal vessels turned narrow, and vascular pseudo-sheathing appeared close to the optic disc. Disc pallor was not maximal until the 12th week, when the peripapillary retina also had acquired a mottled appearance.


Corneal thickness after cataract extraction with air in the anterior chamber. A total of 135 patients had the corneal thickness measured prior to cataract extraction. The chamber was re-established by air in 86, while the remainder acted as controls. On the second postoperative day the corneal thickness had increased by 12.7% in the air-inflated group, and by 17.6% in the control group. On the sixth postoperative day the increases in thickness were 7.2 and 11.1% respectively. On follow-up control 6 to 12 months later the corneal thickness was as before the operation. Epithelial oedema was significantly more frequent in the control group. The conclusion is drawn that an air bubble in the anterior chamber has no unfavourable effect on the corneal endothelium. On the contrary, it seems to protect the endothelium from postoperative damage.


Distribution of ascorbic acid in the ciliary body of albino rabbit, guinea pig and rat. The distribution of ascorbic acid in the ciliary body has been demonstrated by means of a silver nitrate technique. It appeared that the basal cells in the pars plana region and in the valleys between the ciliary processes contain great amounts of ascorbic acid, in contrast to the basal cells over the processes proper which showed only traces. Rabbit and guinea pig revealed mainly the same findings, and quantitative differences occurred before and after intracardial injection of ascorbic acid. On the other hand, ascorbic acid was absent in the ciliary body of untreated rats, whereas only traces were found after intracardial injection of this substance. These species differences are in keeping with previous reports showing high concentration of ascorbic acid in the aqueous humour from rabbit/guinea pig, and no ascorbic acid at all in aqueous humour from rats.


Retinal dystrophy combined with alopecia. Retinitis pigmentosa or pigmentary retinal dystrophy is the most important group among the tapeto-retinal dystrophies. The degenerative process found in the retina has, in many cases, a corresponding counterpart in other parts of the body, most commonly in the CNS. Combinations of retinal dystrophy, and for instance, deafness or mental retardation are well known. Also combinations of retinal dystrophy and metabolic dyscrasia have been reported. Only few reports on the combination of retinal dystrophy and dermatological affections have been found. We have found two cases of almost total alopecia combined with retinal dystrophy. Since we have succeeded in finding a few similar cases in the literature we consider this apparently rare combination worth a somewhat closer analysis as it might constitute a specific entity.


Mediastinal lymphosarcoma simulating pericarditis. A case of lymphosarcoma of the heart in a 10-year-old boy is presented. The clinical picture simulated a pericarditis. Prednisolone had a remarkably good temporary effect. Post-mortem examination showed a highly differentiated lymphosarcoma invading the pericardium and myocardium from a primary mediastinal localisation. Cytologic examination for malignant cells in the pericardial fluid must not be forgotten in a case of unexplained pericardial effusion.


A study of Graves' disease in Iceland.

A study of Graves' disease in Iceland. The incidence of Graves' disease and its response to treatment have been studied in Iceland, where the main environmental factor possibly affecting Graves' disease is a high iodine intake. The incidence was found to be similar or lower to that reported for Europe. The response to treatment with drugs and radioiodine does not differ from that found in other countries but recurrent hyperthyroidism after subtotal thyroidectomy is more common in Iceland.


Hydantoin derivatives and malignancies of the haemopoietic system. Two patients are described who developed malignant lymphoma (lymphosarcoma) after diphenylydantoin therapy because of epilepsy. Malignant lymphoma in a few patients receiving this medication has been described earlier. The literature has been reviewed and discussed recently by Rausing and Trell (2).


Interrelationships between the B-vitamins in B12-deficiency neuromyelopathy. A possible malabsorption-malnutrition syndrome. Five patients presenting clinically with a form B12-deficiency neuromyelopathy, with cord involvement in all and proximal muscle weakness in two of them, were investigated for their neurologic, hematologic and vitamin status. Megaloblastosis and achlorhydria were present in all, and impaired absorption of 57Co vitamin B12 and of D-xylose was detected in four. Total cyanide extracted vitamin B12 (A) was lowered in all cases and noncyanide extractable (B) in four of the five, being zero in three. All five responded to injections of hydroxocobalamin. In two patients sequential estimations showed that both A and B, especially the latter, rose steeply initially, normalizing at 50% of A after some weeks. Moiety B is suggested to be physiologically the more active and dissociable form of vitamin B12. Markedly elevated initial serum folate levels, and their subsequent fall under treatment with B12, indicated the operation of the "methyltetrahydrofolate trap". Blood levels of thiamin, nicotinic acid and pantothenic acid were within normal limits. However, serum riboflavin (B2) total vitamin B6 and pyridoxal were reduced in all where tested. Vitamin B6 deficiency could have resulted from its own malabsorption and have contributed to be B12 deficiency. Vitamin B2 and B6 levels also corrected themselves on B12 therapy. The B-vitamin deficiencies in our patients probably resulted from intestinal malabsorption, with a possible factor of malnutrition consequent to their strictly vegetarian diet.


