Bacterial breakdown of benomyl. II. Mixed cultures.

Experiments with mixed bacterial cultures grown in liquid media which contained the benzimidazole fungicide benomyl, with or without Na-lactate, as source of carbon provided circumstantial evidence for cleavage of the benzimidazole heterocyclic ring. Yet, neither 2-aminobenzimidazole (2-AB) nor benzimidazole, as sole source of carbon, supported any bacterial growth. "Total 14C-balance analysis" experiments conclusively showed production of 14CO2 from [2-14C]methyl benzimidazol-2-yl carbamate (MBC), and thus cleavage of the benzimidazole nucleus: bioassays, however, showed that the actual rate of benomyl and MBC breakdown was only small, the parent compound benomyl being still recovered in substantial quantities after up to 80 days of incubation. Therefore, cleavage of the benzimidazole ring is probably a matter of cometabolism, n-butylamine which originates from the butylcarbamoyl side chain serving as the proper source of carbon. Besides radiolabelled 2-AB and CO2, an unknown metabolite was isolated which showed characteristics of a 2-AB-nucleotide. Probably, 2-AB was incorporated into bacterial DNA, which upon lysis of the bacterial cells gave rise to the nucleotide in question. Therefore, 2-AB might exert its inhibitory action by interfering with the normal functioning of DNA.


The occurrence and taxonomic value of PBS X-like defective phages in the genus Bacillus.

72 strains of 24 Bacillus species were induced with mitomycin C. The lysates were examined for the presence of defective phages resembling PBS X in morphology. All strains tested of B. amyloliquefaciens. B, licheniformis, B. pumilus and B. subtilis contained such phages. Five morphological types of defective, PBS X-like phage could be distinguished, differing in their tail lengths and in the number of cross-striations on the tail. The quaternary structure of the tail, the molecular weight of the main tail protein and the antigenic properties of the phages were identical. The killing ranges of the defective phages have been determined and their possible use in taxonomy discussed.


Relation between the faecal concentration of various potentially pathogenic microorganisms and infections in individuals (mice) with severely decreased resistance to infection.

Lethally irradiated conventional mice were killed at daily intervals after irradiation. A high correlation was found between the occurrence of bacterial overgrowth in the digestive tract and invasion into the regional lymph nodes the spleen and the blood. By oral contamination of mice with quite high doses of either an exogenous or an endogenous biotype of an Enterobacteriaceae species at day 4 after irradiation, it was attempted to induced such condition of intestinal overgrowth. In all animals such an abnormal colonization of the contaminant was indeed achieved in this way and the mice died from an infection caused by the biotype used for the contamination. The interval between contamination and death was different when different biotypes were used for contamination and occurred sooner after irradiation when an endogenous biotype was used for (re)contamination. It is concluded that oral contamination with exogenous as well as with endogenous potentially pathogenic bacteria during a period of severely decreased resistance to infections must be avoided. The colonization resistance of the digestive tract of these animals should be maintained as high as possible.


Candida sonckii sp. nov.

A new yeast species with basidiomycetous affinities is described as Candida sonckii Hopsu-Havu et al. It differs from C. fujisanensis and C. maris by growing with KNO3 as nitrogen source, from C. vanderwaltii by its lower mol% G + C, lower maximum temperature for growth and failure to grow on D-arabinose and citrate.


A new genus: Sporopachydermia.

In two species of the yeast genus Cryptococcus ascospores have been found. A genus is described to accommodate the two species, because the spore wall is extraordinarily thick and its ultrastructure differs from that found in all other yeast genera. The spores are easily liberated from the ascus at maturation. The name Sporopachydermia is proposed for the genus and the names S. lactativora and S. cereana are proposed for the species.


Ultrastructure of the ascospores of the new yeast genus Sporopachydermia Rodrigues de Miranda.

Development of the ascospores of Sporopachydermia lactativora and S. cereana was studied in ultrathin sections. The spores have a very thick wall consisting of a thin dark outer layer and a double light inner layer the outer part of which is very wide and often irregular. During germination, this part disappears, the outer dark layer breaks up and the inner part of the light layer remains around the protoplast during development to a vegetative cell.


Neuropathology of fatal varicella.

Pathological examination of the CNS was carried out in the cases of 32 children who died of varicella. Twelve had acute encephalopathy with fatty degeneration of liver. Eighteen children had underlying disease; two thirds of them had received steroids. Two children had neonatal varicella. Only two brains of the total number of children had demonstrable inclusion bodies, and these were unique cases. One infant brain had focal encephalitis in an area of necrosis around a ventricular catheter, and the other, a case of neonatal varicella, had multiple disseminated necrotic foci. These observations suggest that true encephalitis is a rare event in fatal varicella.


Endocardial fibroelastosis found on transvascular endomyocardial biospsy in children.

Left ventricular endocardium obtained by transvascular endomyocardial biopsy from nine infants and children with various congestive cardiomyopathies showed thickening in five, with hyperplasia of endocardial cells and increase in elastic and collagen fibers (endocardial fibroelastosis). Based on the morphologic findings, we suggest a chronologic sequence of hyperplasia of smooth muscle (SM) cells followed by transformation and translocation. The sequence appears to be (1) proliferation of dark SM cells with many surface vesicles, many myofilaments, and fusiform densities; (2) possible proliferation of light SM cells containing fewer surface vesicles and fewer myofilaments than the dark SM cells; (3) transformation of SM cells to leiomyoid cells that resemble both SM cells and fibroblasts; and (4) transformation to typical fibroblasts. The cells producing the increased elastin and collagen are believed to be the SM cells and the leiomyoid cells.


Perimedial fibroplasia of the renal artery: a light and electron microscopic study.

Six cases of perimedial fibroplasia of the renal artery were studied by light and electron microscopy. The perimedial fibrous area was mainly composed of irregularly proliferated collagen fibers and scattered smooth muscle cells. We could not identify the usual fibroblast in any portion of the abnormal media despite examination with the electron microscope. There were many thin-walled, newly formed vessels sprouting from the adventitia in the fibrous area. We observed the complication of dissecting aneurysms in two cases. We also discussed the possible role of the smooth muscle cells in the fibrous area of perimedial fibroplasia.


Atypical vascular proliferation in benign soft tissue tumors.

Atypical endothelial proliferation and continuing growth of small vessels were found to be the main features of two benign soft tissue tumors. Lack of history of injury and insidious onset suggested neoplasia, but the morphology was that of a reactive rather than neoplastic process. Ultrastructural study of the relationship of the endothelial cells to one another and to perithelial cells was helpful in making this distinction. The process appeared to have begun in an organizing thrombus or hematoma, in one case in relation to an occluded artery, and in the other in an abnormally vascular area of skeletal muscle. It is known that endothelial hyperplasia can occur in reparative reaction of this type. The prominent muscular development of small vessels in the cases reported here suggests that abnormal flow or intraluminal pressure could have been a stimulant to atypical growth.


The relationship of biochemical and histometric determinants of uremic bone.

Simultaneous histometric and biochemical analyses were performed on 16 bone biopsy specimens taken from eight patients with chronic renal failure. The bone calcium and phosphorus contents are inversely related to the relative volume of microscopically measured, nonmineralized bone matrix (osteoid) and to the percentage of trabecular surface covered by this tissue. The magnesium content of uremic bone is positively correlated with the quantity of osteoid. Skeletal calcium and phosphorus contents correlate inversely with the osteoblast population, and phosphorus relates directly to the volume of trabecular bone. Bone hydroxyproline content does not correlate significantly with any histometric variable. As one may now infer biochemical conclusions about the uremic skeleton from morphological observations, these data may facilitate interpretation of nondecalcified histological sections of bone.


Degeneration of the intervertebral disks and spondylosis in aging sand rats.

Aging sand rats (Psammomys obesus) kept on a standard laboratory diet supplemented by salt bush--their natural source of food--were examined for changes of the vertebral column. From about 6 months of age on, degeneration of the intervertebral disks was noted. The changes increased in severity with increasing age, and from 1 1/2 years of age on, massive multiple disk herniations were seen. Associated with these lesions were spondylosis of "intervertebral" as well as hyperostotic type, and osteoarthrosis of the apophyseal joint. The sand rat seems to be an excellent model for the study of the pathogenesis of spinal diseases associated with the aging process.


Infantile fibrosarcoma: report of cases.

Infantile "fibrosarcoma" occurred in a newborn male infant and in a 2-month-old female infant. In both cases, the tumors grew rapidly and showed the histological features of malignancy. However, they were treated successfully with simple resections. Review of the literature shows that infantile fibrosarcoma has a relatively favorable prognosis. Simple local excision is the initial treatment of choice for lesions occurring in infants and children less than 5 years old.


Primary meningeal mesenchymal chondrosarcoma.

A primary meningeal mesenchymal chondrosarcoma initially resembled an angioblastic meningioma because the typical chondroid islands were not demonstrable. Cartilage was seen only in an intracerebral recurrence and in subsequent extracranial metastases. Ultrastructural examination of noncartilaginous regions of the tumor demonstrated mesenchymal cells with features suggestive of cartilaginous differentiation, viz, scalloped cell membranes, sac-like distension of abundant rough endoplasmic reticulum, and a matrix containing fibrillary and finely granular material. Features of meningeal or pericytic cells were not seen.


