Decreased dipalmitoyllecithin content found in lung specimens from patients with so-called shock-lung. Lung specimens were obtained from 9 patients with shock lung (adult respiratory distress syndrome), immediately after death, and from 8 controls. They were analysed for phospholipid content anf for fatty acid composition of sphingomyelin and lecithin. We found an elevated phospholipid content in the affected lungs but a decreased dipalmitoyllecithin fraction of total lecithin as indicated by 127% elevated content of oleic acid in lecithin. As a consequence the relation between the palmitic acid and oleic acid moiety of lecithin shifted from 2.32 in the normal lungs to 1.64 in the diseased lungs. Since the content of dipalmitoyllecithin is closely related to the function of the surfactant system we conclude, that the alteration of surfactant function, observed in patients with adult respiratory distress syndrome may be at least in part a result of an altered surfactant metabolism, but we cannot rule out, that the findings represent an epiphenomenon in shock lung.


Lymphosarcoma in an infant northern fur seal (Callorhinus ursinus). An infant northern fur seal (Callhorinus ursinus) died in a rookery on St. Paul Island, Pribilof Islands, Alaska. Grossly, slight enlargement of the mesenteric lymph nodes was seen. Microscopically, a lymphosarcoma composed of sheets of monomorphic lymphoid cells in sections of lymph node and tonsil was seen. Electron microscopy of formalin-fixed tissues revealed several structures that were possible of viral origin in the cytoplasm of the neoplastic cells.


Prophylactic cranial irradiation in small cell carcinoma of the lung. A randomized study. Twenty-nine patients with small cell carcinoma of the lung and without evidence of brain metastasis were randomized into two treatment groups consisting of 14 patients who received prophylactic cranial irradiation (PCI) and 15 who received none (non-PCI). All patients were treated with irradiation of the primary lesion and concomitant chemotherapy. The response rate and median survival of the two groups were not significantly different: 93% and 7.2 months in the non-PCI; 86% and 9.8 months in the PCI; P larger than or equal to .05. Brain metastasis occurred in 0/14 patients in the PCI and 4/15 in the non-PCI (P less than or equal to .05) and was the cause of major neurologic disability in each. Although PCI did not improve response rate or survival, brain metastasis with its attendant neurologic complications was effectively prevented.


Hypersomnolence and intermittent upper airway obstruction. Occurrence caused by micrognathia. A patient with hypersomnolence, micrognathia, and respiratory insufficiency had been treated eight years for narcolepsy. Sleep apnea because of upper airway obstruction was found, and a tracheostomy was performed. Following this the hypersomnolence and respiratory insufficiency resolved. This case emphasizes the importance of carefully evaluating the condition of patients complaining of hypersomnolence to detect those with intermittent upper airway obstruction occurring during sleep.


Rectal biopsy in patients with Crohn's disease. Normal mucosa on sigmoidoscopic examination. Of 99 patients with Crohn's disease whose rectal segment appeared normal on sigmoidoscopy, there was histologic inflammation in 45% and features characteristic of Crohn's disease in 30% of rectal biopsy specimens. Granulomas were found in 18% of patients, including 13% of those with ileitis, 13% of those with ileocolitis, and 37% of those with colitis. Eleven of the 17 granulomas were small undermarcated microgranulomas. Rectal biopsy specimens are of value to confirm the diagnosis in Crohn's disease and to determine the state of clinical activity even when the sigmoidoscopic appearance is normal.


Food asphyxiation in hospitalized patients. During a five-year period, food asphyxiation caused 1.3% of all deaths of patients who came to autopsy at a hospital for chronic diseases. Patients died suddendly, during or shortly after meals. Acute myocardial infarction was mistakenly diagnosed in eight of the 14 patients until autopsy was performed. Sedation, old age, and poor dentition predisposed to aspiration. Food asphyxiation is a common problem whenever and wherever people eat. To minimize its occurrence in hospitalized patients, sedatives should be prescribed judiciously, and diets ordered appropriately. Physicians should learn the simple methods of extracting inhaled food.


Antibiotic use at Duke University Medical Center. A study of antibiotic use at Duke University Medical Center in June 1973 showed that 34.2% of all patients received antibiotics (43.6% surgical, 21.4% medical patients). Cephalothins were most frequently ordered for surgical patients, ampicillin sodium and penicillin G or penicillin V with potassium for other patients. A retrospective analysis of 50 randomly selected patients, according to the Kunin's categories of use, showed 64% of total antibiotic therapy as not indicated or inappropriately administered in terms of drug or dosage. These results are similar to previous reports of antibiotic surveillance and further establish the need for continuing education of prescribing physicians.


Mortality from pneumonia and risk conditions during influenza epidemics. High influenza morbidity during nonepidemic years. Increases in mortality from pneumonia and high-risk chronic diseases have not occurred during recent influenza epidemics. Excess mortality during the past four influenza epidemics in the United States is attributable to influenza reported as a primary cause of death, and the average excess was only about 4,000 deaths per epidemic. Most clinical influenza severe enough to cause hundreds of millions of days of bed disability during nonepidemic as well as epidemic years is not caused by the influenza viruses. During the nonepidemic year of 1973 to 1974, there were 61,841,000 episodes of clinical influenza severe enough to put people to bed for an average of 3.6 days. In my judgment there is now no basis for recommending annual administration of influenza vaccines to so-called high-risk groups and persons over 64 years of age.


Behavioral treatment of obesity. Limitations and results with the chronically obese. Results of behavioral treatment for obese persons during the first 18 months of clinical operation are presented and other reports in the literature are reviewed. Baseline and follow-up data were gathered from a population of 144 female, chronically obese patients, most of whom were experiencing medical complications associated with obesity. Treatment results were disappointing in comparison with results of similar programs. Difference in patient population groups is offered as a possible explanation for this phenomenon. Covariant analyses of demographic and psychosocial variables failed to yield any clear predictors of weight loss; it is suggested  that biological factors may be important to treatment outcome for some overweight patients.


Pulmonary artery flow-guided catheters in the perioperative period. Indications and complications. The risk factor of pulmonary artery catheterization was assessed in 392 critically ill patients. Major indications for catheterization in the operating room were marginal cardiovascular reserve, anticipated large fluid and blood loss, and hypotensive anesthesia. Immediate complications included cardiac arrhythmia, carotid artery puncture, and pneumotherax. Long-term complications included positive bacterial cultures, pulmonary infarction and neuropathy. None of the complications were directly responsible for the deaths in this series. Pulmonary artery monitoring in critically ill persons is a relatively safe procedure.


Spinal cord infarction following therapeutic renal artery embolization. A patient with dialysis cachexia became paraparetic within hours of therapeutic renal artery embolization. At autopsy, emboli of absorbable gelatin sponge filled spinal arteries, accompanied by spinal cord infarcts. The renal arteries of patients with end-stage renal disease are smaller than normal becaue of intimal fibrosis associated with prolonged dialysis. Embolic material can reflux more readily in these patients than in patients with renal tumors.


Amyotrophic lateral sclerosis in a high selenium environment. During a ten-year period, four cases of amyotrophic lateral sclerosis have been found in a sparsely populated county (population 4,000) in west-central South Dakota. The patients were unrelated male farmer-ranchers between 57 and 66 years of age, living within a 15-km radius of each other. The cases occurred in a region where naturally occurring selenium toxication is endemic in farm animals.


Estrogen receptor assay in the differential diagnosis of adenocarcinomas. Estrogen receptor determination by the sucrose gradient method was applied to 295 tumor tissues of various origins. Estrogen receptor of the 8 S type was found only in adenocarcinoma of the breast, uterus, and ovary. Of 19 patients with metastatic carcinoma of unknown origin, four benefited from estrogen receptor study (ie, appropriate therapy could be initiated) and one was helped retrospectively on the clinical diagnosis. Estrogen receptor assays may also be useful in determining whether bilateral breast involvement represents two primary lesions or metastasis. Estrogen receptor studies should be included in evaluating cancers of unknown origin in female patients.


The spectrum of vitamin K deficiency.

The spectrum of vitamin K deficiency. The coagulopathy induced by vitamin K deficiency commonly results from our lack of awareness of the clinical setting associated with vitamin K deficiency. Thirteen cases are reviewed to illustrate the clinical correlates most frequently observed. Dietary deficiency was always present, but concomitant antibiotic therapy was not an absolute requirement. The postoperative patient is at high risk, as is the patient with cancer or renal failure. Abnormal bleeding was common, but significant hemorrhage occurred only in postoperative patients. Factor assays were helpful and occasionally necessary to make the diagnosis, but a therapeutic trial with parenteral vitamin K was often enough to provide the right diagnosis. Greater awareness of this deficiency syndrome is necessary to avoid the serious morbidity that often results.


Primary carcinoma of the appendix.

Primary carcinoma of the appendix. Primary adenocarcinoma of the appendix is a rare tumor. Fewer than 200 cases are on record. Correct preoperative diagnosis is virtually nonexistent. Two patients with adenocarcinoma of the appendix are described. Although appendectomy appears to be adequate treatment for carcinoid, right hemicolectomy is, in our opinion, the treatment of choice for mucinous cystadenocarcinoma, while it is mandatory in cases of adenocarcinoma of the colonic type.


Acute organic brain syndrome associated with gentamicin therapy. Two patients receiving gentamicin sulfate experienced acute organic brain syndromes that subsided after use of the drug was discontinued. Among the various factors considered as possible causes, time sequences point to gentamicin as the most likely.


Tricyclic antidepressant overdose: incidence of symptoms. Forty consecutively hospitalized patients who had overdosed primarily with a tricyclic antidepressant (TCA) were observed until discharge. The severity of the overdose was documented by serial measurements of plasma TCA levels. Nineteen of the patients became comatose, 16 required supportive respiration, and 2 died. Individual symptoms in the 13 patients having plasma TCA levels greater than 1,000 ng/ml are shown. Plasma TCA measurements more reliably define patients who are at risk for major medical complications following overdose than does the amount of drug ingested by history. In the absence of plasma measurements, a QRS duration of 100 msec or more on a routine ECG within the first 24 hours defined all patients with major TCA overdoses.


Theophylline concentrations in asthmatic patients after administration of aminophylline. To test the efficacy of using a weight-derived formula to determine aminophylline dosages, 50 patients hospitalized for treatment of severe asthma were given intravenous aminophylline infusions at a rate of 0.9 mg/kg/hr to a maximum dosage of 1,500 mg/24 hr. Serum theophylline determinations done 12 to 96 hours after institution of this therapy showed levels greater than 20 mg/liter in 34% of these patients. Reliance on weight-derived formulas can be dangerous.


