Use of 125I-fibrinogen kinetic data to detect disseminated intravascular coagulation and deposition of fibrin in patients with metastatic cancer. A technique using computerized data handling for following the fate of 125I-fibrinogen through various physiological compartments is presented. Its use in detecting fibrin build up in patients with metastatic tumors and cancer-caused DIC is explained. An increase in j3u (fractional catabolic rate as seen in the urine data) throughout the course of a study was found to be an important indicator of extravascular fibrin build up.


Interlaboratory oral anticoagulant quality assessment by the Netherlands Federation of Thrombosis Services. The 50 laboratories of the Netherlands Federation of Thrombosis Services, covering a population of 9 million and responsible for the laboratory control of approximately 150,000 patients under oral anticoagulation, have participated since 1974 in a voluntary external and internal quality control program. The external program comprises a monthly distribution to the member laboratories of a series of artificially prepared control blood samples, two of which are identical. The overall variation of the coagulation times found were 10% (CV) in 1974 and 8% (CV) in 1975. Performance improved rather abruptly at the beginning of 1975, after the application of a tight methodological standardization and improvement by the manufacturer of the thromboplastin preparation (Thrombotest) used by the great majority of the laboratories involved. The main source of variation was found to be random error in the Thrombotest determination, approximately 6%. Interbatch variation of Thrombotest and inter-aliquot variation of control blood samples both do amount to approximately 3%(CV). In terms of rabbit tissue thromboplastins, which have a lower sensitivity than Thrombotest (i.e., a flatter slope of the correlation between the PT and the anticoagulant effect), the total variation in the performance of the Dutch laboratories is 2.2--5.6% (CV), which is unusually low. The main reason for this is the fact that the laboratories can rely not only on the services of the manufacturer but also on a central information office and a reference laboratory responsible for the preparation of the control blood as well as the standardization (calibration) of thromboplastin.


Factor VIII inhibition associated with chlorpromazine-induced hepatic injury. A 90-year-old man was given chlorpromazine for sedation and 2 weeks later developed cholestatic jaundice and subsequently a factor VIII inhibitor. His death 4 weeks after institution of chlorpromazine, from massive bleeding, coupled with the autopsy finding of intrahepatic cholestatic jaundice, suggests that both adverse reactions were due to the drug.


Fibrinolytic, factor VIII and pulse rate responses to repeated adrenaline infusion followed by haemorrhage. The role of catecholamines in the activation of coagulation and fibrinolysis following surgery remains controversial. In this study 5 dogs were infused with 1,2,3,6,9 and 12 microgram kg-1 min-1 of adrenaline at twice weekly intervals and were then reexposed to 3 microgram kg-1 min-1. Pulse rate and factor VIII increased after infusion of 1,2 and 3 microgram kg-1 min-1 but thereafter there was a diminished response and no response on reexposure to 3 microgram kg-1 min-1 although this was not significant in the case of pulse rate. Euglobulin lysis time shortened after each infusion of adrenaline and showed no development of tolerance. A control series of dogs infused with saline showed no similar changes. Both groups of animals were then bled to a blood pressure of 60 mm Hg for 60 minutes. Pulse rate and factor VIII did not change but euglobulin lysis time shortened in both groups. The results suggest that the activation pathways for changes in factor VIII and euglobulin lysis time induced by adrenaline are separate.


Spectrophotometric determination of factor Xa generation in factor IX concentrates. Previous work from this department, concerned with testing the potential thrombogenicity of therapeutic factor IX concentrates, demonstrated that following recalcification of factor IX concentrates thrombin was generated within 3--30 minutes of incubation (Sas el al. 1975). The test developed (known as the TGt 50 test) is a two-stage assay and was thus found to be time consuming, tedious and tended to become inaccurate with long incubation periods and a large number of samples. A semiautomatic version of the test is reported in which the synthetic peptide Bz-ILE-GLU-GLY-ARG-pNA (S-2222) is added to recalcified, diluted factor IX concentrate in the micro-cuvette of a multiple sample recording spectrophotometer. Information can be obtained on (a) the amount of Xa (if any) present prior to recalcification (b) the initial amount of Xa formed and (c) the time taken to activate all factor =X to Xa. Direct graphical interpretation shows a number of qualitative differences between commercial preparations, but by either of the criteria (b) or (c) above, it is possible to place the different products into "activated" and "non activated" groups such that both the Xa generation times and TGt 50 tests identify the same two groups of products. This aggreement also indicates that the TGt 50 test is independent of the intrinsic factor V levels in the various concentrates.


Studies on the tissue thromboplastin during the coagulation-fibrinolytic process--ultrastructural changes. An electron-microscopical study was made on morphological changes in which T-Tbp would undergo during clotting and fibrinolytic process. Morphological appearance of concentrically arranged membrane structure in T-Tbp remained nearly intact during blood coagulation process. T-Tbp, which existed in the sediments following dissolution of fibrin clot by the application of UK, showed an appearance of fine granules adhering to the surface of aggregates of particles through SEM. Through TEM, T-Tbp in the sediments was found to have retained its concentrically arranged membrane structures in most places, while, in some other places the appearance of fused membranes, smaller single vesicles and long sheets of membranes, and the formation of "blebs" etc. were observed. Various morphological changes caused by fibrinolytic substances accompanied the loss in coagulation activities. Our results showed that coagulation activities of T-Tbp must be completely dependent upon the presence of the membrane structures.


Specific vector control methods for prevention and eradication of malaria in Israel. Wide-scale antimalaria activities have been continuously carried out in Israel since 1918. Regular checking and tracing of Anopheles provided important information on the seasonal appearance, life habits, flight range and population density of the malaria vectors. This method enabled us at any time to assess the degree of malaria risk and the effectiveness of the control measures taken. Specific methods of vector control were applied in accordance with the bionomy of the various Anophelines transmitting malaria. No resistance of local malaria vectors to DDT was found in 1961, probably due to the general use of larvicides not containing residual insecticides (including DDT) and the mode of indoor DDT application; spraying in selected localities and special timing in accordance with the bionomy of the local vectors. The relation between the changed status of the various Anopheles vectors and changes in the epidemiology of primary malaria cases in the course of time is also described. Malaria eradication in Israel was practically achieved in 1962.


Benin City mothers: their beliefs concerning infant feeding and child care. One hundred and forty-three mothers residing in a representative area of Benin City were interviewed concerning their beliefs about child care, nutrition, and sources of information related to child care. Although all the mothers believed that breast-feeding was a natural procedure which should start from birth, they were not aware of the importance of breast milk to the baby. 58.7 per cent of the mothers would introduce artificial milk within the first month of life, and only 19.6 per cent would give breast milk alone for the first three months. Kwashiorkor was not widely believed to be related to protein-calorie deficiency, although some other food-related causes were given. The food taboos mentioned were not thought by the investigators to have any significant adverse effect on the sample children's health. Most of the information on health was obtained from friends and relatives and from infant welfare clinics. Recommendations are made for improvement of mothers' knowledge in total child care and use of health facilities.


Growth and morphological characteristics of canine venereal tumor cells in vitro. Canine venereal tumor cells were grown in monolayer and tumor tissue fragments were maintained in vitro for 56 days in medium-199. Attachment and cell replication were evident within 17 hours and monolayer was obtained by the tenth day. Growth at first comprised mainly round cells with abundance of cytoplasm and vesicular nuclei, and a few spindle-shaped cells. Later cells became more elongated and like fibroblasts. Cell degeneration started by the 17th day and most were degenerated by the 24th day. Necrosis and depletion of cell population were prominent in tumor explants during the first 2 weeks. Distinct cell multiplication was evident by the 21st day and tumor fragments were repopulated with cells resembling the original tumor by the 56th day. Two distinct morphological cell types were seen: small cells with vesicular, round to oval nuclei and acidophilic cytoplasm; and the large cells with large hyperchromatic nuclei and acidophilic cytoplasm.


Exudative retinal detachment in retrolental fibroplasia. Four cases of exudative retinal detachment associated with retrolental fibroplasia are presented. The exudation appears to be secondary to leakage from neovascularization as well as vitreous traction on normal retinal vessels. The range in age of onset was between 13 and 17 years, with three of the four cases occurring in patients 23 years of age or younger. Treatment is directed at eliminating the abnormal vasculature which, in our experience, has been accomplished best by an encircling scleral-buckling procedure. One patient, however, required vitrectomy because of the severe vitreous membranes and traction which were present.


[Distribution of aflatoxin M1 in whey and curd during cheese processing (author's transl)]. In model experiments on the distribution of aflatoxin M1 in whey and curd, the influence of the different processing steps was investigated. Taking the same weight ratio between whey and curd, the following results were obtained: a) The aflatoxin M1-distribution in whey and curd was not changed with increasing amounts of rennet, thus decreasing the renneting time at constant renneting temperatures. b) With increasing renneting temperatures, however, the toxin's percentage in the curd decreased at constant amounts of rennet, whereas the whey's content remained stable. For the commonly used temperature variations between 28 and 35 degrees C, the toxin content of the cheese varied in the range of about 12%. c) Processing of curd by acidification with different organic acids at constant temperatures did not show any change in the aflatoxin M1 distribution as compared to rennet coagulation. d) Curd processing by means of starter cultures led to a decrease in the aflatoxin M1 in curd only at higher temperatures; the toxin's percentage in whey remained practically the same. e) Washing of the curd with the 2 1/2 volumes of water decreased the aflatoxin M1 content of cheese by 22%.


Spontaneous regression of enlargement of the sella turcica and of associated panhypopituitary symptoms. The case history of a woman born in 1946 is given. In 1968 she developed a syndrome of headache, fever. elevated antistreptolysin titer, enlarged and ballooned sella turcica, hypothyroidism secondary to TSH deficiency, secondary amenorrhoea of pituitary genesis, probable growth hormone deficiency, and secondary adrenocortical insufficiency. From 1972 all the mentioned pituitary defects of function disappeared, and the sella turcica gradually became normal in size as shown by X-ray examination.


The stimulation of prolactin secretion by sulpiride in "adolescent gynaecomastia". In order to evaluate the function of the hypothalamic-pituitary-prolactin axis in "adolescent gynaecomastia" (AG), sulpiride was administered to 7 normal boys and 7 boys with AG. The maximum increase in serum prolactin (PRL) above the mean baseline level (deltamax) was used as index of response. The sulpiride induced a greater PRL release in boys with gynaecomastia than in the controls. Our data indicate that boys with gynaecomastia may have a greater pituitary prolactin pool. The results also illustrate the usefulness of specific neurotrophic agents such as sulpiride as important tools for evaluating the function of the hypothalamic-pituitary-PRL axis.