Pulmonary calcification: scanning electron microscopic and X-ray energy-dispersive analysis.

Nine patients with chronic renal failure or neoplastic involvement of bone showed metastatic calcification in their lungs at autopsy. On light microscopy, the calcifications were shaped like threads, beads, elongated rods, or tablets, whereas on scanning electron microscopy they were either amorphous or irregularly crystalline. Energy-dispersive x-ray analysis of the calcification showed the presence of calcium and phosphorus in all cases and traces of magnesium, sulfur, and other elements in some. The calcium-to-phosphorus ratio, obtained using Hall's formula, varied from 1.406 to 2.145, which is quite similar to that of normal bone and dystrophic calcification. Calcium phosphates, therefore, seem to be the principal mineral salts in all three types of calcification. In certain diagnostic and investigative problems, a correlative analysis of structure and chemistry at the ultrastructural level, both qualitatively and quantitatively in terms of their element ratios, can be done on tissue routinely prepared for light microscopy.


Mucogenic cells of congenital adenomatoid malformation of lung.

Findings of a histochemical and ultrastructural study of the mucogenic cells of congenital adenomatoid malformation of lung indicate that these cells share features with goblet cells of bronchial or intestinal origin and do not indicate a similarity to normal gastric epithelium or glands, as has been previously suggested.


Legionnaires' disease: ultrastructural appearance of the agent in a lung biopsy specimen.

During the Legionnaires' disease epidemic that occurred in Philadelphia in 1976, we performed a transbronchial lung biopsy on a patient who suffered from Legionnaires' disease that was confirmed by serology. The biopsy was performed in an attempt to detect a causal agent for the patient's pneumonia at a time when the cause of the epidemic was a mystery. We detected pleomorphic microbial structures that were both intracellular and extracellular in location. By electron microscopy, they ranged in size from 350 nm to 2.5 mu. Some displayed cell walls and fine cytoplasmic granules that resembled ribosomes. Our findings illustrate the appearance of the Legionnaires' disease agent in acutely infected, antibiotic-treated human lung obtained from biopsy specimens.


Scanning electron microscopic study of follicular lymphoma.

Nine cases of follicular lymphoma were studied by scanning electron microscopy. The morphological findings by this method emphasizes the heterogeneity of the cellular composition of the follicles, even in the cases not labelled as mixed type, and the degree to which the anatomy of a normal secondary follicle is mimicked. Large nonlymphoid cells, presumably dendritic, are present in the follicles. There are no differences in the surface features of the follicular and interfollicular lymphoid cells.


Cerebral metastasis in Hodgkin's disease.

Hematogenous metastases of Hodgkin's disease to the brain in the absence of contiguous bone and/or meningeal involvement are extremely rare. The clinicopathologic features of six published cases are reviewed and an additional patient with multifocal parenchymal metastases reported on.


Influence of physical factors on morphological features of mononuclear cells in human blood. Lymphocyte-monocyte interconversion.

The recovery of monocytes, following density sedimentation of human peripheral blood, was previously observed to be greater than 100%. An explanation was sought in the present study. No evidence for erroneous estimation of these cells was found. Rather, the data suggest that lymphocytes may take on the appearance of monocytes as a consequence of cytocentrifugation. This phenomenon does not appear to be influenced by the osmolality or viscosity of the suspending medium, nor by the process of sedimentation. Moreover, polymorphonuclear leukocytes do not seem to participate in the process of transformation, which may depend instead on the transfer of cytoplasm from monocytes to lymphocytes.


Color preservation of gross specimens for teaching and medical illustration.

We routinely employ cold Jores' fixative to improve color preservation of gross autopsy specimens for conferences and teaching and to facilitate development of a photographic teaching collection of gross pathological specimens. The fixed specimens also permit light microscopic examination. Additionally, we have found that color restoration of previously fixed gross specimens is possible with McCormick's fixative.


Disseminated histiocytosis and intestinal malakoplakia. Occurrence due to Mycobacterium intracellulare infection.

Disseminated histiocytic proliferation and intestinal malakoplakia due to Mycobacterium intracellulare occurred in a 2-year-old white boy. Light and electron microscopic examination of autopsy material disclosed disseminated histiocytosis and malakoplakia of the intestine with numerous intracellular acid-fast bacilli. The isolated organism produced a similar disseminated histiocytosis and finally death when injected into experimental animals. A review of the literature showed only 12 previously reported cases of disseminated histiocytosis due to M intracellulare infection. We were unable to find a previous report of malakoplakia due to nontuberculous mycobacterial infection.


Papillary endothelial proliferation in cystic lymphangiomas. A lymphatic vessel counterpart of Masson's vegetant intravascular hemangioendothelioma.

Papillary endothelial proliferation similar to that of Masson's "vegetant intravascular hemangioendothelioma" of the blood vessels was observed in two cases of cystic lymphangiomas. They are believed to be the lymphatic vessel counterpart of Masson's entity. Twenty-five other specimens of various lymphangiomas examined (18 patients) did not contain the same change. As was emphasized previously for Masson's lesions, lymphangiomas containing similar endothelial changes should also not be mistaken for malignant vascular tumors, since in these two cases, no unusual clinical course supervened. Although the histogenesis of the lesion as proposed by Masson has been disputed, both primary and secondary endothelial proliferation seem to remain possible in the formation of these lesions.


Endocardial valvuloid in right ventricular outflow tract.

A valvuloid was found in the outflow tract of the right ventricle. Its presence was associated with a hump-shaped area in the right ventricle, below an insufficient pulmonary valve. To the best of our knowledge, this is the first such report in the English literature.


Structural alterations of the liver induced by N,N'-diacetylbenzidine. A new model of cirrhosis.

Little is known about hepatic structural alterations induced by administration of the aromatic amine, N,N'-diacetylbenzidine. Therefore, we injected adult rats with this chemical at a dose of approximately 1 g/kg of body weight. Light and electron microscopy of liver specimens revealed hepatocellular degeneration and prominent changes in bile canaliculi, including dilation, disappearance of microvilli, and an apparent loss of structural integrity of the cell membrane. These findings were seen in the peripheral part of the hepatic lobules. Cirrhotic changes eventually developed. We concluded that N,N'-diacetylbenzidine injected intraperitoneally is capable of inflicting structural damage to the liver in rats.


Effects of paraquat aerosol on mouse lung.

BALB/c mice were exposed to an aerosol of paraquat dichloride solution and were killed six hours, 1, 3, 7, 14 and 28 days later. Initial necrosis and sloughing of the bronchiolar and alveolar epithelia with intact endothelium were followed by type 2 pneumocyte hyperplasia, fibroblast proliferation, and increased synthesis of collagen. These results indicate that inhaled paraquat solution produces pulmonary fibrosis that is morphologically similar to the lesions produced by systemic administration.


Pulmonary structural changes following microembolism and blood transfusion. A light and electron microscopic study.

Blood stored under standard blood band conditions develops microaggregates of platelets and leukocytes. Dog lungs were studied by light and electron microscopy at intervals from 48 hours to six days following exchange transfusions of sublethal volumes of such microaggregate-rich blood through either standard or Dacron wool (Swank) transfusion filters. After transfusion through standard filters, the pulmonary microvasculature was extensively occluded by microemboli. Swelling of capillary endothelial cells, interstitial and alveolar edema, and hypoxic changes in types I and II alveolar epithelial cells were noted. Changes then progressively resolved. These detrimental changes were prevented when microaggregates were removed by Dacron wool (Swank) filters. Mechanical occlusion of the pulmonary vasculature probably plays a minor role in initiating the structural changes observed. Release of lysosomes from disintegrating microaggregates is believed to be the significant factor initiating a chain of events leading to progressive pulmonary damage.


Neuropathologic features of idiopathic respiratory distress syndrome.

Evaluation of the neuropathologic alterations occurring in 170 consecutive autopsies in premature infants dying of the idiopathic respiratory distress syndrome (IRDS) reveals two large groups, hemorrhagic and nonhemorrhagic. Hemorrhages occurred in all possible sites and formed the single largest group. Such hemorrhages appeared to be related to the early death of many premature infants. The nonhemorrhagic group was quite variable, with the largest category of associated lesions being periventricular leukomalacia, the frequency of which increased with increasing age. We suggest that the nonhemorrhagic group may be an important factor in the morbidity of survivors.


Adult form of subactute necrotizing encephalomyelopathy.

Subacute necrotizing encephalomyelopathy (SNE) usually appears before the age of 2 years. Variability in its clinical presentation make antemortem diagnosis difficult. The morphologic diagnosis depends on the present of necrotizing lesions with a characteristic distribution within the CNS. We describe a patient with the uncommon adult form of SNE. The pathologic changes are those accepted as diagnostic of the more common infantile SNE, and permit a separation from Wernicke's encephalopathy. In the adult, the disease is thought to be due to a less severe thiamine-related metabolic defect than that of the infantile form. The infrequent clinical recognition in the adult form may be due in part to lack of medical awareness.