Cooperative study of hospital frequency and character of transient ischemic attacks. III. Variations in treatment. Variations in therapy for patients with complaints suggesting transient ischemic attacks (TIAs) among six participating medical centers are described. Selected treatment, based on clinical interpretation of patient characteristics, varied widely among centers. Therefore, results cannot be attributed to specific treatment. Nevertheless, there was little difference between treatment categories and the likelihood of further TIAs. The mortality of the patients who had received anticoagulants was significantly higher (P less than .001) than those patients receiving other treatment. Possible reasons for these differences are discussed.


Emergency medicine as an academic discipline. Because of an explosive increase in the use of emergency rooms in hospitals across the country, many hospitals have found it expedient to employ full-time emergency physicians. The demand for emergency physicians has prompted the development of training programs in emergency medicine in academic medical centers. The first such training program was instituted at The Medical College of Pennsylvania in 1970. The 32 current programs in the nation are filling a real need in providing manpower for hospital emergency rooms. With the increasing identification and distribution of emergency physicians, there has been an attempt to develop emergency medicine as a distinct discipline and to establish its legitimacy in the structure of academic medical centers. A variety of problems must be addressed to clarify the role of emergency medicine in the academic setting.


Planning for retirement: advice to physicians. Retirement planning has become a legitimate concern of all physicians, especially those employed by agencies where retirement is compulsory. Faced with the possibility of retirement, whether forced or voluntary, and issues of competence and other related matters, many physicians are departing from the traditional pattern of working until they become incapacitated. The typical physician places high values on work and deprecates other activities. Busy practitioners who have spent little time with their families and in recreational pursuits find themselves unprepared for their altered status when they stop working. Little empirical information is available concerning physicians and retirement. Four proposed retirement patterns may help physicians plan successfully for retirement.


Systemic absorption of neomycin irrigating solution. Systemic absorption of neomycin sulfate occurred in ten patients in whom neomycin wound irrigating solutions were used during total hip replacement. The use of neomycin in this manner may be associated with the risk of ototoxicity and nephrotoxicity.


Evaluation of a new antihypertensive agent: prazosin hydrochloride (Minipress). Prazosin hydrochloride is an orally administered vasodilator that recently became available for the treatment of hypertension. It causes less tachycardia than hydralazine but may produce orthostatic hypotension, particularly after the initial dose. The role of prazosin in therapy is limited because of the risk of a first-dose syncopal reaction, and it appears to be indicated primarily in patients who cannot tolerate hydralazine hydrochloride or sympathetic depressant drugs. Like other antihypertensive agents, prazosin should be given with a diuretic.


Method for the isolation of surfactant from homogenates and lavages of lung of adult, newborn, and fetal rats. A method is presented for the isolation of pulmonary surfactant from rat lung homogenates and lavages using differential discontinuous density gradient centrifugation. The isolated surfactant was characterized by electron microscopy, assay of enzyme markers for different subcellular organelles, and its chemical composition. Surfactant that was isolated from lung homogenates appeared to be free of other contaminating cellular organelles. Electron microscopic examination of surfactant isolated from whole homogenates showed the presence of lamellar bodies and tubular myelin figures and, hence, represented total lung surfactant. On the other hand, surfactant prepared from lung lavages had mostly tubular myelin figures and, thus, represented extracellular surfactant. Both preparations were rich in phospholipids, especially lecithins and phosphatidylglycerol, and showed high phospholipid to protein ratios. The method was used to study the quantity and composition of surfactant during lung development in rats. Surfactant was isolated from lung homogenates of fetuses at days 19 to 21 of gestation and from newborn and adult rats. During the period of 19 to 21 days of gestation, there is a 10- and 20-fold increase in the amount of protein- and phospholipids (milligrams per gram of wet lung), respectively. A further 2-fold increase occurs after birth. Phosphatidylcholines account for 65% of the total phospholipids at day 20, 71% on day 21, and 81% at term. A progressive increase in the phosphatidylcholine to sphingomyelin ratios and in the amount of phosphatidylglycerol occurs during this period. The amount of disaturated lecithins (expressed as percentage of total phosphatidylcholines) in the lung surfactant increases from 49% at day 20 to 53% at birth. There is no change in the amount of disaturated lecithins after the newborn stage. The present method for the isolation of lung surfactant is reproducible, is less time consuming, and can be used to isolate quantitatively surfactant from small lung aliquots.


Health and liability hazards in a veterinary hospital. There is a wealth of information available to you concerning the methods and means of making the hospital a safer place for yourself, employees and clients. In addition, a book could be devoted to the safety of the animal patients. Your insurance carrier can help you spot som potentially dangerous conditions and suggest ways in which you can make the changes necessary to bring your hospital up to safety standards. Remember, a good preventive program is one of the best defenses against litigation.


Computed tomography of orbital lesions. A radiological study of 144 cases. During the first two years with the 160 x 160 matrix EMI scanner 144 consecutive patients referred with suspicion of orbital disease were subjected to 190 computed tomography (CT) examinations. The X-ray attenuation and enhancement patterns of the various lesions were analyzed. In general it was difficult to correlate these parameters with the histopathological features. Hemangiomas, however, showed little enhancement and meningiomas a large degree of enhancement, while malignancies, lymphomas and pseudotumors were mainly intermediate. With orbital Graves' disease a low preinjection attenuation and a large enhancement (with normal striated neck muscle as a reference) was found in the external eye muscles. The diagnostic accuracy of CT (n=143) was compared to that of A/scan ultrasonography (US, n=80) and carotid angiography (n=40). CT showed the highest accuracy of the three methods, but CT differed only statistically from carotid angiography.


Interaction between bromocriptine and levodopa. Biochemical basis for an improved treatment for parkinsonism. The present investigation examined the biochemical interaction of bromocriptine and levodopa with respect to monoamine and gamma-aminobutyric acid metabolism in the brain. Rats were treated with levodopa, 250 mg per kilogram of body weight intraperitoneally, with or without carbidopa, 25 mg per kilogram, 1 or 2 hours before sacrifice. Some were also given bromocriptine, 5.0 mg per kilogram, 4 hours before sacrifice. Rats were killed 1 and 2 hours after levodopa and brain levels of gamma-aminobutyric acid and monoamines, and their metabolites were measured. Dopamine levels and metabolism were not markedly altered when bromocriptine was added to levodopa treatment. The level of serotonin, which was reduced 25 to 40 percent by levodopa alone, was close to normal with the combination treatment. Serotonin metabolism was also enhanced by the addition of bromocriptine as shown by increased levels of 5-hydroxyindoleacetic acid. The results suggest that bromocriptine not only may improve the motor disorder of parkinsonism but also may reduce some side effects of levodopa therapy, such as depression, which could be due to serotonin depletion.


Absence of phosphatidylglycerol (PG) in respiratory distress syndrome in the newborn. Study of the minor surfactant phospholipids in newborns. Phosphatidylglycerol (PG) was absent from lung effluent in 41 infants with respiratory distress syndrome of the newborn (RDS), whereas effluent from healthy control subjects of similar gestational age contained this phospholipid (4.9 +/- 2.4% of lipidphosphorus (P), n = 32). Control infants of 28 weeks of gestation or less with various respiratory disturbances other than RDS also had low PG (0.2 +/- 0.2% of lipid-P, n = 5). In RDS surfactant complex often could be isolated from the airways using differential and density gradient centrifugation. The material thus obtained had prominent phosphatidylinositol (PI) (13.6 +/- 2.8% of lipid-P, n = 6), but no PG. Of those 18 infants who had such surfactant even in the early stages of RDS, 13 were 35 weeks of gestation or more, 3 were offspring of diabetic mothers, and 2 had severe perinatal asphyxia. In healthy control subjects PG sometimes appeared first within an hour of birth, but in RDS PG did not appear until recovery from RDS. In RDS type II (transient tachypnea of the newborn) PG in lung effluent also was abnormally low (1.3 +/- 0.6% of lipid-P, n = 5) and PI was correspondingly prominent (9.7 +/- 3.6% of lipid-P, n = 5), indicating immaturity of surfactant similar to RDS. Surfactant with PG and PI has superior surface-active properties compared to that containing PI, but no PG. Surfactant without PG does not seem to stabilize the alveoli of the newborn as well as does surfactant with PG. The failure of PG appearance following birth therefore may precipitate RDS, especially beyond 35 weeks of gestation.


Fatty acids of phospholipids in human neonatal lung surfactant. The fatty acid chains of lecithin, phosphatidyl ethanolamine (PE), and phosphatidyl dimethylethanolamine (PDME) in human neonatal alveolar washes were analyzed. Both alpha- and beta-palmitic acid increased with gestational age on all phospholipids analyzed. No evidence for high concentrations of myristic acid was found on any phospholipid. Babies who were stillborn or who had died of hyaline membrane disease (HMD) had lower proportions of beta-lecithin palmitic acid when compared with babies who breathed normally before death. In the HMD group these levels were significantly lower.


Retrolental fibroplasia and factors influencing oxygen transport. The hospital records of 58 premature infants in whom proliferative retrolental fibroplasia (RLF) developed were matched with the records of 58 infants without RLF for birth weight, gestational age, and duration oxygen therapy. The two groups were compared for factors likely to influence tissue delivery of oxygen by blood. No significant difference was found in incidence of blood transfusions or exchange transfusions, use of phototherapy, or occurrence of acidosis.


A simple noninvasive technique of measuring intracranial pressure in the newborn. A noninvasive approach to measuring intracranial pressure in newborns based on optical principles and devoid of electrical hazards is described. This monitoring technique can be used to detail subtle changes in measurements in ill newborns and to predict hydrocephalus. The mean anterior fontanel pressure in normal infants was 10.14 +/- 0.39 cm H2O. Increased pressure was noted in sick neonates and in infants with hydrocephalus. Good correlation was noted between anterior fontanel pressure and CSF pressure. Pediatrics, 59:957-961, 1977, INTRACRANIAL PRESSURE, ANTERIOR FONTANEL PRESSURE, HYDROCEPHALUS, MONITORING DEVICE.