Pituitary luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin from birth to puberty in female and male rats. Pituitary content and concentration of LH, FSH and prolactin were measured by radioimmunoassay (RIA) at 2-day intervals from birth to puberty in female and male rats. During the first 2 to 3 weeks of life all hormones were low in pituitary content and concentration in both sexes. They all increased in females during the third and fourth week, but decreased sharply during the days before vaginal opening. During the first ovulatory cycle pituitary content and concentration of LH and prolactin increased again, FSH, however, remained low. In males, pituitary LH, FSH and prolactin content reached peak levels during puberty. Our results show a distinct sexual dimorphism for pituitary FSH. Pituitary LH and prolactin content and concentration patterns show similar tendencies in both sexes with a delay of several days in males. The dramatic changes in female pituitary hormone concentrations just before the first ovulation were not detected in males before the first occurrence of mature spermatozoa in the tubuli of the testes.


Development of stress-induced pituitary prolactin and TSH release in male rats. Blood was collected from male rats of various ages under control conditions and after introduction of two stress factors. All animals were sacrificed between 15.00 and 16.00 h. Serum prolactin levels in immature male rats were found to be very low between birth and day 15 after birth. Neither exposure to a new environment, for example removal from the animal rooms for the duration of 10 min, nor exposure to concentrated ether vapour resulted in increased serum prolactin levels. Between day 20 and 35 basal serum prolactin levels were increased, they then fell at adult values. During this period of increasing serum prolactin levels pituitary prolactin release became stress-susceptable; i.e. elevated serum prolactin levels were observed after introduction of stress factors as in adult male rats. Serum TSH levels were found to be high between birth and day 10. Low TSH levels measured between day 15 and 40 and adult values were detected after day 40. Neither ether nor removal of the animals from their normal environment changed serum TSH levels at any age tested. The results indicate that the hypothalamo-pituitary in immature rats reacts in a similar way as that in adult animals from day 16-20 onwards. Serum TSH levels in these animals, however, are reduced, indicating that an increase in serum TSH is not necessary for normal processes of maturation.


Iodopeptides from human thyroglobulin.

Iodopeptides from human thyroglobulin. Human thyroglubulin labelled in vivo by 125I was purified from eight different thyroid glands including normal thyroid tissue, thyrotoxic goitre and euthyroid multinodular goitre. The purified protein was cleaved with cyanogen bromide (CNBr) and the resulting peptides were separated by column chromatography and ion exchange chromatography. Reproducible elution profiles of both protein and iodine were obtained. However, the distribution of iodine depended on the iodine content of the intact thyroglobulin. Small CNBr peptides seemed to be preferentially iodinated, but with a limited capacity. With higher degrees of iodination, larger peptides became richer in iodine. This suggests sequential iodination of the thyroglobulin molecule. The mixture of small peptides was digested by trypsin. Two iodopeptides were identified in this material by peptide mapping and they had identical migration in thyroglobulins of different origin. One of them was purified by ion exchange chromatography and high voltage electrophoresis. Analogous amino acid composition was obtained for the iodopeptide purified from two different thyroglobulins. The data indicates that thyroglobulin iodination occurs in specific portions of the polypeptide chain and probably in a sequential manner.


Effects of amiodarone on thyroid iodine metabolism in vitro. Since alterations of thyroid function have been reported in patients treated with amiodarone, 2-butyl,3-(4-diethylaminoethoxy-3,4-diiodo, benzoyl) benzufuran, the effects of this drug on the active iodide transport, organic iodine formation, thyroid peroxidase and the enzymatic iodotyrosine deiodination, were studied. In pig thyroid slices the iodide transport was affected by amiodarone at concentrations of 10(-4) M and 10(-5) M, showing a decrease of T/M (tissue/medium) ratios of 20% and 23%, respectively. Lower concentrations produced no significant differences from the controls. Iodotyrosine synthesis was only, but poorly, affected by 10(-4) M and 10(-5) M amiodarone. Inhibition of the DIT formation was greater than that produced for MIT. Thyroid peroxidase activity, as measured by the tyrosine-iodinase assay, showed a 20% decrease at 10(-3) M amiodarone. None of the other concentrations have affected the activity of the enzyme, except for 7% at a concentrations of 10(-4) M. The iodotyrosine deiodination was affected by amiodarone only at a concentration of 10(-3) M and 10(-4) M. The inhibitions were of 22.5% and 16.8%, respectively. We have concluded that, under the conditions of our study, amiodarone per se does not affect the intrathyroidal iodine metabolism in concentrations which are usually present in the sera of patients treated with this drug. However, it is not possible to rule out an in vivo direct action, if amiodarone is substantially concentrated in the human thyroid gland.


Distribution of LATS activity in immunoglobulin G subclass. The immunological character of LATS was examined by affinity chromatography on Anti-IgG, Anti-Fab, Anti-Fc and Staphylococcal Protein A bound Sepharose. By affinity chromatography on Anti-IgG, Anti-Fab and Anti-Fc bound Sepharose, it is possible to separate LATS-immunoglobulin from LATS positive serum without loss of activity. Affinity chromatography on Protein A bound Sepharose is useful for obtaining further purified LATS-immunoglobulin. By this method, it is possible to separate IgG molecules of the subclasses IgG(1), IgG(2) and IgG(4) with high LATS activity. LATS activity was not found in the IgG(3) fraction. When IgG(1) fraction was purified from the fraction containing the 3 subclasses of IgG(1), IgG(2) and IgG(4), about 85% of total protein was found in IgG(1). However, specific activity per protein of LATS in IgG(1) fraction did not change remarkably. After papain hydrolysis the thyroid stimulating activity of LATS-immunoglobulin was located in Fab fraction of these 3 subclasses of IgG(1), IgG(2) and IgG(4), and especially in IgG(1). The Fab fraction presents a short acting type of thyroid stimulating activity. These data indicate that LATS activity is mainly distributed in the Fab fragment of IgG(1).


Secretin: high plasma levels in diabetes mellitus. Plasma immunoreactive secretin levels were measured in 22 newly diagnosed non-ketotic, maturity-onset diabetics and 10 healthy control subjects during 50 gram oral glucose tolerance test (OGTT). The test was repeated in the diabetic group after 6 months' dietary treatment. At diagnosis the fasting secretin levels in the diabetics were higher than in control subjects but fell within the normal range following dietary treatment. In the diabetics there was a significant positive correlation between the fasting glucose and fasting secretin levels at the time of diagnosis. Suppression of secretin levels occurred during the OGTT, both in diabetic and control subjects.


Decrease of non-suppressible insulin-like activity after pancreatectomy and normalization by insulin therapy. Non-suppressible insulin-like activity (NSILA-S) was determined in 5 dogs before and after pancreatectomy and again during insulin therapy. All NSILA-S determinations were carried out on serum samples which were passed over Sephadex G-50 columns equilibrated with 1 M acetic acid. The levels of NSILA-S decreased drastically shortly after pancreatectomy and rose slowly after institution of insulin therapy, to normal levels. During the period of severe diabetes after pancreatectomy the concentration of growth hormone was elevated. These findings indicate that 1) the pancreas cannot be the site of synthesis and release of NSILA-S, 2) NSILA-S levels do not always parallel growth hormone levels and 3) the synthesis and secretion of NSILA-S among other factors is under the control of insulin.


A case of adrenogenital syndrome with aberrant 11beta-hydroxylation. A 17 year old female patient with hypertension, amenorrhoea and hirsutism was found to have subnormal levels of plasma and urinary cortisol, significant plasma levels of Reichstein's compound S and 21-deoxycortisol, high urinary levels of THS and pregnanetriolone as well as elevated levels of plasma and urinary testosterone. Treatment with 0.5 mg/day of dexamethasone or 25 mg/day cortisone reduced her hypertension and restored her menstrual cycles, but also resulted in the development of moon face, body striae and a gain in weight. Lower doses of cortisone were without effect. The deficient cortisol production coupled with the presence of unusual intermediates such as Reichstein's compound S and 21-deoxycortisol can be explained by a shift in the substrate specificity of 11beta-hydroxylase from C-21-hydroxylated substrates (i.e. compound S) to C-21-deoxy substrates (i.e. 17-hydroxyprogesterone).


A new assay method for the determination of oestrogen receptors. A new assay method was developed to determine the quantity of oestrogen cytoplasmic receptors which are capable of associating with acceptor sites on chromatin. The quantity of oestrogen receptor complexes associated with chromatin is of paramount importance in the mechanism of action of oestrogen. This method is based on the specific binding properties of oestrogen to the receptor and on the binding of the complex to chromatin. Cytosol was pre-incubated with [3H]oestradiol-17 beta ([3H]Oe2) to form a complex, and further incubated with a constant amount of chromatin. After this the quantity of [3H]Oe2 cytosol receptor complexes specifically associated with the chromatin was determined. The binding activity of the chromatin to the [3H]Oe2 receptor complex was stable for at least six months in 0.15 M NaCl at -20 degrees C. This method enables us to determine the quantity of the biologically active oestrogen receptors more specifically than with other methods.


Statistical inference as applied to bioavailability data--a guide for the practicing pharmacist. Descriptive statistics and statistical tests used in reporting bioavailability data are reviewed in order to give the practicing pharmacist the fundamental knowledge needed to evaluate such data. Using acetaminophen bioavailability data as a model the following concepts are explained: mean, median, mode, standard deviation, range, 95% confidence limit, Student's t-test, analysis of variance, and the Wilcoxon rank sum test.


Androgen dependency in acquired aplastic anemia. We describe three patients with acquired aplastic anemia showing dependency on androgens, with blood counts that correlated directly with variation in oxymetholone dosage. In two of the patients, red cells, neutrophils and platelets showed parallel fluctuations, whereas in one patient the red cells and white cells, but not the platelets, fluctuated in relationship to oxymetholone therapy. There was no hematologic response to dromostanolone in two patients. These results support the benefit of androgen therapy in some patients with acquired aplastic anemia.


