Multifocal pontine lesions in cancer patients treated with chemotherapy and CNS radiotherapy. Multifocal pontine lesions were found at postmortem examination in four patients with various types of malignancy. The patients had undergone extensive evaluation and treatment with multiple chemotherapy regimens as well as radiotherapy to the central nervous system. The histologic character and striking anatomic distribution of the pontine lesions are described and their possible pathogenesis discussed.


[Behavior of blood amylase and plasma deoxyribonuclease I in dogs subjected to intra-operative cholangiography with the use of B 10610]. An experimental study was conducted on the use of a new iodate-molecule, B 10610, synthesized in the Bracco research Laboratory, for intra-operative cholangiographic diagnostics. For the purpose of evaluating the possible rise and the extent of any pancreatic damage in animals subjected to intra-operative radiological exploration of the biliary ducts with the use of the said substance, the blood levels of amylase and plasmatic 1st deoxyribonuclease were assayed after various time intervals, such tests being particularly specific in the humoral diagnostics of both acute and chronic pancreatic diseases. On the basis of the tests made, it is concluded that the introduction of this new dye does not cause irreversible lesions of the pancreas, but only purely functional and transient alterations.


Disappearing abdominal mass: a case report. The remarkable parallel of the clinical course and scintiscans of an abdominal lymphoma in a 52-year-old man are reported.


Cutaneous manifestations of thyroid disease. Of all the endocrinopathies that may have cutaneous findings, thyroid disease is probably the one most likely to be seen by the practicing physician since the skin readily reflects the functional capacity of the thyroid gland. Cutaneous findings may be the only clue to otherwise silent thyroid disease. Skin changes may precede other clinical and laboratory evidence of thyroid malfunction by months or years. Thus, the skin not only aids in the diagnosis of thyroid dysfunction, but also helps the physician select those high-risk patients in whom thyroid abnormalities may later develop.


Regional task force aligns health groups against rising costs. The hospitals, health care associations, HSA, and Blue Cross of Northwest Ohio have formed a task force through which they have conducted successful joint cost containment projects. Some of these projects include a voluntary "cap" on price increases, promotion of hospital cost containment committees, sharing of cost containment ideas for inhospital implementation, educating the public about its role in health care cost control, and communicating with political and business leaders about cost control.


The first fully designated HSAs begin a long, exacting job. Four of the first fully designated Health Systems Agencies (HSAs), located in Buffalo, NY. Cincinnati, Indianapolis, and Rochester, NY, are tackling a variety of health care delivery problems with a wide range of possible solutions. Relationships with providers, the nature of the areas involved, political considerations, and history are all playing a part in shaping the identities of these new agencies.


High-pressure liquid chromatography of the mycotoxins, rubratoxins A and B, and its application to the analysis of urine and plasma for rubratoxin B. The rubratoxins are toxic metabolites produced by Penicillium rubrum and P. purpurogenum on food and feedstuffs. Rubratoxin B is hepatotoxic, mutagenic and teratogenic. Rubratoxins A and B were resolved as sharp peaks in the order A-B by reversed-phase high-pressure liquid chromatography on a small-particle (10 micrometer) column in 3 min by an acetonitrile-water-ethyl acetate elution solvent (11:9.9:3), with detection by ultraviolet absorbance at 254 nm. The relationship between peak height and quantity injected was linear over a range of 0.25-5 microgram for rubratoxin A and 0.05-5 microgram for rubratoxin B. Retention time and peak height and peak area were highly reproducible for both toxins. Detection was very sensitive, allowing detection of 3-5 ng rubratoxin B, and 15-20 ng rubratoxin A. Quantitative recovery of rubratoxin B from spiked urine samples was obtained over a range of 5-40 microgram/ml, with maximum recovery from urine samples adjusted to pH 2 before extraction. Good recovery of rubratoxin B was also obtained from spiked plasma samples subjected to treatment with 3 N hydrochloric acid followed by extraction with ethyl acetate.


Isolation of nontoxinogenic mutants of Vibrio cholerae in a colorimetric assay for cholera toxin using the S49 mouse lymphosarcoma cell line. A mouse lymphosarcoma (S49) cell line that is growth-inhibited by agents that elevate intracellular concentrations of adenosine 3':5'-cyclic phosphate was used in a sensitive and convenient colorimetric assay for cholera toxin. S49 cells suspended in Dulbecco's modified Eagle's minimal essential medium containing 10(-5)--10(-6) M RO 20-1724, an analogue of 4-(3,4-demethoxybenzyl)-2-imidazolidinone and a phosphodiesterase inhibitor, were growth-inhibited by subnanogram concentrations of cholera toxin. Effects of toxin were detected by the absence of a yellow pH change (phenol red indicator) which normally accompanies the production of acid metabolites by lymphoma cells. An assay using S49 cells grown in microtiter plates, which is capable of detecting 10 pg of cholera toxin or 0.01 units of cholera antitoxin, was used in screening for nontoxinogenic mutants of Vibrio cholerae strain 569B. The properties of two mutants of the Tox--phenotype, which lacked biologically and immunologically detectable toxin products, are described.


Pulmonary surface-active materials in the Chediak-Higashi syndrome. Beige mice express the Chediak-Higashi syndrome. Large inclusions, identified as abnormal lysosomes, are found in many cells. The inclusions in type II alveolar epithelial cells are enlarged lamellar bodies and they are associated with an increase in total lung surface-active material and phospholipid. Comparison of recovery of phospholipid in surface-active materials from beige and black (normal) mice indicates that in the beige mice there is an increase in total phospholipid and disaturated phosphatidylcholines in whole lung and in surface-active materials in residual lung after lavage. Hosphatidycholine and phosphatidylglycerol are increased as percentages of total lung phospholipid. Calculated alveolar surface coverage of surface-active materials isolated from residual beige lungs is greater than three times that of normal lungs. Surface-active materials recovered from beige mice are qualitatively similar in phospholipid composition and in surface activity to materials recovered from normal mice. The quantity of surface-active material phospholipid recovered in the lavage of beige mouse lungs was normal. The basis for the abnormal accumulation of lamellar body lipids is not known.


Complications following intraspinal injections of steroids. Report of two cases. Intrapinal steroids have been recommended for the treatment of sciatica and various other conditions. The procedure is controversial; moreover, evidence suggests that the steroid hormones can be delivered to the site of inflammation more easily by systemic administration. Serious complications that have arisen from the procedure are reviewed. The courses of two women who received intraspinal steroids for the treatment of sciatica and who developed severe meningitis as a consequence are reported. It is suggested that the value of intraspinal steroids in the treatment of disc-related sciatica is unproven and if they are used, one must be alert to the complications.


Cerebral mycotic aneurysm of fungal origin. Case report. A young man who had a long history of sinusitis developed subarachnoid hemorrhage and died. Autopsy showed a mycotic aneurysm of fungal origin at the junction of the right posterior cerebral and internal carotid arteries. Four of five reported cases of fungal aneurysm were due to Aspergillus infection.


Sulfisoxazole-induced thrombocytopenic purpura. Immunologic mechanism as cause. During treatment of brucellosis with sulfisoxazole, tetracycline, and streptomycin sulfate, severe thrombocytopenic purpura developed in a young farmer. Verification for an immune mechanism was provided by clinical challenge with a small dose of sulfisoxazole that caused recurrence of thrombocytopenia and by serologic laboratory test results that detected a serum factor causing platelet agglutination requiring the presence of sulfisoxazole. The original antigenic stimulation was considered to come from drinking cows' milk contaminated with sulfonamide drugs. Cross-reactivity with some other sulfonamide drugs was demonstrated.


Neurologic complications of bacterial endocarditis. (1) Neurologic complications remain a significant problem in bacterial endocarditis. Of 218 patients with endocarditis, 84 (39%) had a neurologic complication and 58% of these 84 patients died. In contrast, the mortality rate was only 20% among those endocarditis patients without neurologic complications. (2) Of the neurologic complications, cerebral embolism is the most frequent and important. An embolic stroke occurred in 37 (17%) of our patients, with 30 of these patients dying. Emboli are important not only in terms of the direct morbidity and mortality they cause via cerebral infarction, but also because of their role in the causation of mycotic aneurysms, brain abscesses, and abnormal CSF formulae. (3) Cerebral emboli are particularly common in patients with mitral valve infection, and in patients with infection due to virulent organisms, particularly S. aureus and enteric gram-negative bacilli. (4) Mycotic aneurysms occur more frequently in the course of acute endocarditis rather than late in the course of subacute disease. Management of angiographically demonstrated mycotic aneurysms is dependent upon the presence or absence of hemorrhage, the anatomic location of the aneurysm, and the clinical course of the patient. Healing of mycotic aneurysms can occur during the course of effective antimicrobial therapy, thus obviating the need for neurosurgical intervention in all such patients. (5) Macroscopic brain abscess is a rare complication of bacterial endocarditis. Miliary microscopic abscesses are more common than larger abscesses, particularly in patients with acute disease and miliary infection in other organs of the body. (6) Focal seizures occur most commonly in endocarditis patients with acute embolic disease; generalized seizures are of diverse etiologies, with metabolic factors being most important. Penicillin neurotoxicity should be considered in patients with impaired renal function who are receiving high dose penicillin. (7) With the exception of hemorrhagic complications, lumbar puncture results tend to reflect the nature of the infecting organism rather than the nature of the neurologic complication. Endocarditis due to virulent organisms such as S. aureus is usually associated with a purulent CSF formula while nonvirulent organisms, such as viridans streptococci, susually have aseptic or normal CSF formulae.


Computed tomography in syringomyelia and the associated Arnold-Chiari type I malformation. A total of 20 patients with an Arnold-Chiari Type I malformation, i.e. without skeletal abnormality and associated with a syringomyelic syndrome, were studied using the EMI Whole Body Scanner CT5000. Two groups were considered: (i) a retrospective series of 12 patients without intrathecal water soluble contrast media and (ii) a prospective series of eight patients after the introduction of intrathecal Metrizamide. In the first group tonsillar herniation could not be conclusively identified on CT and cord visualisation was possible in only two cases. In the second group, tonsillar herniation and cord expansion were consistently demonstrated. Cord cavitation has also been detected. In both groups it was possible to assess the size and position of the ventricular system. The results of this study indicate that evaluation of the upper cervical cord cerebellar tonsillar herniation, may be achieved, but only following opacification of the CSF. The precise extent of cerebellar tonsillar herniation may be difficult to evaluate. The reasons for these findings are discussed.