The role of tocopherol in oxygen-induced retinopathy: kitten model. The effect of tocopherol (vitamin E) on oxygen-induced retinopathy was studied in 75 kittens following the development of a 12-point scoring system to quantitate the degree of retinopathy seen at three weeks. The tocopherol was found to be beneficial when given daily from the day of birth (P less than .0001) with oxygen exposures of two to  three days (79% FiO2) beginning on day 3. Caution is urged in applying these data to humans because (1) hepatosplenomegaly was noted in the treated animals, and (2) the kitten model for oxygen-induced retinopathy is not entirely satisfactory, Pediatrics, 59:998-1005 1977, RETROLENTAL FIBROPLASIA, OXYGEN TOXICITY, VITAMIN E, RETINOPATHY, KITTEN.


Phosphorylated protamines. I. Binding stoichiometry and thermal stability of complexes in DNA. To decipher on a molecular level the role of protamine phosphorylation in spermiogenesis, clupeine Z species containing one, two or three serine phosphates were prepared utilizing a recently developed chemical procedure. The melting of complexes with calf thymus DNA showed that thermal stability decreases with increasing degree of phosphorylation. The stoichiometry of the nucleoprotamine complexes was investigated analyzing the melting curves and using the fluorescamine assay recently described. Phosphorylation significantly reduces binding stoichiometry defined as DNA-nucleotides covered by a protamine molecule. Thus, phosphorylated protamines are more densely packed along DNA; the implications on processes occurring in spermiogenesis as i. e. histone replacement, are discussed. A general discussion on the variability in protein-DNA stoichiometry values obtained by different procedures is included.


Ruptured mycotic splenic artery aneurysm: angiographic diagnosis. A case of ruptured artery aneurysm is presented, emphasizing the pre-operative angiographic diagnosis of a difficult clinical problem. Although some patients have been operated on without angiography, this may prove of some difficulty if the diagnosis is not suspected. Awareness of potential routes of spread along soft tissue planes from the pancreatic bed may be of considerable importance in establishing the diagnosis.


[Neuromuscular disturbances in endocrine disorders]. In order to study the character of lesions in the neuro-muscular system in endocrinological diseases the authors examined 156 patients with diffuse toxic struma, hypothyroidism and diabetus with the aid of clinico-EMG methods. A comparison of the investigation results of clinical, bioptic material and EMG data testified to an involvement into the process of all regions of the segmental neuromuscular apparatus. The results of EMG studies may serve as control data in relation to the effectiveness of the used therapy.


Thyroid hormone-binding interactions in cytosol of rat anterior pituitary. Thyroxine (T4) and triiodothyronine (T3)-binding interactions in preparations of rat anterior pituitary gland have been studied. T4 is bound primarily to extranulcear binding sites located in the cytosol fraction of the cell. These sites have a medium affinity for T4: Ka = 2.5 x 10(8) 1/mol and a maximum binding capacity (MBC) of 1.15 pmol/mg tissue (wet weight). Binding of T3 to these sites is minimal. The extent of binding of T4 is influenced by the pH of the system and the temperature of incubation. The relative effectiveness of T4 analogues in displacing bound T4 is tetrac greater than T4 greater than triac greater than D-T4 greater than T3. Similar T4-binding sites are present in other rat tissues, but in all except serum, binding activity is lower than in the pituitary. T4-binding by serum contaminating the pituitary preparations contributed only partially to the total activity observed. Concomitant assessment of T4-binding activity and T4 metabolism in pituitary homogenates prepared at different pH values indicated an inverse relationship between the two processes. The possible role of thyroid hormone binding in cytosol in influencing the intracellular distribution of thyroid hormones is discussed.


Radioimmunoassay for porcine lipotrophic peptide B. A sensitive radioimmunoassay for the lipolytic peptide B from pig pituitary glands has been developed. Antisera were raised in rabbits, which allowed a final dilution of 1:6000. Free and antibody bound [125I]peptide B could be separated by double antibody, by dextran-coated charcoal and by polyethyleneglycol. The smallest detectable amount was 0.5 ng/ml. Peptide B could be measured irregularly in porcine sera; there was cross-reacting material in an extract of a total human pituitary gland, but not in human sera. The assay seems specific except for a strong cross-reaction with porcine neurophysin. There are indications that peptide B consists of neurophysin and a small lipolytically active peptide which remains to be further characterized.


Divergent effects of 6-propylthiouracil on 3,3',5'-triiodothyronine (RT3) serum levels and in man. The effect of 6-propylthiouracil (PTU) on the peripheral conversion of thyroxine (T4) to 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (reverse T3 rT3) was investigated by assessments of the concentrations of T4 T3 and rT3 in peripheral venous blood from T4-treated healthy volunteers given PTU, 4 X 150 mg daily. Within on day of PTU administration, serum T3 concentrations were reduced, and those of rT3 enhanced. These deviations lasted as long as PTU was given (five days), and there was a rapid return towards normal within one day after PTU administration ceased. It seems probable that, in man, PTU can evoke a diversion of T4 monodeiodination, less being converted to the metabolically active T3 and more to the metabolically inactive rT3. It is ppossible that the rapidity whereby PTU can reduce T3 levels can offer an advantage in the treatment of hyperthyroidism.


In vivo studies on thyroxine and triiodothyronine metabolism in the rat. The reciprocal effects of loading amounts of thyroxine (T4) or triiodothyronine (T3) on the in vivo deiodination of their 125I-labelled isotopes by the rat were studied. It was found that the deiodination of a tracer amount of [125I]T3 as measured by the 24-h urinary 125iodide was significantly decreased after administration of a loading dose of non-radioactive T4. A similar decrease in deiodination of [125I]T3 was observed following the injection of a T3 load. In experiments in which the deiodination of [125I]T4 was assessed, the effects on this of loading doses of non-radioactive T4 or T3 differed; while stable T4 induced a significant decrease in deiodination of [125I]T4, stable T3 was without effect. The data is in agreement with the view that T4 and T3 share tissue deiodinating sites and that in such a system T4 appears to have a stronger avidity for those sites.


[Effect of ergotoxin on gastric motility in the skate, frog and turtle]. DG-erotoxine (SPOFA)--200 mg/kh b. w. has no effect to the motor activity in scates. The dose of 500 mkg/kh produces 20-30 min. after injection the excitation of contraction followed by the inhibition. In frogs the dose of 25 mkg/kg produces the excitation of stomach contractions. The dose of 100 mkg/kg initially stimulates motor activity, later on--inhibits it. In the tortoise the dose of 25 mkg/kg increases the contraction of the stomach the dose of 2000 mkg/kg inhibits it.


Long-term turnover of thyroid iodine in the rat as studied by the isotopic equilibrium method. A long-term kinetics study was made in rats in a steady state for iodine metabolism and receiving either 5 microng iodine (group5) or 50 microng iodine (group 50) daily. By using the isotopic equilibrium method, the value of the renewed fraction was followed during at least 120 days in the thyroglobulin (Tg) and the lysosomes of the thyroid and in the plasma hormones. For both groups, only part of the total iodine pool in the Tg as well as in the lysosomes is directly available for secretion. Furthermore, the direct precursor pool of iodine for secretion in the lysosomes is dependent on the daily iodine intake (1.3 times greater in group 50 than in group 5) while the Tg iodine supply in the colloid is not (80% of the total Tg iodine pool for both groups). An iodine pool with a very slow turnover is present in the lysosomes (about 50% in each group), in the Tg of group 5 (more than 15%) and probably in the Tg of group 50 (less than 5%). Thus, the distribution of such a pool between lysosomes and Tg is dependent on the daily iodine intake. The very slow iodine pool is probably not accumulated into the follicles, since every studied pool is in steady state. It is practically not secreted since hormones in the plasma are entirely renewed. Again, it is practically not deiodinated since the thyroid iodide pool is also entirely renewed. These three criteria are valuable for both groups. Although one cannot entirely exclude its participation in secretion, it is postulated that the major part of this pool is re-cycled without deiodination. Both lysosome-lysosome and lysosome-colloid pathways of re-cycling have been postulated. The second pathway is supposed to increase when the daily iodine intake is decreased.


C-peptide in diabetic children after stimulation with clucagon compared with fasting C-peptide levels in non-diabetic children. Fasting serum C-peptide and total immunoreactive insulin (IRI) were determined in 38 non-diabetic children and adolescents 6-22 years old. C-peptide varied between 0.22-0.73 pmol/ml (mean +/- SD, 0.45 +/- 0.11). There was a tendency to higher values during puberty. No difference was found between subjects with or without a family history for diabetes. IRI varied between 0-31 millimcron/m1 (mean +/- SD, 11.3 +/- 6.5). The C-peptide response to glucagon was studied in 10 insulin dependent juvenile diabetics 11-19 years old, who had had measurable amounts of fasting C-peptide on some occasions during the previous years. Duration of diabetes varied between 4-12 years. A slight but significant rise in C-peptide level occurred in 3 patients. Their metabolic control estimated on the basis of daily urinalysis was "excellent" or "good". The results support the hypothesis that even trace remnants of the beta cell function may be of importance for the metabolic control in juvenile diabetes.


Trace elements in the human endometrium and decidua. A multielement analysis. By means of neutron activation analysis, 25 trace elements, which are usually present in biological material, were estimated in 31 specimens of human endometrial tissue obtained at various phases of the menstrual cycle and in 14 specimens of decidua from the 12th to 18th week of pregnancy. Among the 13 trace elements invariably found in all specimens, the levels of copper, potassium, rubidium, antimony and zinc were significantly higher and those of bromine, selenium and sodium significantly lower in the endometrium than in the decidua. No difference was found in the levels of gold, calcium, cobalt, cesium and iron. Among the 12 trace elements which were found only occasionally, chromium, mercury, silver, and cadmium were detected in approximately half and cerium and scandium in approximately one-fourth of the 45 samples studied. Arsenic, barium, lanthanum, molybdenum, samarium and strontium were detected only rarely. The cyclic variations in the endometrial levels of calcium, rubidium and copper were highly significant and those in the levels of gold, cesium, iron, potassium and zinc probably significant.


Oestrogenic activity of oestradiol-decanoate after oral administration to rodents. Oestradiol-decanoate, dissolved in arachis oil and orally administered to rodents, produces oestrogenic effects. Compared on a molecular basis the ester has 0.1-1.0 times the activity of ethinyl oestradiol, dependent on the species and the parameter studied. The effects of oestradiol-decanoate are less or absent when the oil is omitted. It is likely that absorption of the steroid ester takes place via the intestinal lymphatics in conjunction with the oil.