On the origin and significance of neuromelanin.

The amount of cytoplasm within catecholamine neurons occupied by neuromelanin was found to increase progressively with the patient's age. The accretion of neuromelanin was accompanied by an expansion of the cytoplasm of neurons in the substantia nigra and locus ceruleus. These observations support the concept that neuromelanin is a waste product of catecholamine metabolism, derived from the oxidation of dopamine, nonrepinephrine, and related compounds to quinones. The existence of oxidative pathways for catecholamines suggests that defects in their compartmentalization, transport, or degradation may present the cell with sufficient levels of cytotoxic quinones and free radical species to result in the degeneration of neurons observed in Parkinson's disease.


Plasma dopamine-beta-hydroxylase activity and thyroid suppressibility in Graves' disease.

Plasma dopamine-beta-hydroxylase (DBH) activity, serum T4, T3, T3U, and the 24-hr thyroid uptake before triiodothyronine suppression testing were studied in 34 patients with treated Graves' disease. Although all of them were in the euthyroid state, there was a statistically significant difference in presuppression plasma DBH activity between those patients who showed suppression of their RAI uptake with triidothyronine and those who did not. This suggests a relationship between plasma DBH activity and thyroid suppressibility.


The effect of surface charge density on valinomycin-K+ complex formation in model membranes.

The model membrane approach was used to investigate the surface charge effect on the ion-antibiotic complexation process. Mixed monolayers of valinomycin and lipids were spread on subphases containing K+ or Na+. The surface charge density was modified by spreading ionizable valinomycin analogs on aqueous subphases of different pH or by changing the nature of the lipid (neutral, negatively charged) in the mixed film. Surface pressure and surface potential measurements demonstrated that a neutral lipid (phosphatidylcholine) or positively charged valinomycin analogs didn't enhance the anti-biotic complexing capacity. However, a maximal complexation is reached for a critical lipid concentration in the valinomycin-phosphatidylserine mixed film. The role of the surface charge on the valinomycin complexing properties was examined in terms of the Gouy-Chapman theory. As a consequence of the negative charge of the lipid monolayer, the K+ concentration near the surface is larger than the bulk concentration, by a Boltzmann factor. A good agreement was observed between the experimental results and the theoretical predictions. Conductance measurements of asymmetric bilayers containing a neutral lipid (egg lecithin) on one side and a negatively charged lipid (phosphatidyl-serine) on the other, confirm the role of the surface charge. Indeed, addition of K+ to the neutral side of the bilayer containing valinomycin had no effect on the conductance whereas addition of K+ to the charged side of the bilayer caused a 80-fold conductance increase.


Lysolecithin acyltransferase and lysolecithin: lysolecithin acyltransferase in adult rat lung alveolar type II epithelial cells.

1. The specific activity of lysolecithin acyltransferase (EC 2.3.1.23) in sonicated adult rat lung alveolar type II epithelial cells, measured either alone or in combination with acyl-CoA synthetase (EC 6.2.1.3), was found to be an order of magnitude greater than that of lysolecithin:lysolecithin acyltransferase. 2. Lysolecithin acyltransferase in type II cells was found to prefer palmitoyl-CoA over oleoyl-CoA as substrate. The combination of lysolecithin acyltransferase and acyl-CoA synthetase was found to prefer palmitate over oleate for incorporation into phosphatidylcholine. 3. Compared to whole lung homogenate, sonicated adult rat type II cells are highly enriched in lysolecithin acyltransferase but not in lysolecithin:lysolecithin acyltransferase. 4. These observations indicate that in normal adult rat type II cells the deacylation-reacylation cycle is more important for the formation of dipalmitoyl phosphatidylcholine than the deacylation-transacylation process.


Surfactant cholesterol metabolism of the isolated perfused rat lung.

1. The isolated perfused rat lung was used as the principal model to study surfactant cholesterol metabolism. 2. Cholesterol was found to represent over 50% of the neutral lipid of both the total surfactant and the lamellar body fractions. 3. De novo synthesis of cholesterol from [1-14C]acetate accounted for only 1% of the surfactant cholesterol, the remainder being derived from exogenous cholesterol supplied as serum lipoproteins. 4. Lipoprotein [1,2-3H2]cholesterol was incorporated into the lamellar body and extracellular surfactant fractions. The increase in the cholesterol specific activities of these fractions with time was consistent with a precursor-product relationship between the lamellar body cholesterol and that of the extracellular surfactant. 5. Incorporation of [methyl-14C]choline and [1,2-3H2]cholesterol indicated that the metabolism and secretion of lamellar body and extracellular surfactant cholesterol parallels that of phosphatidylcholine and suggests that most if not all extracellular surfactant cholesterol is derived from the lamellar body. 6. Comparison of the relative specific activities of incorporated [1,2-3H2]-cholesterol indicate that 59% of the total surfactant cholesterol is located extracellularly.


Molecular species of phosphatidylcholine from rat gastric mucosa.

Phosphatidylcholine of rat gastric mucosa were found to constitute about half of the total phospholipids. The composition of 20 molecular species accounting for approx. 90% of the total phosphatidylcholine was determined by specific enzymic hydrolyses and AgNO3 thin-layer and gas-liquid chromatography. Disaturated (dipalmitoyl) phosphatidylcholine made up about 31% of the total phosphatidylcholines. Other species which occurred in significant concentrations included 16:0/18:1, 18:0/18:1, 16:0/18:2, 18:0/18:2, 16:0/18:3, 18:0/18:3, 16:0/20:4, and 18:0/20:4. These results indicate that rat gastric mucosa is similar to lung in that both contain elevated amounts of dipalmitoyl phosphatidylcholine. Other similarities between these two tissues are discussed.


A new characteristic karyotypic anomaly in lymphoproliferative disorders.

A new characteristic chromosome anomaly t(11;14)(q14;q32?) in lymphoproliferative disorders (LPD) is described in 4 cases. The extra material was found on a "14 chromosome (14q+) and belonged to the long arm of one "11 chromosome in 3 cases and to the long arm of a "14 in the other case. These cases confirm that the distal end of chromosome 14q may function as a "receptor site," according to the hypothesis of Kaiser-McCaw et al. and also tend to indicate that chromosome "14 may not be unique in showing so-called "donor" and "receptor sites," and that other chromosomes, in casu chromosome "11, may behave similarly.


Pulmonary hyalinizing granulomas in a patient with malignant lymphoma, with development nine years later of multiple myeloma and systemic amyloidosis.

In our patient, multiple bilateral nodular pulmonary densities appeared on a chest x-ray at the time of diagnosis of stage IV diffuse lymphocytic lymphoma. After localized radiation therapy, the patient received no further systemic therapy. The pulmonary nodules slowly became larger and more numerous. Nine years later the patient developed proven multiple myeloma. Pulmonary hyalinizing granulomas have not heretofore been associated with proven lymphoreticular neoplasia, although this has long been suspected. The occurrence of two B-cell tumors at different points in time associated with systemic amyloidosis is an extremely rare event. The authors discuss the possibility that these conditions represent an abnormality in a common cell of origin with differing expression over time. Coincidence, however, remains a likely explanation for the different immunopathies that occurred in our patient.


Hashimoto's thyroiditis: a possible risk factor for lung cancer among Japanese women.

To study the epidemiologic association between Hashimoto's thyroiditis and malignancies, autopsy protocols (1959--1974) were examined at the Tokyo University Hospital. The study cases were classified according to major cause of death, including breast and lung cancer. The relationship between thyroid changes and breast cancer was not significant; however, a significant association between thyroid alteration and lung cancer was identified. This finding suggested that Hashimoto's thyroiditis and related changes could be one of the risk factors for lung cancer among Japanese women.


[Primary pulmonary lymphoma in the light of functional classification of malignant lymphomas].

A primary pulmonary lymphoma associated with paraproteinemia was observed in a man aged 73. Histologically, the tumour was classed as lymphoplasmocytic lymphoma. No metastases were disclosed at autopsy.


On the natural history of Plummer's disease.

Plummer's disease (autonomous goiter) presents a spectrum of forms, raging from solitary autonomous thyroid nodules to numerous small autonomous areas, and from unequivocal to servere hyperthyroidism. Progression is often very slow, but data on long-term follow up are scare, contradictory and limited to solitary nodules. We re-examined 58 untreated patients on one or more occasions. Follow-up time ranged from 1 to 12 years (average 4 years). There were gross clinical or scintigraphic changes in 13 patients. Three included six euthyroidal patients who became (mildly) hyperthyroid, one with a change from single to numerous "hot spots," and one in which the radionuclide disappeared in one of two separate autonomous areas. Minor changes were seen in 14 patients. Changes occurred irrespective of the scintigraphic pattern. In contrast, progression was very rapid in two of 300 other patients with the disease, leading to fatal thyrotoxic crisis withing three months in one. In another patient, transient hyperthyroidism was documented after excessive iodine administration. It is concluded that patients may be left untreated as long as serious complaints and clinical suspicion of associated malignancy are absent.