Diabetes and Graves disease complicating pregnancy. We report here six pregnancies in 5 women with juvenile diabetes and Graves disease. The diabetes was managed in a standard fashion. The Graves disease was managed with propylthiouracil when required. The course of neither the diabetes nor Graves disease was different than expected. When established guidelines for therapy are followed the two have no interaction with one another. One infant was mildly hypothyroid. None developed neonatal Graves disease. Four of the infants had hyperbilirubinemia.


[Clinical conditions and prognosis of retinal detachment in retolental fibroplasia]. In this report two groups of infants with retrolental fibroplasia and retinal detachment are described according to the Tasman classification. In our case report the retinal detachment developed in a 9-year-old girl. The following diagnosis was given when the retina was in the process of detaching: cicatricial retrolental fibroplasia (Owens II-III) with excessive myopia. After episcleral buckling procedure (polyviol, Custodis method) the retina reattached. Follow-up examinations are important because when prompt diagnosis of retinal detachment is made, the involved eye can often be salvaged by surgery.


Altered metabolism of phospholipids in the lung of rats with peritonitis. Pulmonary alterations after shock and sepsis, described clinically as shock lung or adult respiratory distress syndrome, are of great importance in intensive care. Pathogenetically an alteration of the surfactant system of the lung is often discussed. Since phospholipids are constituents of lung surfactants, phospholipid metabolism is investigated in experimental peritonitis in rats in our laboratory. 15 hours after inducing a peritonitis, the lung incorporates more oleic acid than that in animals of the reference group. 33 hours after inducing peritonitis, the capacity of the lung to incorporate choline and fatty acids is markedly reduced, histologically the lungs represent morphological equivalents of the so-called shock lung at this time. Therefore we conclude, that an alteration of phospholipid metabolism with a diminished and/or altered synthesis of lung surfactant plays, at least in part, an important role in the pathogenesis of respiratory distress in sepsis and peritonitis.


Effect of serum albumin on dynamic force-area curve of dipalmitoyl lecithin. In line with previous findings at 25 degrees C, solutions of serum albumin in the subphase stabilized the surface activity of DPL spread films at 25 degrees C as well as 37 degrees C. In contrast, films adsorbed from mixtures of DPL and albumin exhibitied a marked inhibitory action of the albumin on DPL activity. The inhibitory effect increased with the relative protein concentration but, with albumin/DPL ratios smaller than 2, the DPL activity was regained gradually with cycling. With larger albumin/DPE negative effect of albumin was counteracted by higher temperatures (37 degrees C vs 25 degress C) and modest cholesterol concentrations; with greater cholesterol concentrations the known inhibitory effect of cholesterol prevailed. The inhibitory effect of albumin was potentiated by humidity; saturation of the atmosphere with water vapor at 37 degrees C abolished the DPL character of DPL-RSA mixtures and prevented its return (zero surface tension) upon reversal of the atmosphere from saturated water vapor to dry air. The data are important in the interpretation of the surface activity of pulmonary washings and other pulmonary extracts.


Fallopian tube isthmic mucus and ovum transport. The oviduct isthmus is capable of transporting spermatozoa and ova in opposite directions. A column of tenacious mucus that occupies the lumen of the rabbit oviduct isthmus during estrus may permit sperm transport. After ovulation the mucus disappears, with subsequent efforescence of cilia, which probably assist transport of ova to the uterus.


Metabolism of lecithin and phosphatidylglycerol in surfactant fraction of the lung. The metabolisms of lecithin and phosphatidylglycerol in the surfactant and residual fractions of rat lung were compared using the in vitro system where tissue slices and radioactive precursors such as [14C]palmitic acid, [14C]palmitoyl lysolecithin and [14C]stearoly lysolecithin were inculbated. The incorporation of precursors into the residual lecithin proceeded linearly during the incubation time, while the time curve on the incorporation into the surfactant lecithin exhibited a lag period before the incorporation increased significantly. A similar tendency was also observed in the incorporation into phosphatidylglycerol. These findings suggested a precursor-product relationship between the corresponding lipids in both the fractions. The turnover time of lecithin was approx. 340-370 min and that of phosphatidylglycerol was 118 min in the intracellular surfactant fraction. The turnover rates of lecithin and phosphatidlyglycerol were approx. 0.6 and 2 nmoles/g of wet tissue, respectively. The transfer of lecithin from the residual fraction to the surfactant fraction was hardly influenced by the difference of fatty acid moiety at the 2-position of 1-palmitoly-lysolecithin. However, the turnover time of 1-palmitoyl lecithin (360 min) was distinctly shorter than that of 1-stearoly species (730 min). The turnover time of the saturated lecithin was also shown to be 328 min. On the other hand, polyenoic species showed the shorter turnover time; 182 min for the tetraenoic species.


[Change in the antiradical activity of surfactant lipids during the development of nonspecific inflammatory processes in rabbit bronchopulmonary tissue]. Content of total lipids, phospholipids and cholesterol was estimated in surface-active fraction isolated from rabbit lungs. The surface activity and antiradical properties were decreased in the fraction simultaneously with a decrease in phospholipid contents in the course of development of inflammatory process in bronchopulmonary tissue. These data suggested that the antiradical activity, which is essential for protection of the surface-active fraction against free radical peroxidation, was mainly due to the phospholipid component.


[Our experience of the Vest-Margulis test in the differential diagnosis of mechanical and paralytic ileus (author's transl)]. In order to evaluate the Vest-Margulis test in the differential diagnosis between mechanical and paralytic ileus a retrospective study was undertaken on 51 such tests performed before and after operation. Transit of gastrografin (Sodium amidotrizoate) through the caecum 4 hours after ingestion was controlled through roentgenograms. The diagnostic value of a positive test in pure paralytic ileus can be confirmed. Indeed 23 positive cases proved to have paralytic rather than mechanical ileus. On the contrary a negative test has no diagnostic value. Twenty-eight patients in which the contrast medium had not reached the caecum within 4 hours had either form of intestinal obstruction. The attention is drawn on the interesting therapeutic action of gastrografin in patients with a paralytic ileus and the simplicity of the investigation.


Correlative study of radioreceptor assay and radioimmunoassay of serum growth hormone in children. II: Primary, genetic and intra-uterine growth retardation. Growth hormone (GH) was measured by radioreceptorassay (RRA) and radioimmunoassay (RIA) in the sera of 24 children with idiopathic primary growth retardation (PGR), 15 with genetic short stature (GSS) and 11 with intra-uterine growth retardation (IUGR), and compared to results obtained in normal children. The average RRA/RIA ratio was close to normal in PGR (1.02 +/- 0.05) and in IUGR (1.06 +/- 0.07), and slightly though not significantly lower in GSS (0.86 +/- 0.06). Some variability in RRA/RIA ratio was found in individual patients of each group, and some sera gave a non-parallel displacement of the tracer when compared to the standard curve. But no genetic difference of RRA-assayable GH was found between the three groups studied and normal children.


Serum gonadotrophins in rats after catration or heat treatment of the testes. In rats spermatogenesis was disturbed by heat treatment of the testes. This resulted in increases of both LH and FSH. The increased gonadotrophin levels could be suppressed with testosterone. For suppression of FSH to levels of control animals more testosterone was needed than for LH. The increase of gonadotrophins after castration could be suppressed with testosterone released evenly from silastic capsules. For this suppression low serum levels of testosterone relative to testosterone levels in intact control animals were sufficient. This may indicate that testosterone episodically secreted has a lesser suppressive action on gonadotrophin secretion than a constant presence of this hormone. The suppressive action of testosterone on serum gonadotrophin levels after castration was potentiated by 1,4,6-androstatriene-3,17-dione, a steroid which inhibits strongly the enzymatic transformation of testosterone into oestradiol.


Increased vasopressin excretion in patients with hypothyroidism. Twenty-four h urinary vasopressin excretion was measured by bioassay in 15 patients with untreated hypothyroidism and compared with plasma sodium concentration. Four patients had raised excretion of an antidiuretic substance and in 3 of these patients excretion was reduced after thyroid replacement therapy. The criteria applied supported the view that the antidiuretic substance was arginine vasopressin. Plasma sodium concentration was normal in all these 4 patients. A further 4 patients had hyponatraemia without raised arginine vasopressin excretion. The results suggest that: (1) excess arginine vasopressin secretion is not the cause of the hyponatraemia of hypothyroidism and (2) an increased secretion of arginine vasopressin does occur in some cases of normonatraemic hypothyroidism, the cause requiring further elucidation.


The stability of standards for radioimmunoassay of human TSH: research standard A and the international reference preparation initially 68/38. The stability of the International Reference Preparation of human TSH for immunoassay (previously distributed in ampoules coded 68/38) and of Research Standard A for HTSH has been examined by radioimmunoassay of accelerated degradation samples (stored as the dry ampouled preparations). Potency estimates on degradation samples suggest a high order of stability of immunopotency recognisable by two antisera (MRC 72/356 and Hunter 3A). For the International Reference Preparation the loss of immunopotency during storage at -20 degrees C is predicted to have been 0.56% per year.


The relative distribution of thyroxine, triiodothyronine and 3,3',5'-(reverse)-triiodothyronine in various fractions of thyroglobulin. Thyroglobulin fractions rich and poor in new thyroglobulin were separated by means of DEAE-cellulose chromatography of dog thyroid extracts and by zonal ultracentrifugation in a sucrose gradient of guinea pig thyroid extract incubated at low temperature. The distrubtion of thyroxine, triiodothyronine and 3,3',5'-(reverse)-triidothyronine in hydrolysates of the different fractions was estimated by radioimmunoassays. Following DEAE-cellulose chromatography there was a small but statistically significant increase in T4/T3 ratio in thyroglobulin fractions eluted at high ionic strength--that is fractions relatively rich in stable iodine but poor in fresh thyroglobulin. There was no differences in the T4/rT3 ratios between the different fractions. The ratios between iodothyronines were almost identical in the various thyroglobulin fractions following zonal ultracentrifugation in a sucrose gradient of cold treated guinea pig thyroid extract. These findings lend no support to the possibility that a relatively high content of triiodothyronines in freshly synthesized thyroglobulin modulates the thyroid secretion towards a preferential secretion of triiodothyronine and 3,3',5'-(reverse)-triidothyronine at the expense of the secretion of thyroxine.