Study of the effect of oestradiol on hexosamine-containing substances and a possible receptor in the skin of male mice. Male mice were treated with 10 microng of oestradiol for 5 days in order to study the effect of the hormone on both the distribution and the rate of synthesis of glycosaminoglycans and glycoproteins in the skin. Oestradiol exerts a very specific effect on glycosaminoglycans by increasing hyaluronic acid concentration more than 11 times. Effects on other hexosamine-containing substances were much smaller and less consistent. Although the above increase of hyaluronic acid was due mainly to an augmentation of its synthesis, the results also indicate the possibility of a blockage in the breakdown process. Despite the fact that oestrogen produces such large changes, a specific cytosol receptor of the hormone was not discerned and it was concluded that male mouse skin is not an oestrogen receptor tissue in the classical sense.


Congenital generalized lipodystrophy and experimental lipoatrophic diabetes in rabbits treated successfully with fenfluramine. Lipoatrophic diabetes has been produced in rabbits by injection of a fraction prepared from the urine from patients with congenital generalized lipodystrophy. Both these conditions are considered to be hypothalamic syndromes. The animals, and a patient with congenital generalized lipodystrophy and latent diabetes were treated with the dopamine receptor blocker, pimozide, for 4 and 17 months, respectively. The results were discouraging even though the patient got a daily dose of 16 mg pimozide. Fenfluramine has a lowering effect on brain serotonin, and peripheral effects on glucose and triglyceride metabolism. This drug improved the general condition of the rabbits with lipoatrophic diabetes, as well as that of the patient with congenital generalized lipodystrophy. The rabbits became normoglycaemic and insulin sensitive. In the patient a normalization of the urinary excretion of the serotonin metabolite 5-OH-indole acetic acid was observed. His voracious hunger and profuse perspiration were reduced, the hyperkeratotic layer of the skin peeled off, and the pigmentations of the skin decreased. There was observed an improvement of ALAT and ASAT, normalization of the fasting blood glucose, and increased sensitivity to exogenous insulin. After 11 months of 200 mg fenfluramine daily addtitional administration of 2 g clofibrate per day produced normalization of the serum triglyceride concentration and a marked reduction of the resistance to insulin. Three more patients with congenital generalized lipodystriphy, two of whom have manifest diabetes, have now started treatment with fenfluramine and are improving. The rabbits got relapse of their lipoatrophic diabetes when the fenfluramine treatment was stopped. It is suggested that a disturbance in the serotonin metabolism of the central nervous system may be of pathogenetic importance in congenital generalized lipodystrophy.


Reversible plasma and red blood cells volumes increases in acromegaly. Plasma volume (PV) and red blood cells volume (RBCV) were measured in 76 normotensive acromegalic patients (42 males and 34 females) and compared with those of 28 controls on the basis of body surface. In untreated males PV and RBCV were significantly higher than in normals (P less than 0.001) and total blood volume (TBV) was above the normal range in 85%. Untreated females also showed an elevated PV but had significantly lower RBCV than the male patients. The only vascular volume of the patients with correlated significantly with the body weight or surface was RBCV in females. One to five studies were done after treatment in 52 patients and analyzed as a function of plasma GH levels. Plasma volume reverted to the normal range (males) or was significantly lower than in untreated patients (females) in the groups of patients with normal GH levels while RBCV normalized at higher GH concentrations. At similar GH levels, treated patients without pituitary failure (n = 35) or given T4 and/or cortisol substitution for hypopituitarism showed similar vascular volumes. The plasma volume and TBV in both sexes and RBCV in males was significantly correlated with Log 10 GH levels. It is concluded from these data and other experimental evidence that endogenous GH hypersecretion is responsible for the reversible PV and RBCV increases frequently found in acromegalic patients.


A comparison of the effect of TSH, GH and prolactin on the renal iodide excretion in unrestrained rabbits. The immediate effect of graded iv doses of heterologous TSH, GH and prolactin on the renal iodide excretion was sutdied in unrestrained rabbits with implanted Geiger Müller detectors. Both TSH and GH lowered the fractional excretion rate of iodide. The duration of the effect was significantly correlated to the magnitude of the administered dose. The lowest dose with a significant effect was 10-20 mU TSH and 50 mU GH. Prolactin had no similar effect even in high pharmacological doses. An effect similar to that of small TSH doses was recorded following administration of 20-40 microng TRH iv. The immediate effect of GH on the iodide excretion accords with previous reports about similar effect on sodium excretion and suggests, that the effect of GH and TSH on the iodide excretion is secondary to a general effect on kidney function. The demonstration, that the effect is present in unrestrained animals after administration of physiological doses indicates, that the effect is not only of pharmacological significance, but may also have physiological significance.


Bone changes in hyperthyroidism: interrelationships between bone morphometry, thyroid function and calcium-phosphorus metabolism. Iliac-crest biopsies were obtained from 40 untreated hyperthyroid patients after double-labelling with tetracycline. Histomorphometric analyses were performed on undecalcified and decalcified bone sections. The morphometric and chemical data were compared with those in normal control groups and the results of the morphometric analyses were related to thyroid function and to chemical quantities of calcium-phosphorus metabolism. The bone turn-over was increased in the hyperthyroid patients with an increase both in bone resorption and bone formation. Serum alkaline phosphphatase was increased and positively correlated to the amount of osteoid and to the extent of tetracycline-labelled surfaces. The osteoclastic resorption was positively and the bone formation inversely correlated to thyroid activity. This might explain the reduced amount of trabecular bone found in hyperthyroidism. The most striking feature was, however, a pronounced increase in osteoclastic activity in cortical bone followed by increased porosity. The osteoclastic resorption in cortical bone was positively correlated to serum concentrations and urinary excretions of calcium and phosphorus. This indicates that increased cortical osteoclastic resorption is mainly responsible for bone mineral mobilisation in hyperthyroidism.


Stimulation of peripheral T3 formation by oral but not by intravenous glucose administration in fasted subjects. Fasting is known to promote a shift in the conversion of thyroxine (T4), more being deiodinated to an inactive form, reverse triiodothyronine (rT3), and less to active triiodothyronine (T3). The mechanism behind this change is not known, but it has recently been demonstrated that the proportion of dietary carbohydrates influences the serum concentration of T3 and rT3. Therefore, it is possible that the deiodination of T4 is subordinated to gastroenterohepatic regulation. To explore this possibility, we administrated glucose by the oral or the intravenous route to volunteers, who had been fasted for 48 h. It was found that glucose normalized the low fasting T3 concentrations only after oral administration. This supports the assumption that some gastro enterohepatic factor participates in the regulation of T3 formation.


Rapid disappearance of loading doses of thyroxine from blood and their excretion by the bile in rats. The disappearance of loading doses of thyroxine (T4) (100-20 000 microng T4 iv per rat weighing about 400 g) was measured with the aid of new technique allowing frequent blood sampling with maintenance of isovolaemia in anaesthetized animals. It was found that as early as 2 min after the injection more than half of the administered dose disappeared from the blood, while after 300 min only about 2% of that remained in the plasma. The direct relationship between the administered dose of T4 and both the relative and absolute level of free dialyzable T4 as well as of per cent of T4 displaced from plasma by sodium salicylate in vivo was demonstrated. Moreover, it was found that about 60% of administratered T4 is excreted by the bile within 300 min irrespective of the dose given, about 15 and 50% of that being found in the small intestine after 15 and 180 min, respectively. When two loading doses of T4 were subsequently administered and labelled with different isotopes, the amount of T4 from the first dose excreted by the bile was proportional to the amount of T4 from a second dose administered 18 h later. From all these observations it was concluded that, in vivo, an effective system for removal of the loading doses of thyroxine from the blood exists, and is presumably located in rapidly equilibrating tissues, mainly in the liver. From this point of view it appears that plasma protein carriers play an important role in the whole body economy of thyroxine, namely by maintaining a certain level in the blood to cover the actual functional needs of peripheral tissues.


Insulin secretion in insulin-requiring diabetics before and during insulin treatment. Endogenous insulin secretion after different stimuli was determined in insulin requiring diabetics without circulating insulin antibodies. Four groups of non-obese diabetics were investigated and compared with 111 controls. Group I: 14 patients with mild diabetes, not yet requiring insulin; diagnosis before the age of 30 years. Group II: 19 ketonuric patients just before being started on insulin treatment. Group III: 18 patients during remission after an average of 16.5 months' insulin treatment. Group IV: 13 patients with no remission period or relapse after an average of 19.5 months on insulin treatment. Blood glucose and immunoreactive insulin were measured during fasting and after iv secretin, iv tolbutamide, iv GTT, and oral GTT, followed by combined iv tolbutamide and glucagon stimulation. A considerable insulin secretion could be demonstrated in group I, whereas in group II only a very low insulin peak was obtained after secretin and the combined injection of glucagon and tolbutamide. In group III considerable insulin secretion was demonstrated, whereas in group IV only a very low insulin peak was obtained. A significant correlation between the degree of metabolic control and endogenous insulin secretion was found.


Non-suppressible insulin-like activity during acute metabolic and endocrine changes in dogs. Non-suppressible insulin-like activity (NSILA-S) was determined in dogs after acute changes in the blood sugar and after injection of growth hormone. Serum was chromatographed over Sephadex G-50 columns equilibrated in 1 M acetic acid and NSILA-S was determined in the fractions between 55 and 85% column volume using a protein binding assay and the conventional fat pad assay. The results obtained with these two methods correlated rather well (r = 0.74). Hyperglycaemia induced by an intravenous glucose load, by intravenous administration of mannoheptulose or both was not followed by an increase in NSILA-S levels. The injection of insulin and human growth hormone did not lead to alterations of the NSILA-S levels. It is concluded that total NSILA-S levels in the dog do not change acutely following manipulations of the blood sugar and that, in all likelihood, NSILA-S plays no role in the regulation of blood glucose.


Somatomedin A and B in serum from neonates, their mothers and cord blood. Somatomedin A by radioreceptor assay and somatomedin B by radioimmunoassay were measured in serum from women immediately after parturition and from their newborns. The mean levels of somatomedin A in both mothers (0.54 U/ml) and infants (0.50 U/ml) were significantly decreased compared to a reference group consisting of 21 non-pregnant women (0.91 U/ml). There was no difference between the mothers and their children. The mean somatomedin B value in serum from the mothers (63.9 microgram/ml) was above that found in non-pregnant women (19.2 microgram/ml) and the mean value in cord blood and serum from the infants (7.1 microgram/ml) was below it. A positive correlation was noted between somatomedin A and B in cord blood; r = 0.78. The combined somatomedin A and B values in cord blood were positively correlated to birth weight (r = 0.51, P less than 0.05).


