Head-group conformation in phospholipids: a phosphorus-31 nuclear magnetic resonance study of oriented monodomain dipalmitoylphosphatidylcholine bilayers. Angular-dependent 31P NMR spectra of oriented biaxial monodomain DPPC.H2O multilayers are employed to study head-group conformation in this phospholipid. The results indicate that the O-P-O plane of the phosphate, where the O's are the nonesterified oxygens of the phosphodiester, is tilted at 47 +/- 5 degrees with respect to the bilayer normal. This PO4 orientation could result in the choline moiety being extended parallel to the bilayer plane, and it will explain the breadth of the axially symmetric 31P powder spectrum observed for DPPC in excess water. This work is the first direct observation of this conformation for lecithins and it illustrates the utility of high-resolution solid-state NMR in structural studies of disordered systems.


Radiation leukaemogenesis: is virus really necessary? Generalized lymphosarcomatosis (leukaemia) of non-thymic type occurs in mice bearing 90Sr or 239Pu or 226Ra. Tumours passaged from such mice have been tested for tumour-associated transplantation antigens that could provoke a protective immunity which would be expected if such antigens were determined by virus activated by the irradiation. Sub-threshold doses of living syngeneic tumour, large doses of living allogeneic tumour and large doses of killed syngeneic tumour were without protective effect. This suggests that viruses observed electron micrographically in such tumours are passengers and not causative.


Differentiation of the pulmonary surfactant system. Disaturated phosphatidylcholine accumulation in fetal rat lung in vivo and in vitro. Fetal rat lung was placed in organ culture at 15 days gestation (22 days total gestation period), before biochemical and morphological development of the pulmonary surfactant system. At the fifth day of culture numerous Type II cells containing lamellar bodies were present as determined by electron micrography. Phospholipid accumulation in the cultures increased abruptly beginning at 6 days in culture. The phospholipid which accumulated between the sixth and twelfth culture days was composed of 21--27% disaturated phosphatidylcholines. Both the percent of disaturated phosphatidylcholines in the phospholipid fraction and the qualitative pattern of accumulation as a function of time were similar to observations for fetal rat lung developing in vivo. The data presented provide evidence for development of the pulmonary surfactant system in organ culture in vitro.


Distribution of gamma-carboxyglutamic acid in calcified tissues. gamma-Carboxyglutamic acid, previously identified in the vertebrate mineralized tissues of bone and dentin, is not detectable in the calcified skeletons of six invertebrate species representing five phyla. Its absence in all analyzed invertebrate tissues (including calcitic, aragonitic, and apatitic mineral phases) indicates that matrix protein-bound gamma-carboxyglutamic acid is not obligatory for the calcification process in the invertebrates. Further, these data raise the possibility that invertebrates as a group may lack the enzymatic capability for biosynthesizing gamma-carboxyglutamic acid. In contrast, the distribution of gamma-carboxyglutamic acid in the vertebrates has been further extended by this study to include an apatitic shark tooth and an aragonitic fish otolith. No gamma-carboxyglutamic acid was detected, however, in the organic matrix of the calcitic hen egg shell.


[Relationship between the routes of antitoxin administration and the effectiveness of treating experimental tetanus]. Experiments were conducted on 100 rabbits with asscending, hematogenic and cerebral tetanus caused by the administration of tetanus toxin (1 Dcl). The therapeutic efficacy of "Diaferm-3" antitoxin was compared depending on the route--intracysternal or intralumbar--of its administration (400 IU/kg). Intracysternal antitoxin administration proved to be thrice as effective as the intralumbar one (31.4 and 10.2% of the sick animals recovered, respectively). The latter route was effective only in animals with the ascending intoxication, this apparently being connected with the site of entrance of the toxin into the central nervous system by the peripheral nerves of the hind limbs.


Carcinogenic effect of a quanidine pesticide administered with sodium nitrite on adult mice and on the offspring after prenatal exposure. Adult Swiss mice were treated intragastrically during the last week of pregnancy with the fungicide dodecylquanidine acetate (dodine, DGA) together with 0.05% sodium nitrite. The incidence of malignant lymphomas, lung adenomas and hepatomas was 30--70% in females. The first tumors appeared 4 months after delivery in the FO generation and at 6--7 months in the F1 generation. Among the untreated control mice the frequency of spontaneous tumors was 6%, and lymphomas developed, if at all, only after 10 months. The oncogenic activity of DGA with sodium nitrite in the offspring was dependent on the dose of DGA.A and C type RNA virus particles were demonstrated in lymphomas by electronmicroscopy. DGA alone had no effect on the cancer incidence.


[Bilateral pheochromocytoma of the adrenal glands and a solitary neurofibroma of the dorsal mucosa of the tongue associated with a solid medullary carcinoma of the thyroid gland in Hashimoto's lymphocytic thyroiditis]. A female aged 22 died 13 hours after having given birth to a live mature fetus. On autopsy, bilateral phoechromyocytomas, a mucosal neurofibroma of the tongue and a solid medulary carcinoma of the thyroid with amyloid associated with Hashimoto's lymphocytic thyroiditis were detected. After parturition, there occurred bleeding into the left-side pheochromocytoma followed by a release of phenyl alkylamines into the circulation. This resulted in fatal peripheral circulatory failure.


[Collision carcinoma of the thyroid gland in Hashimoto's thyroiditis. Spinocellular carcinoma, arising from a cyst of the thyroglossal duct and a follicular carcinoma with an anaplastic turn]. A collision carcinoma of the thyroid was revealed in a surgically removed thyroid affected with Hashimoto's thyroiditis. A follicular carcinoma composed of rather uniform and spherical cells. The anaplastic carcinoma appeared to collide with structures of a noncornifying squamous cell carcinoma supposed to originate in the isthmic area from a ductus thyreoglossus cyst.


Effects of cordacin on lymphocyte activity in vitro. The effects of cordacin on lymphocyte activity were studied with two parameters in vitro. The cordacin inhibited T lymphocyte E rosette formation by 93% at the concentration of 1,000 microgram/ml and tritiated-thymidine incorporation into PHA-transformed lymphocytes by 66% at the concentration of 10 microgram/ml. The implication of these results on replicating leukemic as well as normal cells is discussed.


Epidemiology of Enterobius vermicularis infection among orphans in orphanages in Taipei City. Children of eight orphanages at the different districts in Taipei were examined with scotch adhesive tape method and flotation of saturated NaCl solution from Sept. 1973 to Jan. 1974. The results are summarized as following: General incidence of Enterobius verminularis was 74.40% in 461 cases examined, male 76.45% (224/293), female 70.83% (119/168). There was no significant statistical difference between the male and female. Incidence of Enterobius among the orphanages was 83.33% (25/30) in Po-Ai, Fu-Ann 82.61% (38/46), Ta-Tung 82.43% (61/74), Hau-Sen 77.25% (34/44), Chung-I 75.00% (51/68), Jen-Ai 72.97% (23/37), Ti-Hwei 72.50% (29/40) and Sen-Tao 63.93% (78/122). There were no significant statistical differences among the orphanages except the differences between Sen-Tao and Ta-Tung; Sen-Tao and Fu-Ann, Sen-Tao and Po-Ai. Incidence of Enterobius according to age-groups: The highest rate was 79.34% (242/305) in primary school group followed by 70.00% (21/30) in kindergarten group, 64.40% (73/114) in Junior high school and the lowest was 63.64% (7/11) in nursery group. There was a significant statistical difference between primary school group and junior school group. (Table 3) The larger the space for the children's free activity was the lower the incidence of Enterobius, and the smaller space resulted in the higher incidence. The distribution of Enterobius ova in the different body parts of the 461 orphans was 80.91% (373/461); The highest 74.40% (343/461) at perianal area and the lowest 11.93% (55/461) at ears. The incidence of Enterobius on the various objects in the orphanages was found as the following: 85.71% (6/7) on bed pans, 83.67% (333/398) on linens, 78.46% (51/65) on w. c. appartus, 77.39% (89/115) on specimens of dust, 13.33% (1/15) on stairrails 8.04% (32/39) on bedposts, 7.33% (11/150) on closets, 4.24% (5/118) on desks and 3.64% (2/55) on toys.


Low serum thyroxine due to anti-thyroxine antibody. In one case of untreated Hashimoto's thyroiditis, the serum thyroxine (T4) value, obtained by radioimmunoassay (RIA) employing resin to separate bound and free T4, was significantly lower than that obtained by competitive protein binding analysis (CPBA). The discrepancy was found to be due to the presence of anti-thyroxine autoantibody in the serum. This phenomenon is considered to be of practical importance in interpreting the T4 value by RIA in cases with autoimmune thyroid diseases.


Autogeny in Piophila casei (Diptera, Piophilidae). Two long-adapted laboratory strains of Piophila casei originating from Prague were found to be autogenous. However, protein-deprived females compared to protein-fed ones showed lower fecundity and fertility, and somewhat retarded oviposition extended over a longer period.


An autoradiographic study of the NK/Ly tumor transplanted into the brain of the mouse. The NK/Ly ascites tumor transplanted into the brain of mice is well accepted and the growth is similar to that of malignant lymphomas in the human brain. The authors studied the incorporation of the tritiated thymidine in the malignant lymphoma cells transplanted into brain of the mouse by autoradiographic method.


Febrile convulsions followed by nonfebrile convulsions: analysis based on a maximum likelihood method and discriminant function. Two hundred sixty-two nontreated patients with febrile convulsions only and 107 with later nonfebrile convulsions were analyzed based on a maximum likelihood method and discriminant function. The formula for discrimination is as follows: y = 2.9193 x (basic EEG abnormality at the first examination) + 2.2134 x (more than 20 minutes in duration of convulsion) + 1.7358 (fever under 38.4 degrees C before convulsion) + 1.7005 x (specific EEG abnormality at the first examination) + 1.6703 x (more than 5 recurrences) + 1.5610 x (over 4 years of age at the last convulsion) + 1.4921 x (exogenous causes) + 0.3741 x (family histroy of febrile convulsions among second or third relatives)--3.0397. If an item is positive, coefficient x 1 is to be used, and if it is negative, coefficient x 0 is to be applied. When one classifies patients with y greater than 0 as the FCC group, and those with y less than 0 as the FC group, misclassification may be theoretically expected in 18.9% of cases (accuracy in 81.1%).


[Dichotic listening performance in children--development of a reliable test (author's transl)]. With a new developed and reliable dichotic test (one part monosyllable words, other part monosyllable digits) we could show a significant Right-Ear-Advantage (REA) in children from age six to eight. The determination of an auditory-dominance-index (DI)--in analogy to the DI of handedness by Schilling (1977)--made it possible to determine the different degrees of REA/LEA in individuals or groups. Within the near future the auditory-dominance-index could be an important measure in diagnosis and therapy of child development (i.e. discrimination of language features like phonematics, syntax, semantic, and their lateralisation within ages) as far as standard-scales for all-over-accuity and lateralisation will exist. Our test is the first step to do this.