HLA antigens in a family with maturity-onset type diabetes mellitus. In a family with maturity-onset type of diabetes mellitus inherited as a dominant, autosomal trait (MODY), the HLA genotypes were compared with the glucose tolerance and the plasma insulin response to oral glucose. In the members with impaired glucose tolerance, the plasma insulin response was of the insulino-tardic type, while those with normal or borderline glucose tolerance had a normal plasma insulin response. HLA tissue typing for A, B, C and D series antigens carried out in 19 of the members showed no association between specific HLA antigens and imparied glucose tolerance. Moreover, when analysing the segregation of the disease and the HLA characters, several recombinants between MODY and HLA would have to be postulated if the gene(s) for this form of diabetes mellitus should be closely linked to the HLA locus.


Participation of antral somatostatin in the local regulation of gastrin release. In anaesthetized pigs gastrin release was stimulated by irrigation of the antrum with bicarbonate and by instillation of a meat extract. The concentration of gastrin and somatostatin was measured by radioimmunoassay both in the antral and peripheral venous blood. The increase in gastrin was coupled to a significant decrease in somatostatin immunoreactivity as measured in the antral venous blood both during instillation of alkali and meat extract. In peripheral blood, the differences were much less evident and not statistically significant. It is speculated that the decrease in release of antral somatostatin during alkalinization and instillation of meat extract is the primary event which is followed by a diminished inhibition of gastrin liberation. Thus, the present data support the hypothesis that antral somatostatin participates in the local regulation of gastrin release.


Adrenal cysts: hormonal contents and functional evaluation. Cortisol, corticosterone, epinephrine and norepinephrine have been identified for the first time in two adrenal cysts removed from patients without endocrine dysfunction. Total concentrations of corticosteroids and catecholamines in both capsule and fluid of these cysts were higher than in plasma of normal subjects but lower than in human adrenal tissue. The cysts contained preformed cholesterol in concentrations similar to normal adrenal parenchyma. Contrary to adrenal tissue, however, homogenates of cyst components failed to utilize [4-14C] cholesterol for steroid formation. The data presented suggest that hormones in adrenal cysts probably arise by passive diffusion from the surrounding gland and that the endocrine status of patients bearing adrenal cysts is determined by the adjacent non-cystic tissue.


Follicle growth in the immature rat ovary. In ovaries of immature rats the following parameters were estimated from autoradiographs prepared after pulse labelling with tritiated thymidine: 1) The time it takes follicles to grow from one stage of development to another. This could be derived from the total number of granulosa cells in these stages and from their doubling times. The doubling time of granulosa cells was determined from their labelling index and the duration of their DNA-synthesis phase. 2) The number of follicles present in the ovary at different ages. 3) The number of follicles, which start on their development at different ages. It was found, that more follicles start to grow in 8 and 16 days old rats (2.0/h) than in 28 days old ones (1.0/h). Moreover, the follicles grow somewhat faster earlier in life than later. The development from a follicle with one layer of granulosa cells to one with several layers and antrum formation takes about 15 days in the first half of the period of immaturity while it takes about 17 days as the animal approaches maturity.


The effects of LH, adrenaline and noradrenaline on testicular blood flow and plasma testosterone concentrations in anaesthetized rats. The acute effects of a 20 min constant rate intra-arterial infusion of LH and catecholamines on testicular blood flow and plasma testosterone concentrations were examined in sodium pentobarbitone anaesthetized rats. Ovine LH (2.5 microgram/min) elicited a 6-fold increase in testosterone concentration and a significant decrease of testicular vascular resistance. Noradrenaline and adrenaline (0.4 microgram/min) caused significant depressions in the plasma testosterone levels. The catecholamines induced no absolute changes in testicular blood flow but noradrenaline caused an increase in testicular vascular resistance. It was concluded that the catecholamine induced reductions in testosterone concentrations were not due to a vascular effect on the testis.


1,25-dihydroxycholecalciferol in hypophosphataemic osteomalacia presenting in adults. The effects of exogenous 1,25-dihydroxycholecalciferol (1,25(OH)2D3) in two adults with late-onset hypophosphataemic osteomalacia were studied. In the presence of elevated 25-hydroxyvitamin D levels 1,25OH)2D3 improved intestinal 47Ca absorption and increased urinary calcium, phosphate and hydroxyproline excretion. Hypophosphataemia, parathyroid hormone and bone mineralization were not significantly affected. The rise of the 1,25-dihyroxyvitamin D concentrations was dose dependent. The results indicate htat the impared renal phosphate conservation--the primary defect in this disorder--is not corrected by exogneous 1,25-dihydroxycholecalciferol.


Retrolental fibroplasia. Cases seen at the Helsinki University Eye Hospital 1956-1974. In the period 1956-1974, 31 new cases of retrolental fibroplasia (RLF) were diagnosed at the Helsinki University Eye Hospital. All were alive in 1974. 90% weighed less than 1500 g at birth and the gestational age of less than 30 weeks at birth was present in 85%. All patients had required supplementary oxygen during the first weeks of life. 84% of the eyes had visual acuity of finger counting 1 m or less and when classified according to the corrected visual acuity in the better eye, 71% of the patients were practically blind according to the classification by Rintelen. 81% of the eyes showed one of the cicatricial stages of RLF, III to V, and 45% showed the grade V of the disease. 11% of the eyes showed corneal opacities, 44% a flat or absent anterior chamber, 11% had intraocular pressure of greater than or equal to 30 mmHg and 21% showed lenticular opacities. When the period of the observation was surveyed, it was found that during the latter half of the observation period, twice as many new cases of RLF were born. At a rough estimate it was calculated that in 1956-1974 at least 50 new cases of RLF developed in Finland.


Ocular hypertension. II. A carbonic anhydrase inhibitor test for early detection of glaucoma. The intraocular pressure before and three h after oral administration of a carbonic anhydrase inhibitor was measured in one normotensive, one hypertensive as well as two glaucoma groups. The ratio between the outflow pressure after and before this treatment was estimated. The percentage outflow pressure was found to be about 50% in the normotensive group and in the two glaucoma groups, but in the hypertensive group 68%. This carbonic anhydrase inhibitor test (CAI-test) seems to give additional information which can improve the possibility of differentiating between high normative pressure and early glaucoma prior to glaucomatous lesions.


A study on the postulated transoptic regulation of the intraocular pressure. The possibility that fibers regulating the intraocular pressure originate in the hypothalamus and course in the optic nerve, has been investigated in albino rabbits with different techniques. By means of horseradish perixodase tracing-technique, oculohypothalamic but no hypothalamoocular connections were observed. The water-loading effect on the intraocular pressure was studied after unilateral optic nerve transection. The transection was performed in three experimental groups in the following way: Intracranial transection of one optic nerve, retrobulbar transection of one optic nerve and sham operation on the other side, retrobulbar transection of one optic nerve without sham operation on the other side. In contrast to previous reports, we found no significant side difference in intraocular pressure after water-loading in any of these groups.


On the interfibrillar matrix of the pseudo-exfoliation material. Lenses with pseudo-exfoliation (PE) were suspended in a 10% solution of ferritin. In order to retain ferritin at the surface of the PE material during the preparation for the subsequent transmission electron microscopy, some of the lenses were coated with a thin layer of gelatin before the application of the ferritin solution. It was found that ferritin particles to a certain extent penetrated into the PE material. But the concentration of ferritin was much higher in the gelatin coating than in the PE material. The concentration changed stepwise at the interface between the gelatin and the PE material. The ferritin particles in the PE material were mainly found adjacent to the PE fibrils, and there was a certain tendency towards a linear arrangement of the particles. In some specimens, in which thin filaments were found in the interfibrillar space, the ferritin was found mainly along these filaments. The results are interpreted in light of earlier works in which other tracers have been applied. The marked lower concentration of ferritin in the PE material than in the gelatin coating, and the stepwise fall in concentration at the interface between the two materials, seem to confirm the presence of an interfibrillar matrix of the PE material.


Calibration of the Goldmann perimeter and accessories used in specific quantitative perimetry. With known radiometric data of the components of the projection perimeter and its accessories it is possible to perform spectral sensitivity measurements which are essential for the performance of quantitative colour perimetry. The authors describes modifications made the Goldmann perimeter for the performance of such measurements. The calibration data of the perimeter and accessories are given. A good fit between the CIE scotopic spectral sensitivity curve (V' lambda) and our experimental results for a dark adapted eye serves as a control of the calibration.


Pituitary adenoma and visual function. The prognostic value of clinical, ophthalmological and neuroradiologic findings in 51 patients subjected to operation. The series studied included 51 patients subjected to operation for pituitary adenoma. The visual status was analysed both pre- and postoperatively. The pre- and postoperative parameters were compared with clinical information, ophthalmological and neuroradiological findings with a view to an evaluation of their prognostic value. In 36 patients with chromophobe adenoma, visual field defects were present in 92% before the operation; visual function improved in 62% and returned to normal in 24%. Among 15 patients with eosinophil or mixed adenoma, only two (13%) had visual field defects pre-operatively. In those patients where operation was followed by a distinct visual improvement, the pre-operative ophthalmological findings were as follows: visual acuity greater than 6/24, normal optic discs, visual field defects up to two quadrants, and pneumoencephalographic findings suggestive of only a small suprasellar tumour.


Effect of tranexamic acid on choroidal melanoma. Four cases of malignant choroidal melanoma have been treated with the antifibrinolytic agent tranexamic acid (Cyklocapron). One patient treated for six months showed no progression in tumor growth. Three eyes have been enucleated, and the histological examination revealed that the tumours were surrounded by fibrin. No side-effects of the treatment were observed.


Photic release of radioactivity from rabbit retina preloaded with [3H]GABA. The in vitro release of radioactivity by light from rabbit retina was studied after intravitreal injection of [3H]GABA (gamma-aminobutyric acid). The site of uptake of [3H]GABA into the retina after intravitreal injection was checked by autoradiography and was localized at 2 h after the injection mainly in glia but at 4 h in amacrine cells and some ganglion cells. If the retina loaded with [3H]GABA was stimulated by light flashes the efflux of radioactivity increased significantly. Chromatographic analysis of the superfusate demonstrated that [3H]GABA was released by light stimulation. However, the efflux was not elicited by constant light, and was abolished in a medium containing 20 mM Mg++ and 0.2 mM++. When the metabolism of GABA was inhibited by amino-oxyacetic acid, light flashes no longer increased the efflux of radioactivity significantly. No light-evoked release of radioactivity could be demonstrated from glia. Pentobarbitone inhibited the spontaneous efflux and prior anaesthetization with pentobarbitone abolished the light-evoked release. These results support the view that GABA is a retinal neurotransmitter in the rabbit.