Combined intravenous miconazole and intrathecal amphotericin B for treatment of disseminated coccidioidomycosis.

A patient received a previously unreported combination of intravenous miconazole and intrathecal amphotericin B for the treatment of disseminated coccidioidomycosis with central nervous system involvement. After first having been treated with amphotericin B, followed by a course of miconazole therapy, the patient responded with remarkable clinical and serologic improvement to the combination of intrathecal amphotericin B and intravenous miconazole. The combination should be considered in the treatment of disseminated coccidioidomycosis with central nervous system involvement.


Absorption of nutrients in lactase deficiency.

The influence of malabsorption of lactose, as a result of primary lactase deficiency, on the absorption of the nutrients in milk was tested in four healthy controls and four subjects with lactase deficiency. An ileal perfusion technique was used to quantify arrival in the ileum of nutrients and a nonabsorbable marker (polyethylene glycol, PEG 4000) ingested as a test meal of milk. The meal was 250 ml of whole milk or milk in which the lactose had been hydrolyzed to glucose and galactose. In the fasting state, ileal flow of volume, protein, carbohydrate, and electrolytes was small and not different in controls and lactase-deficient subjects. Ileal flow increased in all subjects after the test meal of milk; more fluid and nutrient was recovered from the ileum in lactase-deficient subjects after whole milk than in control subjects or in lactase deficiency after hydrolyzed milk. Two deficient subjects showed marked malabsorption of lactose (35 and 50%); two did not. Protein, calcium, magnesium, and phosphorus were also recovered from the ileum in greater quantities in lactase deficients after whole milk. However, apart from decreased absorption of lactose, the nutritional consequences of malabsorption in association with primary lactase deficiency in adults are probably minimal.


Infrared spectroscopic investigations of tuftsin and its analogs.

The ability of tuftsin and its analogs to form folded intramolecularly hydrogen-bonded structures has been investigated by infrared spectroscopy. The appearance of beta-turns is documented for peptides containing proline in position 3 of the chain. Correlation of spectroscopic data with biological activity in the investigated series is attempted.


Lymphoreticular disorders of the gastrointestinal tract: roentgenographic features.

Recent advances have permitted close correlation of characteristic roentgen signs with the pathophysiologic alterations in lymphoreticular disorders of the gastrointestinal tract. The background of primary and secondary immunoglobin disorders with gastrointestinal manifestations is reviewed. The roentgenographic alterations in the small bowel of the enteropathic immunoglobulin deficiency syndromes and in lymphoma of the small bowel, stomach, and colon are discussed and illustrated in detail.


Dermatitis herpetiformis and thyrotoxicosis.

Dermatitis herpetiformis has been associated with a variety of thyroid abnormalties. A case of thyrotoxicosis in a patient with pre-existing dermatitis herpetiformis is reported. Thyroid antibodies were present in the serum. This may suggest an immunologic relationship between dermatitis herpetiformis and thyroid disorders, that may be more than fortuitous.


Lecithin changes in murine Mycoplasma pulmonis respiratory infection.

We examined the lipid content of bronchoalveolar (BA) washes from both mice and rats infected with Mycoplasma pulmonis, an etiological agent of murine pneumonia. During a 30-day period after intranasal inoculation, the total lipid content from infected and control rats (in milligrams per animal) remained relatively equal and unchanged. The saturated, unsaturated, and total lecithin contents in infected rats (in milligrams per animal) all increased. The maximum lecithin values were detected at 7 to 10 days after infection; later, the levels fell to control values. There was essentially no change in any lecithin value from uninfected animals. Although in BA washes from infected animals the mass of disaturated lecithins increased, the percentage of this fraction in the total lecithin pool decreased. The fatty acids of the lecithins from BA washes of infected mice had significantly less palmitic and significantly more oleic and linoleic acids than the lecithins isolated from the BA washes of control animals. Both the relative decrease in the mass of disaturated lecithins in the BA washes and the increase in the percentage of esterified unsaturated fatty acids in the lecithins may be directly related to the reduced lung function reported to occur during the course of murine M. pulmonis pneumonia.


A pharmacokinetic model for predicting the concentration of methotrexate in plasma subsequent to intrathecal injection.

A pharmacokinetic model has been established in which plasma methotrexate (MTX) concentrations following intrathecal administration are predicted. The model is based upon cerebrospinal fluid MTX concentrations following intrathecal injection of MTX, and plasma MTX levels subsequent to i.v. injection of the drug in dogs. Anticipated plasma MTX levels were compared with actual measured concentrations. The model predicts changes in the plasma MTX concentration curve as a result of varying of the injected dose, reduction in plasma MTX clearance, and reduced transfer of MTX from cerebrospinal fluid to the blood. It is suggested that plasma MTX levels be measured at 3, 5, 7 and 10 h following intrathecal injection to facilitate an early assessment of unusually slow plasma MTX decay. Thus, administration of leucovorin, to prevent systemic toxicity, may be more rapidly commenced. Also, if such measurements indicate that the transfer of MTX from cerebrospinal fluid to the blood is reduced. MTX dose of the subsequent intrathecal injections should be reduced to minimize risks of systemic toxicity and neurotoxicity.


Injury to the anterior cruciate ligament producing the pivot-shift sign.

The clinical entity termed the pivot shift was studied in cadaver specimens and its significance was evaluated. It was found to be highly correlated with a tear of the anterior cruciate ligament, and it corresponded to a sudden anterior-internal rotation subluxation-dislocation of the tibia and posterior horn of the lateral meniscus beneath the lateral femoral condyle.


Avoiding adverse effects of cycloplegics in infants and children.

Cycloplegics are very safe and useful medications. To avoid the unpleasant side effects of these medications, six precautions are considered. They are: 1. dosage, 2. cycloplegic selection, 3. toxic reaction, 4. biologic variations, 5. topical anesthesia, 6. environmental temperature and humidity.


Improved antitumor effects in 3'-branched homologues of 2'-deoxythioguanosine. Synthesis and evaluation of thioguanine nucleosides of 2,3-dideoxy-3-(hydroxymethyl)-D-erythro-pentofuranose.

The 3-(hydroxymethyl) branched homologue of 2-deoxyribofuranose was synthesized from the corresponding branched ribofuranose 2-O-(S-methyl dithiocarbonate) with tributyltin hydride in the first direct, one-step deoxygenation at C-2 of a ribofuranose. Nucleoside coupling afforded the corresponding 3'-branched 2'-deoxyribonucleosides of thioguanine. The alpha- and beta-nucleosides were equally inhibitory to growth of WI-L2 human lymphoblastoid cells, were phosphorylated and incorporated into the DNA of Mecca lymphosarcoma in mice to the same degree, and were more effective in these tests than the parent analogue alpha-2'-deoxythioguanosine. These results indicate that the hydroxy functions at the 3' and 5' positions of 2'-deoxynucleosides are interchangeable and that acceptance by the that the furanose ring oxygen and 2'-methylene are corresponding interchangeable, and that acceptance by the enzymes is improved if primary hydroxyls are provided at both the 3' and 5' positions.


Causes of death in marine mammals stranded along the Oregon coast.

Sixty-eight marine mammals stranded on the Oregon beaches were examined at necropsy. Gunshot was the primary cause of death in 30% of the pinnipeds examined. Bacterial infections (27%) and parasitism (27%) were also of major importance in the death and debilitation of Oregon marine mammals. Traumatic death or debilitation other than gunshot was observed in 11 animals (16%). Predation, starvation due to neonatal abandonment, viral encephalitis (presumptive diagnosis), dystocia and neoplasia were diagnosed as primary or contributory causes of stranding.


Species difference and characterization of intestinal esterase on the hydrolizing activity of ester-type drugs.

The ability of the esterase from intestine was studied for hydrolysis of ester-type drugs during absorption. The intestinal esterase is present in the absorption sites in the intestine and hydrolyzes to a large extent during the absorption. In a study of the dietary effect on intestinal esterase, the esterase activity increased in rats fed a high-fat diet, decreased in those fasted or fed a fat-free diet, whereas the esterase activity in the rat treated with phenobarbital showed no marked change. Thus the esterase from intestinal mucosa appears to be characteristically quite different from hepatic esterase. The esterase from human intestine was characterized and compared with esterase from rats, mice, rabbits, guinea pigs and dogs. There was a difference in the substrate specificity of the esterase and there were significant species differences in the electrophoretic behavior of the enzyme among the species tested. These results indicate that intestinal esterase from humans differs characteristically from esterases in experimental animals.


Independence of the lethal actions of glucocorticoids on lymphoid cells from possible hormone effects on calcium uptake.