Influences on the absorption of diphenylhydantoin preparations. The absorption of different preparations of diphenylhydantoin was studied in 9 healthy persons under different conditions. With both galenic preparations of two different factories (diphenylhydantoin-acid) the absorption was significant by less in the fasting state than after breakfast. Whereas the absorption was almost identical for both preparations in the fasting state, it differed significantly after ingestion of a breakfast: the one preparation, DPH-A, was less well absorbed than the other, DPH-B (7,9 mcg/ml serumconcentration 5 hours after oral administration of 5 mg/kg DPH-B versus 5,7 mcg/ml serumconcentration 5 hours after administration of 5 mg/kg DPH-A).


Leukocyte docosahexaenoic acid in juvenile form of ceroid-lipofuscinosis. Leukocyte glycerolipid fatty acid compositions were determined in four patients of juvenile form of neuronal ceroid-lipofuscinosis (Battens disease), their parents and age-matched controls. A 54 to 93% reduction in docosahexaenoic acid (22:6, n-3) was noted in patient leukocytes. The parents also showed reduction in docosahexaenoic acid content, but to a lesser degree. The levels of linolenic family (n-6) polyunsaturated fatty acids were unchanged suggesting that the metabolic defect in this disease is specific to the linolenic family (n-3) of fatty acids.


Pseudohydrocephalus-megalocephaly, increased intracranial pressure and widened subarachnoid space. Seven children with rapid enlargement of the head and other clinical features resembling hydrocephalus are described. All children remained with relatively large heads, developed slowly and all but one had various degrees of mental and motor handicaps. The EEG was disturbed in all cases; two children developed seizures. Increased intracranial pressure was present. In all patients the subarachnoid space was markedly widened while the ventricular system was normal or minimally dilated. The characteristics of this syndrome, the features distinguishing it from similar conditions as well as its possible mechanism are discussed.


Occipital 3-4/s-rhythms in childhood EEG. Report of follow-up studies in 65 children with occipital slow rhythms in the EEG (287 records). Two types of occipital rhythms can be differentiated: Paroxysmal bursts of 3--4/s-rhythms with high amplitude (I) accentuated by closing eyes and continuous usually regular occipital 3--4/s-rhythms (II). Type I is identical with the sinusoidal occipital 3/s-rhythms, which are observed especially frequently in childhood epilepsies. It could be demonstrated by follow-up studies, that the phenomenon usually disappears at latest during puberty. --The second type may also disappear during puberty or may even persist until the adult age. This persisting type is identical with what is quoted as "Grundrhythmusvariante" in the German literature. The continuous occipital rhythms could be demonstrated at earliest at age 3. The rhythms change their shape, amplitude, frequency and localisation during growth: In children prior to age 10 the rhythms show more often occipital accentuation in monopolar leads (against ear as reference); the amplitudes are higher on average; the frequency is often less than 4/s, and alpha groups preceding the rhythms after closing the eyes are less pronounced than in older children. Subharmonic waves are frequent. In the same manner as in adults a mostly right sided lateralisation can be seen. Genetic factors may be involved in the development of the occipital rhythms, although a simple mendelian transmission could not be confirmed. The EEG phenomenon is correlated with symptoms of psychic and vegetative lability. There is no correlation to epilepsy. The high incidence of anamnestic risk factors suggests that exogenous factors are at least contributing to the development of the rhythms. The continuous occipital 3--4/s-rhythms must be understood as the symptom of a disturbed development of central pacemaker systems. It can lead to persisting abnormalities or only occur transitorily in certain stages of the brain maturation.


Benign familial neonatal convulsions.

Benign familial neonatal convulsions. A male neonate presented with very frequent seizures, from the second day of life until the age of two weeks. Subsequently, convulsions did not recur. The patient, 7 years of age at present, has developed normally. Family history revealed transient neonatal convulsions in 8 other family members. The condition is inherited as an autosomal dominant trait.


Congenital Pelizaeus-Merzbacher disease (Seitelberger type), malformation and cystic degeneration of the central nervous system. The present paper reports on the case of a neonate child with multiple malformations affecting osteogenesis and the central nervous system (microcephaly, pachygyria). Morphologically, myelin staining supplied evidence of the total lack of myelin sheaths (myelin aplasia). The cerebellar cortex was malformed and altered by cystic degeneration. Electron microscopy confirmed the aplasia of the myelin sheaths and revealed the presence of concentric multilamellar formations in the glial cells (myelination glia), and in areas of cystic degeneration. The morphologic aspects clearly showed the relationship of this congenital aplasia of the myelin sheaths with the congenital Pelizaeus-Merzbacher disease (Seitelberger type). The cystic degeneration differs from the spongy degeneration of the brain (van Bogaert-Bertrand disease) and should be considered a result of maldeveloped nervous tissue.


An unusual case of phenytoin intoxication. A case of a ten years old boy is reported who developed a severe intoxication after changing the phenytoin treatment from the calcium salt to the free acid. The difference in bioavailability reduced the drug requirement to 55% of the previous dose. The child was receiving also sodium valproate and clonazepam. Serial measurements revealed a significant inverse correlation between the toxic phenytoin serum concentration and the serum level of valproic acid. The measurements of phenytoin as well as of valproic acid in this case have shown again the value of routine monitoring of anticonvulsant therapy.


Hereditary mirror movements--a case report. A five-year-old girl with abnormal mirror movements is described. The phenomenon is observed in the distal parts of the extremities and is most marked in the hands. An extensive neuropediatric examination including computerized tomography of the brain has not revealed any further abnormalities, nor has it been possible to identify the pathogenetic mechanism. The clinical picture corresponds to that previously reported in cases of hereditary mirror movements--a condition with unknown pathogenesis affecting individuals that in other respects are neurologically normal. The disorder is considered to be dominantly inherited but in this case available data suggest a recessive mode of inheritance. There is no doubt that the girl of this report is getting increasingly embarrassed by her condition. Obviously mirror movements of this degree constitute a slight to moderate handicap.


[Emergency surgery of tumors of the small intestine]. Ten cases of serious complications requiring emergency surgery in patients with tumours of the small intestine are presented: 3 cases of peritonitis due to perforation of a fibroleiomyoma, a jejunal adenocarcinoma, and an ileal lymphosarcoma; 3 invaginations (1 ileocolic due to an ileal polyp, and 2 ileoileal due to lymphoma and polypoid metastasis of melanoma; 3 stenosis (ileal owing to metastasis of melanoma, and duodenal and of the duodenojejunal flexure due to histologically unascertained neoplasias); 1 massive enterorrhagia from ileal anaplastic carcinoma. The frequency of such pictures is not negligible when assessed in terms of emergency surgical pathology and compared with other emergency situations arising in patients with tumours. Preoperative diagnosis is difficult even from the clinical history. Tumours of the small intestine appear to give rise to such complications in their initial stages.


[Epicutaneous electrical recording for immediate diagnosis of the site of intestinal occlusions and subocclusions]. 64 patients have been studied by means of an original abdominal epicutaneous electric recording technique. Cases of intestinal paralysis did not show up waves of particular importance while cases of intestinal occlusion showed waves of three basic types. A close relationship was found between types of waves and occlusion localization. The physiopathological and clinical implications of this diagnostic approach are discussed.


Effect of aminophyllin and dexamethasone on secretion of pulmonary surfactant in fetal rabbits. Aminophyllin, dexamethasone, or saline was injected into 27.5-day fetal rabbits 2.5 hr before sacrifice, after which static pressure-volume curves with air were performed. In further similar experiments the lungs were lavaged with physiologic saline which was analysed for total phospholipid content. There were no changes in total lung capacity (TLC) induced with either aminophyllin or dexamethasone. The lungs of fetal rabbits injected with saline retained 44% TLC (+/-3 SE) after deflation to 10 cm H2O trans-pulmonary pressure compared with 48% TLC (+/-3 SE) in those injected with dexamethasone, a difference which was not statistically significant. In contrast, the lungs of fetal rabbits injected with aminophyllin retained 53% TLC (+/-2 SE) after deflation to 10 cm H2O pressure, a significant increase when compared with saline controls (P less than 0.01). There were no changes in lung weight or lung water. These results were interpreted to mean that aminophyllin decreased surface tension and augmented secretion of pulmonary surfactant. This was supported by finding significantly increased total phospholipid recovered in the lung lavage fluid of fetal rabbits injected with aminophyllin, 62 microgram/g dry lung weight (+/-6 SE) compared with 32 microgram/g dry lung weight (+/-3 SE) in saline controls (P less than 0.05). Phospholipid recovered from dexamethasone-injected fetal rabbits was not significantly increased, 38 microgram/g dry lung weight (+/-4 SE).


Surface viscosity of surfactant films from human lungs. The surface shear viscosity of films of human lung surfactant was measured using a rotary traction viscometer. At low shear rates dilute surfactant films (surface coverage 2.5--10 cm2/microgram lung extract) exhibited a low viscosity. Increasing the film concentration initially produced only a small increase in viscosity but, after a certain concentration, the film viscosity increased very markedly. The viscosity range for the most disperse (coverage 10 cm2/microgram extract) to the most concentrated film (0.6 cm2/microgram extract) was about 2.0 X 10(-4) g . sec-1 to 2.2 X 10(-2) g . sec-1. Surfactant film viscosity was also found to depend on the temperature of the subphase, higher viscosities being achieved when the subphase temperature was lowered. At low surface concentrations, surfactant films behaved in a strictly Newtonian manner. In contrast, at concentrations above 5.5 cm2/microgram extract they showed mildly non-Newtonian behaviour in that the magnitude of their surface viscosity was dependent on the rate of shear. The results suggest that films of human lung surfactant probably consist of both lipids and protein, and that the protein fraction plays a major part in determining the rheological properties of the films.


The HLA B w4/w6 diallelic system in Graves' disease. We studied the diallelic system HLA--Bw4/w6 in patients with Graves' disease and control subjects. Twenty-one out of the 22 patients with Graves' disease were found to be HLA--Bw6 positive and 16 of these were homozygous, contrasted with 28 and 9 out of 34 controls, respectively. HLA--Bw6 positivity results in a relative risk for Graves' disease of 3.27; homozygosity for that allele further increases the risk to 7.4. It is possible that the increased risk attached to HLA--Bw6 is secondary to the increase in HLA--B8 previously described in Graves' disease.