Accumulation of 8-methoxypsoralen in the rat retina. The distribution of 3H-8-methoxypsoralen (3H-8-MOP) has been examined by autoradiography in albino and pigmented rat eyes. Very high concentrations were seen in the pigmented layer of the retina, ciliary body and iris in pigmented rats. Cornea concentrations in both rat strains were about twice that of blood, and lower concentrations were seen in the lens.


Functional evaluation in Harada's disease. A case report. A 21-year-old woman suffering from Harada's disease was carefully evaluated during a three year follow-up study. In the acute stage of the disease the electroretinographic changes were found to parallel the clinical course. The functional parameters indicate that the retinal involvement is localized in the layers which generate the electroretinogram. Some attempts to explain the discrepancy between the decreased positive amplitude of the electroretinogram and the normal sensory threshold findings give credence to the concept that such paradoxical behaviour can be explained by the focalized nature of the retinal involvement.


Retinal arteriolar tortuosity with retinal haemorrhage. A case report. Retinal arteriolar tortuosity with retinal haemorrhages was first described in 1958. In the present article, a case of recurring retinal haemorrhages combined with retinal arteriolar tortuosity is reported. The medical examination and laboratory tests did not reveal pathology except for a slightly increased bleeding time. There were no similar cases in the family. The cause of the haemorrhages is still unknown.


Nutrition and social correlates in iron deficiency anemia. This study was designed to ascertain some nutrition and nutrition related social factors in the environment of the child with anemia. In this study, it was found that the child with iron deficiency anemia consumed less iron per kilogram per day, drank more milk, was less likely to have been given supplemental iron, was introduced to strained foods at an older age, and had a greater number of siblings. The mother was more likely to be separated or divorced, view the child as having more feeding problems and be an inappropriate weight for age, have somewhat different expectations of his ability to perform certain tasks, and be, in general, less satisfied with the child. The family group spent less per capita on food and cared for the child in the home more of the time. A better understanding of these factors, important in the development of iron deficiency anemia, may eventually lead to amelioration of the problem.


[Anaesthesia problems in massive transfusion (author's transl)]. It is essential for adequate anaesthesia during massive transfusion to avoid further shift of the oxygen dissociation curve to the left by hyperventilating the patient, by not rewarming the cold blood and by an overenthusiastic correction of an eventually arising metabolic acidosis. The occurrence of coagulation disorders during massive transfusion has been overestimated in the past and is a poor basis for "blind" substitution. The additional use of blood microfilters and caustious attitude towards the use of crystalloid solutions e.g. Ringer lactate, are indispensable measures for counteracting impending pulmonary insufficiency. The avoidance of surfactant irritating inhalation anesthetics such as halothane or methoxyflurane seems advisable. In this context the use of adequate PEEP plays an important role. Circulatory stability is guaranteed by using ketamine or fentanyl for general anaesthesia and analgesia, and by the use of pancuronium for relaxation.


Experimental evaluation of reexpansion pulmonary edema. Reexpansion pulmonary edema following pneumothorax is clinically uncommon but occasionally life threatening. This study documents the functional and anatomical abnormalities that occur when a collapsed lung is reexpanded. Right pneumothorax was created through open tube thoracostomy in 30 goats. The animals were divided into six groups by duration of pneumothorax (24, 48, or 72 hours) and technique of reexpansion (waterseal vs 10 cm H2O suction). Arterial blood gases and alveolar-arterial oxygen tension difference (A-aDO2) were analyzed before pneumothorax and after reexpansion. Each lung was reexpanded for 2 hours, chest roentgenograms were obtained, and both lungs were removed. The left lung served as the control. Both lungs were checked for surfactant activity and pulmonary extravascular water volume (PEWY). Light and electron microscopy were also performed. Anatomical and functional changes were present in the reexpanded lung after relief of pneumothorax. Both increased time of collapse and suction reexpansion tended to correlate with increased PEWV, decreased surfactant and arterial PO2, and increased A-aDO2.


Effects of guanadrel on patients with thyrotoxicosis. Eleven patients with Graves' disease were treated with guanadrel sulfate and observed for changes in neuromuscular and cardiovascular manifestations. No notable changes in pulse rate or muscle strength were detected in either these patients during a three-day pretreatment period or in five control patients with Graves' disease receiving placebo for six days. Thyroid hormone levels were not altered by seven days of guanadrel sulfate therapy (5 to 20 mg orally every six hours), and no adverse side effects were encountered. Mean supine resting pulse fell from 102 +/- 6 (mean +/- SEM) to 90 +/- 3 beats per minute (P less than .02). The patients' proximal and distal muscle strengths were initially decreased, when compared with healthy subjects, and improved substantially with guanadrel therapy. We conclude that guanadrel sulfate may be useful in the symptomatic management of patients with thyrotoxicosis.


Past and present hazards of working with infectious agents. Over 4,000 cases of laboratory-associated infection have been recorded. Some of the agents involved often in the past have been less frequently the cause of such infection in recent years, and some agents are more likely to infect those working with them than others. Pipetting, the use of a needle and syringe, and spills have been most frequently involved in accidents resulting in infection, but in the majority of cases no recognized accident occurred. In these instances, infectious aerosols, produced in various ways, are probably the most frequent causes of laboratory-associated infection. The introduction of protective devices and emphasis on safe procedures seem to be reducing the risk of accidental infection. Although work with tumor viruses and recombinant DNA research may not be as hazardous as was originally feared, continued caution and surveillance is advised.


Legionnaires' disease. Pathological and historical aspects of a 'new' disease. Autopsy tissues and protocols from 26 epidemiologically defined fatal cases of Legionnaires' disease occurring during the 1976 Philadelphia outbreak were reviewed. Consistent pathologic features were limited to the lung, where an acute pneumonia characterized by intra-alveolar exudation of neutrophils, macrophages, and fibrin was observed. An etiologic agent common to most of the victims of Legionnaires' disease was identified within the pneumonic process by application of the Dieterle silver impregnation stain. In some cases, other pulmonary histologic findings were noted, chiefly acute diffuse alveolar damage. However, the importance of acute diffuse alveolar damage is not understood.


The pathology of Legionnaires' disease. Fourteen fatal cases from the 1977 outbreak in Vermont. Fourteen fatal cases from the 1977 Vermont outbreak of Legionnaires' disease have been analyzed. Serious underlying diseases were present in all patients. The only consistent lesions were in the lungs. Bronchopneumonia was present in all cases and was confluent in most. No lobe of the lung was preferentially involved and consolidation was usually bilateral. Abscesses were evident macroscopically in only two cases. Microscopically, there was an extensive alveolar infiltrate of polymorphonuclear neutrophils and macrophages. Lysis of the inflammatory cells was frequently present and was associated with an increased number of bacteria. Coagulative necrosis of lung was present in a few cases, and the possibility of a bacterial toxin must be considered. Bacteria were well stained by the Dieterle stain and appeared Gram-negative in tissue imprints from the unfixed lung.


Differentiation between Prototheca and morphologically similar green algae in tissue. Evidence that algae are pathogens was provided by the results of electron microscopic studies of tissues from five cattle and sheep suspected of having green algal infections. Chloroplasts were demonstrated in the algae in each case. Prototheca organisms, considered by some to be achloric mutants of green algae, are causative agents of disease in man and animals and may appear morphologically similar to green algae in tissue. However, electron microscopy showed that chloroplasts were absent in these organisms. Light microscopy revealed not only similarities in size, shape, and mode of reproduction, but also a striking difference between the Prototheca organisms and green algae. Unlike Prototheca, the green algae contained abundant cytoplasmic starch granules that were strongly positive by several staining procedures; these granules, which were PAS-negative following diastase digestion, provide a means of differentiating green algae from Prototheca cells in tissue.


Myocardial involvement in Rocky Mountain spotted fever. Rocky Mountain spotted fever (RMSF), an acute febrile exanthematous illness caused by Rickettsia rickettsii and transmitted by ticks, is endemic in the southern Atlantic states. This report is based on the clinical and pathological findings of myocardial involvement in 16 children who died with severe RMSF. All 16 children had myocardial lesions to some degree, but it was not believed that these could be evaluated in terms of cardiac function and death in the face of the usual peripheral vascular collapse caused by the widespread vascular lesions throughout the body.


Human lingual tuberculosis. An ultrastructural study. According to morphological criteria, the predominant cells from human oral tuberculosis granulomas are classified as monocytes, epithelioid cells, and multinucleated giant cells. The morphology of each cell type is related to its speculated function. It is theorized that macrophages and epithelioid cells represent an in vivo line of differentiation from undifferentiated monocytes and that giant cells form from a coalescence or syncytium of macrophages. The role of these phagocytic cells and other participating inflammatory cells in granulomatous inflammation is discussed.


Fatal measles (rubeola) pneumonia in adults. Fatal measles (rubeola) pneumonia, confirmed by viral culture and electron microscopy, occurred in a previously healthy 19-year-old man. Autopsy disclosed measles pneumonia but no recognizable disease that would predispose to such an infection. However, the prolonged course of the measles infection and very low levels of serum antibodies to measles indicate that an immune deficient state existed. Nearly all other adults dying of measles pneumonia have had impairment of the immune system, typically due to a lymphatic or hematologic malignant neoplasm treated with chemotherapy. An immunodeficient state may be a precondition for death from measles pneumonia in adults. Enlargement of air spaces with fibrosis in the anterior portions of both lungs is suspected to be due to tissue necrosis and high mechanical ventilatory pressures.


Epidemic of toxic hepatitis in India of possible mycotoxic origin. An epidemic of liver disease, characterized by onset with high fever, rapidly progressive jaundice, and ascites occurred in a rural area of India. Several hundred people were affected and mortality was high. The epidemic was heralded by the appearance of similar features in the village dogs. Liver biopsy specimens from eight cases and autopsy material from one human case and two dogs were studied. Characteristic features were centrizonal scarring, hepatic venous occlusion, ductular proliferation and cholestasis, focal syncytial giant-cell tr-nsformation of hepatocytes, and pericellular fibrosis. Toxic quantities of aflatoxin B1 were found in samples of corn, the staple food grain of the people, that was obtained from the domestic food stores. The etiology of the disease could not be unequivocally established, but aflatoxins, perhaps in combination with other factors, may have been the cause.