Antinociceptive effect of intrathecally administered serotonin. It has been suggested that serotonin neurons and their pathways may mediate sensitivity to nociceptive stimuli by activating the descending inhibitory mechanisms at the spinal cord. This antinociceptive effect may be induced by direct administration of serotonin into the cerebrospinal fluid pathways. The experiment is designed to demonstrate the changes in the tail-flick response latency after the intrathecal injection of serotonin. Serotonin, 100 or 200 microgram, administered into the lumbar intrathecal space, produced an analgesic effect for as long as 40 minutes. Behavioral and morphologic observations after serotonin injections showed no adverse reaction. It is assumed that serotonin molecules penetrate the spinal cord tissue and activate the antinociceptive serotonergic pathyways.


Possible pathogenetic mechanisms producing bovine milk protein inducible malabsorption: a hypothesis. The feeding of bovine milk to five highly allergic pediatric patients with bilateral family histories of atopy led to transient malabsorption of glucose and fat as well as systemic autonomic functional changes which may be attributable to pharmacologic actions of histamine and/or acetylcholine. It is hypothesized that during allergic reactions endogenously released smooth muscle stimulating neuromediators could provide rapid propulsion of nutrients through the absorbing portion of the gut, leading to suboptimal absorption, and that bovine milk inducible malabsorption in the atopic patients has an immuno-pharmacologic basis in its pathogenesis.


Failure of a "prophylactic" antimicrobial drug to prevent sepsis after fiberoptic bronchoscopy. A 53-year-old patient with lymphoblastic lymphoma developed progressive interstitial pulmonary infiltrates. The patient was believed to have Pseudomonas bronchitis and was given parenteral gentamicin. Transbronchial lung biopsy performed through a fiberoptic bronchoscope was complicated by the development of Pseudomonas septicemia. The organism isolated on blood culture, like the one isolated on sputum culture, was fully susceptible to gentamicin in vitro. A prophylactic antimicrobial drug did not prevent bacteremic Pseudomonas infection in our immunosuppressed patient with pre-existent Pseudomonas bronchitis.


[Study of the toxicity and antiblastoma activity of antibiotics echinomycin and 6270 in complexes with DNA]. Studies with the use of intact inbred albino mice showed that in intravenous administration the acute toxicity of antibiotic No. 6270 and echinomycin in complexes with DNA increased 3--4 times as compared to the toxicity of the same antibiotics used without the complex. Under the experimental conditions with 3-fold intravenous administration at 72-hour intervals in doses equivalent by their acute toxicity, the antitumor activity of the echinomycin complex with DNA against the solid form of lymphosarcoma L10-1 was approximately 4 times lower than the activity of the antibiotic used alone. Like echinomycin, antibiotic No. 6270 in complex with DNA used according to the same administration scheme in doses equivalent by their acute toxicity had a lower inhibitory effect on growth of lymphosarcoma L10-1 and sarcoma 180 as compared to its use alone.


Multiple mycotic aneurysms due to Candida endocarditis. Candida endocarditis is a serious condition which should be suspected in any patient with signs and symptoms compatible with bacterial endocarditis when cultures are negative. It should be managed by a medical-surgical approach which combines resection of all infected heart tissue and repair of any preexisting heart defects with appropriate antifungal therapy. Mycotic aneurysms should be treated by ligation of the vessel above and below the aneurysm, resection of the aneurysm, and implementation of appropriate antifungal or antibacterial therapy. Revascularization is not always necessary. When required, an extra-anatomic approach is preferable to placing a graft through the bed of the aneurysm.


Evidence for a specific transport of D-hexoses across the human term placenta in vitro. Isolated cotylidons of human term placentas are perfused artificially on the fetal and maternal side. The relative transfer rates of radioactive labelled D-glucose, L-glucose, D-mannose and D-mannitol across the placenta are measured and the inhibition of these transports by phloretin is studied: 1. Transfer rates of D-glucose and D-mannose exceed that of L-glucose about 1.5-4 times. 2. Phloretin (10(-3) mol/l) decreases the transports of D-hexoses, whereas the transport of L-GLUCOSE REMAINS UNAFFECTED. 3. If the concentration of D-glucose is increased, the transport of D-mannose is inhibited competitively. 4. L-glucose and D-mannitol equal in transfer rates. These results show, that D-hexoses cross the human placenta by a specific carrier and by simple diffusion.


[Problems of distinction of normal, arteficial and pathological structures in mature human placental villi. I. Ultrastructure of the syncytiotrophoblast (author's transl)]. Thirty-four mature human placentae were punctured in situ during cesarean section and fixed immediately. The ten cases which seemed normal according to clinical and morphological criteria were examined electron-microscopically. Findings won in ideal conditions after perfusion fixation of the guinea-pig placenta were compared to the human punction samples. The granular endoplasmic reticulum in the syncytium proved to be the most susceptable parameter. Its cisternae are narrow and arranged parallel to each other after optimal fixation. The larger the ischemic phase--already detectable after 2 min--, the more disorientated and dilated they become. The mitochondria only react considerably later. Similar structural alterations also occur in the course of pathological processes. The meaning of arteficially and pathologically induced ultrastructural changes and their interdependance are discussed.


[Biochemical studies on hypotrophy and hypoplasia in the post partum uterus of the rat (author's transl)]. In post partum rat uteri, the wet weight, the soluble protein and the DNA content were measured for ten days following delivery. After a lag period of 48 h, the weight and protein content of whole uteri decreased in parallel to one twelfth of the initial values. The DNA content did not change significantly. Hypoplasia contributed not more than 20% to the weight loss, so that at least 80% of the loss was due to hypotrophy. The protein content per cell nucleus (mg protein/mg DNA) decreased by 85% within 10 days. In non-pregnant control animals, uterus weight and protein content per cell nucleus were greater than those of animals measured on the tenth post partum day. In contrast, the protein concentration of the tissue (mg protein/g wet weight) was lower in the control group. It is suggested that this hyperinvolution is caused by the low estrogen levels of the lactating animals.


[Some experiences concerning the effect of fetal respiratory movement (author's transl)]. The effect of negative pressure by intrauterine respiratory movements of 115 fetal rabbits is examined between the 25th and 28th day of gestation. An intraamnial injection of Burri-ink with particles of the size between 20 and 50 nm and of a suspension of polyamid (size between 25 and 40 micrometer) in physiological NaC1-solution was done. Both markers are not inspirated during the time of 24 h p.i. However you can find them after 19 min in the circulated fetal blood. There is the same effect if you block respiratory movements by drugs. There is a correlation to the concentration of the markers in the amniotic fluid, but no correlation to the size of the particles of those markers.


[Quantitative investigations of the human placenta under normal conditions and in case of preeclampsia correlated to the human placenta-lactogen blood-level in the last third of pregnancy (author's transl)]. Thirty-two human placentas from normal and from pregnancies complicated by preeclampsia in last third of gestation were morphologically and morphometrically examined and correlated with human placenta-lactogen blood-level. HPL was determined by the radio-immunoassay (Carbon-Dextran-method). HPL-values, placenta villous surface, the weight of the newborn and placenta showed significant correlation. The placentas were classified according to the morphologic degree of severity (placenta-morphological-index) and compared to preeclamptic index (Goecke) and HPL-values. The results showed correlation between the studied datas according to the severity of preeclampsia. The significance of these results is discussed.


The nuclear DNA content of lobular neoplasia of the mammary gland. Twelve cases of lobular neoplasia and three cases of invasive lobular carcinoma of the breast were examined by Feulgen microspectrophotometry. Two different ranges of nuclear DNA values were observed. Eight cases of lobular neoplasia fell within the diploid range and the four remaining cases within the diploid to tetraploid range, while the three cases of invasive lobular carcinoma showed a DNA distribution between the diploid and tetraploid range. Cytophotometrically, lobular neoplasia with diploid DNA values can be considered to represent a precancerous condition, whereas lobular neoplasia with diploid to tetraploid values are regarded as a more advanced stage of an non infiltrating carcinoma still confined to the performed spaces.


Palmitic acid concentration of amniotic fluid in diabetic pregnancy. The fatty acid composition of total lipid and phospholipid contents was determined in the amniotic fluid of normal and diabetic pregnant patients. Disturbance of lipid metabolism which is not related to the severity of diabetes, causes difficulties in the determination of L/S ratio. The palmitic acid content of total lipid and lecithin is increased in diabetic pregnancy. The lecithin synthesis is significantly decreased as result of a transitory or prolonged acidosis.


[The problem of the ploidy reduction in carcinogenesis of the uterine cervix: numerical chromosome anomalies in carcinoma in situ (author's transl)]. The authors report on cytogenetic studies of the uterine cervix in 11 carcinoma in situ. In six cases with intact epithelium the cells were no longer normal and five cases showed beginning stroma invasion. The numerical chromosome anomalies observed indicate the presence of ploidy reduction. In accord with cytogenetic findings in precancerous conditions and in carcinoma of the uterine cervix published in the literature, the ploidy reduction may be regarded as a probable causal principle for malignancy at the uterine cervix.


Effect of follicle-stimulating hormone (FSH) and estrogen on follicle growth in rats. The effect of follicle-stimulating hormone (FSH) and diethylstilbestrol (DES) on ovarian follicle growth was studied in hypophysectomized rats, using histologic, autoradiographic and histochemical techniques. The administration of FSH to immature hypophysectomized rats stimulated the follicle growth with thickening of the theca layer and repair of "deficiency cells". Although DES given to hypophysectomized rats also stimulated the follicle growth, the theca layer was relatively thin compared with that in FSH-treated rats. In order to detect cell division in a growing follicle, the number of labelled granulosa cells with tritiated thymidine as a proportion of the granulosa cells in a growing follicle were counted and the labelling indices of the granulosa cells were calculated. The labelling indices increased by the administration of FSH (p less than 0.05) or DES (p less than 0.05). The uptake of tritiated thymidine and leucine by the theca cells was enhanced only by FSH and was not stimulated by DES. The administration of FSH resulted in an increase of the histochemically demonstrable enzyme activity such as delta5-3beta-hydroxysteroid dehydrogenase (3beta-HSD) or alkaline phosphatase in the theca cells. In contrast, the administration of DES did not stimulate the enzyme activity of the theca cells. Furthermore, FSH stimulated a release of estradiol and estriol from the ovary of hypophysectomized rat, whereas DES did not. Although ovarian follicle growth was stimulated by both FSH and DES, the effect of the two hormones on the theca cells was quite different and the secretion of estrogen was stimulated by FSH. The results suggest that FSH induced follicle growth of the ovary might be mediated by estrogen produced by the theca cells.