HLA/Bf haplotypes in a Newfoundland family. HLA/Bf haplotypes were examined in a large three-generation Newfoundland family with a high incidence of Graves' disease. In that family Graves' disease was inherited in association with the haplotype HLA Aw24, Bw39 in some instances and with HLA B8-containing haplotypes in other instances. As all seven members of the family who suffered from Graves' disease were homozygous for the Bf S allele, the study for Bf was uninformative. However, the examination of other HLA/Bf haplotypes disclosed some interesting associations. One-hundred-and-five out of 168 HLA-A, -B, -Bf haplotypes were Bf S. Although numerically deviant, no unusual HLA B/Bf associations were observed. Bf F entered the family only once. A new finding is the association between HLA B27 and Bf S1; the haplotype entered the family once and was passed on to eight family members over three generations. Bf S1 was previously reported in association with HLA B12 or W21. None of these family members had ankylosing spondylitis. The Bf allele F1 entered the family three times, always in association with HLA B18.


The incidence of thyroiditis lesions in nodular goiter. On the basis of clinical and biological data, surgical investigation and histopathological aspects, a number of 35 localized froms of thyroiditis have been given a diagnosis in order to assess their incidence in case of both nodular goiter and chronical inflammatory processes at the thyroid gland level. Three possibilities are considered: the proper inflammatory lesions--granulomatous, lymphoplasmocitary and ligneous thyroiditis, the cystic formations circumscribed by the glandular tissue with inflammatory signs as well as the association of thyroid cancer with chronic thyroiditis--seldom reported in literature--upon which 2 observations have been made.


[Radionuclide therapy of malignant tumors]. A survey is given on the modern possibilities of the therapy of malignant tumours with radiopharmaca. In detail the following methods of treatment introduced into the nuclearmedical therapy are described: 1. Radioiodine therapy in folliculary and papillary carcinomas of the thyroid gland, 2. Radiophosphorus therapy in polycythaemia vera and myeloproliferative syndrome, 3. Radiogold therapy in peritoneal and pleural carcinoses, 4. Intrathecal radionuclide application in meningeosis leucaemica, 5. Intralymphatic radionuclide application to the therapy of malignant lymphomas, 6. Radionuclide therapy of multiple bone metastases. With the help of literature and own experiences the author enters the indication and the performance of the therapy as well as the possible successes of treatment, when using the therapy forms mentioned.


[Regional epidemiologic characteristics of combined foci of tick-borne encephalitis, endemic rickettsioses and leptospirosis in Western Siberia]. The authors carried out complex study of combined foci of infections with natural foci in Western Siberia and their reflection in human pathology. The results of serological examination of 5917 persons and of 1743 of farm animals in respect to tick-borne encephalitis, Asian tick-borne rickettsiosis, Q-rickettsiosis, and leptospiroses are analysed. Affection of the population with all the four infections in all the landscape zones under study was shown; the intensity of this affection with different infections differed. Combined natural foci of the mentioned infections were found to be widespread; epidemiological significance of such combination was unequal in different ladscapes, this depending on the ladscape characteristics of the natural foci of infections under study and of different ways of transmission of their causative agents.


Meniscectomy. A comparison of two series treated as outpatients and inpatients. A total of 129 patients were operated on for meniscus lesion in the knee joint. Of these, 64 were operated as outpatients and 65 as inpatients. The outpatients reported to the operation department in the morning and left the hospital in the evening of the same day, after the operations. The inpatients were admitted to the hospital the day before the operation and were discharged 1--3 days after the operation. Objective postoperative findings, sick-leave periods and the number of visits to the outpatient clinic show no differences between the groups. The end result in the two groups is the same. This investigation also shows that it is possible to operate on patients with meniscus injury as outpatients without increased discomfort for the individual and without medical risks. Thus expensive nursing resources are released for other groups requiring more nursing care.


Immediate effects of meniscectomy on the knee joint. The effects of tensile load on knee joint ligaments in dogs. Tensile strength variables for the collateral ligaments were compared after excision of the meniscus in one knee, the corresponding meniscus in the contralateral knee of the same dog being intact. Removal of the meniscus was associated with a three-fold increase in initial laxity, two-fold for the lateral and three-fold for the medical ligament. The maximum tensile load uptake of the medial collateral ligament was reduced by more than 10 per cent after medial meniscectomy; the load uptake of the lateral ligament was not affected by lateral meniscectomy. It is proposed that tensile loads are distributed more favourably in the medial collateral ligament by the intact medial meniscus with firm capsular attachments than in the "normal" ligament after meniscectomy.


Serum complement level in dogs with neoplastic disease. The hemolytic reactivity of complement obtained from 119 dogs with and without cancer has been determined. Dogs with cancer were divided retrospectively, into 2 groups--dogs with lymphosarcoma (37) and dogs with malignant neoplasms other than lymphosarcoma (31). Normal dogs (21) served as a control group. Also, for comparison, complement reactivity was determined on sera from a 4th group composed of a limited number (30) of dogs with serious systemic illnesses other than neoplasia. There was no significant difference among means for hemolytic complement reactivity of the 4 groups. However, when the dispersion of hemolytic complement values within each group of abnormal dogs was compared with that of normal dogs by variance ratio testing, it was found that all abnormal groups had highly significant greater variances than did normal dogs.


Metabolic and toxic behaviours of phthalimide derivatives in albino rat II. Placental passage of chloromethyl phthalimide, oxymethyl phthalimide and phthalimide--their fetal metabolism. Chloromethyl phthalimide, oxymethyl phthalimide, and phthalimide are absorbed by the albino rat at a comparatively high rate. Only phthalimide, the metabolic product, will be recordable from fetuses, following oral administration of chloromethyl phthalimide and oxymethyl phthalimide topregnant rats. Those findings, in conjunction with metabolic studies applied to fetuses isolated by caesarian section, appear to suggest the occurrence of an intensive metabolism in fetal tissue. Certain differences established between results of thin-layer chromatography, on the one hand, and 15N studies, on the other, are likely to support the assumption that phthalimide is further metabolised by splitting the imide ring yielding phthalamic acid.


[Acute fatal copper intoxication. Casuistic and considerations on differential diagnosis (author's transl)]. If the diagnosis of copper-intoxication cannot be made by determination of copper in the collected specimen of the intestine, there may be problems in the differential diagnosis. In Wilson's disease and other cases of symptomatical hypercupriaemia copper content of brain tissues is elevated, while it is normal in acute copper intoxication.


Effect of acute and chronic cadmium treatment on hepatic drug metabolism in male rats. The effect of acute and chronic cadmium administration on hepatic drug metabolism was investigated in the male rat. 3 days after the acute administration of cadmium by either the intraperitoneal (0.84 mg Cd/kg) or the oral (greater than 80 mg Cd/kg) route, there was a significant potentiation in duration of hexobarbital hypnosis and inhibition of hepatic microsomal metabolism of hexobarbital and aniline. Administration of cadmium in the drinking water at levels of 100 or 200 ppm Cd for periods of 2--12 weeks or at levels of 5 or 20 ppm Cd for 50 weeks did not produce alterations in either drug response or hepatitic drug metabolism. Significant levels of metallothionein, a cadmium binding protein, found in the liver of the rats receiving cadmium chronically may offer an explanation for the observed differences in drug metabolism between the acute and chronic administration of cadmium. In additional studies, pretreatment of the rats with subthreshold doses of cadmium (0.21 or 0.42 mg Cd/kg) intraperitoneally produced a tolerance to the alterations in drug metabolism induced by the previous cadmium dose (0.84 mg Cd/kg, i.p.). However, chronic cadmium treatment (5 or 20 ppm Cd for 50 weeks) did not impart any such tolerance to subsequently administered Cd (0.84 mg/kg) by the intraperitoneal route. The hepatic levels of metallothionein induced by the chronic cadmium treatment were only 30--60% of those induced by the subthreshold cadmium and thus may not have bound enough of the large challenge cadmium dose to produce the tolerance phenomenon.


The modifying effect of multiple generation selection and dietary cadmium on methyl mercury toxicity in Japanese quail. Japanese quails were exposed to dietary methyl mercury chloride in graded amounts from 2--8 ppm through a series of multiple-generation experiments with the experimental periods lasting from 6--12 weeks, starting with the experimental diets when the birds were 6 weeks old. Cadmium chloride was added to diets with and without mercury and fed to groups in three of the five experiments. Hatchability was depressed at 8 ppm mercury. The mortality of chicks from 8 ppm exposed parents was 100% in the first two generations, while chick mortality at the 4 ppm level in the same experiments was 54--63%. After six generations mortality in chicks hatched in 8 ppm group was reduced to about 50%. Cadmium supplementation at a level of 5 ppm counteracted the mercury-induced toxicity but failed to be effective in preventing the effects of mercury toxicity when added at 15 ppm level. Significant toxic effects of cadmium alone did not occur until the level was raised to 60 ppm. The morphology of mercury-induced encephalopathy was similar to the brain lesions reported in other bird species, with the injuries predominantly being localized to the cerebellar cortex and medulla.


Amino acid sequences of alpha-helical segments from S-carboxymethylkerateine-A. Tryptic and chymotryptic peptides from a type-II segment. 1. Amino acid-sequence studies were done on a peptide of mol.wt. approx. 12500 that was isolated from the highly helical fragments obtained by partial chymotryptic digestion of the low-sulphur proteins (S-carboxymethylkerateine-A) from wool. 2. The peptides obtained by tryptic and chymotryptic digestion of this large peptide were separated by ion-exchange chromatography on DEAE-cellulose at pH8.5 with an (NH4)(2)CO(3) concentration gradient and, where necessary, purified further by paper electrophoresis. 3. Determination of the sequences of many of these peptides showed that a high proportion of the cationic residues occurs in pairs. 4. Although two of the four S-carboxymethylcysteine residues are located in what appears to be a non-helical region near the N-terminus the other two S-carboxymethylcysteine residues occur in or near sequences suggesting a helical conformation. 5. Some peptides were obtained, in low yields, that appeared to be homologues of more major ones. These suggest either homologies in the helical portions of the low-sulphur proteins or the presence of closely related amino acid sequences in helical regions of completely different origins. 6. A partial sequence of the complete peptide is proposed.


Amino acid sequences of alpha-helical segments from S-carboxymethylkerateine-A. Complete sequence of a type-II segment. 1. The helical fragments obtained by partial chymotryptic digestion of S-carboxymethylkeratine-A, the low-sulphur fraction from wool, were fractionated into type-I and type-II helical segments in aqueous urea under conditions limiting carbamoylation. 2. The amino acid sequence of a 109-residue type-II segment was completed by using the sequenator. 3. When the data were incorporated into a helical model of 3.6 residues per turn the hydrophobic residues generated a band aligned at a slight angle to the helical axis. This result is in accord with the postulated coiled-coil structure of the crystalline regions of alpha-keratin.