Contribution of lactic acid by the ampullary and isthmic parts of rabbit Fallopian tube under altered hormonal conditions. The capability of the ampullary and isthmic parts of the rabbit Fallopian tube to contribute lactic acid (LA) to the tubal lumen was examined using an in vitro method of study. In addition concomitant study was also made using the uterus. It was found that in the oestrous rabbit, the isthmus contributed LA at a higher rate than that of the ampulla; the uterine contribution was minimal. Ovariectomy reduced while exogenous oestrogen enhanced this ability in all the three tissues. In mated post-ovulatory rabbits the contributory efficiency of either tubal part changed and appeared to exhibit a peak value in the presence of the ovum; the uterus showed no such changes. This is discussed in relation to the ability of the egg to secure its energy source until it attained morula/the pre-blastocyst stage.


Senile cataract account of cateract extractions performed in an urbanized population during the third quarter of the present century. Since the late 1940's the annual number of cataract extractions performed at the Eye Department of the Municipal Hospital of Copenhagen has quintupled. This increase has been followed by a tendency towards stabilisation. An increase of the potential cataract clientele by about 60 per cent and an extended indication for operation are considered obvious causes of this rise, to which must be added an increase-inducing factor due to the popularisation of a visual rehabilitating operation in a community with a relative preponderance of old inhabitants. An attempt at a statistical calculation of the percentage of the population subjected to cataract extraction in a defined area, related to age, is presented. This calculation may be of some guidance in the planning of ophthalmosurgical facilities.


On the molecular biology of the vitreous in the aphakic eye. The vitreous of aphakic and phakic eyes was assayed for hyaluronic acid. Intracapsular cataract extraction was regularly followed by decreased hyaluronic acid concentration and studies on the distribution of hyaluronic acid within the vitreous cavity showed that removal of the lens facilitates diffusion of hyaluronic acid into the anterior chamber. Based on these studies certain postoperative features of the aphakic eye are discussed. The instability of the vitreous gel, as reflected by rupture of the anterior vitreous face and an increased incidence of vitreous detachment supports the hypothesis of hyaluronic acid as a stabilizer of the gel. The decreased adhesion of the neural retina in the aphakic eye might be caused by the loss of hyaluronic acid. Normally the high concentration of hyaluronic acid adjacent to the retina contributes to the resistance of bulk flow of fluid into the subretinal space making it possible for the active transport system of the pigment epithelium to maintain a pressure drop across the neural retina. It is anticipated that saccades create currents in the fluid vitreous close to the eye wall after vitreous detachment. Model experiments showed that these currents were greatly enhanced, when the concentration of hyaluronic acid was lowered.


Formation of after-cataract by regeneration of human and rabbit lens epithelium in tissue culture. Regeneration of lens epithelium on the lens capsule was studied in tissue culture. The entire capsule with attached epithelium was taken from rabbit lenses and from human lenses with cataract. Generally, the epithelium grew in a monolayer but multilayered masses of cells were also seen. Most lens fibers degenerated during the first days and formed spherical membrane enclosed vesicles containing cytoplasm but no nuclei. The lens fiber remnants, together with regenerating epithelium, created structures that were similar in many ways to the clinical appearance of after-cataract.


Retinal detachment in aphakia.

Retinal detachment in aphakia. In a prospective study five hundred consecutive cases of cataract operations were followed during ten years. Nine cases of retinal detachment were observed. In a retrospective study 77 cases with aphakic retinal detachment were studied according to type of cataract operation, interval between this operation and the onset of retinal detachment, refraction, area of detachment and results of treatment. About fifty percent of the cases of retinal detachment are observed during the first year after the cataract operation. At the first examination the detached area is usually larger in aphakic eyes than in phakic eyes. The anatomical and functional cure after detachment operation is probably less in aphakic than phakic eyes.


Visual complaints and binocular function in bilaterally aphakic persons with cataract glasses. Seventy-one consecutive patients who underwent operation for senile cataract in both eyes during the period 1969-1973 were examined and questioned about visual complaints an average of 18 months after being fitted with cataract spectacles. In the distance situation none had complaints, either reported spontaneously or after questioning. Except for a few immobile patients, all could manage on their own in the street and on stairs. In the near situation 16 of the 71 patients had permanent alternating or intermittent exotropia which, however, gave rise to diplopic complaints in only two. The diplopia in these two patients disappeared after the glasses had been decentered. On questioning, complaints of diplopia could be elicited in another 5 patients. Investigation of sensory binocular function using Titmus' sterotest showed that 35 of the 71 patients could manage the test at the level 40 inches/arc. Division of the material into two groups by duration of monocular visual function during the development of the cataract and during the period between the operations on the two eyes, disclosed that this factor was of no importance to the postoperative motor and sensory binocular function.


The use of contact lenses in children with unilateral traumatic aphakia. Seveteen children under the age of ten years with unilateral traumatic aphakia, who had been fitted with contact lenses, were reviewed by an ophthalmologist and an orthoptist, on average three years after the injury. Thirteen children were still using their lenses. Of the seventeen, none were deeply amblyopic. Only one had orthophoria. Twelve of the seventeen had heterotropia, which in most cases was moderate. Six of the children achieved stereopsis in the synoptophore, only four by the Titmus sterotest, all of these were six years old or more at the time of the injury, and had had lenses fitted within the first six months of the injury. All the patients, as well as their parents, were motivated for lens-wearing, and the lens played an important part in the treatment of amblyopia. It is concluded that the sooner the contact lens is supplied, the better are the changes of obtaining binocular function. Beginning with a soft lens a few weeks after achieving clear pupil is recommended.


Unilateral traumatic cataract in children. A survey is presented of the course of unilateral traumatic cataract in 15 children of 8 years of age and below, admitted consecutively to the Ophthalmological Department of the Odense University Hospital over a period of 9 years. The follow-up examination revealed that four patients had visual acuity of more than 6/18, and of these two retained binocular single vision and used contact lenses. The size of the material does not permit any conclusive statements to be made. Thus it is impossible to select the patients who will have either a good or a poor final result from the treatment, with regard to vision and binocular single vision.


Social and medical aspects of unilateral traumatic aphakia. Twenty-one males between 16 and 50 years of age were admitted during a five year period and treated for a corneal perforation and traumatic cataract. One did not attend the follow-up examination. Five patients were not offered contact lens owing either to their occupation or to bad visual acuity. Twelve patients were offered contact lens, but only four patients made permanent use of them and have good binocular function. Three patients were given an intraocular lens, two of these with good results. Many of the patients had considerable problems at work, and there appears to be a certain amount of relationship between the length of the sick leave and their later employment. Half of the patients had to change their occupation either totally or partly. Social security and social problems are discussed.


Correction of aphakia with intraocular lens implants. 40 cases of intraocular lens implants are reported. 33% had an optimal post-operative vision of greater than 1.0; 56% and larger than or equal to 0.9 and 84% 0.5 or better. After a postoperative follow-up of 1 month to 32 months, mean 15.1 months, the patients were all satisfied with the pseudophakic eye, and no endothelial corneal dystrophy, chronic uveitis or glaucoma was detected. Several minor post-operative complications were seen, most without consequence. One case had recurrent iridial haemorrhages.


Results from lens implantation. A material from four Danish hospitals. A retrospective evaluation of the results obtained with primary implantation of an iris clip lens, performed in four Danish eye departments, is given. Altogether 203 implants were carried out. The mean age of the patients at the time of operation was 77 years. Seventeen patients had bilateral implantation. Besides the cataract, the age of the patients was main indication for implantation. Contributing indications were monolateral cataract, macular degeneration, and general somatic or psychic incapacity. The incidence of more serious complications was (more than one complication in some eyes): corneal dystrophy 13/203, deposits on the clip lens or in the pupil 18/203, secondary glaucoma 2/203, macular oedema 2/203, late recurrent hyphaema 2/203 and dislocation of the clip lens 6/203. Seven clip lenses were removed. A corrected visual acuity of 6/12 or above was found in 56% of the cases postoperatively. In spite of the complications it is considered justifiable to continue with clip lens implantation in elderly patients, to solve the optical problems following aphakia.


Congenital glaucoma before and after the introduction of microsurgery. Results of "macrosurgery" 1943-1963 and of microsurgery (trabeculotomy/ectomy) 1970-1974. Primary trabeculotomy (in five eyes "converted" to trabeculectomy) normalized the tension in all 21 eyes with congenital glaucoma without associated diseases, (mean postoperative tension 12 mmHg, range 8-20 mm). Re-operation was needed for only one eye. Preoperatively glaucomatous cupping was present in 18 of these 21 eyes. Ten of the 18 eyes with glaucomatous cupping were operated upon before the age of 6 months two before 11 months and the appearance of the disc was normalized in these 12 eyes. Repeated trabeculotomy, -ectomy was without success in three of five operated eyes in patients with congenital glaucoma of several years duration previously treated by "macrosurgery". In patients with associated diseases normal tension was achieved by means of trabeculotomy/-ectomy in two eyes in two Sturge-Weber children with unilateral congenital glaucoma and in both eyes in a child with a chromosomal defect with bilateral congenital glaucoma. Repeated trabeculotomy/ectomy was on the other hand without success in a child with bilateral aniridia with congenital glaucoma and hydrocephalus. Presupposing acute or subacute microsurgery, the present operative results of congenital glaucoma without diseases are far better than those obtained in previous decades by "macrosurgery" which, despite frequent re-operations, effected normalization of the tension in only 61% of the eyes (11 of 26 patients (42%) with bilateral congenital glaucoma without associated diseases and treated by macrosurgery in previous decades were under the Care of the Blind).


The distended disc in early stages of congenital glaucoma. In 12 out of 18 eyes operated upon for congenital glaucoma without associated diseases the preoperative glaucomatous cupping had disappeared at follow-up 2 weeks to 3 months after the operation (trabeculotomy ab externo on 9 eyes and trabeculectomy on 3 eyes). Of the 12 eyes, 10 had had the operation performed before the age of 6 months, in contrast to the group in which glaucomatous cupping of the disc was irreversible where operation had been performed in the age range 6 months--12 years (mean 6 years). The mean postoperative tension value in the 18 eyes was 12 mm (range 8-20) mm) without medication, mean observation time 3 years. It seems likely that during the first phases of congenital glaucoma the disc is distended, i.e. of increased diameter and depth. This form of glaucomatous cupping and the increased diameter of the disc may be due to pressure-conditioned enlargement of the scleral canal and omnidirectional distention of the lamina cribrosa. This distention manifests itself mainly in the central areas of the lamina cribrosa and the disc, and usually disappears when the tension is normalized by surgery during the first phases of the disease.