We have examined the possibility that hormone-induced increases in calcium uptake might initiate the lethal actions of glucocorticoids in two types of lymphoid cells. Hormone-induced increases in nuclear fragility are used as the measure of hormone action, since in both rat thymus cells and in mouse P1798 lymphosarcoma cells increased nuclear fragility (the inability of nuclei to survive lysis of the cells by hypotonic shock) precedes other indices of cellular deterioration by several hours. In the case of the tumor cells, those from corticosteroid-sensitive lines are less able to withstand incubation in vitro than resistant cells. Such differences in cell survival are predicted both by earlier changes in nuclear fragility and also by differences in calcium uptake. However, there is no detectable early glucocorticoid effect on calcium uptake that precedes or coincides with the substantial hormone-induced increases in nuclear fragility that develop in the sensitive cells by 2 h. In rat thymus cells the absence of calcium in the medium does prevent some of the increase in nuclear fragility and cell disintegration that occurs spontaneously during incubation in vitro. Nevertheless, when cells are exposed to hormones the glucocorticoid effect on nuclear fragility develops in the absence of calcium and is similar in magnitude to that seen in the presence of calcium. We conclude that calcium seems to enhance the spontaneous deterioration of lymphoid cells, and there is a large increase in calcium uptake that occurs as cells deteriorate. It nevertheless seems unlikely that hormone-induced changes in calcium uptake initiate the lethal actions of glucocorticoids. The data also support a proposal made earlier [2] that resistance to glucocorticoids in tumor cells may develop by the selection of cells with hardier membranes.


Some technical modifications of surgical treatment of lumbar disc lesions.

The author's experience in the surgical treatment of lumbar disc lesions is reported. The following technical devices have been adopted: -- curved unilateral incision into deep fascia --interlaminar space widening by chisels and gouges, avoiding the use of rongeurs -- sodium succinate methylprednisolone injection into dural sac. -- early ambulation (within the first 18 hours). Benefits obtained by these procedures are: -- earlier disappearance of pain -- remarkable reduction of stay in hospital -- earlier and more complete recovery.


The experimental transmission of Parafilaria bovicola to cattle in South Africa using Musca species (subgenus Eumusca) as intermediate hosts.

In controlled experiments in an insect-free stable, cattle became infected with Parafilaria bovicola when Musca lusoria, infected with the larvae of this worm, were allowed to feed on a fresh skin incision, and when infective larvae were placed on fresh skin incisions, injected subcutaneously or into the jugular vein, or instilled into the eyes. The sites of blood spots caused by ovipositing P. bovicola females and the sites of carcass lesions were seldom close to the site of infection, an indication that the worms had migrated. The prepatent period of P. bovicola in 4 cattle which developed blood spots ranged from 242--319 days. Neither of the infected cattle that were kept continuously in a shady stable showed blood spots, but 4 out of 7 infected cattle which spent some time in the sun bled. However, carcass lesions on shaded cattle were similar in appearance to those on cattle kept outdoors. Infective larvae were stimulated to escape from the mouth-parts of infected M. lusoria and Musca xanthomelas s.s. when these were fed citrated ox blood warmed to 38--40 degrees C. No escape took place when the flies were fed warmed saline or warmed 15% sucrose solution.


Obstruction of the major pediatric airway.

1. Do not create an emergency obstruction unless you are prepared to handle it. (It may be best to do nothing until the diagnosis is clear.) 2. Support the patient with oxygen, humidity, and positioning and monitor vital signs. 3. Take as brief, concise, and accurate a history as possible. 4. Determine the anatomic level of obstruction. 5. Estimate the degree of obstruction with the maximal potential hazard. 6. Carry out a physical examination of the nose and neck and, except in suspected epiglottitis, the pharynx, larynx, trachea, and lung. 7. Special x-ray studies--lateral, neck and chest, swallowing function, and inspiratory and expiratory films--are obtained as indicated. 8. Therapeutic support: oxygen, humidity, antibiotics, steroids, and recemic epinephrine. Mechanical support: naso-oral airways, appropriate endotracheal or bronchoscopic tubes. tracheotomy.


[Anaemia and microcytosis during thyrotoxicosis. Physiopathological discussion. 36 cases (author's transl)].

Study of 36 cases of thyrotoxicosis demonstrated the prevalence of anaemia (17 cases) and of microcytosis (26 cases). In patients with a microcytosis, serum iron was measured in 9, being found to be low in 5 of them, whilst amongst twelve 10 had anti-thyroid antibodies and anti-gastric antibodies. Atrophic gastritis was seen in the 5 patients who underwent endoscopy. Four biopsies revealed 3 cases of atrophic gastritis and one of simple gastritis. The types of anaemia seen and their mechanisms are discussed: microcytic anaemia related to disturbed iron metabolism or to its impaired intestinal absorption; normocytic anaemia; macrocytic anaemia possibly preceding pernicious anaemia. It would seem to be possible to distinguish two pathogenic categories: thyrotoxicosis reversible changes in iron metabolism, and atrophic gastritis associated with hyperthyroidis in an "auto-immune context" and which has led to the concept of "thyro-gastric" disease.


[Thyroid tissue link of hemostasis in diffuse toxic and euthyroid goiter].

Blood coagulation system and fibrinolysis factors contained in the thyroid gland tissue of patients with diffuse toxic and euthyroid goiter and also of apparently healthy persons were investigated. The thyroid gland of healthy persons was shown to possess thromboplastin, antithrombin, anticoagulant, antiheparin, and fibrinolytic properties and to contain plasminogen, plasminogen activators, antiplasmins. The function of the external hemocoagulation system was reduced due to diminished thromboplastin and antiheparin activity of the gland tissue, reduction of aggregation and increase of disaggregation properties of the gland tissue. External blood coagulation system was undisturbed in patients with euthyroid gland. Local fibrinolysis was enhanced in patients with diffuse toxic goiter on account of increase in the thyroid gland of plasminogen activators, reduction of antiplasmin activity, and increase of the nonenzymatic fibrinolysis activity. Analogous changes in local fibrinolysis occurred in patients with euthyroid goiter.


[Cutaneous leukemia in a horse (author's transl)].

The case of a 16-year-old mare with multiple dermal lymphosarcoma of the histiolymphocytic type is described. Leukaemic changes were not found to be present in the superficial and internal lymph nodes or in the visceral organs.


Alien H-2 antigens on a chemically induced fibrosarcoma: further evidence in crude membrane and soluble extracts of the tumor.

Crude membranes (CM) were obtained from in vivo subcutaneous nodules of the methylcholanthrene-induced BALB/c fibrosarcoma C-1 by forcing tumor fragments through a mechanical press and subsequent differential centrifugation. This immunogenic tumor has been previously shown to express both H-2d and extra H-2k-like antigens. Original H-2d and alien H-2k antigenic activities were present in CM C-1 as judged by the specific inhibition of the C'-dependent cytotoxicity of monospecific H-2 alloantisera on normal 51Cr-labelled lymphoid cells. Both K- and D-end private H-2d antigens (31 and 4), and H-2d public antigens 8, 29, 35 were detected in CM C-1. In addition, the alien H-2Kk.23 private specificity and the public H-2k.1, 5, and 25 were also found in CM C-1. A weak but reproducible activity attributable to the Dk private antigen 32 was also revealed in this material. A hierarchy in the expression of both H-2d and H-2k specificities was evident in CM C-1 which paralleled, although with an overall lower antigenic activity, those of two other BALB/c (H-2D) FIBROSARCOMAS AND OF A C3Hf (H-2k) lymphoma, respectively. CM from normal BALB/c and C3Hf spleens, while expressing higher amounts of all the tested H-2 antigens, displayed a hierarchy of the different specificities similar to that of neoplastic tissues. Crude soluble (CS) material was obtained from CM C-1 by deoxycholate treatment and was tested in the inhibition assay for the presence of H-2d and alien H-2k antigens. Only specificities with the highest expression in CM were found in CS, i.e. H-2.4 and 29 for H-2d and H-2.25 for H-2k. Both CM and CS from C-1, but not from another control BALB/c sarcoma, were able to significantly inhibit the activity of an oligospecific serum to the Kk-coded antigens.


Serological evidence for the presence of rickettsial infections in parts of Nigeria.

Weil-Felix tests using OX19 and OXK proteus antigens reveal high antibody titers to OXK and OX19 antigens in patients reporting at the University of Nigeria Teaching Hospital, Enugu with clinical diagnosis of pyrexia of unknown origin. These findings suggest the presence of either or both scrub typhus fever and Epidemic typhus fever in this community. While the advisablility of using other diagnostic techniques to support and confirm positive Weil-Felix reaction will be useful, it is felt that the above findings are strong evidences for the prevalence of these diseases in this part of Nigeria.


[Control of sexually transmitted diseases in Senegal].

STD are an important public health problem in numerous developing countries. Although satisfactory diagnostic and therapeutic means are available, the incidence of STD is increasing. Among the causes for this are sociological factors, like the weakening of customs and the family unit, and the development of tourism, which stimulates prostitution. There is a marked ignorance of the population in respect to STD. The Senegalese Government, WHO, and the Geneva-based Sandoz Institute launched in 1976 a joint programme of service, training and sesearch. The research aims at developing a preventive approach, especially through health education. While the three centers set up have accomplished good work locally, results are still disappointing from a public health point of view. Weak spots are in particular: - inadequacy of the social and contact-tracing services; -lack of action at the periphery and of integration with primary health care; -lack of coordination with other sectors (including police), and with professionals of various disciplines who should contribute to the socio-economic investigation of the problem. Several groups have recently been created in Senegal to support the project. An evaluation will soon be carried out. Such programmes should be implemented in other countries of the region.