[Investigation of pregnancy hypertension as a consequence of utero-placentar ischemia (author's transl)]. An attempt at provoking gestosis by constricting the uterine artery was made using pregnant rats and rabbits. The experiment failed. Reducing the circulation by means of Z-sutures in the region of the nidation site failed to produce symptoms of gestosis also. The result of the uterine manipulations was abortion and intra-uterine retardation of the product of conception. Though it was not possible to verify the pathogenesis of gestosis due to impaired circulation of the uterus. On the basis of these experiments previous gestosis hypotheses stemming from animal experiments cannot be questioned. However, it is though-provoking that a review of the literature reveals that the results of these "classical model experiments" cannot always be interpreted uniformly.


[A mathematical model for the description of oxygen-diffusion in the intervillous space of the human placenta (author's transl)]. The oxygen consumption has a central place in the complicated interaction between diminished oxygen supply and degenerative trophoblastic tissue change. In the present investigation, that serves as a mathematical model, the problem of the diffusion equation for the constant state is discussed and solved. It is shown that the diminishing of length of the radius of the maternal blood compartment has the same meaning as the decrease in the flow velocity. The influence of the mass transfer coefficient h on the oxygen partial pressure and on the oxygen transfer is investigated. The influence of parameter variations on the placental alterations during toxemia is discussed and their clinical importance is obvious. Our theoretical model elusidates the value of an early therapeutical approach in the case of toxemia.


Glomerulocystic kidney. A hypothesis of origin and pathogenesis. Glomerulocystic kidney, a disease primarily of infants, is characterized by dilation of Bowman's space. We describe an infant whose mother had regularly taken phenacetin during the latter half of her pregnancy. This history, with the renal morphologic features of our patient and those described in the literature, suggests that medullary obstruction contributes to the pathogenesis of this lesion.


Renal amyloidosis in KK mice that may be misinterpreted as diabetic glomerulosclerosis. A normoglycemic, normoinsulinemic, "lean" phenotype KK mouse having a morphologically normal pancreatic islet had renal lesions reminiscent of diabetic glomerulosclerosis described in the literature for KK mice. Most of these animals also had splenomegaly. Using histochemical and ultrastructural methods, the renal and splenic lesions were demonstrated to be amyloidotic. Extensive deposits of amyloid were found in the liver and adrenals. Amyloidosis was found in all lean KK mice 4 months of age or older and in five of 11 C57BL/6J mice over 1 year of age. The validity of data attributing glomerulosclerosis to diabetes in mice that are neither glucosuric nor hyperglycemic or that show normal tolerance to glucose load should be questioned until amyloidosis is ruled out.


Fucosidosis with angiokeratoma. Electron microscopic changes in the skin. An electron microscopic investigation was performed on the skin from three patients suffering from fucosidosis accompanied by diffuse angiokeratoma. Storage of fucose containing substances was represented by the following two kinds of cytosomes: lamellated bodies, found in Schwann cells and myoepithelial cells of sweat glands and membrane-bound vacuoles, located in various other cellular elements of the skin. Storage in endothelial cells caused narrowing or occlusion of some dermal blood vessels; in the papillary plexus, angiectasis was the result. Extensive vacuolation of the secretory cells of sweat glands could account for hypohydrosis. The characteristic distribution of cytosomes in various kinds of cells is helpful in differentiating fucosidosis from some other storage diseases on the basis of skin biopsy.


Ventricular preexcitation syndrome. Accessory left atrioventricular connection and rhabdomyomatous myocardial fibers. A necropsy study of the heart of a 16-year-old girl with ventricular preexcitation syndrome and supraventricular tachycardia showed an accessory left atrioventricular connection partially within the mitral valve. Both the accessory pathway and the ventricular musculature showed multiple foci of cardiac muscle fibers with rhabdomyomatous features having the characteristic appearance of rhabdomyomatosis. The case is discussed in the context of a literature review of necropsy findings in cases of ventricular preexcitation.


Juxtaposition of atrial appendages. Reinterpretation as an accessory appendage or atrial diverticulum. The pathological features of 13 cases with juxtaposition of the atrial appendages in the autopsy files of The Johns Hopkins Hospital were studied. The anomaly occurs most frequently in association with transposition of the great vessels, ventricular septal defect, patent foramen ovale, and obstructive lesions of the tricuspid and pulmonic valves. The malformation complex of tricuspid atresia, atrial and ventricular septal communication, and the transposition of the great vessels seems particularly common with juxtaposition of the atrial appendage. A recent case showed a small accessory right atrial appendage lying in juxtaposition to the left atrial appendage. In addition, a normally situated right atrial appendages in addition to well-formed accessory appendages lying in juxtaposition to the left atrial appendages. It seems that juxtaposition of the atrial appendages should be reinterpreted as an accessory appendage or atrial diverticulum.


Specificity of cellular and myofibrillar disorientation in hypertrophic obstructive cardiomyopathy. The specificity of the ultrastructural myocardial abnormalities in hypertrophic obstructive cardiomyopathy (HOCM) is undetermined. We undertook a quantitative study using myocardial biopsy specimens from the subaortic area in a patient with classical HOCM and compared them with hypertrophic left ventricular myocardium from a patient suffering from rheumatic valve disease. Myofibrillar disarray and side-to-side junctions were chosen as strictly quantifiable features. The former was seen as representing intracellular disorganization; the latter was seen as criterion for intercellular disorganization. The results showed that there is no preference for these abnormalities to occur in HOCM. Indeed, intracellular abnormalities more frequently occurred in the hypertrophic myocardium the patient without HOCM. Neither intracellular nor intercellular features can be regarded as specific for HOCM, even in a quantitative sense.


Skeletal muscle capillaries in intermittent claudication. The ultrastructural dimensions and density of capillaries in 23 gastrocnemius or rectus femoris muscles in patients with intermittent claudication due to arteriosclerosis obliterans (ASO) were studied. Constant ultrastructural alterations that were not seen in the control patients were thickening, replication, and remnants of the capillary basement membrane (BM). Compared with the control patientes, the percentual area of the BM was significantly larger (P less than .01), the lumen was significantly smaller (P less than .01), and the ratio of capillaries to muscle fiber was significantly higher (P less than .01) in patients with ASO. These changes were probably due to ASO since they increased with growing severity of claudication.


A study of the effects of bromocriptine on serum prolactin, follicle stimulating hormone and luteinizing hormone and on ovarian responsiveness to exogenous gonadotrophins in anovulatory women. Twelve anovulatory patients with normal serum prolactin values and six with elevated values were treated with bromocriptine and the effects on serum prolactin, FSH and LH levels were recorded. Ovulation resulted in one patient who had normal prolactin values and in all six who had raised values. No patient with normal basal prolactin values showed an increase in serum FSH during therapy with bromocriptine, whereas 5 of the 6 patients with elevated values showed significant increases. Similar results were obtained for LH. Although these differences were highly significant (P less than 0-005) the majority of the serum FSH and LH values remained within the normal ranges. Five patients with normal basal prolactin values and one with elevated values were also treated with human pituitary gonadotrophin (HPG). An increase in ovarian responsiveness to HPG during therapy with bromocriptine was recorded in the one patient with initially elevated prolactin values. It was concluded that bromocriptine acts by allowing FSH to rise above threshold requirements for follicular stimulation.


The embryonic development of the marine caddis fly. Philanisus plebeius Walker (Trichoptera: Chathamidae). 1. P. plebeius, a trichopteran with marine intertidal larvae, oviposits in the coelom of a starfish, Patiriella exigua. Oviposition occurs mainly in the spring and autumn months. 2. In spite of the intracoelomic location of the embryos, the development of P. plebeius follows an unmodified trichopteran mode, including the characteristic blastokinesis. Nutrients are not supplied to the caddis embryos by the host starfish. 3. Hatching takes place in the starfish coelum after 17-18 days. The newly hatched caddis larvae quickly escape to their rock pool habitat. 4. The form of the female ovipositor indicates that other species of Chathamidae utilize starfish species as oviposition hosts. 5. This mode of oviposition offers protection to the caddis embryos in the intertidal habitat.


Equilibrium and metastable states in lecithin films. We have considered whether lecithin surface films below the gel-liquid crystal transition temperature, Tc, are in unique physical states. In general, below Tc, equilibrium films do not exist when surface pressures, pi, exceed about 0.1 dyn/cm. Since surface pressure-surface area isotherms of lecithin films below Tc always encompass pi's much greater than 0.1 dyn/cm, the film states are metastable. We show that the film properties under these conditions depend strongly on the history of the film, particularly the method of film formation. Lecithin surface films below Tc are thus in arbitrary metastable states, so that pi-area isotherms are difficult to interpret. The physical significance of such isotherms remains to be determined. The utility of pure lecithin surface layers below Tc as models for biological systems is also challenged by our results.


Herpes zoster and paralytic ileus: a case report. A case of herpes zoster presenting as intestinal obstruction is described. Clinical and radiological evidence of intestinal obstruction was obtained. The mechanisms by which herpes zoster may cause an ileus are discussed.


Death and injury of Staphytococcus aureus during thermal treatment of milk. Staphylococcus aureus isolated from milk and grown in milk was heated in milk. The phenomena of death as well as injury was investigated in the range of 50 to 75 degrees C. The D60 value (decimal reduction time on salt-free medium) was 0.87 min, the D'60 value (decimal reduction time in salt-containing medium) was 0.62 min. Cultures were injured as soon as heating started. This initial thermal shock increased with increasing temperature. At 50-60 degrees C injury was more rapid than death. At greater than 60 degrees C death became faster than injury and the two processes coincided at 70 degrees C. The Z value was 9.46 degrees C and the Z' value was 9.93 degrees C.


What do family physicians see in practice? Health care problems dealt with in their practices were recorded by seven family physicians over a period of 1 year (two others recorded for 3 months), each diagnosis being coded according to the Canuck Disease Classification Index. Problems were classified into four types: physical, psychosocial, diseases of choice (or lifestyle) and diseases of social impact. More than 85% of the 23 108 problems recorded were physical in origin and had physical manifestations. More time was spent on routine checkups and treatment of respiratory disease than on any other activity. Venereal disease and alcoholism were infrequent problems. The family physician is in a favourable position to act as health educator and counsellor and must be throughly trained in the physical aspects of disease.