Secretion and adenylate cyclase in thyroid nodules. Thyrotropin (TSH)- and sodium fluoride (NaF)-sensitive adenylate cyclase (AC) activity was measured in ten cases of "cold" thyroid nodules and compared with perinodular tissue. Findings were correlated with the ultrastructure of the nodular and perinodular tissue. Comparisons of the results of assay studies revealed an increase of basal and NaF- and TSH-stimulated AC activity in cold lesions. There was no dissociation of NaF- and TSH-sensitive AC. Ultrastructural findings disclosed a lack of correlation between elevated AC activity and the expected organelle profile indicative of stimulation. Since organelle modulations that are associated with increased protein synthesis were not observed in the face of increased AC activity, an unknown intracellular defect may exist in the expression of the AC-cyclic AMP (adenosine 3':5'-cyclic phosphate) system in cold thyroid nodules.


Alcoholism and alcoholic liver injury: new diagnostic and prognostic tests. Recently developed tests that measure levels of alpha-amino-n-butyric acid (AANB) and serum glutamic dehydrogenase (GDH) may improve screening for early detection of heavy drinking and liver injury, respectively. With these tests, a "three-level" approach to the problem is now possible: (1) detection of heavy drinking on the basis of a biochemical marker (such as AANB); (2) detection of liver injury (necrosis and inflammation) on the basis of serum liver tests (such as GDH); and (3) detection of alcoholics in whom cirrhosis is prone to develop by the screening of liver biopsy specimens for precirrhotic lesions (such as pericentral sclerosis).


Noncirrhotic nodulation of the liver.

Noncirrhotic nodulation of the liver. Nodular hyperplasia of the liver is characterized by small, uniformly distributed nodules that are delineated by marginal condensations of reticulin. There is no cholestasis and the liver is of normal size and shape. The cause is unknown, but it is not a precursor of cirrhosis, is not preneoplastic, and is not associated with contraceptive use. It is easily distinguished from adenoma, hamartoma, focal nodular hyperplasia, and partial nodular transformation, all of which are focal lesions. Disorder in the terminology that now exists will be minimized by suggesting a new term only when a specific cause is identified or a morphologic feature is distinct.


Reduced ratio of portal tracts to paucity of intrahepatic bile ducts. The syndrome of "paucity" of intrahepatic bile ducts is characterized by a reduction of the ratio of interlobular bile ducts to portal areas. The present unidirectional study of liver biopsy specimens in cases of so-called intrahepatic biliary atresia, controlled essentially by age-matched autopsy control, showed that there is also a reduced number of portal areas in the livers of these subjects. This fact suggests an injury to the vascular anlage associated with biliary injury.


Mucosa of the Heister valve in cholelithiasis: transmission and scanning electron microscopic study. Light, transmission, and scanning electron microscopic studies were performed on 24 gallbladders with thin walls, without inflammation, extirpated by cholecystectomy because of gallstones and on five, free from biliary diseases, obtained by autopsies. Examination of gallbladders and epithelium covering the valvula spiralis (Heister) of the ductus cysticus showed the surface structure of the epithelium covering the Heister valve to be mulberry-like and characteristically pleated, similar to the epithelial lining of the gallbladder. In cases of cholelithiasis, several denuded areas were detectable on the valves. The epithelial lining of the gallbladder was intact. As a new observation, we describe the appearance of worm-like processes on the lateral surface of detached epithelial cells, seen during the course of scanning electron microscopic study. These probably correspond to interdigitating cell junctions observed by transmission electron microscopy.


Endomyocardial fibrosis with calcification of the myocardium. A case of endomyocardial fibrosis with intramyocardial calcification was characterized by symptoms of restrictive cardiomyopathy resembling constrictive pericarditis. Pathological findings were typical of those found in classical Davies' disease, originally encountered and described in Uganda.


Glomerular lesions in congenital endocardial fibroelastosis: clinical manifestations and ultrastructural studies in two patients. Two children with congenital fibroelastosis and recurrent episodes of heart failure had overt proteinuria and hematuria; one also had a reversible nephrotic syndrome. Urinary manifestations persisted during periods of cardiac compensation. Renal biopsies revealed mesangial hyperplasia by light microscopy, identical ultrastructural lesions in the glomerular basement membrane, and deposits of fibrin in one of the biopsy specimens studied by immunofluorscence. These changes detected by electron microscopy may result in an increase in glomerular permeability independent of the renal hemodynamic disturbances associated with cardiac insufficiency. The progression of the lesions appears to be slow, although urinary manifestations may simulate an intercurrent glomerulonephritis. Pulmonary hypertension and renal venous stasis with glomerular intravascular coagulation were discussed as possible pathogenic mechanisms.


Triventricular heart with three atrioventricular valves in a conjoined twin. An infant, who was conjoined to a partially formed twin, died from congenital cardiac disease which could not be diagnosed accurately by catheterization and cineangiography. Pathologic examination showed a triventricular heart with three atrioventricular valves. One great vessel system was present, and the aorta was transposed. The findings in this infant suggest that the incorporation of cardiac anlage from an incompletely or abortively formed fetus may explain the presence of supernumerary structures in complex congenital cardiac malformations.


Cardiac index and incidence of heart failure cells. Inverse correlations were established between the percentage of iron-laden macrophages (heart-failure cells), found in the sputum of patients with various types of heart ailment, and cardiac index. Less than 2% iron-laden macrophages were seen when cardiac index was in the region of 3 liter/min/sq mm of body surface area (BSA). This fraction increased to approximately 75% when the cardiac index attained 1 liter/min/sq mm of BSA. Since there was noticeable heterogeneity of data when the cardiac index was below 3 liters/min/sq mm of BSA and above 1 liter/min/sq mm of BSA, it was concluded that a second factor was probably at play: this was the degree of activity of the reticuloendothelial system of the subjects concerned.


Sacrococcygeal teratomas in infants and children: relationship of histology and prognosis in 40 cases. Histological grading of teratomas is a useful method for evaluating patient prognosis. Although this has been repeatedly shown with ovarian teratomas, those of the sacrococcygeal area have not been scrutinized to a comparable extent. We believe that histologic grade and clinical behavior correlate closely in congenital sacrococcygeal teratomas. Correlation with clinical staging is less clear. There are some taxonomical and conceptual problems posed by the congenital nature of these tumors. The worst prognosis is dictated by the presence of yolk sac tumor areas, which was seen in seven of 40 teratomas examined. Although a neuroectodermal component is common, and was here proved to have metastasizing capacity, its inherent tendency may be toward spontaneous self-limiting differentiation. Vitelline differentiation, however, seems to imply irreversible progression and a uniformly bad prognosis.


Annulate lamellae in human malignant tumors: report of three cases. During the course of applying electron microscopy to diagnostic surgical pathological specimens, three malignant tumors (malignant melanoma, fibrous mesothelioma, lymphoblastic lymphoma) were found to contain annulate lamellae, distinctive intracytoplasmic organelles composed of membrane stacks interrupted by constrictions or pores. In one case both annuli and lamellae were present, a combination rarely described in human tissue and in animal models. In this material, the annuli of the annulate lamellae were structurally similar to nuclear pores. It is postulated that the abundant fibrils are probably related to the unusual configuration of the annulate lamellae. A morphologic relationship of the annulate lamellae to both the endoplasmic reticulum (cases 1 and 2) and the nuclear membrane (case 3) supports the theory that annulate lamellae may be related to both of these structures.


The nephrotic syndrome in massive obesity: a study by light, immunofluorescence, and electron microscopy. The morphologic features observed in the renal biopsy specimens from three patients with massive obesity complicated by the nephrotic syndrome are described. In the two patients with active disease, the majority of the glomeruli showed focal to extensive fibrin deposition both within and adjacent to capillary loops, associated with adhesions to Bowman's capsule, with a variable endocapillary proliferative response. In the patient with inactive disease, the majority of the glomeruli appeared normal. However, fibrin-like material, similar to that seen in the active phase, was infrequently found ultrastructurally in the subendothelial portion of the capillary loops. Subendothelial vacuolated material was also observed. Although intravascular coagulation was suggested in this disorder, only minor coagulation abnormalities were discovered. In two of the patients, the massive proteinuria has resolved with weight reduction.


Miconazole therapy for fungal meningitis. Eight patients with fungal meningitis (5 with the coccidioidal type, 2 with cryptococcal, and 1 with histoplasmosis) were treated with intravenous (IV) and intrathecal (IT) miconazole after previous therapy with amphotericin B proved unsuccessful. Miconazole was well tolerated with both IV and IT administration. The CSF concentration of miconazole one hour after an IV infusion of 800 mg was 0.1 to 0.3 microgram/ml. When 20 mg of miconazole was administered intrathecally via lumbar injection in patients with coccidioidal meningitis, 6.5, 2.4, 0.77, and 0.24 microgram/ml, respectively, was found in the CSF at the cisternal level at 12, 24, 48, and 72 hours, respectively. Miconazole is apparently an effective fungistatic drug of low toxicity and is a potentially useful agent in the treatment of systemic mycoses and fungal meningitis, in particular.


Undifferentiated lymphosarcoma of the orbit resembling Burkitt's lymphoma. A 3-year-old boy was admitted with an orbital apex syndrome that histologically was proven to be an undifferentiated lymphosarcoma. He subsequently developed systemic multifocal extranodal involvement and died eight months later. Clinical findings were consistent with those seen in Burkitt's lymphoma. Some, but not all, of the cytologic findings were characteristic of Burkitt's lymphoma.


Isolation and structural characterization of alkali-labile oligosaccharides from bovine milk-fat-globule membrane. Treatment of sialoglycopeptides derived from bovine milk-fat-globule membrane with alkaline borohydride released a reduced oligosaccharide fraction from which a tetrasaccharide and two trisaccharides were isolated. Periodate-oxidation studies coupled with methylation analysis and g.l.c.-mass spectrometry established their structures as: N-acetylneuraminyl-(2 leads to 3)-beta-D-galactopyranosyl-(1 leads to 3)-[N-acetylneuraminyl-(2 leads to 6)]-N-acetyl-D-galactosaminitol, N-acetylneuraminyl-(2 leads to 3)-D-glactopyranosyl-(1 leads to 3)-N-acetyl-D-galactosaminitol and beta-D-galactopyranosyl-(1 leads to 3)-[N-acteylneuraminyl-(2 leads to 6)]-N-acetyl-D-galactosaminitol respectively.


Evidence for stereospecific phospholipid-cholesterol interaction in lipid bilayers. The CH2 proton NMR linewidths of sn-3 and sn-1 dipalmitoyl phosphatidylcholine respond differently to the addition of cholesterol to the lipid vesicles. This result points to a stereospecific phospholipid-cholesterol interaction in the "hydrogen belt" region.