Mycotic aneurysm. Report of two cases.

Reference is made to two cases of mycotic aneurysm with different peripheral localizations, arising from a bacterial endocarditis. The cause, localizations, complications and histological findings are discussed.


Serum thyroglobulin in patients with toxic and non-toxic goitres compared to sex- and age-matched control subjects.

To study serum thyroglobulin (Tg) levels in patients with thyroid disorders compared to sex- and age-matched control subjects and to correlate the Tg levels to the thyroid function, 71 patients were investigated before treatment was started. Serum Tg, measured by a double antibody radioimmunoassay, was elevated in all groups with thyroid disorders, as compared to their controls, but the values showed large overlaps between groups. The highest median values were seen in the two groups of patients with toxic goitres (toxic adenoma and Graves' disease). The Tg values in patients with non-toxic goitres (diffuse and nodular) and in controls showed a log normal distribution, whereas the distribution of values from patients with toxic goitres was different. No correlation was found between serum Tg and serum thyroxine, serum triiodothyronine and serum TSH, respectively. It is concluded that determination of serum Tg is of little diagnostic value in thyroid diseases.


Electrolyte abnormalities in lymphosarcoma after chemotherapy.

A 12-year-old female with lymphosarcoma responding to treatment including vincristine and cyclophosphamide developed clinical and laboratory findings compatible with the syndrome of inappropriate secretion of antidiuretic hormone. Some additional findings were observed, i.e. uremia, hypopotassemia and alkalosis, that have not so far been recorded in that syndrome. All abnormalities were corrected upon water restriction. A similar episode occurred after a 2nd drug course. It too was corrected upon water restriction. The patient was clinically free from her malignancy in both episodes. It is suggested that our child had probably an expanded form of the syndrome of inappropriate secretion of antidiuretic hormone.


The effects of prolactin on pulmonary maturation in the fetal rabbit.

The effect of ovine prolactin administration on the fetal rabbit pulmonary pressure volume relationship was determined. Using pentobarbital anesthesia, on Day 24 of gestation, a midline incision on the maternal abdomen was made to expose the bicornuate uterus. Fetal rabbits in one horn of the uterus were injected intramuscularly with a dose of 1.0 mg (0.05 ml) of prolactin solution. Similarly, fetuses in the opposite horn were administered an equivalent volume of control vehicle. On Day 26 of gestation, no significant enhancement of lung maturation, as judged from the pressure volume relationship, was found to result from prolactin administration. These results suggest that prolactin does not initiate the secretion of surface active material into the alveolar lumen of the fetal lung in sufficient amounts to induce physiologic maturation of the rabbit fetal lung.


Antenatal prediction of graduated risk of hyaline membrane disease by amniotic fluid foam test for surfactant.

We measured amniotic fluid surfactant by the semiquantitative foam stability test within 24 hours before delivery of 410 infants, 64 of whom developed HMD diagnosed by standard criteria. When surfactant titers were ranked in eight categories, they predicted graded risks of HMD. On this basis we defined five "risk groups" with significantly different incidences of HMD (I = 0.5%; II = 10%; III = 25%; IV = 41%; V = 79%). Infants in Groups I and II were heavier and more mature than those in Groups III to V. However, among infants of equivalent GA or birth weight, the incidence of HMD still correlated significantly with the foam test results. Within each risk group the incidence of HMD was equal among infants delivered by vagina and by cesarean section, slightly greater among males than females, and inversely proportional to GA. In Group V the incidence of HMD was 100% among infants at less than 33 weeks' GA. We used this relationship to devise a system that improved prediction of HMD by combining the foam test results with GA.


Retrolental fibroplasia in hypoxic newborn.

A premature infant with hypoxia caused by severe cardiac malformations developed stage IB retrolental fibroplasia, which was documented after death. Despite arterial oxygen partial pressures of 91 mm Hg or less the classical histologic changes were observed in the temporal periphery of each eye.


The effects of metoclopramide on postoperative ileus. A randomized double-blind study.

Metoclopramide or placebo was administered postoperatively in a randomized, double-blind fashion to 115 patients undergoing laparotomy. The effect of metoclopramide on postoperative adynamic ileus (PAI) was evaluated. The patients were stratified into two groups: Group A--those with laparotomy without a gastrointestinal anastomosis or ostomy procedure, and group B--those with laparotomy undergoing an anastomosis or ostomy procedure. Metoclopramide reduced nausea and emesis postoperatively. However, the only significant effect on postoperative adynamic ileus was an earlier return to tolerance of solid foods in the patients in Group A.


Multiphasic view of medial meniscectomy.

In a retrospective study, the records of a group of 816 patients who had tears of the medial meniscus alone were selected for review from a total of 6,000 records of patients who had had knee surgery (1966 to 1976). According to the operative reports, these 816 patients had no other structural or pathologic findings at the time of medical meniscectomy. In an average of 2.0 years after initial surgery to the knee, 210 patients required subsequent surgical procedures for progressive meniscal pathology (38), articular cartilage damage (64), or ligamentous instability (108). The recognition of the possiblility for future surgery after medial meniscectomy is an important finding which must be acknowledged by the treating physician and to the patient. The evidence from the review suggests that others should review series of patients with tears of the medial meniscus and should attempt to gain understanding of the basic pathologic processes.


Primary biliary cirrhosis and scleroderma. The possibility of a common pathogenetic mechanism.

A woman with clinical manifestations of progressive systemic sclerosis had liver disease with histologic and immunologic features of primary biliary cirrhosis. Biopsy specimens of salivary gland showed necrosis and lymphocytic infiltrates in and around ducts similar to those observed in hepatic ducts, whereas neither of these tissues exhibited immunoglobulin or complement deposition. The ultrastructural and immunohistochemical studies suggest a common cell-mediated immunologic mechanism for the two disorders.


Extramedullary hematopoiesis in the liver in sudden infant death syndrome.

This study was undertaken to confirm or refute the findings of Naeye with regard to the pathologic continuation of extramedullary hematopoiesis in the livers of infants who die of the sudden infant death syndrome (SIDS). In general, our findings confirm his; however, although the data for SIDS do differ from those of controls, the differences are not statistically significant. Nevertheless, these results would seem to indicate the need for further investigation of the possibility of hypoxemia and/or anemia in affected infants.


Surgical reconstruction of chronic anteromedial rotatory instability of knee. A review with computer analysis of 149 cases.

The clinical records were reviewed of 142 men and 7 women (average age 26.8 years; range, 15 to 58 years) who had surgical reconstruction for anteromedial rotatory instability of the knee. All were treated consecutively at the same clinic during a 15-year period (1960 to 1975). Preoperative and postoperative symptoms were rated both subjectively and objectively by devised scales and analyzed by a computer program. Comparison of the three major surgical procedures show that the subjective success rate was 87% for the pes anserinus transfer, 70% for the posterior oblique ligament reconstruction, and 72% for the combination procedure. Of the 149 patients, 130 had been injured in sportive activities and 110 were able to return to some degree of athletics. Accurate and detailed recording of clinical data allowed construction of subjective and objective rating systems for computer analysis in review of a large series over a period of years. This approach enhanced our ability to obtain correlation and objective evaluation of the data. Commercial equipment for evaluating the quadriceps and hamstrings is beneficial in determining that a patient has achieved complete rehabilitation or if there will be a permanent decrease in function after surgical intervention.


Immediate mucosal effects of short-term, soft-cuff, endotracheal intubation. A light and scanning electron microscopic study.

Little is known regarding the early pathogenesis of intubation-induced laryngotracheal damage or the effects of presently used soft-cuff endotracheal tubes. We have examined the pathological changes of short-term intubation (four hours) in six mongrel dogs. Interaction of the endotracheal tube with the mucosa produced a variety of lesions ranging from superficial abrasions to ulcerations with the most severe lesions in the respiratory epithelium. Changes are present at the free surfaces of ciliated cells that include flattening, fusion, and erosion of cilia of sufficient extent to compromise ciliary function. The ischemic and mechanical modes of injury are compared; the latter is considered causal with modern soft-cuff tubes. These studies reveal tube-induced mucosal damage of an extent and nature not previously appreciated.


Steatosis of granular pneumocytes in alcoholics with acute alveolar injury.

Accumulation of neutral lipid in the type II alveolar epithelial cells of the lung has been described in experiments involving animals with conditions such as hypoxia or on alcohol administration. In two cases involving human subjects, this change was observed at autopsy by histochemical stains and electron microscopy. In both instances, the patients had had severe alcoholic liver disease, as well as extreme hypoxia resulting from acute alveolar injury. The lungs of six alcoholic patients with liver disease but without acute alveolar injury showed no lipid vesicles on histochemical staining. These observations suggest that a metabolic insult or combination of insults, such as alcohol or hypoxia, might lead to accumulation of neutral lipid, especially in regenerating alveolar epithelial cells that may be more susceptible to such injury.