Studies on Thermoactinomyces sp. TM9208. I. Description of the strain. A strain of Thermoactinomyces sp., TM9208, isolated from a soil sample in the Taipei area showed antagonistic activity to Gram positive bacteria but not to the Gram negative on the potato extract agar plate by the cross streaking method. The strain showed strong starch hydrolysis, beta type of hemolysis, brownish yellow growth on the potato extract agar and green on the nutrient agar. Its aerial mycelium, white to grayish white, was long and straight with short branches. The spores are single and have smooth surface. It is a good utilizer of starch, maltose and cellobiose as carbon source, but utilizes dulcitol, salicin, sucrose, rhamnose and sorbitol poorly.


Humoral components of immunological response in nephrotic syndrome. Serum and urine were collected from 58 patients with nephrotic syndrome. Immunoglobulins (IgA, IgG and IgM), complement (C3) and transferrin levels were measured by single radial immunodiffusion. The extent of glomerular injury was estimated by determining the selectivity of proteinuria. The relationship between the severity of glomerular damage and serum concentrations of immunoglobulins and complement was assessed. Higher IgM and lower IgG serum concentrations were found in nephrotic patients than in normal controls (157 +/- 108 mg+ vs 127 +/- 38 mg% for IgM, 929 +/- 537 mg% for IgG). The difference was statistically significant (p less than 0.05 for IgM, p less than 0.001 for IgG). No correlation was present between the selectivity of proteinuria and serum levels of IgA, IgM, IgG or C3. The results indicate that abnormalities in humoral components of the immune system are present in nephrotic patients and are probably related to a basic immunological defect in the patients rather than to the severity of glomerular damage.


[Isolation of anaerobic bacteria from clinical specimens and the drug susceptibility of Bacteroides fragilis]. In the routine bacteriological examination of 8,423 clinical specimens, 906 strains of anaerobic bacteria were isolated at National Taiwan University Hospital between April 1972 and April 1976. Most of the strains were isolated from sites allied to the abdominal cavity and genito-urinary tract. Bacteroides fragilis was the most commonly isolated pathogen. The minimal inhibitory concentrations of 10 different antimicrobial agents to 74 clinical isolates of B. fragilis were determined by an agar dilution method under anaerobic conditions. The percentages of the strains susceptible to clindamycin, carbenicillin, ampicillin, cephalothin, and tetracycline were 98, 92, 75, 41 and 5%, respectively. Rifampin, metronidazole and chloramphenicol also inhibited all isolates in clinically attainable concentrations. All strains were resistant to the aminoglycoside antibiotics, kanamycin and gentamicin.


New technique for movement analysis: application to biological systems. A new system for motion analysis is described. Modulation of light intensity of an organism's movement over an opaque and transparent checkerboard grid is monitored by a photocell. The photocell's output is proportional to the organism's amplitude and frequency of movement. This output is analyzed by a continuous interval dot display and spectrum analysis. The system was tested by analyzing the activity of 4 Drosophila strains which are known to differ in their activity. General applicability of the system is discussed.


Lack of association between Hashimoto's thyroiditis and SD-locus HLA antigens. All at present serological detectable HLA antigens and humoral antithyroid immunity have been studied in 26 patients with Hashimoto's thyroiditis and 450 controls. No statistical significant difference in frequencies of the 36 HLA antigens tested could be found. These findings suggest that serological defined (SD) genes of the histocompatibility complex are not the major factors involved in the predisposition to Hashimoto's thyroiditis. By analysing prevalence of thyroid antibodies in HLA-B8 positive and HLA-B8 negative groups of Hashimoto's thyroiditis patients an association between B8 and thyroglobulin and thyroid microsomal antibody formation was found. Although frequency of HLA-B8 was not increased in the patients, B8 positivity may reflect an increased susceptibility for humoral antithyroid immunity.


Ventilatory and cholinergic control of pulmonary surfactant in the rabbit. Four sets of experiments on surfactant secretion were performed using New Zealand rabbits under light pentobarbital anesthesia. Pa02, Paco2, and pHa remained normal during all experiments. In controls lung lavage yielded 1.62 +/- 0.26 (SD) mg of alveolar phospholipid (PL)/g lung; disaturated phosphatidylcholine comprised 55.5% of total PL. a) Acetylcholine infusion into the left pulmonary artery for 1-4 h caused a 13% increase in alveolar PL of left as compared to right lung. b) Efferent left vagus stimulation for 1 h increased alveolar PL of right and left lungs 31% as compared to controls (P = 0.012). c) Increasing minute ventilation by 100% by augmenting dead space for periods of 1, 2, and 4 h, increased alveolar PL 45% (P = 0.001), 54%, (P = 0.002), and 25% (P = 0.004), respectively, compared to controls. d) Administration of atropine prevented the increase in alveolar PL caused by increased ventilation. These findings show that increased ventilation can stimulate surfactant release through a cholinergically mediated mechanism but do not rule out the participation of other mechanisms.


Pulsating bubble technique for evaluating pulmonary surfactant. Surface tension is determined with an apparatus which records pressure across the surface of a bubble, expanded in the sample liquid and communicating with ambient air. The disposable sample chamber, with a volume of 20 microliter, communicates with a pulsator and a pressure transducer. The volume displacement of the pulsator's moving piston is hydraulically geared down 1,000 times, which gives the pulsator a stroke volume of 0.43 microliter. When this volume is moving into the sample chamber, it causes the bubble radius to change from a maximum of 0.55 mm, accurately measured through a microscope, to a minimum of 0.4 mm. The pulsator speed is usually 20 rpm, but it can be changed from 0.02 to 80 rpm. From the known pressure gradient across bubble surface, and bubble radius, surface tension is calculated with the law of Laplace.


Reverse phase high pressure liquid chromatography of vitamin A in margarine, infant formula, and fortified milk. Retinal was determined in margarine (50 mg), infant formula (1 ml), and fortified milk (1 ml) by saponification in centrifuge tubes, extraction of the unsaponifiable lipid with hexane, and high pressure liquid chromatography (HPLC) in 90% methanol on a 25 cm x 3.2 mm column containing 10 micrometer LiChrosorb reverse phase. beta-Carotene was determined using the same column and 99% methanol as eluant. The vitamins in the eluate were identified and measured from their absorption at 325 (retinol) and 453 nm (beta-carotene), using a computing integrator. Retinol and carotene were prominent peaks in the chromatograms from properly fortified samples and were satisfactorily separated from other materials. In a survey of 12 different margarines for retinol, the results from liquid chromatography agreed with those of a variety of spectrophotometric and fluorometric procedures but they were obtained with greater ease and they could be interpreted more confidently. The recovery of retinol from oil was better than 99%. The coefficients of variation was 6.8% for 12 replicate analyses of a margarine for retinol and 5.4% for 10 replicate analyses of a margarine for beta-carotene.


Gas-liquid chromatography and liquid chromatography of ethylenethiourea in fresh vegetable crops, fruits, milk, and cooked foods. The Onley-Yip procedure for determining ethylenethiourea (ETU) in milk and crops was modified to reduce interferences by the ethylenebisdithiocarbamates (EBDCs). A 20 g crop-methanol extract is cleaned up by adsorbing the sample onto Gas-Chrom S. desorbing ETU, and eluting ETU from aluminum oxide with chloroform containing ethanol. ETU is converted to the S-butyl derivative for gas-liquid chromatography (GLC) and flame photometric detection (sulfur mode). For liquid chromatography (LC), ETU is cleaned up on another aluminum oxide column and injected directly. LC and GLC results are confirmed by thin layer chromatography. A cooking procedure based on conversion of EBDCs to ETU is included for surveying crops for possible EBDC content. Recoveries from 8 crops and milk fortified at 0.05 ppm ETU ranged from 73 to 100%.


Gas-liquid chromatographic method for determining ethylenethiourea in potatoes, spinach, applesauce, and milk: collaborative study. Eight laboratories collaboratively tested a gas-liquid chromatographic method for determining ethylenetiourea (ETU) in potatoes, spinach, applesauce, and milk. In the determinative step, ETU is converted to the S-butyl derivative (2-n-butylmercapto-2-imidazoline) which is detected by a flame photometric detector, sulfur mode. For unknown fortification levels of 0.06, 0.12, and 0.30 ppm, the collaborators reported an overall average recovery range of 85-97% in the various commodities. The method has been adopted as interim official first action.


Geographical pathology as a method for detecting occupational cancer. Geographical pathology points to environmental factors in cancer and helps estimate their potential magnitude. An occupational contribution was established by 1972 for cancer of the mouth, lung, bladder, and skin. Additionally partly based on geographical pathology, an occupational etiology is accepted for some cancer of nasopharynx, brain, liver, pleura, nasal sinus, bone and bone marrow, and possibly stomach. For identifying new occupational factors based on geographical comparisons, both an optimal size of work force to be followed-up and a sufficiently high proportion of work force in the geographical unit's population are necessary. Hypothetical variations based on 30-year follow-up of asbestos workers illustrate this. Cancer surveys and registries can greatly facilitate detection of occupational cancer. Evidence for occupational factors in the geographical pathology of lymphosarcoma is briefly summarized; but no conclusions are reached.


The relation between surface tension and area in the alveolar lining film. 1. The properties of the rat alveolar lining film have been studied by observing the behaviour in a hanging drop, under reduced or increased ambient pressure, of bubbles derived from the lung.2. When such a bubble, covered by a metastable film of surfactant, is made to shrink, the material displaced from the surface usually remains in a form in which it can be re-adsorbed to the surface and retains its surpellic properties.3. When an excess of surfactant is available for adsorption to the surface of such a bubble in water, an increase in area to about 1.25 (varphi) times the metastable area is both necessary and sufficient for additional adsorption to the surface to take place.4. No significant variation of the ratio varphi with temperature between 22 and 37 degrees C has been found.5. It is concluded that during quiet breathing (involving a twofold change in lung volume in the rat) the variation in alveolar surface area is less than 25%. This finding is compatible with the extant morphometric data, but not with any assumption that the surface area is proportional to the 2/3 power of the gas volume.6. The behaviour of the bubbles in blood serum is similar to that in water. In a 2% solution of the detergent Tween 80, further adsorption of surfactant to the bubble surface does not take place.7. The fact that bubbles obtained from the lung by instillation of a solution of Tween 80 have surfactant linings similar to those of bubbles obtained with water or saline demonstrates that the bubble lining layer consists of the original alveolar lining layer detached.8. When a metastable bubble is stretched, it sometimes behaves as if some or all of its surfactant had been lost from the surface. The causes of this are unknown.9. The amount of surfactant associated with metastable bubbles freshly squeezed from a fragment of lung varies from bubble to bubble; the amounts found have ranged from 1 to 4.5 times (mean, 2) that required to cover the original bubble area with a metastable film. This would be compatible with an alveolar lining film of very uneven thickness.10. The maximum surface tension reached in the early stages of expansion of a lung bubble from the metastable state is about 34 mN/m.