Binding of iodomercurates to sulfhydryl-blocked beta-lactoglobulin-A, -B, and -C. Sulfhydryl-blocked beta-lactoglobulins (beta-LG-S-SCH2CH2OH)-A, -B, and -C bind only one iodomercurate species, HgI3-, at only one site, with a dissociation constant of 4.0 X 10(-5) M at 25 degrees, pH 5.0, 0.10 ionic strength. (Binding to native beta-LG-SH-A, -B, and -C is more complex, involving the sulfhydryl and two other sites and several iodomercurates.) The red shift of the HgI3- spectrum on binding would ordinarily suggest a hydrophobic site, but the HgI3- site is distinct from, and independent of, the alkane-binding site of native and blocked beta-LG; HgI3- may bind a group that shifts its trigonal planar structure toward the tetrahedron of HgI4(2-). Binding of HgI3- to blocked beta-LG interferes with the well-known association of beta-LG-A to octamers at pH 4.6 and low temperature. The relation of the HgI3- site to the crystallographic iodomercurate-binding sites of beta-LG-SH is examined. To facilitate these and future studies of iodomercurate binding, the 200-400 nm spectra of HgI2, HgI3-, and HgI4(2-) in aqueous solutions and the thermodynamic formation constants at 25 degrees for the equilibria HgI2 + I- = HgI3- (4.9 X 10(3) M-1) and HgI3- + I- = HgI4(2-) (0.118 X 10(3) M-1) were obtained.


Leukemic lymphosarcoma (LLS) with monoclonal IgM: idiotypic specificity on the cell surface and in the cytoplasm of lymphosarcoma cells. A case of leukemic lymphosarcoma with a small amount of monoclonal IgM in the serum is described. Immunologic investigations showed that about 10% of the abnormal cells formed EAC rosettes, that most of these cells had IgMlambda on the cell surface, and that 40% of them contained IgMlambda in the cytoplasm. Monoclonal IgM was detected in the 19S fraction of the serum despite the lack of monoclonal change as determined by serum electrophoresis or immunoelectrophoresis. The common idiotypic specificity was found in the monoclonal serum IgM, surface Ig, and cytoplasmic Ig of lymphosarcoma cells using antiidiotypic antiserum prepared against purified serum IgM. After chemotherapy, cells with idiotypic determinants disappeared and the serum IgM changed from a monoclonal to a polyclonal distribution.


Encephalomyelopathy following intrathecal methotrexate treatment in a child with acute leukemia. A previously undescribed type of encephalomyelopathy after prophylactic intrathecal methotrexate (MTX) treatment for acute leukemia is reported. The patient was treated systemically with vincristine, MTX, stereoids and mercaptopurine. Radiation therapy was not given. The neurologic symptoms started 24 hours after the completion of the fifth intrathecal MTX instillation and death ensued 18 days later. The lesions consisted of superficial and sharply circumscribed areas of incomplete necrosis with astrocytosis on the base of the brain and along the insula regions, around the foramina of Luschka, and over the superior and inferior colliculi. Similar superficial lesions were found over the surface of the cerebellum and along most of the surface of the spinal cord. Most of the affected areas in the brain were located under the large subarachnoid cisterns. In the cord the lesions were most pronounced along the entrance zones of the roots. There was also a severe loss of anterior horn cells. There were no signs of meningeal leukemia, no pathological changes were caused by the intrathecal MTX treatment.


Effect of glucocorticoid hormones in vitro on the structural integrity of nuclei in corticosteroid-sensitive and -resistant lines of lymphosarcoma P1798. Exposure of rat thymus cells to glucocorticoids leads to a decreased ability of nuclei to survive the lysis of whole cells by hypotonic shock. In this study, a similar glucocorticoid-induced increase in "nuclear fragility" was found in both corticoid-sensitive and -resistant lines of P1798 mouse lymphosarcoma cells. In corticoid-sensitive cells a small increase in nuclear fragility is seen after a 2-hr exposure to cortisol (10(-6) M); by 3 hr it is 20 to 40% above control values. This effect appears to be a specific glucocorticoid response. Both cortisol and dexamethasone at 10(-7) M produce an effect, 10(-6) M testosterone is inactive, and cortexolone, which binds to glucocorticoid receptors, reduces the effect. Cycloheximide, at concentrations that inhibit protein synthesis, also blocks this effect. While the corticoid-resistant line also demonstrates an effect of similar magnitude, it requires a much longer exposure to the hormone (6 hr). Distinct differences in the "hardiness" of the two cell lines (nuclei of the corticoid-resistant line are less fragile) measurable in the absence of hormones appears to account for the differential susceptibility to steroids. On this basis a new theory of resistance is advanced where the emergence of resistance is related to structural differences in the cells.


Behaviour of murine lymphosarcoma cells during prolonged cultivation in vivo. Transplantable strain of murine lymphosarcoma growing as a free suspension in the peritoneal cavity of isologous hosts was isolated after fractionated irradiation of C57BL mice. A 14-year cultivation led to changes in its properties; the mean survival time of the hosts was shortened, the modal number of chromosomes changed from 41--42 to 39 and their radioresistance increased slightly. Strain specificity remained unchanged.


[Detection of circulating immune complexes using a laser-nephelometric assay (author's transl)]. Using Laser nephelometric measurement a method is described to detect immune complexes, which seems to be suitable for routine studies as well as for specific complex characterisation. Tetanus-Antitetanus complexes are used as standard thus the result is expressed as tetanus complex units (TCU). The method is simple and permits the direct measurement of complexes in native sera. Furthermore it is possible to characterise the complexes either by the immuno-globuline class of the antibody involved or the antigen respectively. Complexes were found with this method in various frequency in all but one group of patients under study (SLE, RA, other connective tissue diseases, malignomas, myelomas, thyroiditis, Grave's disease and healthy controls). Their was a high correlation with two other common techniques to measure immune complexes, e.g. C1q-deviation and C1q-PEG precipitation.


Leukocyte migration inhibition responses in canine lymphosarcoma. The leukocyte migration inhibition (LMI) responses of 16 cases of canine lymphosarcoma were assessed at several stages of a combined chemotherapy immunotherapy regime. Pooled allogeneic lymphosarcoma cells used in treatment together with other allogeneic lymphosarcoma cells and autochthonous tumour cells were employed as antigens. Positive inhibitions were detected at all stages of treatment when medium controls were used but were not detected in five normal dogs with the same control. There was no association between relapse and remission and LMI response. When a normal lymph-node cell control was used only four dogs produced positive responses, all of which occurred after allogeneic cell administration. These positive responses could not be completely accounted for by sensitization to histocompatibility antigens but as they occurred both in remission and in relapse, including very advanced cases necessitating euthanasia, they were of no value in determining prognoses.


Synthesis and biological activity of tuftsin and of [O = C Thr1]-tuftsin. A novel synthetic route to peptides containing N-terminal L -O = C Thr and L - O = C Ser residues. The cyclization, under alkaline conditions, of N-benzyloxycarbonyl-L-threonine and of N-benzyloxycarbonyl-L-serine to produce 5-methyl-2-oxo-oxazolidine-4-carboxylic acid (O = C Thr1 and 2-oxo-oxazolidine-4-carboxylic acid (O = C Ser), respectively, was investigated and found to be efficient and racemization-free. Similar was the cyclization which accompanied the basic hydrolysis of N-benzyl-oxycarbonyl-L-threonyl-L-phenylalanine methyl ester and of N-benzyloxy-carbonyl-L-seryl-DL-valine ethyl ester, and which resulted in the formation of L - O = C Thr-L-Phe and L - O = C Ser-DL-Val, respectively. The reaction was applied to the synthesis of [O = C Thr1] tuftsin, an active analog of the phagocytosis stimulating peptide tuftsin. A new synthetic route to tuftsin is also described.


Effects of medial meniscectomy in patients older than forty years. Forty-nine of the sixty-five consecutive patients who were more than forty years old when medial meniscectomy was performed returned for follow-up evaluation one to twelve years postoperatively. Pain was present in 62.2 per cent of the patients with so-called degenerative tears and in 75 per cent of those with so-called traumatic tears. The medial joint space was significantly thinner in the patients with degenerative tears than in those with traumatic tears. The roentgenographic findings of osteoarthritis were significantly more severe on the side operated on. The femorotibial angle was always in relatively more varus angulation on the involved side (mean, 5.3 degrees) than on the uninvolved side.


Alveolar stability of altitude raised rats. On the lining of alveolar membrane of the lung presence of surfactant, a surface tension lowering agent which is a phospholipid in nature, is well established. A good correlation exists between pulmonary lecithin, the principle constituent of surfactant system and alveolar stability. The production of surface active material in the type II cells is oxygen dependent and is affected by hypoxia. The chemical and physical nature of the surfactant in the lungs of the rats raised at high altitude has been studied in comparison with that of sea level control. Eighteen male adult rats raised at high altitude (3520 m) were used. Phospholipids (Phosphatidyl Choline, Phosphatidyl ethanolamine, Lysophosphatidyl choline, Lysophosphatidyl ethanolamine and Sphingomyelin) were estimated by thin layer chromatography, stability index by Pattle's bubble technique and dynamic surface tension have also been studied to assess the surfactant activity of the lung. The results indicate that there was a decrease in lung surfactant as measured by chemical analysis. However, stability ratio measurements showed that there was very little change in the stability ratio (Sr) as the value of both groups lay in the normal range namely 0.6 to 0.9 hence the lungs of high altitude raised rats had normal alveolar stability. Surface tension values of alveolar lavage in altitude raised animals were also similar to those of normal rats. It is concluded that the rats raised at altitude show a lowering of surfactant as estimated chemically but the stability ratio is not significantly altered to indicate alveolar instability. In the altitude rats lesser quantum of surfactant is adequate to maintain alveolar stability.


Tears of the anterior cruciate ligament in young athletes. During a meniscectomy, thirty competitive athletes who were less than thirty years old were found to have a non-functional or absent anterior cruciate ligament. Preoperative examination without anesthesia had revealed minimum to mild anterior instability without a positive pivot-shift or jerk test. They all had a meniscectomy without reconstruction of the ligament and all were followed for up to four years (average, 2.6 years). Twenty-five (83 per cent) returned to full athletic activity. All had relief of the symptoms of the meniscal lesion and improved significantly, but six progressed to moderate anterior instability with a positive pivot-shift and jerk test. Nevertheless, four of the six were able to resume unrestricted athletic activity.