Benign clear cell tumor of the lung.

Light microscopy of a benign clear cell tumor of the lung showed considerable central necrosis, making the differential diagnosis from metastatic clear cell tumor of the kidney difficult. Nevertheless, distinguishing features were seen on both light and electron microscopy that helped make this important distinction.


Acid phosphatase in squamous cell carcinoma.

Surgical specimens of oral squamous cell carcinoma were processed for cytochemistry of acid phosphatase using Gomori's substrate. Reaction product was deposited in the cytoplasmic dense bodies, autophagic vacuoles, cytoplasmic projections, and advancing cell borders. Results of this study suggest that acid phosphatase and its associated lysosomes seem to play a role in the invasiveness of cancer cells.


Neonatal cystic choristoma in submandibular salivary gland simulating cystic hygroma.

A congenital cystic malformation occurred in the submandibular salivary gland of a neonate. The embryogenesis and differential diagnosis are discussed. Since it seems to be a product of endodermal heterotopic differentiation or entrapment of foregut epithelial rests in the submandibular gland, it is classified as a cystic choristoma.


Renal involvement in adult Gaucher's disease after splenectomy.

Gaucher's disease with severe clinical and pathologic renal involvement is exceptionally rare. This article describes severe renal involvement and proteinuria in a young black woman with Gaucher's disease. The accumulation of glucocerebroside (Gaucher bodies) in glomerular mesangial and endothelial cells and in interstitial cells of the kidney is indicative of the phagocytic potential and the deficiency of glucocerebroside-cleaving enzyme in these cells. Severe proteinuria in this patient was attributed to the extensive glomerular involvement by Gaucher's disease.


Hepatic ultrastructure in secondary syphilis.

We describe the ultrastructural findings in liver biopsy specimens from 19 patients with secondary syphilis. These patients were unselected, had negative tests for hepatitis B surface antigen, and were not jaundiced. Most hepatocytes appeared normal; a few showed minor nonspecific changes, including some prominence of lipofuscin. Kupffer cell and endothelial cell hyperplasia were noteworthy in some specimens, occasionally forming clusters with mononuclear cells. However, these findings, have no specificity. Although treponemes were seen in Warthin-stained sections by light microscopy in three instances, no organisms were detected in the blocks selected for electron microscopy.


Ultrastructure of hydatid cyst.

Material from a surgically excised hydatid cyst of the liver was examined with an electron microscope. The integument of the parasite was studied in particular detail and has been defined as the tissue enclosed by the external cytoplasmic membrane of the distal cytoplasm and the basement membrane. The ultrastructural features of the different parts of the integument, ie, distal cytoplasm, lucent zone, fibrous zone, muscular layer, and the basement membrane are described. The germinal membrane covering the protoscolices had no anatomic connections with the distal cytoplasm except at the point of attachment of the protoscolex to the brood capsule. The biogenesis of the mitochondria has been traced from infoldings of the cytoplasmic membrane to calcified dense bodies.


A quantitative ultrastructural study of a parotid oncocytoma.

A quantitative electron microscopic study was performed in a case of parotid oncocytoma. The mean nuclear radius was estimated to be 3.4 mu, and the mean nuclear volume 171 cu mu. The mean cell volume was calculated to be 958 cu mu. The mitochondrial volume density value averaged 59% of the cytoplasmic volume, and the mean nuclear volume density was 24% of the cell volume. These findings are compared with previous quantitative electron microscopic data on various epithelial cells from the digestive system, including the salivary glands.


Etiologic variability of nephropathy in juvenile diabetes mellitus.

Clinicopathologic studies of four patients with juvenile diabetes mellitus and renal disease demonstrated the pathogenetic variability of nephropathy in diabetic patients. Only in one patient was the clinical nephropathy associated with the typical diabetic glomerulosclerosis. Another patient had steroid responsive nephrotic syndrome superimposed on minimal diabetic glomerulosclerosis. A third patient had steroid resistant nephrotic syndrome associated with mild diabetic glomerulosclerosis and with later appearance of Grave's disease. The fourth patient, in addition to moderate diabetic glomerulosclerosis had prominent tubulointerstitial nephritis, the latter probably being responsible for the rapidly declining renal function. The poor prognosis associated with diabetic nephropathy warrants a careful search for other potentially treatable causes of nephropathy in patients with juvenile diabetes mellitus.


An in-vitro technique for studying fleece-rot and fly strike in sheep.

Fleece-rot was experimentally induced in-vitro by wetting and incubating Merino wool samples embedded in serum-agar. Gravid Lucilia cuprina were readily-attracted to these wool culture plates to oviposit. Where serum was freely available to newly-hatched larvae, fly strike and larval development ensued. Using this technique, fleece-rot and oviposition were found to be markedly influenced by the availability of protein and by bacterial activity, particularly that of Pseudomonas spp. The results indicated that odours emanating from wool culture plates containing the latter species played an important role in oviposition. Furthermore, these events varied according to the type of fleece selected, and could be prevented by the addition of a bactericide.


Passive transmission of Campylobacter fetus by immunised bulls.

Two groups of 24 heifers were mated with 3 immunised and 3 susceptible bulls respectively. Six heifers in each group were infected artificially with Campylobacter fetus sub-sp. fetus biotype venerealis. Among susceptible heifers mated with immunised bulls, 13/18 became pregnant and 5/18 yielded evidence of infection with C. fetus. Among susceptible heifers mated with susceptible bulls, 7/18 became pregnant and 10/18 yielded evidence of infection. C. fetus was isolated on one occasion from an immunised bull, but the immunised bulls failed to develop carrier status and one was shown to be refractory to artificial challenge. Susceptible bulls developed carrier status during the breeding period. It is suggested that passive transmission of C. fetus by immunised bulls can occur under conditions of intensive sexual activity.


[Situation and problems of the research-oriented pharmaceutical industry (author's transl)].

The inherent factors in the drug development strategy of a research-oriented pharmaceutical company, the actualities of the pharmaceutical market and the interdependence of the different determinants in terms of their meaning for innovation potential are presented. The applicability and the specificity of animal experimental results in regard to their human clinical relevance are particularly indicated as well as the reasons which in the future will narrow the chances for real and realizeable therapeutic advances in the area of psychotropic substances. Exaggerated, unrealistic and/or scientifically non-convincing requirements from the authorities can be an important inhibitory factor. For the main groups of psychotropic substances a series of desirable elements are enumerated and, at the same time, the chances for innovation are formulated. With the aim of improving the chances for innovation it is postulated to search for possibilities of a more rapid and more efficient feed-back from the clinic. Indeed this should be an integrated part of the activities in the early phases of development of new products.


[Neuroendocrinology in depression and schizophrenia (author's transl)].

In the introduction the heuristic basis of neuroendocrinology and the relationship to current concepts in biological psychiatry is analyzed. Various neuroendocrinological approaches to the study of depressive and schizophrenic disorders are then exemplified by the discussion of selected papers. In contrast to studies in schizophrenic patients abnormal findings have been found, by several research approaches, in endogenous-depressive patients. These findings are consistent with the hypothesis of a disfunction of biogenic amines in endogenous depression; however, considering the neuroendocrinological methodology at hand these findings are not conclusive.


[Influence of single and repeated administration of desipramine (DMI) on the secretion of growth hormone (GH) (author's transl)].

DMI leads to stimulation of GH in healthy male subjects 60--120 min after i.m. injection and 150--210 min after oral application. During a 20-day administration of 2 x 75 mg DMI per day a repeated stimulation of GH was provable on days 0, 10 and 20 in two male patients, whereas no stimulation of GH occurred in two female patients who underwent the same treatment. The GH basic secretion did not increase in any of the four after patients 10 and 20 days, respectively. Neither prolactin (PRL) nor thyreotrophin (TSH) serum concentrations are influenced by DMI. The increase in PRL and TSH, which is induced by the thyrotrophin releasing hormone (TRH), is provable after acute as well as after chronic administration of DMI.


[Relationships between effects and plasma levels of clozapine (author's transl)].

Relations between clozapine plasma levels and effects were investigated in 32 hospitalized patients. Clozapine dosage and plasma levels correlate linearly. The clinical improvement due to clozapine treatment was significant. A relationship between the rate of improvement and the plasma levels could be seen on the third day of treatment only. Of the side effects, body temperature elevation and orthostatic disregulation temporarily correlated with the plasma levels. Development of tolerance was seen with regard to the sedative effect and orthostatic disregulation. Linear correlations between pulse frequency as well as dopamine-beta-hydroxylase activity in serum and clinical improvement were observed during the second half of the 30-day treatment period.


[Quantitative determination of tricyclic antidepressant drugs by high-pressure liquid chromatography (author's transl)].