The value of vaginal cultures in general practice. One hundred and eighty high risk cases in a hospital special treatment centre and 50 low risk cases of vaginal discharge from general practice were investigated by the cultural examination of vaginal secretion. The results show this procedure is of value in diagnosing sexually transmitted diseases.


Prevalence, goals and complications of heterosexual anal intercourse in a gynecologic population. In a prevalence study of 526 consecutive gynecologic patients, a history of heterosexual anal intercourse (AI) was elicited in 25% and was a regular means of sexual gratification in 8% and was thus deemed active, pleasurable, and intercourse (APAI). The prevalence of AI and APAI was similar in patients of Mexican-American, Black-American and Anglo-American background and in patients older or younger than 30 years. The APAI participants were evenly distributed between cancer detection, family planning, free clinic and private consultant populations. The goals of the APAI group associated with heterosexual anal intercourse were pleasure, orgasm and contraception. The reported complications were infrequent and were related to infectious diseases, local irritation and trauma. Although the average duration of APAI was two years, no unusual pelvic or rectal characteristics were noted in these patients.


Status asthmaticus. A nine-year experience. A retrospective analysis of 811 patients admitted to the hospital for status asthmaticus over a nine-year period was performed. Eight patients died, and 19 required mechanical ventilation. All persons who died of status asthmaticus were in the group that required mechanical ventilation. In 12 of the patients who received ventilation, no definite cause for the acute exacerbation could be identified, although initial arterial blood gas analyses showed profound hypoxemia, hypercapnia, and acute respiratory acidosis. Seventy-eight major complications occurred during mechanical ventilation. Pneumothorax, endotracheal tube malfunction, alveolar hypoventilation on the ventilator, and pneumonia were associated with decreased survival. Mucous plugging of the airways was found in all autopsied patients. Mechanical ventilation in status asthmaticus is a life-support system associated with substantial morbidity and should be instituted only when it becomes evident that maximal medical therapy will not be efficacious.


Skin immunofluorescence in infective endocarditis. Immunofluorescent microscopy was performed on the clinically normal skin of 3 patients with infective endocarditis, 3 patients with bacteremia, and 6 normal subjects. Perivascular deposition of immunoglobulin and complement was demonstrated in two of the three patients with infective endocarditis and in none of the bacteremic or control subjects.


Influenza A infection simulating pulmonary embolism. The diagnosis of pulmonary embolism is generally established when the patient has characteristic pulmonary perfusion abnormalities in the setting of an appropriate clinical history and with no concurrent cardiopulmonary disease on chest x-ray film. The initial evaluation, including positive pulmonary perfusion scan, of four young black women suggested the diagnosis of pulmonary emboli. A syndrome of respiratory tract viral infection then developed, and further evaluation by angiography and perfusion scans contradicted the diagnoses of pulmonary emboli. Each patient had substantial convalescent-phase complement-fixation titers to influenza A. Thus, if reliance is placed in pulmonary perfusion scans, an erroneous diagnosis of pulmonary emboli may be made for patients with influenza A.


Nontreatment of hip fractures in senile patients. Five elderly patients with hip fractures were deemed unsuited for surgical repair because of severe organic mental syndromes. All survived the postfracture period without the morbidity of decubitus ulcers and pulmonary complications, or the pain, mental anguish, and expense of hospitalization and surgery. Surgical repair of a hip fracture is not necessarily a mandatory or life-saving procedure. For patients unlikely to walk again, nonoperative management is a reasonable alternative--provided good nursing care is available.


Nonhemorrhagic decrements in hematocrit values after percutaneous renal biopsy. Seventy patients without bleeding after a percutaneous renal biopsy (PCB) were studied to define the incidence of decrements in hematocrit values, hypotension, and bradycardia. Hematocrit values decreased greater than or equal to 0.5% in 60% of the patients, greater than or equal to 1% in 44%, and greater than or equal to 2% in 34% of patients. After PCB, an increase of greater than or equal to 1% occurred in 55% of the patients with hematocrit nadirs of greater than or equal to 1%. Hematocrit values increased 3.0% +/- 0.6% in 8/19 patients with a previous decrease of greater than or equal to 2% but continued to decrease in 13% of the patients. A weight gain or positive fluid balance occurred in 29%, hypotension in 7%, and relative bradycardia in 4% of the patients. These studies show that a decrease in hematocrit values and hypotension may occur in patients after PCB without bleeding. This may result from hemodilution and increased parasympathetic discharge and as part of a natural spectrum of decreasing hematocrit levels coincident with PCB.


A prepaid medical plan. Cost, use, and effects in a retirement home. A model experience of a prepaid medical plan for a group of people is analyzed. No-barrier cost and physician access lead to altered use characteristics. Among these are increased physician, nurse, and nursing home use, and decreased hospital use. The overall cost is increased. Any comprehensive health-care plan that would propose comprehensive first-dollar coverage would likely encounter similar use characteristics.


Hematologic changes in a patient with Hodgkin's disease in relapse. A patient with Hodgkin's disease also had anemia, hypochromia, and thrombocytosis, which were clues to an otherwise silent relapse. These features were corrected following chemotherapy. Repeated lymphangiography is shown to be of value in diagnosis.


Military rubella.

Military rubella. An epidemic of rubella in 46 young adults occurred. Detailed descriptions of clinical signs and symptoms, basic laboratory evaluation and serologic investigation are provided. None of the vaccinees who became ill lacked IgM antibody. An interesting clinical observation was the 25% incidence of testicular pain.


Schistosomiasis haematobium.

Schistosomiasis haematobium. In our patient, schistosomiasis haematobium was not diagnosed and was treated as a urinary tract infection by several physicians. Physicians are urged to become increasingly aware of the need to recognize strange and exotic diseases normally not present in this country.


Hyperthyroidism from thyroid metastasis of pancreatic adenocarcinoma. A nontender goiter rapidly developed in a 54-year-old patient with suspected disseminated carcinoma. Thyroid function tests showed increased thyroxine, triiodothyronine resin uptake, free thyroxine index, and free thyroxine. Radioactive iodine uptake by the gland was near zero, and thyroid-stimulating hormone (TSH) was undetectable. Histologic examination of the thyroid before and after death showed invasion and disruption of the thyroid follicles by adenocarcinoma (pancreatic primary). Release of thyroglobulin by follicular disruption probably resulted in hyperthyroxinemia and suppression of TSH and radioactive iodine uptake, as occurs in subacute thyroiditis.


Prognostic value of the stress response following stroke. The systemic metabolic response following intracranial vascular damage was measured in 65 consecutively seen patients (56 with cerebral infarction and nine with subarachnoid hemorrhage). Significantly (P less than .01) greater mortality and eventual disability occurred in patients excreting more than 200 microgram of urinary norepinephrine and epinephrine daily early in their acute illness. These patients also had significantly (P less than .001) elevated plasma cortisol levels; this measurement may prove useful in predicting prognosis after stroke. Cardiac abnormalities resulting from the elevated catecholamine levels may contribute to the excess mortality in those patients with an intense stress response.


Transbronchial lung biopsy in the compromised host. Thirty-eight immunocompromised patients underwent transbronchial lung biopsy via the fiberoptic bronchoscope as part of a diagnostic evaluation for fever and roentgenographic evidence of a new pulmonary infiltrate. Diagnostic information was obtained from lung biopsy in 29 patients (76%), with infection accounting for ten cases and a nonspecific interstitial pneumonitis in 13 patients. Concomitant bronchial brushings were diagnostic in only three patients (all with infections). Diffuse roentgenographic infiltrates were expecially amenable to bronchoscopic lung biopsy diagnosis (84%), while in localized infiltrates, there was only a 43% diagnostic yield. Although thrombocytopenia and hypoxemia were common in these patients, morbidty was low (four patients had pneumothoraces with no noteworthy bleeding) and there were no deaths resulting from this procedure. Prebiopsy platelet transfusions were used in five patients with severe thrombocytopenia (platelet cound, less than 50,000/cu mm). The diagnostic efficiency and low morbidity associated with transbronchial lung biopsy indicate that this procedure can safely play a role in the evaluation of pneumonia in the compromised host.


Cocaine-codom ingestion. Surgical treatment. We report one survivor and two deaths from cocaine toxicity. Cocaine, packaged in condoms, was deliberately ingested to avoid detection by customs agents. Because cocaine is a toxic drug, we recommend surgical removal of the ingested packages, as alternative methods of removal are unreliable and potentially dangerous.


Pregnancy outcome in women with sickle cell trait. A prospective study was carried out to discern the outcome of pregnancy and distribution of birth weights of infants delivered of 85 women with sickle cell trait (AS) compared with a control group of 85 women with normal hemoglobin (AA) who were matched for race, age, parity, and sex of offspring. The distribution of birth weight of offspring of primiparous and multiparous women and the proportion of low-birth-weight infants did not differ significantly between infants born to mothers with AS and those in the control group. Similarly, there was no statistically significant difference between the birth weight of infants born to primipara or multipara. Also, the overall incidence of complications among women with AS did not differ from the incidence in the control group. The findings do not support previous reports that there may be definable pathologic correlates of childbearing in women with AS.