Goniotomy and congenital glaucoma.

Goniotomy and congenital glaucoma. A survey is presented of the operative results  obtained in 45 eyes suffering from congenital glaucoma, primarily operated on using micro-surgical techniques, either goniotomy as described by Worst, or trabeculotomy. Thirty-eight of the 45 eyes have, during an observation period of 1-10 years, average 5.5 years, a normal pressure of less than or equal to 18 mmHg measured using Draeger's technique. A relatively high frequency of recurrence has been found following an average observation period of 3.5 years in patients who were primarily normalized by Worst's goniotomy.


Variation and heritability of ocular dimensions. A population study among adult Greenland Eskimos. Adult Greenland Eskimos from Umanaq town (age 15+) and villages (age 40+) were examined. Optical pachymetry, ultrasonic oculometry, corneal diameter and curvature measurements, and subjective refraction were performed in 5-600 persons. Frequent occurrence of primary angle-closure glaucoma motivated the survey. Age-, sex- and family-variations were studied by linear regression analyses. Conspicuous age effect was found with respect to increase of lens thickness and forward displacement of the lens with age. Almost no age influence was found with respect to increase of lens thickness and forward displacement of the lens with age. Almost no age influence was found with respect to corneoscleral size, i. e. axial length, corneal size and corneal radius of curvature. Conspicuous heritability (h2=0.6-0.8) was found in corneoscleral size parameters as well as lens position, while refractive error showed a much smaller genetic influence.


Fluorescein and indocyanine green fluorescence angiography in study of affected males and in female carriers with choroidermia. A preliminary report. 26 males and 13 female carriers of different ages with choroideremia of varying severity were investigated using sodium fluorescein (FAG) and/or indocyanine green (ICG) fluorescence angiography. Females with minor changes present in pigment epithelium amy stay unchanged throughout life or gradually develop into a more advanced stage resembling the fundus picture of severely affected males. In moderately affected females there is a patchy degeneration of pigment epithelium in the macula. Peripapillary degeneration is seen also in indocyanine green fluorescence angiograms. In males, atrophic areas and the remaining choriocapillaris are clearly demonstrated in FAG and less well visible in ICG angiograms. ICG angiograms show choroidal vessels more clearly in cases where the pigment epithelium and the choriocapillaris are still present. In advanced cases in males and females, the choroidal blood circulation is slow.


Photocoagulation in retinal venous occlusion. Results of retinal photocoagulation therapy in 26 eyes with retinal branch vein occlusion (RBVO) and in 18 eyes with central retinal vein occlusion (CRVO) are presented. The final visual outcome in eyes with macular oedema (non-ischaemic type of occlusion) did not significantly differ from that reported in various untreated series of branch or central retinal vein occlusion. Neovascular complications in eyes with capillary non-perfusion (ischaemic type of occlusion) could not be prevented with the relatively mild photocoagulation technique (less than 200 xenon burns in CRVO) used in this study. On the basis of this series the value of photocoagulation therapy in improving the visual prognosis in venous occlusion is questionable, and, in order to prevent neovascular complications in the ischaemic type of occlusion, a more extensive treatment seems to be necessary.


Haemorrhagic maculopathy in young adults. The results from a retrospective clinical study of a group of patients with a specific macular disease are presented. The group includes young adults, otherwise healthy, with no hereditary diseases. The macular disease is as a rule monolateral. The lesion consits of a small central nodule surrounded by subretinal haemorrhages, retinal oedema and degenerative changes in the adjacent pigment epithelium. Fluorescein angiography demonstrates subretinal neovascularization in the central part of the lesion. The disease is selflimiting and the lesion develops into a fibrotic scar. In some cases, small, atrophic spots are seen scattered in the eyeground. There is no vitreous reaction and no signs of anterior uveitis. The clinical picture is identical with the macular lesion reported in the presumed ocular histoplasmosis syndrome.


Argon laser treatment of exudative senile maculopathy. Fourty-nine eyes with exudative senile maculopathy (ESM) have been treated with argon laser photocoagulation. Fluorescein angiography studies were done pre- and postoperatively. The follow-up time is 6 to 12 months after end of treatment. The results suggest a beneficial effect in selected cases of ESM.


Contrast sensitivity in macular disease. A preliminary report. Psychophysical measurements of contrast thresholds for sinusoidal gratings of variable frequency were made in normal controls and in patients with macular disease. Normal controls showed a U-shaped contrast sensitivity function comparable with previous reports. Patients with relatively well conserved visual acuity showed a marked impairment in contrast sensitivity for targets of high and intermediate spatial frequencies, while patients with more advanced disease showed a pronounced impairment across a larger spectrum of frequencies. Our findings provide insight into the visual difficulties of daily life of patients with macular disease. The determination of contrast sensitivity seems to be an important and very sensitive tool for the detection of early disturbances.


Central serous retinopathy and presenile disciform exudative macular degeneration. Is there an aetiological relationship between these two exudative conditions of the macula? The clinical syndromes central serous retinopathy (RCS) and presenile exudative disciform macular degeneration (PEDMD) are well known, but the causes of the pathophysiological and pathoanatomical changes in the choriocapillaris, Bruch's membrane and pigment epithelium as predisposing factors are unknown. Apparently these two degenerative macular conditions are different. However, they possibly represent two manifestations of the same nosological entity, which is initially dominated by a subretinal exudation in the macular region. It is therefore also reasonable to consider that RCS can be part of, or an initial stage of PEDMD. In the present study these possibilities have been demonstrated by a follow-up examination, using among other things fluorescein angiography of a selective material of 20 patients with RCS. In addition, it is shown that RCS can be a more serious condition with regard to the central vision than is generally accepted.


Disciform detachment of the macula. I. Juvenile haemorrhagic macular choroidopathy. The clinical findings in six patients with juvenile haemorrhagic macular choroidopathy are described. There was no evidence of infection with Histoplasma capsulatum. The history, clinical features and course of the disease suggested that at least in some cases intravascular coagulation in the central choriocapillaris may form the choroidopathy inducing the disciform detachment of the macula. Oral corticosteroids could not prevent progression of the lesion which had a poor visual outcome. In one patient, good therapeutic response was achieved with acetylsalicylic acid, which may be useful together with lasercoagulation in the early treatment of this syndrome.


Disciform detachment of the macula. II. Fluorescein and indocyanine green fluorescence angiographic findings in juvenile haemorrhagic macular choroidopathy. Six patients with juvenile haemorrhagic mascular choroidopathy were studied with fluorescein and indocyanine green fluorescence (ICG) angiography, and red-light and red-free light photography in different stages of the disease. The primary lesion consisted of multifocal, whitish, dot-like areas of choroidal infiltration showing hyperfluorescence in the late phase of the fluorescein angiograms. Red-light photographs revealed depigmentation of the pigment epithelium overlying the choroidal lesion, and clearly demonstrated the subsequent pigment-ring lesion. Fluorescein angiograms revealed subretinal neovascularization at the site of the disciform-stage choroidal lesion. ICG angiograms revealed the choridal lesion to be located in the region of greatest supply of short posterior ciliary arteries, wheras the lesion itself remained underfilled throughout the angiogram suggesting vascular decompensation at the site of the lesion. The results suggest a vascular basis, namely intravascular coagulation in the central choriocapillaris, for this uveitis entity.


Toxoplasmic chorioretinitis affecting the macula. To study macular changes in toxoplasmic chorioretinitis 41 patients with ocular toxoplasmosis were reviewed. Of the 41 patients, seven had central, large, deep, pigment ringed scars of congenital toxoplasmosis with poor central vision; squint was seen in two and nystagmus in two; 32, including 11 cases with a macular lesion, had recurrent active toxoplasmic chorioretinitis with a focal, yellowish-white, elevated lesion with indistinct borders mostly at the margin of an old scar and associated with vitreous opacities in all, secondary anterior uveitis in 28, macular oedema in 22, papilloedema in 14, and retinal perivasculitis in 16 cases; two had rare acquired toxoplasmic chorioretinitis affecting the macula. The results show that active toxoplasmic chorioretinitis often causes a widespread intraocular inflammation with vitritis, macular oedema, papilloedema, retinal perivasculitis and secondary anterior uveitis, and suggest a combined treatment of active lesions with antimicrobial agents and corticosteroids.


Inotropic action and myocardial uptake of digoxin and betamethyldigoxin in isolated guinea pig atria. The chronotropic and inotropic effects as well as the tissue levels of digoxin and methyldigoxin were studied in isolated guinea pig atria. Higher concentrations of methyldigoxin than of digoxin were required to cause arrhythmias. The inotropic potencies of the two glycosides did not differ from each another in equimolar concentrations in the organ bath. The increase in contractility correlated with the level of the glycoside in the organ bath and in the tissue. Digoxin was more effectively taken up by the heart tissue than methyldigoxin. Thus, when the tissue levels of the glycosides were the same, the contractility was greater after methyldigoxin than after digoxin.


Pharmacokinetics of methylergometrine (methylergonovine) in the rabbit and man. Methylergometrine concentrations in human and rabbit plasma were determined by a new radioimmunoassay after a single intravenous injection (0.2 mg in man and 0.05, 0.1 and 0.2 mg/kg in rabbits). Both in man and in the rabbit methylergometrine disappeared quickly from the plasma with a mean T1/2alpha of 1.8 and 1.2-1.7 min. respectively. Similarly, the T1/2beta-values were 32.1 and 27.3-93.2 min. tthe mean maximal response in the rabbit uterus in situ after 0.05, 0.1 and 0.2 mg/kg intravenously dose was found at 40 sec., 26 sec., and 26 sec. after the drug administration, respectively, and the dose response curve was quite steep. A significant correlation was found between the dose and response.


Chronic copper poisoning in sheep. III. The distribution of soluble copper- and zinc-binding liver proteins of lambs compared with adult sheep. The distribution of copper and zinc among soluble hepatic proteins in lambs from 1 normal and 1 copper dosed ewe was studied by gel filtration. It was found that the distribution pattern is similar in newborn lambs and transfer and accumulation of copper is possible in lambs.