The displacement of albumin bound bilirubin by free fatty acids in vivo. Variations in bilirubinaemia in response to alterations of the free fatty acid level was studied in conscious and unstressed Gunn rats. When only one molecule of bilirubin is bound to albumin (without bilirubin overload), no displacement of bilirubin is observed, even if the protein binds as much as 6 molecules of free fatty acids. After overloading with exogenous unconjugated bilirubin, the second site of fixation of bilirubin on albumin is partly occupied; in this situation, a displacement is observed, but only when more than 3.5 molecules of free fatty acids are simultaneously bound to the protein. In vivo, free fatty acids do not spontaneously reach such levels as those responsable for the observed displacement of bilirubin. In the ranges of bilirubin and free fatty acids concentrations likely to be encountered clinically, free fatty acids might not represent an effective agent of displacement for bilirubin, as it is commonly thought.


Problems of venereal infections in Latin America and the Caribbean and means of fighting them. Rather than providing a comprehensive overview of the sexually transmitted disease (STD) picture in the Americas, this presentation contrasts the STD problem in Latin America and the Caribbean with the situation in both less developed and more developed regions of the world. It also points out three areas of opportunity for improving preventive and curative STD services, specifically: (1) more effective utilization of social security institutions in Latin America, (2) incorporation of STD services into primary health care programs, and (3) development of pilot projects in the smaller Caribbean territories. It is noted, in addition, that the more developed countries of the region are showing increased interest in sexually transmitted diseases. Among other things, the recruitment of a PAHO epidemiologist in venereal diseases on Jamaica--to assist in the development of a national STD program--opens up a new area for PAHO technical assistance which, if successful, may be extended elsewhere.


Common mistakes in infant feeding: survey from London borough. A survey of infant-feeding practices among 265 mothers of 12-week-old infants in a London borough showed that only 18 gave breast milk alone, 236 giving bottle feeds, and 197 solids. Serious mistakes in feed preparation were common, and only 51 mothers followed manufacturers' instructions exactly. Most mothers (239) had attended a well-baby clinic, but clinic staff gave conflicting advice on infant feeding. Health workers must pay greater attention to educating mothers on the details of infant feeding if the risks of hypernatraemia and obesity are to be reduced.


Kinetics of hydrolysis of dispersions of saturated phosphatidylcholines by Crotalus atrox phospholipase A2. Dispersions of lamellar phase dipalmitoyl phosphatidylcholine (DDPC) and dimyristoyl phosphatidylcholine (DMPC) in 0.01 M CaCl2 were subjected to hydrolysis by phospholipase A2 (EC 3.1.1.4) from Crotalus atrox venom. The reaction was followed continuously by titrating the released fatty acids. For hydrolysis of gel phase phosphatides, the steady-state initial velocities were hyperbolic functions of bulk lipid concentrations. At the 'pre-transition' temperature (34 degrees C for DPPC, 15 degrees C for DMPC), there was a large increase in the Michaelis parameter Vmax but no change in the parameter Km. A model was devised to account for these observations, in which the enzyme desorbs from the lipid surface after hydrolysis. The desorption rate constant is postulated to increase above the pretransition temperature. For hydrolysis of liquid crystalline phosphatides, the reaction consisted of a short initial burst of hydrolysis, a long 'lag' period of very slow reaction, followed by a dramatic increase in the reaction rate. Addition of 10 mol% lysolecithin or fatty acid abolished the 'lag' period. It was postulated that the enzyme adsorbs irreversibly to the surface of the liquid crystalline phase. Reaction products are postulated to stimulate desorption of enzyme from the surface. Thus, temperature-dependent changes in the rate of hydrolysis of dispersed phosphatidylcholines are attributed to changes in the rate of desorption of the enzyme from the lipid surface.


Resistance to 9-beta-D-arabinofuranosyladenine in murine tumor cells. Two lines of the 6C3HED (Gardner lymphosarcoma), 6C3HED-LeP and 6C3HED-ADL, were studied. The former is exquisitely sensitive to 9-beta-D-arabinofuranosyladenine (ara-A) and the latter is resistant. Cytological examinations and strain specificity tests indicated that they are both 6C3HED. DNA synthesis in the sensitive line was found to be more sensitive to ara-A in whole-cell incubations than it was in the resistant line. In cell-free extracts, the DNA synthesis of the sensitive line showed greater inhibition by 9-beta-D-arabinofuranosyladenine 5'-triphosphate. Lower ability to form 9-beta-D-arabinofuranosyladenine 5'-triphosphate or to allow access to the intracellular space was eliminated as an explanation for the resistance. Cells from an ara-A-resistant human leukemia were tested, and the DNA synthesis of the cells, in either whole cells or cell-free extract, was unaffected by ara-A or 9-beta-D-arabinofuranosyladenine 5'-triphosphate, respectively. This suggests that resistance has emerged by reason of change in the DNA polymerase(s) and that the finding may be important in the clinical use of ara-A.


[Presence of free amebae of the Limax type in waters of the urban center of Rennes and of Liffre. II]. We confirm the results of our preliminary study in the Rennes district (France) (January to April 1974): free-living Limax amoebae are found in all the examined waters samples (56 per 62) except for the ones directly originated from underground waters and a difference upon the moment of the year appears as for the encountered species. We have not found Naegleria species. Some of these amoebae show a satisfactory growth at high temperature and on different nutritional media, but none are able to grows in liquid axenic media.


[A new focus of urinary bilharziasis in Algeria]. In 1976, 161 new cases of urinary bilharziasis were discovered in El Harrach, which until then had been free of the disease. The authors point out the dangers of the disease spreading in view of the presence of Bulinus in Algeria outside the normal foci of bilharziasis.


[Epidemiological study of intestinal helminthiasis in the island of Tortuga (Haiti). I. Prevalence of trichocephalosis, ascaridiasis and necatoriasis studied from elimination of eggs in the stools]. An epidemiological survey is conducted by spot-checks over about 10% of the population of Tortuga Island in order to estimate the prevalence of intestinal helminthiasis in that region of the Republic of Haïti, by researching the presence of eggs in faeces. Population sample is representative of the whole of the island's population excepting the 0-4 years old group whose faeces are difficult to obtain. Faeces are examined through the Kato method, a very simple, quick and remarkably accurate procedure. Trichuriasis and ascariasis, which are transmitted in the area around the house, affect mainly children, but also adults. Women seem to be more often infested than men by Ascaris lumbricoides. Necatoriasis, the farmer's disease, hits primarily young men and elderly women who spend most time in the fields. It is observed in inland villages where people are engaged in agricultural production, with a higher incidence if they are located in a not so sloping zone.


Variola minor in Bragança Paulista County, 1956. Respiratory manifestations in cases of variola and in household contacts of cases. A respiratory complication was recorded for 62 of the 485 cases of variola minor occurring in Bragança Paulista County, Brazil, 1956. The respiratory complication preceded onset of the classical variola minor in 2 cases; lasted only the pre-eruptive phase in 38 cases; lasted only the eruptive phase in 9 cases; lasted both the pre-eruptive phases in 1 case and had an unrecorded relationship to the clinical course in 12 cases. Six of the 17 household contacts with a respiratory syndrome contemporaneous with variola in the household had previously suffered from variola.


[Epidemiology of leishmaniasis in Algeria. 7. Visceral leishmaniasis in the Grande Kabylie focus]. The authors present the results of a survey on visceral leishmaniasis in the Grande Kabylie region (Algeria). With a 2.6 human cases per 100,000 annual prevalence, and a 11.4 per cent incidence of canine leishmaniasis, the Grande Kabylie appears to be the most important focus of visceral leishmaniasis in North Africa. The endemicity ecological factors are discussed and a control program is proposed.


[Epidemiological study of intestinal helminthiasis in the island of Tortuga (Haiti). II. Evaluation of the parasite count by means of the Kato method]. Results of the numbering of T. trichiura, A. lumbricoides et N. americanus eggs found in the stool, taken from a representative sample of the population of Tortuga island, shows the importance of parasital load borne by people attacked by the parasites. Those who produce the greatest number of eggs for a gram of faeces are young children. For adults, the evolution of the parasital load follow that of the prevalence, for each Nematodes, with an increase of the average number of eggs of A. lumbricoides per gram of faeces for adults aged 30 to 44, and of the average number of N. amercanus per gram of faeces for adults aged 45 to 59. Moreover women adults show a higher number of parasites than men. Farmers from villages within the interior of the island who are more often attacked than those from the coast, also bear a parasital load which is twice as high. Victims less than 5 years old and more than 30, particularly women, whose faeces are richest in eggs, seem to present the greatest danger for the transmission of ascaridiosis and necatorosis in Toruga Island.


[Presence in France of a selvatic Xenopsylla: X. cunicularis Smit, 1957 (Siphonaptera, Pulicidae), a parasite of wild rabbits]. The authors point out, for the first time in France, a selvatic Xenopsylla: X. cunicularis Smit, 1957, parasite on the European rabbit, well-known in Morocco and Spain until today. The paleogeographical, ecological, and epidemiological interest of this parasite is laid stress on. The other fleas linked to the European rabbit are evoked, and the acclimatization of Euphoplopsyllus glacialis affinis (Baker, 1904), in France and Italy, introduced with its host Sylvilagus? floridanus is related.


[Culicidae of the French Territory of Afars and Issas. 2. The genus Culex]. During an entomological survey conducted in French Territory of Afars and Issas from November 1973 to June 1975, seven Culex species were collected: C. sitiens, C. tritaeniorhynchus, C. univittatus, C. simpsoni, C. laticinctus, C. pipiens fatigans, C. tenagius, to which we must add two other doubtfully identified species (C. ethiopicus and C. decens), and one unidentified species.


Malaria and anemia of pregnancy in an African savanna zone. Epidemiological, hematological, biological and immunological study of 2 villages of the Bamako region, Republic of Mali. An haematological, biological, parasitological and immunological study about anaemia of pregnancy was carried out in two rural village of Mali Republic, where P. flaciparum malaria is hyper-endemic. The 25 pregnant women found in the villages were compared with 23 controls. One could observe that anaemia more often normochromic and regenerative usually appears during the second trimestre of pregnancy. Only a few cases with haemaglobin levels below 8 g. % are hypochromic. Serum transferrin levels were slightly higher among pregnant. None among 31 bone marrows examined showed megaloblastic changes. Haptoglobin levels below 10 mg. % were observed in 3/4 of the pregnant women versus 1/4 in controls. Like some others, this study confirms the primary responsability of malaria haemolysis in the aetiology of anaemia of pregnancy and the interest of systematic chemoprophylaxis, at least from the third month of pregnancy. Vitamin and iron therapy is to consider therafter in hyper-endemic areas of P. falciparum malaria when nutritional problems are not predominant.