Recurrences and sequelae of rheumatic fever in Nashville. A follow-up study. A follow-up study of 311 patients who acquired rheumatic fever in Nashville, Tenn, during the period from 1963 to 1969 showed that 53% took penicillin prophylaxis regularly, 36% did not take it as recommended, and 11% did not take it at all. There were no recurrences among those who received prophylaxis by injection regularly, six recurrences among those who took oral prophylaxis regularly, and no recurrences among 45 subjects who did not take prophylaxis. Among these 45, however, were 29 for whom prophylaxis was not recommended by their physicians. The original study indicated that the incidence of acute rheumatic fever among blacks was twice as high as among whites. In the present study, incidence of rheumatic heart disease and recurrences was substantially higher among blacks than among whites.


The natural history of calcium urolithiasis. The course of untreated calcium renal stones, derived from the retrospective study of 300 patients with defined metabolic disorders and from the analysis of two prospective, published studies, is complex and heterogeneous. Generally, stones provoke considerable morbidity; hyperuricosuria is associated with an unusually severe stone disease. Stone recurrence rates usually remain stable, or rise with successive stones; in a minority of patients, the reverse is true. A single stone is likely to be followed by a recurrence. The mean time to recurrence averages 6.78 years, with peaks at 1.56 and eight years. Because the disease is likely to be morbid and chronic and does not wane with age, diagnostic evaluation and treatment should be strongly considered for any patient with recurrent stones, and for those in whom recurrence is likely to pose more than the usual risk.


Estrogen treatment of postmenopausal women. Benefits and risks. Estrogen treatment of postmenopausal women is effective in relieving the symptoms of vasomotor instability and urogenital atrophy; estrogen treatment is effective in preventing accelerated bone loss and osteoporosis in young women following castration, but in postmenopausal women aging is a more important determinant of accelerated bone loss than is decreased estrogen secretion. Low-dose estrogen treatment of postmenopausal women neither prevents nor increases the risk of arteriosclerotic cardiovascular disease or cerebral vascular disease. It cannot be definitively established that estrogen treatment of postmenopausal women causes an increased incidence of breast tumors, but it is clear that such treatment does not prevent these tumors. It is established that estrogen treatment of postmenopausal women increases the risk ratio of endometrial carcinoma.


Human milk contaminated with Salmonella kottbus. A cause of nosocomial illness in infants. Human milk contaminated with Salmonella kottbus caused an outbreak of illness in seven of 22 infants in a neonatal intensive care unit. A case-control investigation failed to identify any risk factor except consumption of milk from a single donor, whose milk was subsequently found to be contaminated with S kottbus. Collection of human milk from properly instructed donors screened for microbiological pathogens, refrigeration of this milk at 1 to 5 degrees C after collection, and controlled distribution by a milk bank should minimize the few hazards associated with its consumption.


Selective renal artery embolization. Treatment of acute renovascular hypertension. A critically ill patient with severe renovascular hypertension following surgical repair of an aortic dissection was treated by percutaneous selective embolization of the ischemic kidney. Correction of the hypertension and subsequent complete recovery of the patient resulted.


Unproved cancer remedies. A survey of use in pediatric outpatients. Sixty-nine patients or parents of patients were interviewed during a five-week period. Each interviewee was given a questionnaire listing commonly recommended unproved drugs, diets, and miscellaneous treatments, and was instructed to respond to each remedy as follows: Have you tried it? Have you considered trying it? Has it been recommended by someone else? Six patients (8.7%) had tried at least one unproved remedy, four (5.8%) considered trying some other remedy, and recommendations to seek other remedies had been made to 17 patients (24.6%). Laetrile and assistance from faith healers were the remedies named most frequently.


Evaluation of amikacin sulfate (Amikin). A new aminoglycoside antibiotic. Amikacin sulfate, the first semisynthetic aminoglycoside antibiotic introduced in this country, is resistant to the bacterial enzymes that specifically inactivate kanamycin sulfate, gentamicin sulfate, and tobramycin sulfate. This agent is potentially effective, therefore, against many serious infections caused by Gram-negative organisms resistant to other aminoglycosides. It appears to be similar to gentamicin in its in vitro spectrum, in clinical applications, and in the incidence and severity of adverse reactions reported. Like the other drugs in this class, amikacin can cause renal and otic toxic reactions.


Changing distribution of primary cancers in the large bowel. Analysis of the changing distribution of origin site of 1,990 colorectal cancers observed at a large midwestern hospital shows a statistically significant trend of a decreasing percentage of distal (rectum, P=.0192) and an increasing percentage of proximal (cecum, P=.0015) large-bowel lesions during a period of at least 30 years. Mortality data for 11,635 colorectal cancers in the state of Kansas for this period confirm this trend (P less than .0001). The respective decrease and increase may well be the result of more than one factor. Results of digital examination of the rectum and sigmoidoscopy are less likely to diagnose large-bowel cancer as they did 30 years ago. Stool screening for occult blood, barium enema roentgenographic examination, and colonoscopy become more important diagnostic tools in light of this trend.


X-linked mental deficiency megalotestes syndrome. Members of two kindreds had mental deficiency and megalotestes. The familial occurrence suggests an X-linked recessive trait or autosomal-dominant trait with male sex limitation. The increased testicular size was apparently due to excess fluid content.


Brain death. I. A status report of medical and ethical considerations. Use of neurologic criteria to pronounce death, although accepted by many, has caused controversy among physicians, lawyers, legislators, philosophers, and theologians. The present work attempts to resolve this by accomplishing four objectives. (1) It summarizes scientific information that establishes the ability to determine the state of brain death with certainty on the basis of presently available clinical and laboratory criteria. (2) It shows that the concept of brain death is in accord with secular philosophy and the three major Western religions. (3) It documents the need for legislative recognition that death may be pronounced on the basis of neurologic criteria. (4) It reviews the present status of judicial and statutory law relating to the determination of death in the United States.


Medical malpractice and negligence. Sociodemographic characteristics of claimants and nonclaimants. We compared a sample of 200 patients who filed a claim of malpractice or negligence against a large urban teaching hospital and its physicians, with a randomly drawn sample of 549 patients who had never filed a claim against the hospital. The two groups were compared on distributions by race, religion, occupation, age, and sex. In proportion to their representation in the control group, whites filed significantly more claims than nonwhites (P less than .001), Jewish people filed more claims than Protestants, and blue-collar workers brought fewer claims than white-collar or retired/unemployed workers. Claimants were significantly older than nonclaimants (P less than .05). Women filed a statistically nonsignificant greater number of claims than men did (P greater than .20).


Combination chemotherapy with doxorubicin and lomustine. Treatment of refractory Hodgkin's disease. Ten patients with advanced Hodgkin's disease refractory to combination therapy with nitrogen mustard, vincristine sulfate, procarbazine, and prednisone (MOPP) were treated with a combination of doxorubicin hydrochloride and lomustine. Toxicity was acceptable. Five patients (50%)attained complete remission (median duration, 15 months). Three patients attained a partial remission (median duration, four months). Survival ranged from three to more than 40 months, and five patients are still alive. One patient remains disease-free after a course of radiation therapy to a site of localized nodal relapse. The doxorubicin-lomustine regimen has induced meaningful remissions in a patient population with very refractory disease.


Allopurinol-associated hand and foot deformities in chronic tophaceous gout. Telescoped digits of the hands and feet developed in a 69-year-old male with severe chronic tophaceous gout during allopurinol treatment. Extensive osseous tophi, resorbed rapidly during therapy with this xanthine oxidase inhibitor and not replaced by new bone matrix, were responsible for the deformity. Several hypotheses are advanced to explain the failure of bone erosions to heal.


Withdrawal of antihypertensive therapy. Hypertensive crisis in renovascular hypertension. Hypertensive crises were reported in three patients with hypertension associated with underlying renovascular occlusive disease during reduction of antihypertensive therapy. In each case, rebound hypertension was observed during clonidine hydrochloride withdrawal. Therapy with propranolol hydrochloride and diuretics had also been discontinued in two of the three patients. This and other reports of rebound hypertension during clonidine withdrawal are contrasted with the absence of reports of this syndrome in the setting of cessation of beta-adrenergic blockade therapy. This suggests that the discontinuation of clonidine therapy was primarily responsible for the hypertensive crises herein described. It is further concluded that rebound hypertension may follow gradual as well as abrupt reduction of clonidine dosage, and that patients with renovascular hypertension may be at greatest risk.


Corynebacterium sepsis in oncology patients. Predisposing factors, diagnosis, and treatment. Bacteremia due to a newly described species of Corynebacterium was identified in 12 patients during a two-year period. Infection occurred after a long period of hospitalization, extended granulocytopenia, and treatment with several antibiotics. Breaks in the mucocutaneous surfaces were the origin of infection in eight patients. All patients had evidence of colonization reported by cultures before infection. The invading organism caused death in three patients. Vancomycin hydrochloride was the antibiotic of choice. Corynebacterium is increasingly recognized as a primary cause of morbidity and mortality of patients with tumors.


Changing values for the normal thyroid radioactive iodine uptake test. The normal range for thyroid radioactive iodine (RAI) uptake values in the Minneapolis area has shifted twice in the past 20 years. The mean 24-hour thyroid RAI uptake value in 29 normal subjects was 20.5% +/- 6.1% (SD) in 1975, whereas only four years previously it was found to be 11.5% +/- 4.4% (SD) in 51 normal subjects. In a previously published study, the mean thyroid RAI uptake value in normal subjects in this area was 25% +/- 8% (SD) in 1957. The iodine content of commercially baked white bread currently available in this area was found to average only 26 microgram per single slice of bread; the change in the mean 24-hour thyroid RAI uptake value that we observed between 1971 and 1975 is most likely due to a marked reduction in this source of dietary iodine.


Megavitamins for minimal brain dysfunction. A potentially dangerous therapy. Vitamin A intoxication as a consequence of megavitamin therapy for minimal brain dysfunction occurred in a 4-year-old boy. An early clue to diagnosis was provided by an abnormal bone scan.


Removal of phenytoin by hemodialysis in uremic patients. The removal of phenytoin by hemodialysis was determined in seven uremic patients. Four patients were receiving phenytoin sodium for therapeutic purposes; three received one dose each intravenously to quantitate its disposition in uremia. The drug was measured in whole blood, plasma, saliva, and dialysate. Only 2% to 4% of the intravenous dose was recovered in the dialysate. Phenytoin clearance by dialysis was 7 to 14 ml/min; plasma clearance was 53 to 133 ml/min. Since hemodialysis contributes little toward shortening to 11-to-18-hour half-life of phenytoin in the uremic patients, no supplemental dose is necessary for uremic patients undergoing hemodialysis.