Fertilization in brown algae. I. SEM and other observations on Fucus serratus. The cell wall secreted immediately following sperm entry into an egg can be visualized by the fluorescent dye Calcofluor white. Cell wall secretion precedes nuclear fusion by 10-20 min. SEM observations of the surface of unfertilized and fertilized eggs and sperm attachment to eggs are described. These results are discussed in relation to fertilization in sea urchins and the biochemical phenomena associated with egg-sperm recognition in Fucus.


Failure to detect an effect of prolactin on pulmonary surfactant and adrenal steroids in fetal sheep and rabbits. Recent reports have indicated an association between low cord prolactin (PRL) and the occurrence of respiratory distress syndrome in premature infants, and it is reported that PRL administration increases the lecithin content of fetal rabbit lung. We administered 1 mg ovine PRL to 32 rabbit fetuses on day 24 of gestation and evaluated lung phospholipid synthesis and content on day 26. Compared with diluent-injected littermates, PRL had no effect on the rate of choline incorporation into lecithin, tissue content of phospholipid and disaturated lecithin, or plasma corticoids. However, both choline incorporation and corticoids were increased in all animals undergoing surgery compared with unoperated controls. We also infused PRL (1 mg/day, i.v.) into three fetal sheep continuously over five periods of 5-8 days. Although supraphysiologic concentrations of PRL were achieved in plasma and amniotic fluid, there was no effect of this treatment on the flux of tracheal fluid surfactant or on plasma concentrations of corticoids of dehydroepiandrosterone sulfate. Thus, in this study, we failed to detect either a stimulation of the surfactant system or an adreno-corticotropic effect by PRL as previously postulated. This suggests that the relationship between PRL and respiratory distress sundrome is an indirect association.


[Present aspects of sexually transmitted diseases (STD) (author's transl)]. The emotional repercussion of STD remains very important. New present clinical aspects and new possibilities of diagnosis are pointed out. Concerning syphilis, the incubation period may be very long, cutaneo-mucous lesions of the secondary period very atypical . Concerning gonorrhea, the incubation period may be long (20 days); female or male asymptomatic forms are frequent: the existence of non-genital localizations is to be known. As to non-gonococcal infections, the frequence of Chlamydiae Tr. etiology is emphasized. Therefore an absolute priority must be given to the laboratory results which make the prescription of epidemiological treatment possible.


Comparing the effects of anileridine, alphaprodine and fentanyl on schedule-controlled responding by pigeons. The effects of anileridine, alphaprodine and fentanyl were studied on responding by pigeons under a multiple fixed-ratio, fixed-interval schedule of food presentation. Generally, all three drugs produced dose-related decreases in responding under both components of the multiple schedule, but rate increases were observed after low doses of anileridine and alphaprodine in some birds. Naloxone (1 mg/kg) antagonized the rate-increasing and rate-decreasing effects of doses of anileridine and alphaprodine of 10 mg/kg or less, whereas the effects of higher doses were not antagonized by naloxone. Likewise, chronic methadone or morphine (120 mg/kg/day p.o.) dosing produced only a slight cross-tolerance to the rate-decreasing effects of anileridine and alphaprodine. In contrast, naloxone (0.01, 0.1 and 1 mg/kg) and chronic methadone or morphine administration shifted the dose-effect curve for fentanyl to the right, indicating narcotic antagonism and methadone and morphine-induced cross-tolerance. These data indicate that the rate-decreasing effects of anileridine and alphaprodine are related only slightly to narcotic effects, whereas the rate-decreasing effects of fentanyl are primarily narcotic effects.


A review of the role of radiation therapy in the treatment of non-hodgkin lymphomas. Until recently, non-Hodgkin lymphoma has been difficult to understand. This was due to a lack of appreciation for histologic types, their sub-classifications, modes of spread, and sites of recurrence.The treatment of choice for stage I-II disease is radiation therapy. The value of irradiating adjacent uninvolved node areas or the more extensive Hodgkin-type mantle or inverted "Y" fields is uncertain.Most patients already have reached stage III or IV when first seen. Stage III cases should be treated by a combination of radiation therapy and chemotherapy. There are protocol studies evaluating the role of chemotherapy alone in stage III disease. The primary treatment of stage IV disease probably should be chemotherapy followed by radiation therapy to involved areas or to residual bulky disease.


Hypertrophic subaortic stenosis. Operative methods utilized to relieve left ventricular outflow obstruction. The methods currently used at the National Heart Institute in the operative treatment of patients with hypertrophic subaortic stenosis (IHSS) are described. Features of the operation that facilitate exposure of the septum and the criteria of an adequate myotomy are emphasized.


Effects of para-methoxyamphetamine and 2,5-dimethoxyamphetamine on serotonergic mechanisms. A comparison of serotonergic effects of (+/-)-para-methoxyamphetamine (PMA) and (+/-)-2,5-dimethoxyamphetamine (2,5-DMA) was studied in rats. The activation of myoclonic twitch activity (MTA) of suprahyoideal muscle in urethane-anesthetized rats has been reported previously to involve central serotonergic and dopaminergic mechanisms. PMA (0.1--3.2 mg/kg i.v.) and 2,5-DMA (2--16 mg/kg i.v.) increased the MTA. The increased MTA caused by both PMA and 2,5-DMA was blocked by a 5-HT receptor blocker, methysergide, indicating that a serotonergic mechanism was involved. The increased MTA induced by PMA was reduced by a 5-HT synthesis inhibitor, para-chlorphenylalanine, (pCPA), and by a 5-HT uptake inhibitor, chlorimipramine. On the other hand, the increased MTA induced by 2,5-DMA was not blocked by pCPA or chlorimipramine. Using a ventricular perfusion technique in urethane-anesthetized rats, PMA (1.6 mg/kg) effectively increased the release of 3H-radioactivity from brain preloaded with 3H-5-HT before the initiation of perfusion whereas 2,5-DMA (16 mg/kg) decreased the release of 3H-radioactivity. Analysis of the perfusate by thin layer chromatography for 3H-5-HT and 3H-5-HIAA revealed an increased release of unchanged 3H-5-HT in the perfusate after the injection of PMA. The ratio of 3H-5-HT to 3H-5-HIAA was markedly increased after PMA but no alteration of this ratio was observed after 2,5-DMA. It is concluded that PMA elicits its pharmacological action indirectly by releasing 5-HT while 2,5-DMA acts directly on 5-HT receptors.


Evaluation of some alternative mechanisms for interface-related stress relaxation in lung. Lung surfactant might exchange reversibly between the alveolar gas-liquid interface and the liquid lining layer. This solubilization process could then contribute to time-dependent pulmonary mechanical phenomena. Theoretical analysis of a model alveolus shows how solubilization can produce recoil pressure relaxation of the lung. The analysis shows that for most experimental observations reported the solubilization kinetics probably could not have been determined by the actual fitting in, or squeezing out, of surfactant in the surface film. Most data are consistent with a solubilization rate controlled by diffusion in the liquid sublayer. However, in order for a diffusion-controlled mechanism to be significant the diffusing substance should be large, such as a micelle, and the alveolar liquid layer should be at least 1 micrometer thick. These conditions are quite realistic for slightly edematous lungs and thus might apply to many experimental, or pathological, situations.


[Hyperthyroidism in older patients].

[Hyperthyroidism in older patients]. This study comprises 81 thyrotoxic patients with onset after the age of 60. In elderly persons, toxic multinodular goiter is the most common cause (68%) of hyperthyroidism, followed by solitary thyroid nodules (16%) and Graves' disease (16%). Cardiovascular disorders (cardiac failure, arrythmias etc.) constitute the first and often the only symptom in 62% of the cases. The other forms of appearance are both various and deceptive: depression, slight fever, asthenia or nausea. Separate analysis of the three forms of hyperthyroidism did not reveal clinical, biological or therapeutic differences between them, except an inferior rate of captation for the toxic nodules. Isolated measurement of T3 or T4 is often insufficient to confirm the diagnosis because either of these hormones may appear at a normal rate. In three cases only the free thyroxin index was pathological on first determination. The authors have established that the autonomous nodules are larger and more active after, rather than before, 60 years of age, and have attempted to define their morphological identity. The results of the treatment are analyzed and preference is expressed for radioactive iodine in every form of hyperthyroidism.


Alveolar phospholipids in pulmonary alveolar proteinosis. The biochemical compositions of lung lavage fluid from three patients and that of the lung tissue obtained by a biopsy from a patient with alveolar proteinosis were analyzed. The lung lavage fluid was separated to the supernatant and the insoluble precipitate fractions by a brief centrifugation and the lung tissue was separated to surfactant and residual fractions by sucrose density gradient centrifugation. The supernatant of lung washing contained larger quantities of protein and less lipid which was mainly composed of lecithin and sphingomyelin. In contrast, the insoluble material of lung washing contained 4--8 fold of lipid as compared with the supernatant, and lecithin was a predominant phospholipid. From the analysis of fatty acid and individual molecular species of major phospholipids, the higher contents of dipalmitoyllecithin and sphingomyelin containing palmitate were found in the insoluble material. The phospholipid composition and fatty acid composition of lecithin were similar between the precipitate fraction of lung washing and the surfactant fraction of lung tissue. The ratio of protein to phospholipid in the precipitate fraction was similar to that of lung washing. These analytical data suggest that the materials accumulated in the alveoli of the patients may be derived mainly from the lung surfactant fraction. The metabolic studies showed that lecithin synthesis through de novo and lysolecithin pathways works in human lung with this disease as actively as in rat lung. The secretion of lung lecithin to the surfactant fraction also appeared to be normal. From these analytical and metabolic findings, the causes for the accumulation of the materials which cover alveolar surface and impair gaseous exchange in the alveoli of pulmonary alveolar proteinosis, were discussed.


Herpes zoster at the NIH: a 20 year experience. One hundred and seven cases of herpes zoster in a hospitalized population with a variety of illnesses during a 20 year period were reviewed. Zoster occurred throughout the year, without seasonal predominance, and was most frequent in lymphoproliferative malignancy. In the majority, lesions were confined to the skin in one or more adjacent dermatomes (localized zoster) and were most frequent in the thoracic region. In 15 per cent of the cases, cutaneous dissemination of the lesions developed; this occurred four to 11 days after the onset of dermatomal lesions, and in one-third of these there was central nervous system involvement. Dissemination of zoster, however, directly resulted in only one death. Predisposing factors for zoster included local irradiation and, occasionally, surgery in subsequently involved areas. There were trends for more frequent splenectomies in patients with Hodgkin's disease in whom zoster subsequently developed, and for more frequent corticosteroid therapy in patiens with disseminated zoster. Advanced stage of Hodgkin's disease, in itself, was not associated with development of zoster, and the onset of zoster did not herald a poor prognosis for the underlying disease. Herpes zoster was, thus, largely a source of increased morbidity rather than mortality in the population studied, and multiple factors appeared to predispose to the development of zoster in this group of patients.