Hexachlorobenzene induction of 2,4-diaminoanisole mutagenicity in vitro. Hexachlorobenzene (HCB)-pretreatment of rats leads to an increase in liver microsomal 2,4-diaminoanisole activation to a mutagen after a dose of 10 mg/kg intraperitoneally and to an increase in ethylmorphine N-demethylase after a dose of 50 mg/kg intraperitoneally. 2,4-Diaminoanisole mutagenicity was increased 24 hrs after HCB-pretreatment, whereas ethylmorphine N-demethylase first increased after 48 hrs. There is a sex difference in the inducing effects of HCB on ethylmorphine N-demethylase, but not on 2,4-diaminoanisole mutagenicity. HCB-pretreatment also leads to increases in 2,4-diaminoansiole mutagenicity in the kidneys, but not in the lings or in foetal liver.


Bioavailability of oxazepam: absence of influence of food intake. The possible influence of food intake on the bioavailability of the anxiolytic drug oxazepam was assessed in eight healthy volunteers taking a single dose of the drug both on an empty stomach and together with a standardized breakfast meal. The serum concentrations of oxazepam were determined by gas chromatography on samples obtained before, and at numerous occasions up to 48 hours after drug administration. The results indicate that concomitant food intake has no essential influence on the bioavailability of oxazepam.


[Persistence and hyperplasia of the primary vitreous body]. Persistent hyperplastic primary vitreous is a disease whose spectrum has continued to widen throughout the years; in fact, it probably comprises a number of nosological entities considered as isolated symptoms until today. Our study has shown that the disease can be congenital and affect both eyes in the same individual. The possibility of an etiopathogenic connection with retrolental fibroplasia cannot be excluded.


Nasal heterotopia of the macula in retinopathy of prematurity. A 27-year-old woman with retrolental fibroplasia developed a retinal detachment in her only eye. She demonstrated an extreme degree of nasal retinal dragging and nasal macular heterotopia.


Noradrenaline turnover rate in the mediobasal and anterior hypothalamus of the rabbit. Noradrenaline turnover rate in the mediobasal and anterior hypothalamus of the rabbit. Acta Physiol. Pol., 1977, 28 (1): 39-43. The rate of noradrenaline (NA) turnover in mediobasal hypothalamus (MBH) and anterior hypothalamus (AH) of the rabbit was estimated by steady-state isotopic method with a tritiated noradrenaline (3H-NA) as a tracer. The disappearance rate of 3H-NA both in MBH and in AH was found to be biphasic; the first rapid phase of the NA half-life of about 30 min, followed by the second phase of slower decay of the half-life of 2.4 h and 10 h for MBH and AH respectively. The results suggest an existence of more than one metabolic pool of endogenous noradrenaline in MBH and AH and indicate regional difference in the metabolism of NA stores in the hypothalamus.


Monoaminergic influences on the incorporation of 35S in the hypothalamic and neurohypophysial proteins following intracerebroventricular injection of 35S-cysteine in dehydrated rats. In the rats dehydrated for 48 h the mean specific activity of hypothalamic and neurohypophysial TCA-precipitable proteins following intracerebroventricular injection of L-cysteine-35S-hydrochloride was significantly higher than that found in the dehydrated and reserpinized. Under influence of amphetamine sulfate however, no change of 35S-uptake by TCA-precipitable hypothalamic and neurohypophysial proteins could be detected in rats similarly dehydrated.


Corneal ulcer caused by Pasteurella multocida. A 44-year-old woman with Graves' disease and exophthalmos developed a severe corneal ulcer caused by Pasteurella multocida after being bumped on her right eye by her pet dog. The organism was transferred from the patient to an abraded rabbit cornea and produced a similiar corneal ulcer and hypopyon.


Modification of the classification of the eye changes of Graves' disease. The original (1969) classification of the Eye Changes of Graves' Disease has been retained except for Classes 1 and 3. Class 1 has been limited so that proptosis of 23 mm or greater is placed in Class 3, even if the patient is asymptomatic. Grading of Classes 1 and 2 has been left to the individual physician or clinic, but we urge that the suggested criteria for grading Classes 3 through 6 be used. Progression of disease is not necessarily sequential through each of the classes, and ethnic factors and myopia may influence the extent of proptosis in normal subjects.


Immunosuppression. Role on the infectious diseases of oncologic children. Cancer patients show an immune deficit whose beginnings are influenced to one extent or another, by two factors: the cancer itself, and the antimitotic-immunosuppressive treatment to which the patient is subjected. The immune deficit will have repercussions in the anti-infectious defense that these patients show: --Greater number of infections. --Greater severity of infections. --Tendency towards generalization and showing of septicemic states. The problem is most serious in hematological tumors (leukemia, lymphosarcoma) where the primary cause of death is infection. During the period of activity of the disease, and also in relation to the antimitotic treatment, the PMN will decrease in absolute count and will function poorly. The consequence will be a high frequency of bacterial infections, sepsis, pneumonia, skin infections, etc., predominantly caused by gram-negative germs and staphylococcus (any germ considered not to be "very virulent" can be found); and it will result in a high mortality rate. When these children are in remission or have solid tumors, the problem is not so acute, and bears more relation to antimitotic treatment and other extraneous factors (hospitalization, catheters, antibiotics, gastrointestinal ulcers...). Patients most frequently show localized bacterial, viral and protozoon infections (varicella, zooster, herpes simplex, cytomegalia, pneumocystis) because of the predominance of cellular immunity deficit.


Behavior of rats in various stages of the sexual cycle after injection of noradrenaline into the lateral ventricle of the brain. The influence of intraventricular injection of 50 microng of noradrenaline (NA) on behavior of female Wistar rats in various phases of the sexual cycle, and the influence of 17-beta-estradiol and progesterone in castrated female rats were studied. Changes in motor and exploratory activity were observed in the course of the sexual cycle in female rats. Sensitivity to NA injected intraventricular varied significantly in different phases of the sexual cycle. Castration depressed the action of NA on motor and exploratory activities in rats, and progesterone prevented the depressive effect of NA in castrated rats.


Immunohistologic findings in the lung in systemic lupus erythematosus. A 29-year-old woman with systemic lupus erythematosus (SLE) developed dyspnea, hemoptysis, pleuropericarditis, and azotemia shortly after an episode of arthritis and progressive hair loss. She had a high titer of radioimmune anti-DNA Antibodies, positive fluorescent anti-smooth muscle antibodies, and depressed C3 levels in her serum. Antiglomerular basement membrane antibodies were negative, and the titer of antibodies against extractable nuclear antigen was within normal limits. Cryoglobulins and lupus erythematosus cell preparations were negative. Despite steroid therapy and other supportive measures, including dialysis, she died ten days after admission. Percutaneous renal and pulmonary biopsies were performed postmortem at bedside and were processed for immunohistology. Identical granular deposits of C3 and IgG were found in both the lungs and the kidneys. This finding suggests that a common pathogenetic mechanism is operating in the development of pneumonitis and nephritis in SLE, and is in agreement with the currently held views on immune-complex diseases.


Hemolytic uremic syndrome with hypocomplementemia, serum C3NeF, and glomerular deposits of C3. A 4-year-old boy had hemolytic uremic syndrome (HUS) associated with depression of serum C3 level, a B-hemolytic streptococcal throat infection, and an elevated level of antistreptolysin O titer. In addition to the characteristic histologic changes associated with this syndrome, substantial infiltration of polymorphonuclear leukocytes and nodular deposits of C3 globulin were seen in the glomeruli of the first biopsy specimen. Two months after clinical remission, he had a recurrence of hemolytic anemia, thrombocytopenia, and acute renal failure. The serum C3 concentration had decreased again, and serum C3NeF was detected in the serum. The typical changes associated with HUS were still present on electron microscopy. Bilateral nephrectomy and renal transplantation were done because of the development of uncontrollable severe hypertension and increasing azotemia. This patient had three manifestations of HUS, but because of several differences, such as hypocomplementemia, serum C3NeF, a recurrence, and persistent glomerular deposits of C3 globulin, he appears to have had a different form of the syndrome.


Immunologic myopathy. Linear IgG deposition and fulminant terminal episode. The histopathologic characteristics of a patient with progressive myopathy, renal failure, hemoptysis, and a fulminant terminal event demonstrated a diffuse vasculitis, type 2 fiber atrophy of muscle, and linear IgG staining of the basement membranes of skeletal muscle fibers and of glomerular capillary basement membranes. Interpretation of electron micrographs confirmed that there was thickening of muscle basement membranes. The data suggest the presence of an antibody to a basement membrane antigen shared by muscle and kidney.


Disseminated choroid plexus papilloma. An ultrastructural study. Choroid plexus papilloma is a rare intracerebral neoplasm that occasionally disseminates along the neuraxis. The fine structure of such a metastatic papilloma appears to correspond very closely to that of normal choroid plexus. Lack of capillary endothelial pores is the only meaningful difference. There does not appear to be an ultrastructural feature that is unique to disseminating choroid plexus papilloma.


Osteolipomas of the tuber cinereum.

Osteolipomas of the tuber cinereum. Osteolipomas of the tuber cinereum traditionally have been classified as meningeal lipomas that are located at the tuber cinereum. Examination of two cases and a review of 22 others found in the literature show that these lesions exhibit a remarkable consistency in their size and in their location between the corpora mamillaria and the pituitary stalk, and that approximately half of them contain a well-organized bone spherule with a central marrow space. These aspects differ from the features of meningeal lipomas in general; reasons are given for considering that the osteolipomas are displaced elements of the mesenchyme encompassing walls of the craniopharyngeal duct.


Cellular leiomyomas of the stomach in 49 patients. The cellular leiomyoma of the stomach is composed of tightly packed, generally uniform spindle cells arranged in palisades, whorls, or interdigitations. Although these neoplasms have been variably considered to arise from gastric smooth muscle or Schwann cells, the morphogenesis is incompletely resolved. Perhaps they derive from a multipotential gastric stromal stem cell that is capable of differentiating toward smooth muscle. A cellular gastric tumor composed of fairly uniform, elongated spindle cells is unlikely to be malignant. Of 49 such tumors, only one metastasized. The combination of an increased mitotic rate and large tumor size is possibly indicative of malignant potential.