[Early ERG-signs of retrolental fibroplasia (author's transl)]. Examinations of retinograms of premature infants by the authors showed a time lag, changes in the wave form and reduction of the bioelectric activity of the retina (which shows itself very early) in association with the first signs of retrolental fibroplasia. In their experience the ERG becomes normal when the fibroplasia stabilizes itself early or when the retinal changes regress. In conclusion it must be stressed that with progression of the fibroplasia and retinal changes the biological activity of the retina also suffers.


An evaluation of the American Medical Association's Physician masterfile as a data source--one state's experience. An evaluation of the American Medical Association's (AMA) Physician Masterfile is presented here on a state level. Both completeness and reliability of the AMA data were assessed for physicians licensed and living in Washington State. Comparison of the AMA data with state -LICENsure data indicated excellent agreement, with only a small proportion of license physicians "missing" from the AMA Masterfile. Their absence was due largely to differences in the manner in which the two systems updated their files. The reliability of the AMA data was checked by comparing it with similar, independently gathered survey data on birth date, birthplace, medical school, type of practice, specialty, board certifications, and employer. In general, despite some minor deficiencies, the AMA data were shown to be highly reliable.


[Carbohydrate absorption and malabsorption (author's transl)]. Starch is digested intraluminally by alpha-amylase to maltose, maltotriose, and alpha-limit dextrins. These products, as well as the disaccharides sucrose and lactose, undergo enzymatic hydrolysis to monosaccharides at the brush border surface. The monosaccharides enter the absorbing cell by specific transport mechanisms ("carriers"). Primary carbohydrate (CH) intolerance is characterized by the congenital or acquired absence of individual brush border enzymes or of monosaccharide "carriers" without morphologic abnormalities of the intestinal villus: lactose, sucrose and trehalose intolerance and glucose-galactose malabsorption (brush border diseases). Secondary CH intolerance arises when surface digestion and absorption are reduced due to structural changes of the intestinal mucosa: e.g., decrease or absence of villi with sprue and reduction of the absorbing surface with intestinal resection. Watery diarrhea is the lead symptom. Many drugs delay or interfere with CH absorption. This action may be viewed either as an unwanted side effect or as a welcome therapeutic principle.


Effect of methotrexate sorbed on modified 2-hydroxyethylmethacrylate carriers in mice of C3H strain with a solid Gardner lymphosarcoma. A aminohexylderivative of 2-hydroxyethylmethacrylpolymer has been prepared in the form of a microporous sponge, and Methotrexate (MTX) has been bound to this carrier by chemical sorption. Implantation of the carrier with sorbed MTX resulted in a decrease of tumor weight, while an implantation of the carrier alone or an i.p. injection of an identical dose of MTX had no effect on tumor growth. Tumor regression was found to be greater than after a repeated injection of MTX in a fourfold dose directly into the tumor.


[Intracranial mycotic aneurysm--report of a case (author's transl)]. A case of intracranial mycotic aneurysm has been reported. The case was a 26-year-old female and was admitted to our hospital on November 11, 1975. She was semicomatous and showed right hemiplegia. On auscultation systolic murmur radiating from the mitral area to the left axilla was found. Left carotid angiogram showed a saccular aneurysm 5 mm in diameter, arising from peripheral portion of the percentral cerebral artery and accompanied by intracerebral hematoma. Emergency craniotomy was performed. A thin subdural hematoma, coated with pus, was found and microabcesses were seen to be scattered in the nearby subarachnoid space. After aneurysmectomy and removal of intracranial hematoma, the patient improved without complications. On histological examination of the aneurysmal wall, moderate degree of neutrophilic infiltration was found. It was especially marked around the vasa vasorum. Heretofore only eight cases of intracranial mycotic aneurysm have been reported in the domestic literature.


Changes in pituitary hormones serum levels in bromocryptine-treated parkinsonian patients. In the course of a clinical trial with 2alpha-bromoergocryptin in Parkinson's disease, the serum levels of several pituitary hormones have been studied in the assumption that the drug active on nigro-striatal dopaminergic system might also interfere with hypothalamus-protuberantial neurotransmission, and have effects on the function of the pituitary. No changes in serum levels of FSH, LH, STH and TSH were detected for every dose of the drug employed. Only prolactin serum levels diminished since the beginning of the treatment, the decrease being significant (p less than 0.05 and p less than 0.01). This effect on prolactin does not change in the dose range considered. Clinical improvement was observed for doses of drugs above 15 mg/day, whereas the effect on prolactin secretion occurred with the dose of 7.5 mg/day.


Critical evaluation of the role of immunization as an etiological factor of infantile spasms. One hundred and ten cases of infantile spasms with detailed information about immunization available were selected as the masterial to evaluate the significance of immunization as an etiological factor of infantile spasms. In 80% of the cases, immunization could not be considered to have any relation with causation of infantile spasms, because 44 cases (40%) never had innoculations as yet, and other 44 cases (40%) had been immunized by some vaccines over one month before or after the onset of the disease. The remaining 22 cases, in whom immunization had been performed within one month before the onset of the disease, constituted the candidates for further study. The age of onset of the disease of the candidate group ranged from 3 to 9 months of age with peak incidence at 4 to 5 months old, exactly identical with that of patients with infantile spasms in general. The kind of vaccines concerned included DPT triple vaccines in 15 cases, smallpox vaccine in 4, antipolio live vaccine in 1, anti-Japanese encephalitis vaccine in 2. Causal relationship of immunization with infantile spasms in each patient was evaluated on the basis of the following three apsects: 1. Any other causal factors except immunization should be absent. 2. Psychomotor development before onset of the disease should be normal. 3. Interval from immunization to onset of the disease should be lied: a) Within 48 hours, in the case of pertussis vaccine, b) within 18 days, in the case of smallpox vaccine or anti-Japanese encephalitis vaccine or antipolio vaccine. Only five cases (4.8% of the total) were able to classify into the compatible group which should fulfill all the above three criteria. The small figure may easily be explicable on the assumption that the natural onset of spasm is chronologically superposed by chance over immunizations which have to be done within the first year of life.


Isoelectric focusing pattern of acid hydrolases in cultured fibroblasts, leucocytes and cell-free amniotic fluid. The activities of 9 acid hydrolases were determined in cell-free amniotic fluid, leucocytes and cultured fibroblasts using fluorogenic substrates. The specific activities of beta-glucosidase, alpha-fucosidase, beta-hexosaminidase, and arylsulphatase A and B were found to be in the same range in cell-free  amniotic fluid and in leucocyties. The isoenzyme pattern of these 5 hydrolases as well as that of acid phosphatase and alpha-mannosidase showed some similarities in all three specimens studied; the pattern of alpha- and beta-galactosidase obtained by isoelectric focusing was different in the 2 types of cells studied and in the cell-free amniotic fluid.


Perinatal hypoxia and bioelectric brain maturation of the newborn infant. Bioelectric brain maturation of twenty infants who had suffered acute perinatal hypoxia (patients) was compared with that of twenty healthy newborns (controls). None of the patients had suffered any other pre- or perinatal complications that could have influenced the bioelectric brain maturation. All infants (postmenstrual age: 40--42 weeks) were subjected to a polygraphic recording. The patients were examined after the acute phase of their disease; all were in good clinical condition at the time of recording. Statistic evaluation revealed significantly retarded bioelectric brain maturation in the patient group. Furthermore, a more immature EEG pattern was found to correspond to greater extent of oxygen deprivation. The study shows: determination of bioelectric brain maturation can be used to obtain information about suffered hypoxia and extent of oxygen deprivation.


Acquired aphasia in childhood with seizure disorder: a heterogeneous syndrome. The authors report six children with acquired aphasia of unknown etiology. The clinical picture was clearly different from that seen in the usual childhood aphasias and resemble other cases initially reported as "syndrome of acquired aphasia with convulsive disorder". All had associated paroxysmal EEG abnormalities, and 5 have had clinical seizures. The language disorder has improved or remained stationary and no other neurological signs have developed. Our review of the literature and the study of our personal cases show no uniform clinical picture in these children. Three different clinical patterns seem to emerge. The first group show rapid onset and recovery of aphasia, frequent fluctuations in the severity of the language deficit typical of so-called epileptic aphasia. These children appear to have a better prognosis. The second group show worsening of the aphasic deficit after repeated seizures or episodes of aphasia. In the third group progressive deficit in language comprehension (auditory agnosia) with a variable degree of recovery and rare or no clinical seizures. The possible significance of the EEG abnormalities has been discussed and the importance of the aphasia on general behavior and the problems of differential diagnosis have been stressed.


The unusual features of traumatic neurogenic muscular atrophy in the infant: an anatomic study. A biopsy from the deltoid muscle of an 8-week old girl who had sustained a bilateral traumatic Erb's brachial plexus paresis at birth revealed the neurogenic atrophy to be different from that of adult muscle in that small, round fibers, similar to those observed in Werdnig-Hoffmann disease, were found. Detailed histochemistry of the fibers is submitted. On electron microscopy, there was focal degeneration of sarcomeres; a loss of myofibrils and myofilaments accompanied by increased autophagocytosis and increased amounts of glycogen; occasionally, preferential drop out of thick myofilaments and a peculiar displacement and deformation of the T-system, triads. In spite of the fact that the injury was sustained at one well defined point of time, the degree to which the muscle fibers were affected was quite variable from area to area. It is proposed that denervation in infantile muscle results in typical small rounded fibers and that this process, so different from that of adult neurogenic atrophy, is age-dependent.


An effective dose schedule for phenytoin treatment of status epilepticus in infancy and childhood. Fifteen infants and children were treated with phenytoin for status epilepticus. They received doses 31.5 mg/kg (18--46) in the first 24 hours, 18.5 mg/kg (10--28) on the second day and 11 mg/kg (7.7--15.4) on the third day controlled by frequent serum level determinations. After reaching the upper therapeutic range (8--25 microgram/ml) within 24 hours these serum concentrations were maintained over the next days. Twelve of fifteen--including five newborns and infants below four months of age--were thus successfully treated; the remaining three in whom phenytoin had no effect, no other anticonvulsant drug or a combination of several other drugs were successful. A dose schedule based upon serial serum concentration measurements is given. It enables an efficient phenytoin treatment of status epilepticus or equivalent convulsive states in infancy and childhood.