Stimulation of secretion of disaturated phosphatidylcholine from isolated alveolar type II cells by 12-O-tetradecanoyl-13-phorbol acetate. Alveolar type II synthesize and secrete pulmonary surface-active material; the stimuli for secretion in vivo and the mechanisms by which secretion occurs are not well understood. We studied the secretion of disaturated phosphatidylcholine, the principal component of surfactant, from a purified population of type II cells. We isolated type II type from the lungs of adult male rats by treatment with trypsin, centrifugation over discontinuous density gradients, and adherence in primary culture; our preparations were 93 +/- 5 per cent (mean +/- SD; n = 10) type II cells. Basal secretion was 2.9 +/- 1.0 per cent (n = 16) of total cellular carbon-14 [14C]-disaturated phosphatidycholine in 3 hours. We found that 10(-8) M 12-O-tetradecanoyl-13-phorbol-acetate (TPA), a substance that has been shown to stimulate secretion in other cell systems, caused a release of 14C-disaturated phosphatidylcholine that was 8.4 times the basal rate. TPA caused a greater release of disaturated phosphatidylcholine than did any other substance that we have tested. Low temperature (4 degree C) inhibited the basal release by 85 per cent and the TPA-stimulated release by 98 per cent. The effect of TPA was also inhibited 25 per cent by 10(-6) M colchicine and 33 per cent by 10(-5) M vinblastine. Medium from control cells contained 6.3 +/- 1.3 per cent (mean +/- SD; n = 5) of total cellular lactate dehydrogenase (a marker for cell damage) after a 3-hour incubation period; medium from cells treated with TPA contained a similar amount, 6.7 +/- 1.5 per cent (n = 5). We concluded that the TPA-induced secretion of disaturated phosphatidylcholine is an active process probably mediated by microtubules. Because it has a large stimulatory effect on secretion, TPA may be useful for the study of the mechanisms by which surfactant is secreted.


Ultrastructural observations in disseminated candidiasis. Infected tissues from four patients with disseminated candidiasis were examined by electron microscopy in order to study the host-parasite relationship at the cellular level. Blastospores and pseudohyphae were capable of invading parenchymal cells in the spleen, liver, myocardium, kidney, and esophageal and rectal mucosa. The Candida cells were typically well preserved despite the autolytic changes in parenchymal cells. Extracellular fungi were often coated with fibrin or associated with capillary thrombi, which suggests that Candida cells synthesize a procoagulant substance. The outer flocular coat of the yeast cell appeared to be partially of host origin since it diminished in thickness when organisms were cultured in media devoid of serum protein. Organisms cultured in vitro were ultrastructurally similar to those that invaded tissue.


Placental coccidioidomycosis without fetal disease. We encountered two cases of maternal coccidioidomycosis with placental involvement. Altered cell-mediated immunity during pregnancy makes the diagnosis of desseminated coccidioidomycosis difficult by the routine serologic tests; placental examination provides specific information. A high index of suspicion regarding this disease and prompt institution of appropriate therapy are necessary in order to decrease maternal and neonatal mortality.


Experimental meningococcal septicemia. Effect of aspirin therapy. In previous studies we have presented morphological evidence that the terminal shock-like phase of fatal meningococcemia is caused by the occlusion of the pulmonary microcirculation with thrombi composed of platelets, leukocytes, and fibrin. We have also shown that in experimental meningococcemia, pretreatment of rabbits with heparin sodium prevents fibrin formation but does not influence the cellular pulmonary thrombi and does not prolong survival. If our theory is correct, drugs that inhibit platelet aggregation and leukocyte adhesion in rabbits should prolong life. The present experiment demonstrates that pretreatment with a small dose of aspirin doubles the survival time without altering the mortality.


Experimental streptococcal endocarditis. The early vegetation. Aortic valve vegetation were studied in rabbits before and after intravenous injection of streptococcus mitis. Uninfected vegetation sections revealed compact eosinophilic masses with smooth-appearing edges and scattered polymorphonuclear leukocytes inside and on the surface. Scanning electron microscopic views demonstrated erythrocytes, small leukocytes, and platelets; the surface was markedly irregular. Fifteen minutes after injection of 10(10) streptococci, large mononuclear cells and polymorphonuclear leukocytes lined the vegetation edge; scanning electron microscopy showed large and small leukocytes. One and six hours after infection, there were more polymorphonuclear leukocytes inside the vegetation but few superficially. Bacteria were first seen at six hours as microcolonies inside the vegetation. Twenty-four-hour sections showed large bacterial colonies inside with few bacteria at the edges. Despite the smooth appearance of the vegetation edges, all electron microscopic views revealed very rough surfaces.


Immunopathology of the skin in acute poststreptococcal glomerulonephritis. The immunohistologic features of the skin were studied in 26 cases of poststreptococcal glomerulonephritis. Twenty-two patients had vascular and extravascular dermal deposition of IgG. Positive stains for C3 (eight patients). IgM (two patients), and fibrinogen (five patients) were confined to vessel walls. Staining with anti-IgA serum was uniformly negative. Circulating antiskin antibodies could not be detected. Extravascular accumulation of IgG has a widespread distribution in the dermal papillary layer that is highly characteristic. It was absent in 7 patients with chronic glomerulonephritis and in 11 patients with various other renal diseases. The described findings appear to occur consistently in acute poststreptococcal glomerulonephritis. The distinctive extravascular demonstration of IgG may prove to be valuable in the diagnosis of this entity.


Glomerulonephritis with Hodgkin's disease and herpes zoster. A patient who had been treated for Hodgkin's disease was infected with herpes zoster. Shortly thereafter, glomerulonephritis mediated by anti-glomerular basement membrane (anti-GBM) antibody occurred. The diagnosis was confirmed by the presence of circulating anti-GBM antibody, immunofluorescence, and elution. Results of immunofluorescence of a lymph node disclosed deposits of IgG on the vascular and stromal connective tissue, in a pattern similar to that seen when heterologous anti-GBM antibody reacted with the node. Because of the known nephritogenic potential of solid lymphoid tissues, this finding suggests a possible relationship between his tumor and his glomerular disease. The role of zoster infection remains undefined.


Elastofibroma. A pseudotumor of myofibroblasts. The fine structure of the cell of origin in elastofibroma showed features of both fibroblasts and smooth muscle cells with fibrils that formed parallel stacks 100 A in diameter and 100 A apart and occupied large areas of the cytoplasm of some cells and an abundance of rough endoplasmic reticulum. The myofibroblast has been reported in a variety of lesions and is also present in granulation tissue and hypertrophic scars. It is postulated, in accordance with previous reports, that myofibroblasts are instrumental in the repair process and that elastofibromas are a product of constant subclinical trauma and repair.


Ureteral involvement by malignant lymphoma. Ten years' experience. Ureteral involvement is an uncommon complication of disseminated malignant lymphoma. We recently reviewed our ten-year autopsy experience with 127 cases of non-Hodgkin's lymphoma. Ureteral involvement was observed in 21 (16%) cases, with morphologic evidence of ureteral obstruction in 18 of the 21.


Visceral Kaposi's sarcoma. Occurrence in a patient suffering from celiac disease. A case of visceral Kaposi's sarcoma occurred in a patient with adult celiac disease. A search of the literature has failed to disclose any previous case showing this association, although Kaposi's disease has been reported to occur in a variety of situations in which immunological abnormalities have been manifest. Conversely, celiac disease has been shown to predispose to the development of a variety of malignant neoplasms.


[Lung surface tension in acute respiratory infections]. Experiments in 9 dogs showed that 24 hours after death there was only an insignificant decrease in the activity of surfactant which remained within normal limits. Similar data were obtained in examinations of the lungs of 14 children dying without respiratory pathology. In the main part of the study lungs from 20 children and 1 fetus dying with various respiratory infections were examined. It was found that the greatest effect on the decrease of formation of the surfactant was exerted by crude damage of the epithelium of distal parts of the respiratory ways. No relationship of this phenomenon to the etiology of the process was established, although there was a trend for retention of the normal surfactant activity in mycoplasmal and mycoplasmal-bacterial involvement of the lungs, whereas in viral and viral-bacterial processes the surfactant activity was more frequently decreased. This, however, seemed to be due to differences in the predominant localization of the process.


Postmortem changes in the surpellic activity of lung surfactant. The surpellic activity of lung surfactant in mouse lungs stored in the cadaver persists for times much longer than those after which gross morphological changes at electron microscope level have been recorded.


[Functional role of pulmonary surface-active substances]. Freshly prepared from the rat lung solution of the surfactant active substances (SA1) accelerated oxygen absorption at the borderline of the phases. The oxidized SA1 solutions produced an inhibitory effect. As suggested, functional role of SA1 in the realization of external respiration is not limited to reduction of surface tension and alveoli stabilization, but also includes participation in oxygen absorption and its transport regulation through the aerohematic barrier.


A survey of the effectiveness of a telephone-answering service. A survey was carried out over a two-year period in Exeter to find out what source of information led patients to attend the local clinic for venereal diseases and to evaluate the effectiveness of a tape-recorded telephone message advertising clinic times. Based on the response from patients it seems difficult to justify the cost of installing a telephone-answering service.


Antinociceptive effects of intrathecally administered human beta-endorphin in the rat and cat. Rats chronically implanted with intrathecal catheters displayed a dose-dependent increase in the hot-plate and tail-flick response latencies following the injection of human beta-endorphin into the lumbar spinal subarachnoid space through the indwelling catheter. beta-Endorphin was approximately 25 times more potent than morphine on a molar basis. Matching morphine and beta-endorphin doses such that approximately equal submaximal submaximal effects occurred, it was observed that the antinociception produced by beta-endorphin lasted approximately three times longer than that produced by morphine. Experiments with intrathecal injection of beta-endorphin into the spinal subarachnoid space of cats fitted with intrathecal catheters also revealed a potent antinociceptive effect which was completely antagonized by naloxone. In the rats, naloxone administered systemically in doses of 10--100 microgram/kg produced a parallel shift in the dose-response curves of both nociceptive measures suggesting a competitive antagonism. Using a dose ratio analysis, an in vivo pA2 of 7.1 for naloxone was obtained. These data and those derived from previous work based on the pA2 suggest that the interaction of morphine, certain pentapeptides, and beta-endorphin is the same with regard to the spinal opiate receptor population mediating behaviorally defined analgesia.