Palpation thyroiditis (multifocal granulomatour folliculitis). Disseminated inflammatory lesions constituting a multifocal granulomatous folliculitis in the thyroid are described. These lesions were present in the majority (greater than 83%) of thyroids removed surgically because of thyroid or nonthyroid (carcinoma of the larynx) disease. They also were found at autopsy in patients who died while hospitalized but not in those who died at home. An identical lesion was produced experimentally in dogs by vigorously squeezing their thyroids. The human folliculitis is believed to result from traumatic injury or rupture of isolated thyroid follicles caused by palpation of the gland (palpation thyroiditis). Palpation thyroiditis may have little, if any, clinical importance. The remote possibility that it might be associated with iatrogenically produced metastasis of thyroid carcinoma is being investigated.


Extrarenal erythropoietin and erythrogenin production in the anephric rat. Serum erythropoietin and liver erythrogenin activity were studied in nephrectomized, male rats under variations in intensity and length of hypoxic exposure. In the anephric rat, serum erythropoietin levels parallel liver erythrogenin activity under both mild hypoxia (0.42 atm of air) and severe hypoxia (0.35 atm of air) over a 30-h time period. Further studies demonstrate that anephric rats subjected to 24 h of mild hypoxia, at a time when no elevated serum erythropoietin was detected, could once again be stimulated to produce extrarenal serum erythropoietin which was associated with elevated liver erythrogenin activity. These observations suggest that extrarenal erythropoietin production involves an erythrogenin-serum mechanism similar to the one postulated for renal erythropoietin production.


[The influence of enflurane (ethrane) on surface activity of the lung (author's transl)]. Enflurane (Ethrane), a new inhalation anesthetic, was examined for possible surfactant alterating properties. To elucidate this question two groups of rabbits underwent investigation: the first group (5 animals) was mechanically ventilated with room air over a five hour period. In the second group (7 animals) for the same period Enflurane in clinical dosages was added the inspired gas. At the end of the procedure in neither group could signs of impaired lung surface activity be detected: All rabbits showed normal blood gas values, normal pressure volume diagrams and physiologic behaviour of lung extracts in the wilhelmy balance. We conclude first that artificial ventilation "per se" does not harm lung surfactant and second that Enfluran anesthesia is a good choice for outstanding long procedures as well as for patients with already impaired surface activity of the lung, because there seems to be little risk of aggravating the situation.


Chemotherapy for canine lymphosarcoma.

Chemotherapy for canine lymphosarcoma. Twenty dogs with naturally occurring lymphosarcoma were histologically diagnosed, clinically staged, and treated with combinations of drugs, including corticosteroids, alkylating agents, plant alkaloids and antimetabolities. Clinical response was categorized as complete, partial, or unsatisfactory. Of the 20 dogs, 17 responded to the chemotherapy completely or partially, with a mean objective remission duration of 104.8 days. The mean survival time for 19 dogs was 211.5 days, whereas the mean survival time for 16 dogs which responded completely or partially was 233.7 days.


Malabsorption syndrome with cow's milk intolerance. Clinical findings and course in 54 cases. Fifty-four infants with the malabsorption syndrome and cow's milk intolerence seen during 1962-1971 were investigated. All had diarrhoea and failed to thrive. Most had vomiting and about 20% had atopic eczema and recurrent respiratory infections. Laboratory investigations revealed malabsorption, raised serum IgA, and precipitins to cow's milk. Biopsies showed that the jejunal mucosa was damaged, and in about half the cases was flat. The patient did well on human milk but reacted clinically to cow's milk challenge, either in a few hours or gradually during 3-4 weeks. Some patients showed first a quick, but later a slow, reaction. Clinical symptoms of cow's milk intolerance disappeared at the age of about one year. At that time 81% had normal faecal fat, but only 29% had a normal proximal jejunal mucosa. Many of the patients developed intolerances to other food proteins, such as soya and wheat, if these were given during the sensitive period. Forty-two patients have been followed up for 2 years on a normal gluten-containing diet. Of these, 37 have a normal or nearly normal jejunal mucosa and 5 (12%) have subtotal villous atrophy indicative of coeliac disease. It is concluded that the malabsorption syndrome with cow's milk intolerance is a clear-cut clinical entity. However, the symptomatology, results of laboratory tests, and jejunal biopsy findings closely resemble those of other entities where damage to the intestinal mucosa causes a malabsorption snydrome. Follow-up studies showed that the disease is transient, but about 10% of the patients have coeliac disease, regarded in such cases as the primary disorder.


Netherton's syndrome: an electronmicroscopic study. An ultrastructural study of 2 patients with Netherton's syndrome (bamboo hair, scaling dermatosis, and an atopic diathesis) showed features of psoriasis and a dermatitis. Although the biopsies from the patients showed histological and ultrastructural similarities, the clinical presentations were different. One patient had ichthyosis linearis circumflexa, while the other had a generalized ichthyosiform eruption. The ultrastructural findings in the 2 patients, while not specific, may help distinguish the eruption of Netherton's syndrome from other scaling dermatoses.


Study of the action of some centrally acting drugs on the EEG and on a conditioned avoidance reflex in the rabbit. A study was carried out on the effect of perphenazine, diazepam, benactyzine, morphine and a new central analgesic, viminol, onboth EEG and behaviour in rabbits with chronically implanted electrodes trained to a conditioned escape reflex. The results obtained are discussed considering the mechanism and site of action of the different drugs: the experimental procedure adopted is recommended to obtain additional informations on the properties of centrally acting drugs.