[Multiple echinococcosis. Therapeutic trials of fluoromebendazole]. The authors describe 3 cases of hydatic cysts (two diffuse echinococcosis and one surgical dissemination) which have been treated by fluoromebendazole for several months. The drugs has been well tolerated. Results seem encouraging, although the little amount of cases does not allow any definite conclusions. More works should help knowing more about the effects of this broad-spectrum anti-helminthic drug, which has, else where, proved itself very efficient against experimental echinococcosis of mice.


[Culicidae of the French Territory of Afars and Issas. I. The genus Anopheles]. During an entomological survey conducted in French Territory of Afars and Issas from November 1973 to June 1975, eight Anopheles species were collected: A. rhodesiensis, A. azaniae, A. dthali, A. macmahoni, A. gambiae, A. turkhudi, A. salbaii and A. pharoensis. One can note particularly the presence of A. gambiae which does not seem to be observed in the Territory since the beginning of the century.


[Ischemic cardiopathies in Africans in Djibouti. Study of 431 cases in 5 years]. Ischemic cardiopathies in Eastern Africans at Djibouti  are frequent: 2.9 % of the in patients and 73 % of the cardiac diseases. Male prevalence is marked. Coronary insufficiency is most often demonstrated by the usual symptomatology. Three groups of electrocardiopathic manifestations have been individualised: ischemia proving angor (288 cases), anginose syndromes revealing a myocardic infarct (81 cases), acute myocardic infarcts (62 cases). The patients come for the most part from Djibouti and belong to any social class. The part played by a food mainly constituted of complex glucids, refined sugar and lipids is pointed out. Arterial hypertension, diabetes, essential hypercholesterolemia and tobacco intoxication are the most frequent risk factors. This coronary pathology is closer the one met with in the Near East than ischemic cardiopathies observed in tropical Africa which begin to emerge.


[Cellular immunity in 18 cirrhotic African carriers of hepatitis B virus surface antigen (HBsAg)]. The cell mediated immunity has been studied by 3 different tests on a population including 32 african patients with cirrhosis; amongst those, 18 were HBs Ag carriers and 14 were Hbs Ag-. In those 2 groups, the intradermal tuberculin test and the DNCB cutaneous test showed a striking imminutary deficiency in half cases. The lymphoblastic transformation induced by PHA gave less striking results.


Malignant lymphomas and undifferentiated small cell carcinoma of the thyroid: a clinicopathological review in the light of the Kiel classification for malignant lymphomas. The paper reports a re-evaluation--based on the Kiel classification for non-Hodgkin lymphomas--of a group of cases initially diagnosed as undifferentiated small cell carcinomas or primary lymphomas of the thyroid. Twelve such cases were found among the 155 cases of primary malignant tumours of the thyroid recorded at the Institut Jules Bordet between 1955 and 1975. The review of the clinical charts and the histology showed that all the cases were in fact malignant lymphomas fitting easily into one of the groups described in the Kiel classification. These findings support the growing opinion that undifferentiated small cell carcinoma of the thyroid does not exist as a distinctive clinicopathological entity. Furthermore, the Kiel classification proved to be an excellent prognostic indicator, since all the cases classified as highly malignant were indeed fatal, whereas the surviving cases--three of which had shown tumoral extension beyond the thyroid capsule--fell into the group of low malignancy. Lastly, this study acknowledges the frequently observed association of malignant lymphoma of the thyroid with stigmata of Hashimoto's disease, and thus supports the concept that the continuous antigenic stimulation observed in the latter could trigger the development of a malignant lymphoma.


Initial tumor cell arrest in animals of defined coagulative status. Experiments were made to evaluate the potential role played by thrombogenic factors on the hematogenous arrest of circulating tumor cells in mice with demonstrable coagulopathies associated with the presence of a primary tumor, by administration of "therapeutic" doses of anticoagulants. The effects of warfarin, aspirin and heparin administration on the early arrest patterns of 125IdUrd-labelled TA3 carcinoma and Gardner lymphosarcoma cells injected intravenously into tumor-bearing mice were examined. Several hematologic parameters of carcinoma- and lymphosarcoma-bearing animals were measured prior to anticoagulation experiments and the results indicated that mice had coagulopathies similar to those found in cancer patients with disseminated intravascular coagulation syndrome, i.e., thrombocytopenia and elevated fibrinogen levels. Despite the presence of coagulation abnormalities and effective anticoagulation in recipient animals, all three agents were without effect on localization patterns of both tumor types. It was concluded that the proposed involvement of thrombogenesis in metastasis was probably not due to any role played by those clotting factors inhibited by aspirin, warfarin and heparin in early intravascular tumor cell arrest.


[Some new fleas of Chile (Siphonaptera) parasites of Ctenomys (Rod., Octodontidae)]. The authors examined 355 fleas of 9 species from Chili. These were collected from 7 species or subspecies of Ctenomys (Rod., Octodontidae). Tiamastus callens and Polygenis platensis cisandinus are new for this country; Tetrapsyllus maulinus sp. n., Plocopsylla fuegina sp. n. and Plocopsylla reigi sp. n. are described in this work.


Tricyclic aryl-substituted anticoccidial azauracils. Syntheses of tricyclic aryl-substituted 6-azauracils are described. These compounds showed anticoccidial activity when tested against Eimeria tenella and E. necatrix. Compound activity was correlated with the chemical shift of the azauracil ring proton. No correlation existed between activity and compound lipophilicity. One of the compounds, 2-(11-oxo-6,11-dihydrodibenzo[b,e]thiepin-3yl)-as-triazine-3,5(2H,4H)-dione (23), was tested extensively against E. tenella and E. brunetti both in vivo and in vitro. Compound 23 controlled mortality due to E. tenella at 62 ppm, and it afforded protection as measured by weight gain at 31 ppm. Compound 23 afforded little protection against E. brunetti. In vitro experiments with 23 showed that it exerted a coccidiostatic effect.


The science of infant nutrition and the art of infant feeding. Using the recommendations of the Committe on Nutrition of the American Academy of Pediatrics for infant formulas as a scientific base, practical guidelines for feeding infants are given. Breast feeding or the use of a prepared formula meets these recommendations while evaporated milk, fresh cow's milk, and skimmed milk, despite widespread use for many years, do not. The feeding of strained foods and infants cereals should be begun when the infant has reached the stage of development appropriate for feeding from a spoon and swallowing nonliquid foods, usually between 3 and 6 months of age. Lifelong eating patterns begin during this period. Adjusting caloric intake to needs and learning to enjoy a variety of foods are major objectives of feeding practices.


Primary lymphoma of lung.

Primary lymphoma of lung. Five cases of primary lymphocytic lymphoma of the lung are described. One patient died 14 years after diagnosis, with spread of the tumour to the opposite lung. The remaining four patients were alive and well 18 months to 25 years after diagnosis. The pathological features of these five cases are described and the nature, diagnosis, therapy, and prognosis are considered in relation to experience in the literature. The tumor is rare. It is important because of its good prognosis and diagnostic difficulty.


Juvenile rhegmatogenous retinal detachment. Between Jan 1, 1966, and June 30, 1974, 179 children, birth through 16 years of age with rhegmatogenous retinal detachments, underwent scleralbuckling procedures at Wills Eye Hospital. The detachments were associated most frequently with trauma (44%), myopia (15%), aphakia (10%), and retinopathy of prematurity (8%). Successful reattachment was achieved in 80% of the cases. Vision of 20/100 or better was present in 22% preoperatively and 58% postoperatively.


A new approach to the problem of retinal neovascularization. Tumor cells introduced into the rabbit vitreous produced a form of retinal neovascularization, but only when the tumor cells were in direct contact with the vascularized retina. This contrasted with the production of neovascularization at a distance of several millimeters in other angiogenesis models. An extract of adult rabbit vitreous was found to inhibit the growth of limbal neovascularization induced by tumors implanted in the rabbit corneal stroma. The experimental model of retrolental fibroplasia provides a bioassay to investigate further the apparent inhibitory substances in the vitreous.


Local anesthetic effect of intrathecal normal saline. The effects of intrathecally administered normal saline have been studied in patients undergoing graduated spinal anesthesia. The injection of 5 or 10 ml volumes resulted in segmental hypesthesia to pin-scratch and cold stimuli extending from the lower thoracic to the sacral dermatomes. There was also partial sympathetic block evidenced by a diminished psychogalvanic skin reflex. The sites and possible mechanisms of action of saline are discussed; its use as placebo in graduated spinal anesthesia is questioned. It is concluded that normal saline acts as a weak local anesthetic when injected intrathecally.


Surfactant lecithin fatty acid composition and its relationship to the infantile respiratory distress syndrome. In order to evaluate the role of surfactant lecithin composition in the development of the infantile respiratory distress syndrome (IRDS) we have examined lecithin fatty acid composition from gastric aspirates obtained at the time of delivery from 14 full term healthy infants, 9 control premature infants without respiratory distress, and 16 premature infants who developed IRDS. The latter had significantly reduced concentrations of palmitic acid (48.4 +/- 1.8% vs. 65.3 +/- 1.5% in fullterm and 59.5 +/- 0.8% in control premature infants, P less than 0.001). None of the infants in whom palmitic acid was more than 60% of total lecithin fatty acids developed IRDS, whereas 10 of 11 infants with values below 50% did develop this complication. Lecithin from gastric aspirate was shown to be similar in fatty acid composition to lecithins from tracheal washings and amniotic fluid. Palmitic acid concentrations in lecithins of serial tracheal washings paralleled the clinical course of eight infants with IRDS.


[Development of ixodid ticks in the northern limits of their geographic range in Amur Province]. In the northern part of the Amur district the life cycle of I. persulcatus and H. concinna lasts three, four and five years while that of D. silvarum--one year. The distribution of I. persulcatus and H. concinna further to the north is limited by an unsufficient heat for the development of eggs while for D. silvarum heat is not enough to complete its life cycle within a year.