Diffuse well-differentiated lymphocytic lymphoma (DLWD): response and survival. 34 patients with the diagnosis of diffuse well-differentiated lymphocytic lymphoma (DLWD), confirmed by a Pathology Panel, who were entered on a previously reported Eastern Cooperative Oncology Group study (EST 1472), were analyzed for response and survival. The response rates were as follows: CR 32%, PR 39%, NC or PD 29%. Survival analysis according to chemotherapy response revealed an estimated two-year survivorship of CR 89%, PR 65%, NC 69%, and PD 44%. Comparison with NLPD entered on the same study showed a two-year survival of 83% for NLPD and 67% for DLWD, indicating significantly poorer survival for DLWD as compared to NLPD (p less than .05). Median survival for DLWD from diagnosis was 39.0 + months. The presence of lymphocytosis over 4000/mm3 had little effect on response rates or survival. We conclude that DLWD is a less favorable lymphoma type than NLPD and should be treated with aggressive chemotherapy since achievement of CR seems to effect survival favorably.


Probenecid inhibition of methotrexate-cerebrospinal fluid pharmacokinetics in dogs. Cerebrospinal fluid (CSF) and plasma concentrations of methotrexate (MTX) were followed in dogs for 72 hours after intracisternal injection of MTX with and without probenecid pretreatment. CSF levels declined as a biexponential function of time. Probenecid pretreatment of the animals prolonged the second phase half-disappearance time of MTX from 5.20 +/- 0.89 to 7.086 +/- 0.23 hours (mean +/- SD). The peak mean plasma concentration of MTX was lower in the presence of probenecid. Also, the rate of decline of plasma MTX concentrations was slower after treatment with probenecid, with mean half-disappearance times of 7.60 +/- 0.77 and 11.32 +/- 1.08 hours. These CSF and plasma data support the proposal that probenecid inhibits the transfer of MTX from CSF to blood.


Rational basis for foam-stability assays of amniotic fluid surfactant. We evaluated the relative contributions of various phospholipids to the formation of foam in the amniotic fluid "foam stability test", by use of an artificial system of saline, ethanol, and dipalmitoyl 3-sn-phosphatidylcholine to determine the relationship between dipalmitoyl 3-sn-phosphatidylcholine concentration, ethanol volume fraction, and the threshold of formation of stable foam. At dipalmitoyl 3-sn-phosphatidylcholine concentrations of 20, 40, and 80 mg/liter, the threshold ethanol volume fraction was 0.46, 0.48, and 0.51, respectively. We similarly evaluated the ability of other phospholipids to form stable foam at various concentrations and ethanol volume fractions and found: bovine brain sphingomyelin greater than dipalmitoyl 3-sn-phosphatidylcholine greater than egg sphingomyelin greater than egg lecithin greater than phosphatidylglycerol. The corresponding propensities of different chemical species of phosphatidylcholine to form foam at 40 mg/liter were: dipalmitoyl 3-sn-phosphatidylcholine greater than dioleoyl phosphatidylcholine greater than dimyristoyl phosphatidylcholine greater than dilauroyl phosphatidyl-cho-line.


Autoperfused heart-lung preparation: a structurally appropriate experimental model for the metabolic study of the isolated lung. This study was carried out to confirm the hypothesis that an autoperfused heart-lung preparation provides a favorable situation to analyze the dynamics of the biosynthesis of alveolar surface-active material, because the model did not produce any significant changes in the structure of the lung. Light and electron microscopy confirmed the absence of pulmonary lesions throughout the whole time of perfusion. A relevant finding was the periodic delamellation of the type II pneumocytes observed ultrastructurally, which coincided with the data obtained from the study on 14C-glycerol-3-phosphate and 3H-palmitic acid incorporation into total lipids and phosphoglycerides from lung tissue. This confirmed that the biosynthesis of pulmonary surfactant is rhythmic and periodic. From a structural point of view, the results suggest that the autoperfused heart-lung preparation constitutes a useful method for the in vivo metabolic study of the isolated lung.


Prediction of response to ergocryptine in the galactorrhea-amenorrhea syndrome. Forty women with secondary amenorrhea and galactorrhea, thirty-six of whom had associated hyperprolactinemia, were studied prior to therapy with ergocryptine. Abnormal sella tomographic findings were present in 23. The findings on sellar tomography, basal serum prolactin concentrations, and pharmacologic stimulation/suppression of the serum prolactin failed to predict subsequent responders and nonresponders to ergocryptine. Pituitary stimulation for hormone responsiveness did differentiate subsequent responders to ergocryptine from nonresponders. The serum growth hormone response to hypoglycemia was the most definitive predictor. Return of apparently ovulatory function occurred in 29 patients, 11 of whom conceived and have delivered healthy infants.


Migration enhancement by tuftsin of human mononuclear cells and its effect on the migration inhibition factor test with tumor antigens. Tuftsin, a physiological tetrapeptide which stimulates the phagocytic activity of polymorphonuclear neutrophils and macrophages, is found to enhance the migration of normal and sensitized human mononuclear cells. Furthermore, it abrogates the migration inhibition effect of human malignant melanoma antigen. This finding may represent a possible explanation for the unexpected migration enhancement often observed when the migration inhibition test is employed.


The pathology of thyroiditis.

The pathology of thyroiditis. Although the term "thyroiditis" suggests inflammation, many disorders of the thyroid that are of unknown etiology are also currently included under this heading. Thus, only infective thyroiditis and subacute thyroiditis are clearly inflammatory; autoimmune thyroiditis is a result of lymphocytic and fibroblastic infiltration secondary to immune processes, and Riedel's struma (a rare disorder) results from a curious form of fibroblastic proliferation of unknown nature. The pathology of infective thyroiditis  is that of the particular infective organism. The picture of subacute thyroiditis is that of a unique type of follicular disruption with histiocytes surrounding extravasated colloid masses, producing the appearance of giant cells. Autoimmune thyroiditis is characterized by lymphocytic infiltration, lymphoid follicles. Askanazy cells, and fibrosis, each to a variable degree, with atrophy of follicles. The fibroblastic proliferation in Riedel's struma transcends the thyroid capsule and involves adjacent tissues. The electron microscopic appearance of each form of thyroiditis is also briefly described.


Adjuvant chemotherapy with intraventricular methotrexate and CCNU after surgery and radiotherapy of medulloblastomas. Seven patients were treated with a combination of intraventricular methotrexate (MTX) and oral CCNU after resection and whole CNS irradiation of medulloblastomas. 3 patients survived 3 or more years after the operation which is not different from reported series with postoperative radiotherapy only. Adjuvant chemotherapy is experimental and should be employed only in controlled studies. The inadequate bone marrow reserve after previous spinal irradiation is a major problem. Because of its delayed and unpredictable myelotoxicity, CCNU is in our experience not a suitable substance for adjuvant combination chemotherapy of medulloblastomas. No complication was observed with 81 intraventricular injections of MTX. It is a good agent and deserves further clinical trials in less myelotoxic combinations.


Transferred pulmonary surfactant film: chemical analysis and contact angle study. The Langmuir dip plate transfer technique was adapted to isolate the interfacial film formed at the surface of lung wash. The chemical analysis of the film showed that the weight ratio of lipid to protein of this surfactant film and its content of surface active substances were higher than those of lung wash. It was found that the wettability of the surfactant film could be simulated by a Dipalmitoyl lecithin and albumin film. When the surfactant film was transferred at condensed state (one of low air-lung-wash surface tension), we found the film exhibited a low critical surface tension which indicates the dominance of the lipid in the outer most layer of the film. On the other hand, insignificant amount of lipid was found in the film transferred at expanded state (one of high surface tension) and its surface behavior was shown to be similar to that of a protein film.


Metrizamide demonstration of the subarachnoid space surrounding the optic nerves. Intrathecal instillation of metrizamide has provided a useful tool for the in vivo evaluation of smaller structures adjacent to or within the subarachnoid cisterns. The authors report a case in which metrizamide filled the thin subarachnoid space surrounding the optic nerve in its course through the orbit. The finding appears to be infrequent, however, since it was not observed in any instance in a review of 80 metrizamide computed tomographic cisternograms in patients with normal intracranial pressure.


Effects of processing milk on concentrations of glucocorticoids in milk. Concentrations of glucocorticoids were measured by protein binding in milk subjected to various processing methods. Raw whole milk was collected once per week for 3 wk from bulk milk tanks of each of 10 farms. Nine combinations of processing were tested: 1) none, 2) high-temperature short-time pasteurization of whole milk, 3) high-temperature short-time pasteurization and homogenization of whole milk, 4) bulk pasteurization of whole milk, 5) bulk pasteurization and homogenization of whole milk, 6) high-temperature short-time pasteurization of skim milk, 7) high-temperature short-time pasteurization and homogenization of skim milk, 8) bulk pasteurization of skim milk, and 9) bulk pasteurization and homogenization of skim milk. Mean concentrations of total glucocorticoids ranged from .46 to .65 ng/ml and were not different among either processing methods or whole versus skim milk classifications. No correlations were positive between percentage of fat and concentration of glucocorticoids in whole milk (-.22) or skim milk(-.09).


Biliary excretion of iodipamide and iodoxamate in normal and common bile duct-obstructed dogs. Iodipamide and iodoxamate were compared at equimolar clinical dosages in dogs with normal, incompletely obstructed and completely obstructed common bile ducts. Forty-eight experiments were performed under general anesthesia in six cholecystomized chronic bile fistula dogs. The peak biliary iodoxamate excretion rate, but not the peak bile iodoxamate concentration, was significantly higher with normal and incompletely obstructed common bile ducts. In complete obstruction, both a significantly higher total biliary iodoxamate excretion and concentration were obtained, but this was still insufficient for radiographic opacification by conventional technique. Lesser toxicity of iodoxamate is suggested by its significantly lower serum levels, its higher bile: urine excretion ratio and its faster compensatory urinary excretion in complete common bile duct obstruction. Iodoxamate appears on this evidence to be a better cholangiographic contrast agent than iodipamide.


Rate of egg penetration in vitro accelerated by T/t locus in the mouse. Spermatozoa from fertile mice heterozygous for tw32, a recessive lethal allele of the T/t locus, were compared to normal spermatozoa in a fertilization in vitro system. The rate of egg penetration following insemination in vitro was determined for epididymal spermatozoa from C57BL/6-tw32/+ mice and for epididymal spermatozoa from C57BL/6-+/+ mice. At one hour after insemination, the mean of penetration +/- standard deviation for spermatozoa from BL/6-tw32/+ mice was 20% +/- 2.1 (109 eggs observed, 5 experiments), while the mean for spermatozoa from BL/6-+/+ mice was 1% +/- 1.5 (107 eggs observed, 4 experiments). By five hours post-insemination, the levels of egg penetration were not significantly different. These results suggest that tw32 increases the initial rate of egg penetration. Preliminary observations of sperm motility and sperm-egg association at one hour post-insemination in vitro do not support the hypothesis that this earlier penetration is due to improved sperm progress to the egg. Rather, the earlier penetration may be a result of changes in the timing of capacitation, the acrosome reaction, or sperm-egg fusion. It is possible that the earlier penetration may play a role in the distortion of the transmission ratio of tw32.