Mycoplasma-like structures in granulomatous angiitis of the central nervous system. Case reports with light and electron microscopic studies. Two patients had granulomatous angiitis of the central nervous system. The typical vasculitis involved the small branches of the cerebral arteries in both patients and resulted in thrombosis of the left middle cerebral artery in one. Electron microscopy demonstrated structures resembling Mycoplasma organisms. These were present in small numbers in the wall and in the granulomatous reaction within the lumen. Giant cells were observed cintaining particles suggestive of Mycoplasma within the perinuclear cisternae. Virus-like particles were not observed.


Uhl's anomaly in the mink. Partial absence of the right atrial and ventricular myocardium. Congenital marked hypoplasia of the right atrial and ventricular myocardium (Uhl's anomaly), without other cardiac anomalies, was observed at autopsy in a mink. The animal died unexpectedly without previous symptoms at the age of 2 years, suggesting that the cause of sudden death was acute congestive heart failure. This cause demonstrates that this malformation can occur in species other than man. Embryologically, this anomaly might be due to myocardial injury to the right cardiogenic fold at a relatively early stage of embryogenesis.


Density of mucous glands in the normal adult nasal turbinates. On 13 normal inferior and middle turbinates the mucous membrane was freed, stained by the PAS-alcian blue whole-mount method, and the mean density of glandular orifices was determined by counting in 4 mm2 fields. The median density fell in both turbinates in the anteroposterior direction, being in the inferior turbinate 8.2 glands/mm2 anteriorly, 7.9 in the middle, and 7.1 glands/mm2 posteriorly. In the middle turbinate it was 8.4 glands/mm2 anteriorly, 8.1 in the middle, and 7.3 glands/mm2 posteriorly. There were no significant differences in median density between the medial and lateral wall or between the superior and inferior half of the inferior or middle turbinate as a whole. The median total number of glands in the inferior turbinate was 9,200 with a very wide interindividual range of 6,100-12,700. In the middle turbinate the median count was 6,700 glands and the range 4,400-11,500. The pathology of the mucous glands of the nose is discussed.


[On the oscillation form of the stapes as a function of the volume. Experimental investigations into the human temproal bone preparation (author's transl)]. In order to further clarify the change in the oscillation form of the stapes as a function of the volume, measurements were performed in 10 fresh temporal bone preparations at two points at the short and long diameters of the base of the stapes from the labyrinthine side. The oscillations were recorded from two channels, first, by two electro-dynqual stress on the base of the stapes, also optically by modulating a light beam and electronically scanning by means of a phototransistor, and the oscillations were then recorded on a two-beam oscilloscope. The result was that it is not possible to prove any phase shift between the two measurement points at the short or at the long base of the stapes in a volume range within the physiological limits. Thus, any sweep phenomenon at high volumes does not exist. Also, a volume-dependent shift of the oscillation axis on a line within the base was not to be observed.


[Tonsillectomy and age (author's transl)]. We evaluated the case histories of 149 patients aged over fifty who were tonsillectoprived in our ENT-clinic in Freiburg between May 1970 and April 1975. Neither the rates of damages nor of complications were higher than those of younger patients. If necessary, even older patients can be operated.


[Aspects of labyrinthectomy (author's transl)]. Since the introduction of Antibiotics labyrinth operations have become very seldom. In those days before the Antibiotic Era the indication to function-destructing radical surgery was justified in cases of suppurative labyrinthitis. Only in cases of mild serous (irritative) labyrinthitis were conservative treatments with drugs successful. Nowadays, labyrinthoperations are not necessary in most cases. Endocranial complications and high mortality rates of the disease are no longer feared today. All the same, there are cases were the labyrinth operation is justified despite high dosis of Antibiotica. Spceial problems and indications for labyrinthectomy are discussed with own examples.


[Active otosclerosis of the stapes footplate: histological and clinical aspects of its influence on the  perilymph (author's transl)]. Pathologic capillaries are usually seen in the center of an otospongious process. Next to obliteration, dilatation and increased permeability a loss of basement membrane structure is evident. Around the capillaries exists a wide network of mesenchymal cells which have a glycogen like mass within the cytoplasm; glycogen can be delivered into the extracellular fluidspace. Free erythrocytes are located around many vessels. Near the margin of the lacunae decalcificated areas are seen; in the center of these areas osteocytes undergo lysis; they show intracytoplasmatic deposits of apatite which we assume to be located within the mitochondria. The collagen structure in the neighbourhood of the osteocytes seems to be damaged. Once the resorptive process has reached the perilymphatic surface of the footplate there comes to an connection between the  otospongiotic lacunae and the vestibule. Free erythrocytes, glycogen like drops and lysosomes are delivered into the perilymph. Comparing the histological results with the operative results in patients with floride otosclerosis we conclude that operation should be done as early as possible to prevent damage from the inner ear, caused by the continuous intoxication of the perilymph from the otosclerotic focus.


[Body weight, body height and menarche. Epidemiological study, in the Province of Pordenone, of the school population from 12 to 15 years old (12,000)]. The relation between body weight, height and the commencement of menstruation was studied in 5324 girls aged 12--15 yr attending secondary schools in the province of Pordenone. The mean age of menarche was 12 2/12 yr and varied little throughout the province. Weight and height appeared closely related to menarche. A threshold of 49.2 kg and 157.3 cm was noted. Attainment of these critical values was apparently the factor that influenced the age at which menstruation commenced.


[2-Carbethoxymethylene-thiazolidones-(4), a novel series of Heterocycles with choleretic properties]. Base-induced condensation of alpha-mercapto-carboxylic esters with  activated acetonitriles yields 2-methylene-thiazolidones-(4). The paper presented describes the development of ethyl (Z)-(3-ethyl-4-oxo-5-piperidino-thiazolidin-2-ylidene) acetate (30; piprozoline, Gö 919, Probilin), a novel choleretic with exocrin pancreas stimulating and hepatoprotective properties, by following-up the choleretic parent compound 2, which belongs to the 2-carbethoxymethylene-thiazolidones-(4) series. Synthesis and properties of piprozoline are reported. Structure-activity relationship is discussed in short.


[On the pharmacology of piprozoline (author's transl)]. Ethyl (Z)-(3-ethyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)- acetate (piprozoline, Gö 919, Problin) is a new potent choleretic which can be classified as a true cholepoietic agent. Accordingly the substance increases bile fluid and solid content as well. A dose-dependent choleretic effect could be shown in all species investigated. The choleretic effect of piprozoline is long-lasting and superior to that of the other choleretics compared with. There was a significant inhibition of experimentally induced liver damage in animals by piprozoline given prophylactically. Our experiments did not reveal any pharmacological properties interfering with the use of piprozoline as a choleretic.


[Method for direct measurement of choleresis and secretory function of the exocrine pancreaas demonstrated by sodium dehydrocholate and secretin (author's transl)]. A method has been described that enables to check secretory processes in animals directly. This has been demonstrated in dog exocrine pancreas stimulated by secretin and on bile secretion induced by sodium dehydrocholate. The design of this method permits to run experiments on pancreas and choleresis separately as well as simultaneously. The directly recorded absorption curves are in good agreement with the data obtained from the collected fractions. Based on the optical density curves, it is possible to determine the contents of the fractions more directly and more specifically. It is also possible to study kinetic problems and time dependent reactions by using this method and this design.


[Pharmacological effects of piprozoline on bile secretion in dogs (author's transl)]. Ethyl (Z)-(3-ethyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)-acetate (piprozoline, Gö 919, Probilin) and its main metabolite Gö 3284 induce a strong choleretic effect in dogs after i.v. and i.d. administration as well. Intestinal absorption is fast, and already 3.5 min after administration of the substances a rise of the bile volume and of the optical density of the secreted bile can be observed. The secretion rates of bile solids and bile acids per time (min) increase almost at the same time, too. Moreover, piprozoline presumably stimulates the synthesis of bile acids and of the other matter in addition to the raised secretory rate. In the group of choleretics, piprozoline is to be placed among the cholepoietics. Under the influence of piprozoline and Gö 3284, the content of solids sometimes decreases for a short period immediately after administration of substances. A strong linear correlation occurs between the secretion rate of bilirubin and bile acids. The increase of bile volume under the influence of piprozoline and Gö 3284 may be seen as osmotic effects caused by the stimulation of the bile acid dependent and the bile acid independent (Na+-ion dependent) canalicular mechanisms of choleresis.


[Pharmacological effect of piprozoline on the exocrine pancreas of dogs (author's transl)]. Ethyl (Z)-(3-ethyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)-acetate (piprozoline, Gö 919, Probilin) and its main metabolite Gö 3284 cause a long-acting stimulation of the ecbolic function of the exocrine pancreas in the dog after intraduodenal administration or after i.v. injection. This has been demonstrated by canulation of the ductus pancreaticus accessorius and by perfusion of the small bowel as well as by photometric evaluation of the perfusion streams and determinations of the activities of alpha-amylase, lipase and trypsin in the 2-min fractions thereafter. Piprozoline does not cause a rise of the bicarbonate secretion and volume. In its action to the exocrine pancreas it resembles very much cholecystokinin-pancreozymin. The value of piprozoline is discussed with  regard to its stimulating effect on the ontogenetic unit of the epigastric region.


[Toxicological study on piprozoline (author's transl)]. The compatibility of ethyl (Z)-(3-ethyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)acetate (piprozoline, Gö 919, Probilin) was tested orally in rats and intragastrically in dogs for 6 months. Moreover, the effect of the substance was studied on pregnant rats and rabbits and their foetuses after intragastric administration and on the fertility and breeding capacity of rats after oral application. In the course of the chronic experiments, in the highest dosage group of rats a slight sedation and a decrease of body weight gain and food intake could be observed. The female animals showed an enlargement of the adrenal glands. A small hyperemesis was noted in the highest dosage group of dogs. Subtoxic doses applied to rats and rabbits during gestation did not induce malformations in the newborns. Even treatment with large doses did not influence fertility and breeding capacity.


[TLC-method for quantitative densitometric determination of piprozoline and its main metabolite using internal standards (author's transl)]. A determination method is described for ethyl (Z-3-ethyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)acetate (piprozoline, Gö 919, Probilin) and its main metabolite (Gö 3284) extracted from the sample to be analyzed at different pH-values, after the addition of two internal standards to the sample. The extracts are then recombined and applied to TLC plates. After developing twice in a cyclohexane/isopropanol mixture, the substances are determined densitometrically on the plates at 275 nm. By comparing the peak area ratios (substance/internal standard) the peaks were quantitated after plotting a calibration curve. The lower sensitivity limit was approx. 100 ng after extraction of a 1 ml sample.