[Importance of thyroid diseases in internal medical hospital]. Retrospective analysis of 2627 and prospective analysis of 289 inpatients (mean age: 57 years) of the Department of Internal Medicine, University of Berne, disclosed euthyroid goiter in 33.9%. 65% of the patients had urinary iodine excretion below 100 microgram per gram creatinine. Thus, iodination of salt (raised to 10 mg potassium iodide per kg in 1962) is still inadequate. 1.4% of the inpatients had hyperthyroidism. Hypothyroidism was diagnosed in 0.5% of the inpatients, which is about three times less than in comparable prospective English studies. The finding raises the possibility that cases of hypothyroidism have been frequently missed. Antibodies against thyroglobulin and/or microsomal antigen were present in 8.5% of 105 goiter patients and 4.0% of 124 patients without goiter. This is a definitely lower incidence than has been reported in comparable English populations and confirms reports from other Alpine endemic goiter areas. Among the 2916 patients of the entire study only 3 cases (0.1%) of clear-cut chronic lymphocytic (Hashimoto) thyroiditis were found.


[Unrecognized hyperthyroidism in hospital patients. Analysis of clinical symptoms compared to aged euthyroid goiter patients]. During a 14-month period hyperthyroidism has been diagnosed in 39 of 2916 inpatients of a general medical service. Graves' disease was present in only 8 cases. 21 patients had solitary autonomous nodules or multiple autonomous nodules (toxic multinodular goiter). In 10 patients the type of hyperthyroidism could not be established. The referring practitioner suspected hyperthyroidism in all 8 patients with Graves' disease, but in only 5 of the 31 remaining cases. The relative rarity of Graves' disease in inpatients reflects the fact that this form of hyperthyroidism is easily recognized by the practitioner and treated on an out-patient basis. Graves' disease patients and those with autonomous solitary or multiple nodules were of comparable age and had an identical serum free-thyroxin. Thus, neither higher age nor lower thyroxin is responsible for the atypical clinical presentation of autonomous nodules. A comparison with age- and sex-matched carriers of euthyroid goiters identified weight loss, resting pulse rate over 90 and auricular fibrillation as reliable clinical features. A thyroid function test is therefore indicated in every patient with a goiter and one of the three above clinical findings.


Platelet function in hyperbetalipoproteinemia. Individuals with familial hyperbetalipoproteinemia are at increased risk of premature atherosclerosis and thrombosis. Although there is controversy whether platelet survival is shortened or normal in this disease, several in vitro tests of platelet function are abnormal including a decreased threshold concentration for stimulation of aggregation by ADP, epinephrine and collagen and increased release of nucleotides to the same agents. These functional changes are accompanied by an increase of cholesterol to phospholipid ratio in the platelet membrane and in low density lipoprotein in individuals with type IIa hyperlipoproteinemia. Clofibrate and halofenate reverse some of the abnormalities in vitro and the former drug, when administered for 6 weeks to patients with type IIa hyperlipoproteinemia decreases platelet sensitivity to ADP and epinephrine. The platelet hypersensitivity to aggregating agents can be reproduced in vitro by increasing the cholesterol to phospholipid rather in normal platelets. These artificially hypersensitive platelets can be returned to normal by halofenate in vitro. Incorporation of cholesterol into platelet membranes increases the basal level of the membrane associated enzyme adenylate cyclase. However, the enzyme no longer responds to stimulation by prostaglandin E1, and this is associated with relative resistance of the platelet to inhibition by this pharmacologic agent. These functional alterations produced by cholesterol enrichment of platelet membranes occur is parallel with an increase in platelet membrane microviscosity suggesting that the more rigid membrane can alter the behavior of membrane associated enzymes and receptors. A correlation appears to exist between the ability of certain drugs to induce phase separation in model membranes and the potency in inhibitory platelet aggregation.


Platelet aggregation in rats in relation to hyperuricaemia induced by dietary single-cell protein and to protein deficiency. A major limitation to single-cell protein (SCP) as a human food is its high nucleic acid content, the purine moiety of which is metabolised to uric acid. Rats given a Fusarium mould as a source of SCP in diets containing oxonate, a uricase inhibitor, showed elevated plasma and kidney uric acid concentrations after 21 d, which were related to the level of dietary mould. ADP-induced and thrombin-induced platelet aggregation was greater in the hyperuricaemic rats than in controls and a progressive increase in aggregation with increasing levels of dietary mould was observed. Furthermore a time-lag, exceeding the life-span of rat platelets, was observed between the development of hyperuricaemia and the increase in aggregation. A similar time-lag was observed between the lowering of the hyperuricaemia and the reduction of platelet aggregation when oxonate was removed from the diet. If human platelets react to uric acid in the same manner as rat platelets this might explain the link that has been suggested between hyperuricaemia and ischaemic heart disease. In that event diets high in nucleic acids might be contra-indicated in people at risk from ischaemic heart disease. In rats given a low protein diet (50 g casein/kg) for 21 d ADP-induced and thrombin-induced platelet aggregation and whole blood platelet count were reduced compared with control animals receiving 200 g casein/kg diet but not in rats given 90 or 130 g casein/kg diet. A study of the time course on this effect indicated that the reduction both in aggregation tendency and in whole blood platelet count occurred after 4 d of feeding the low protein diet. These values were further reduced with time.


Platelet metal levels in normal subjects determined by atomic absorption spectrophotometry. A method has been developed for the estimation of iron, copper, zinc, calcium and magnesium in human platelets using atomic absorption spectrophotometry. Fe and Cu are either absent or present in very low concentration approaching the limit of detection: Zn, Ca and Mg are readily detectable. EDTA is preferable to ACD(A) or heparin as the anticoagulant for collection in that the platelet yield is reliable: however, slightly low results for Ca and Mg are obtained. Corrections for residual plasma and contaminating red cells are essential. Plasma and platelet metal levels in 33 normal subjects are reported together with the findings in four studies undertaken on platelets obtained from subjects with polycythemia vera.


Relationships of adenine nucleotide metabolism to platelet-collagen adhesion. Adhesion of platelets to collagen fibrils in a stirred system was inhibited by preincubation of platelets with combinations of 2-deoxy-D-glucose and oligomycin or antimycin. The inhibition of adhesion was associated with a decrease in metabolic ATP to 6% of control levels. Without metabolic inhibitors, platelets adherent to collagen fibrils were found to have catabolized approximately 57% of their metabolic ATP, and converted a major part of this to IMP. Storage pool ATP and ADP contents were also diminished in the adherent platelets. Pretreatment with imipramine resulted in 76% inhibition of the release reaction, but only 5% inhibition of adhesion. Imipramine-treated platelets that were adherent to collagen showed significant depletion of metabolic ATP, but markedly diminished conversion of ATP to IMP as compared to control adherent platelets. Inhibition of deamination of platelet AMP by coformycin or erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) did not inhibit adhesion, although platelets adherent to collagen after treatment with these agents showed depletion of metabolic ATP. These studies suggest that adhesion is an energy dependent process, occurring independently of release, and not associated with conversion of ATP to IMP. The energy dependent portions of the adhesion process are probably disc to sphere transformation and pseudopod formation, the ATP threhold requirement is relatively low, and the ATP utilized can probably be regenerated during the adhesion process via glycolysis and oxidative phosphorylation.


'Spontaneous' platelet aggregation: its characteristics and relation to aggregation by other agents. Platelet aggregation results of 117 patients were analysed. All had documented evidence of stroke, recurrent transient ischemic attacks and other neurologic symptoms, and all were hospitalized in the same Rehabilitation Center. Attention was specifically directed to the 'spontaneous' platelet aggregation (SPA) phenomenon, in terms of its characteristics and relationship to platelet count and aggregation induced by 3 physiologic agents. About 50% of the samples showed SPA but not all of them were hyperaggregable by other aggregating agents. A great deal of variation was found in the aggregation time, slope and extent of SPA. These variations do not always appear to relate to platelet count, or the responsiveness of platelets to other aggregating agents.


Specific inhibition of platelet agglutination and aggregation by aromatic amidino compounds. A series of aromatic amidino compounds were investigated for their inhibitory effect on platelet agglutination and platelet aggregation. Agglutination of fresh or fixed platelets was produced by bovine plasma or by human plasma in combination with ristocetin, while aggregation of fresh platelets was induced by ADP, thrombin or collagen. Highly effective inhibitors were found for both types of platelet clumping, but there was no parralelism between the inhibitory activities in the two test system. 5-(5-amidino-2-benzimidazolyl)-2-(4-hydroxybenzene)benzimidazole suppressed agglutination exclusively. Pentamidine, on the other hand, strongly blocked the aggregation reaction, but did not interfere with agglutination, even at high concentrations. Compounds which inhibited aggregation also prevented the liberation of serotonin from the platelets.


Immobilization of plasminogen activator, urokinase, on nylon. Urokinase (UK), a fibrinolytic enzyme activator purified from human material was immobilized on nylon using different procedures. One was a modified method of immobilization of antigen or antibody initially carried out by Edelman and others in 1971 (Procedure I). The other was our newly devised method (Procedure II) (Sugitachi et al. 1976). Major specificities of the immobilized UK are as follows: 1. The UK revealed properties of a plasminogen activator and the optimum pH of the immobilized UK was between 7.2 and 7.4, these values being in good parallel with that of soluble UK. The immobilized UK maintained a stable fibrinolytic activity after long-term preservation and heat-treatment. 2. As the fibrinolytic activity of immobilized UK was found to be inhibited by the antiplasmin in human plasma, an antiplasmin inhibitor was immobilized on the nylon together with the UK. The antiplasmin activity was to some extent prevented using this procedure. 3. Nylon tubes immobilized with UK and antiplasmin inhibitor were used for thrombotic coagulation studies carried out according to the method of Chandler. Thrombus formation time (TFT) of UK-immobilized tubes was 30 min, while that of the non-treated tubes was no longer than 10 min.


The effect of plasma fibrinogen levels on measures of fibrinolytic activity. It has been claimed that lysis time methods may be inappropriate as measures of fibrinolytic activity on the grounds that they are largely determined by plasma fibrinogen levels. The dilute blood clot lysis time (DBCLT) has therefore been measured in 103 subjects; fibrinolytic activity (expressed as 100/DBCLT) has been compared with the fibrin plate area (FPA) lysed by the euglobulin fraction, the latter method being, of course, virtually independent of plasma fibrinogen. Plasma fibrinogen levels have also been measured; they ranged from 167 to 416 mg%. Results have been analysed by the technique of multiple regression. The incorporation of plasma fibrinogen levels in the regression equation relating 100/DBCLT to FPA does not result in a significant increase in the proportion of the variance in 100/DBCLT that can be explained. It is concluded that there is no evidence that DBCLT is influenced by plasma fibrinogen levels within the physiological range.