Drug abuse and alcoholism teaching in U.S. medical and osteopathic schools. This is a report of the principal findings of a survey of drug abuse and alcoholism teaching in U.S. medical and osteopathic schools. It was found that required teaching activities during all four years of medical school averaged 25.7 hours, with a range of 0 to 126. The proportion of the total required hours devoted to substance abuse was 0.0 to 3.1 percent, with a mean of 0.6 percent. Schools also differed widely in the number and type of electives offered in drug abuse and alcoholism, as well as in number of clinical assignments available. Findings in osteopathic schools were generally similar. Two factors which were significantly related to the number of required hours were the presence of a career teacher in the addictions and the size of the school.


Studies of factors influencing lung stability: biochemical changes of pulmonary surfactant and morphological changes of terminal air spaces in the developing rat. Aging changes of the pulmonary surfactant were studied with regard to phospholipids and cholesterol and to the physical properties in the rat. Newborn rats had remarkably high content of lecithin compared to other age groups and the content was lowest at around 5 days after birth on the basis of wet weight of lungs. Calculated concentration per unit area of alveolar surface based on the body weight was highest in newborn rats and it fell down abruptly at 3 days after birth followed by a gradual decrease to adult level. The content of cholesterol was lowest and the lecithin:cholesterol ratio was highest in the newborn surfactant. The ratio was the same among rats at other ages. Surface activity examined by Wilhelmy balance was not different between newborn and adult with respect to minimum surface tension and stability index but surface spreading of surfactant was faster in neonatal surfactant than in the adult one. The size of the termnal air spaces was remarkably large at birth. It decreased gradually after birth with its minimum at around 17 days after birth and again it increased to adult level. From these observations it was concluded that high stability of excised lungs of normal newborn rats is brought about by these biochemical and morphological differences and these characteristics seem to facilitate the adaptation of lungs to normal breathing at birth.


Physiological changes during prolonged seizures and epileptic brain damage. The role of physiological changes occurring during prolonged seizures in the causation of epileptic brain damage has been investigated experimentally in baboons and rats. Prolonged drug-induced myoclonic seizure activity is associated with initial arterial hypertension and subsequent hypotension, increased venous pressure, early hyperglycaemia and subsequent hypoglycaemia, variable arterial hypoxia and lactacidosis, and hyperpyrexia. Cerebral metabolic rate for oxygen and glucose is increased 2--3 fold throughout prolonged seizures provided the physiological status of the animal is well maintained. Ischaemic neuronal change is found after seizures lasting 1.5--7 hours, involving the small neurones of the third cortical lamina, Purkinje and basket cells in the cerebellum, and pyramidal neurons in the endfolium and Sommer sector of the hippocampus. Muscular paralysis and artificial ventilation minimise late physiological changes such as arterial hypotension and hyperpyrexia, and protect against cerebellar damage, but only slightly against neocortical and hippocampal damage. When arterial hypotension, hypoxia or hypoglycaemia lead to a reduction in the intensity of seizure discharge in paralysed, ventilated rats, there is also a reduction in hippocampal and neocortical damage. Factors intimately related to the intensity and duration of the neuronal discharge are responsible for neocortical and hippocampal lesions.


Myopathy with multiple central cores. A case with hypersensitivity to pyrexia. An eight-year-old male suffered from long-standing proximal muscle weakness, dramatically aggravated by febrile episodes. Neuromuscular work-up disclosed a myopathy with multiple central cores of non-familial nature. The presence of central cores in this patient as well as in the myopathy of malignant hyperpyrexia might suggest a pathophysiological basis common to both conditions.


Long term studies of untreated phenylketonuria I: intelligence or mental ability. A group of 90 patients over the age of 2 years with untreated phenylketonuria was studied by 3 independent observers in 3 different ways for evidence of mental deterioration. In a small subset (N = 10), psychometric tests showed a fall in Intelligence or Developmental Quotients between the ages of 4 and 18 years; the same was found in a matched group of nonphenylketonuric patients from the same institution. In a second subset (N = 83), a Habit Score derived from the observations of the patients' caretakers showed a small overall improvement in adaptive behaviour over an average span of 19 years. In a third subset (N = 81), clinical assessment by one observer detected no significant change in mental ability over an average span of 11 years. No evidence of progressive mental deterioration was found in untreated phenylketonuria from middle childhood to middle age.


Long term studies of untreated phenylketonuria II: the plasma phenylalanine level. The plasma phenylalanine level was measured on at least two occasions, usually more, in 81 patients with phenylketonuria on unrestricted diets. The distribution of the individual levels was gaussian and the mean (31 mg/100 ml) did not change significantly over an average span of 12.7 years. Persistent individual differences were found but so were unexpected and inexplicable high or low plasma phenylalanine levels in particular patients. Variations in dietary phenylalanine intake did not explain the differences in plasma phenylalanine levels between individuals. There was no clear relationship between the degree of mental disability and the average plasma phenylalanine except that those with the least brain damage had slightly lower average levels (24.2 mg/100 ml). The difficulties of demonstrating genetic heterogeneity in phenylketonuria are illustrated even though this is likely present. It is argued that the assumption of a direct quantitative relationship between the degree of brain damage and the height of the plasma phenylalanine level is an oversimplification.


[RNA synthesis in bone marrow hematopoietic stem cells]. The effect of inhibitors of DNA-dependent RNA synthesis (sibiromycin and actinomycin D) and radio toxic doses of 3H-uridine on the bone marrow stem hemopoietic cells in adult mice was studied by means of spleen colonies. The short-term in vitro preincubation of the bone marrow cell suspension with the antibiotics and 3H-uridine resulted in the practically complete inhibition of colony formation. The bone marrow stem hemopoietic cells incorporated 3H-uridine intensively. In the normal adult animals the number of stem cells with the high level of RNA synthesis attained 40% whereas the rest 60% of cells were capable to activate the ribonucleic metabolism upon their in vitro preincubation.


The in vitro production of erythropoietin and thrombopoietin. In order to determine if there were any relationships between thrombopoietin, erythropoietin and erythrogenin, supernatant fluids from culture lines of foetal mouse liver, foetal and adult bovine kidney, and adult rabbit kidney cells have been assayed for their content of the presumptive humoral regulators of haematopoiesis. Hormone production varied markedly from one culture line to another confirming other studies that the optimal culture conditions for the generation of haematologically-active hormones have not been delineated. The lack of any discernable relationship between the production of thrombopoietin and erythropoietin, thrombopoiet in these and erythrogenin or erythropoietin and erythrogenin suggests that materials represent three distinct entities.


[Lithium acetate, a useful and well tolerated thyrostatic for selected cases of hyperthyroidism]. Lithium acetate treatment of 6 patients with hyperthyroid Graves' disease and 6 patients with toxic nodular goiter is reported. Lithium acetate was administered either as monotherapy (group A) or combined with 45 mg carbimazole or methimazole (group B). A control group of 8 patients received methimazole or carbimazole only (group C). Lithium either alone or combined with thionamide drugs consistently lowered serum thyroxine and triiodothyronine with marked clinical improvement. After 7 days of treatment thyroxine was reduced by 28% (group A), 43% (group B) and 36% (group C). The respective decrease in triiodothyronine was 42%, 50% and 46%. The differences between three groups were not statistically significant. We conclude that lithium is a useful antithyroid agent for selected patients, since it is safe and effective even in severe cases, does not interfere with radioiodine uptake for diagnostic or therapeutic purposes and provides an alternative for patients allergic to thionamides.


Evaluation of the shake test to predict respiratory distress syndrome. An analysis of the relationship of amniotic fluid shake test titers and the subsequent fetal lung maturity as evinced by the development of the respiratory distress syndrome (RDS) has been conducted. Over a four-year period, 131 amniotic fluid samples were tested within 48 hours of delivery. RDS was diagnosed in 16 infants. When the shake test was positive at a 1:2 dilution, one child developed a mild case of RDS (2.3%). If the test was postivie at a 1:4 dilution, none developed RDS. RDS occurred in 15% of the cases with a positive test at a 1:1 dilution and in 30% of the cases with a negative test. This test has proved to be an excellent screening method for predicting fetal lung maturity if it is positive at 1:2 or greater. If the result is positive at a 1:1 dilution, or negative, other methods must be used for assessment. Its advantages are its rapidity, simplicity, and low cost.


The role of antibacterial preparation of the intestine in the reduction of primary wound sepsis after operations on the colon and rectum. A consecutive series of 320 patients undergoing operations on the colon and rectum, under the care of one surgeon, was studied to determine the influence of oral antibacterial preparation of the intestine on the incidence of postoperative wound sepsis. Thirty patients were excluded from the analysis, and the rates of major wound sepsis in the remaining 290 patients were 21.7 per cent when no antibacterial preparation was used; 18.6 per cent when the intestine was prepared with phthalylsulfathiazole and neomycin, and 1.6 per cent when the intestine was prepared with phthalysulfathiazole, neomycin and tetracycline. Other important determinants of the rate of wound sepsis were obesity and the use of cephaloridine prophylaxis. Results of bacteriologic studies showed the effectiveness of triple antimicrobial preparation of intestine against gram-negative aerobes and Bacteriodes species.


[Nonocclusive vascular insufficiency of the bowel (author's transl)]. The particular problems of nonocclusive mesenteric vascular insufficiency are discussed on the basis of reports in the literature and 4 patients observed by the authors. Diminution in splanchnic blood flow as a manifestation of splanchnic compensation to low cardiac output seems to be the most common cause. The symptoms are described and the necessity for early diagnosis and immediate treatment are stressed. Our results of treatment in 4 patients with nonocclusive mesenteric vascular insufficiency are presented.


[Evaluation of fetal lung maturity using a modified lecithin-sphingomyelin determination and Clements' foam test]. The modified thin layer chromatographic method for the determination of the phospholipids lecithin and sphingomyelin from amniotic fluid is useful in estimating fetal pulmonary maturity. The foam test of Clements is a simple rapid method for screening of suspicious cases of pregnancies at risk and of great value as bed side test even performing by the doctor. In comparing Clements-Test with thin layer chromatographic for L/S-Ratio determination we found a good correlation of 81,8% of all cases.