With regard to the increasing importance of determining plasma levels of antidepressant drugs a procedure has been worked out which makes it possible to analyze these substances in a simple and sensitive way. 5 ng )ca. 20 pmol) amitriptyline, nortriptyline, imipramine, desmethylimipramine, chlorimipramine, desmethylchlorimipramine, and protriptyline can be detected with a high-pressure liquid chromatograph and a UV-monitor without prior derivatisation. The extraction is made from 1 ml serum. Because of their retention time the substances can be identified. This fact allows simultaneous analyzation of all tricyclic antidepressants.


[On the effect of the antidepressant viloxazin on EEG and optimization of the system driver-vehicle-road (author's transl)].

The effects of a single dose of 100 mg 2-[(o-ethoxyphenoxy)-methyl]-morpholine hydrochloride (viloxazin) on EEG and optimizing control behaviour of drivers were investigated under double-blind conditions in 5 male subjects with many years' driving experience. The study was carried out on a special test course using a car equipped with measuring devices. The following signals were recorded: EEG and EOG, driving speed, steering torque, steering angle and angle rate, longitudinal and lateral acceleration, and yaw rate. As evaluated by means of spectral analysis with a subsequent principal component analysis the EEG showed an increase of the power in alpha- and beta-frequencies indicating a drug induced decrease of EEG vigilance. In correspondence the optimization of the system driver-vehicle-road was reduced indicating an impairment of the driver's control behaviour.


[The effect of tinofedrine on the EEG].

The effect of 4 mg tinofedrine i.v. on the EEG of 10 healthy volunteers was tested by serial spectral analysis. In a controlled study, production of alpha-waves rose significantly, while delta-activity decreased. This is thought to be indicative of activation of the central nervous system by tinofedrine.


[Experimental study on the effect of ephedrine in an anger-provoking situation].

The purpose of this study was to investigate the effects of ephedrine-induced sympathetic arousal on emotional reactions in an anger-provoking situation. The effects of ephedrine were compared with a placebo condition while the effects of the anger-situation were compared to a neutral control situation. 60 male students were randomly assigned to one of the four conditions of the two-factor design. The dependent variables were various peripheral-physiological measures and self rating of physical and emotional states. Both independent variables were found to be effective. Contrary to expectation, ephedrine decreased subjective emotional reactions to the anger-provoking situation rather than increase it. Methodological problems and possible conclusions about the role of sympathetic arousal for emotional reactions are discussed.


[Two psychosis-specific test systems (author's transl)].

Psychopathological procedures for assessment of severity of mental disorders will often be applied in follow-up studies of drugs. Their application can be performed relatively economically because the nosological and syndromal allocation of patients has usually been accomplished before the measurement of severity. In order to facilitate and establish economy, empirically testable conceptions on the relationship between the severity of the psychic disorder in question and the results of measurement are to be favoured. In addition they help avoiding systematic misjudgements as they sometimes occur in application of self-assessment scales in functional psychoses (physically induced reversible psychosis) or endogenous depression. According to this rule two economic psychopathometric testing systems have been developed for endogenous depression and functional psychosis. Both are introduced briefly.


[Detecting psychopathological symptoms in psychopharmacological studies on the course of disease (author's transl)].

Rating scales and self-rating scales are still indispensable for the estimation of psychopathological symptoms and their variations in the course of treatment with psychopharmacologic agents. So significant progress can be recognized in measurment of intelligence, degree of severity of functional psychoses, states of cerebral defects and of endogenous depressions. The promising results of this experience encourage intensifying the development of such test instruments concerning non-psychotic psychic disturbances as well as schizophrenic psychoses.


[Development of new antiepileptics. V. Pharmacological activity of some derivatives of sulfanilamide (author's transl)].

9 derivatives of sulfanilamide were tested for anticonvulsant properties against electroconvulsive shock in mice and rats and against pentylenetetrazole shock in mice. Reference standard in these tests was sulfanilamide. Their toxic, analgesic and sedative activities were also examined. The anticonvulsive activity of sulfanilamide could be enhanced by substitution of the phenyl ring with a halogen atom. Substitution of the sulfonamide group diminishes the anticonvulsant and increases the sedative activity of sulfanilamide. Detoxication of the basic substance by substitution of the aromatic amino group only little influences the anticonvulsant activity and may even enhance it. Of the tested substances, 1742 (3-chloro-4-phenacetamido-benzene-sulfonamide) exhibited the best anticonvulsant activity; slightly weaker was PB 311 (3-chloro-4-amino-benzene-sulfonamide). The ED50 for the activity against electroconvulsive shock of both substances was about 30 mg/kg p.o. in mice. The relationship between anticonvulsant activity and inhibition of the renal and cerebral carbonic anhydrase is discussed.


[Pharmacological effect of tinofedrine on cerebral and peripheral hemodynamics in the dog (author's transl)].

l-(+)-alpha-(1-[(3,3-Di-3-thienylallyl)amino]-ethyl)-benzyl alcohol hydrochloride (Tinofedrine, D 8955, Novocebrin), a new drug, synthetized in our research laboratories, has been tested in dogs with regard to the improvement of cerebral and peripheral blood flow. Direct electromagnetic flow measurement at the vertebral artery as well as 133xenon wash-out method showed a strong and long-lasting increase of cerebral and femoral blood flow following intravenous as well as oral administration. No decrease of activity was observed after repeated intravenous application. Comparative studies with several standard drugs of the same field of indication proved a remarkable superiority of tinofedrine in our experimental conditions.


[The influence of tinofedrine on cerebral energy metabolism in normotensive, hypotensive and hypoxemic rats after carotis ligation (author's transl)].

l-(+)-alpha-(1-[(3,3-Di-3-thienylallyl)amino]-ethyl)-benzyl alcohol hydrochloride (tinofedrine hydrochloride, D 8955, Novocebrin), a new cerebrally active substance, synthetized in our research laboratories, was investigated for its action on the disturbed cerebral metabolism in rats. By variation of the arterial blood pressure (normal, 100 and 70 mmHg), and O2-concentration for the artificial ventilation of 30 or 15 vol% and carotis ligation for 15, 30 and 60 min different degrees of cerebral disturbances could be induced. The glucose concentration and energy state of the brain were used as criteria of the degree of cerebral disturbance. After intravenous injection of tinofedrine such a disturbed cerebral state could be normalized partially or completely.


[Studies on the pharmacokinetics and metabolism of tinofedrine].

Pharmacokinetics and biotransformation of l-(+)-alpha-(1-[(3,3-di-3-thienylallyl)-amino]-ethyl)-3-benzyl alcohol hydrochloride (tinofedrine hydrochloride, D 8955, Novocebrin) were investigated in rat and dog by means of the 3H-labelled drug. After i.v. administration similar biphasic time courses of the plasma levels are seen in the rat and the dog. The elimination is linear with a half-life of 3.0 and 3.8 h, respectively. After peroral administration 3H-tinofedrine is absorbed much more rapidly by the dog than by the rat. Radioactivity is subsequently eliminated from plasma by both species at nearly identical speed, which corresponds to that after i.v. administration. Quantitative analysis of the organ distribution after i.v. administration in the rat reveals a distinct affinity of 3H-tinofedrine for the lung. All tissue bindings, however, after both routes of administration are reversible. After preoral administration the drug is absorbed nearly quantitatively in the dog and in the rat with 50--63%. Only unchanged tinofedrine can be detected in the blood of the mesenteric veins. Tinofedrine is completely metabolized. In the rat and in the dog three different conjugates are formed, two of which are excreted with the bile. During their way through the intestine they are split again into tinofedrine, which is found in the feces. 3H-Tinofedrine after i.v. and peroral administration is mainly excreted fecally by the rat and the dog. This is caused by the great extent of the biliary excretion of the metabolites.


The central action of various arecaidine esters (arecoline derivatives) on blood pressure and heart rate in the cat. Comparison with the peripheral effects.

The central action of various arecaidine esters (arecoline derivatives) on the cardiovascular system has been studied. Central injection of these cholinergic drugs into the vertebral artery of the cat gives rise to a hypotensive effect, whereas heart rate is not affected. It is concluded that the blood pressure lowering effect is brought about by stimulating central muscarinic receptors. Moreover, the experimental results indicate that the central muscarinic receptors behave in the same way towards their agonists as do the peripheral muscarinic receptors.


[Phosphoric acid ester poisoned rats after antidote therapy. 2. Determination of serum enzyme activity].

Paraoxon in doses of one LD50 (0.426 mg/kg), eight times and eighty times LD 50 was applied s.c. to female Sprague-Dawley rats. After 3, 6, 10, 24 and 36--48 h the activities of enzymes GOT, GPT, GLDH, SDH, CPK and ChE were measured, once after i.m. antidote application of Toxogonin only, of Toxogonin + atropine and the next one after application of combination Toxogonin + atropine + Solcoseryl (low-molecular components of deproteinized blood from young calves. The values obtained showed that in spite of treatment with Toxogonin or Toxogonin + atropine the activities of the enzymes increased; this enhancement could be prevented by addition of Solcoseryl to Toxogonin + atropine. The ChE-activity after 36 h was equivalent to that of the control value. The effect of paraoxon in the initial phase of poisoning was discussed in connection with hypoxia and acidosis resulting from a respiratory insufficiency as well as the inhibition of ATPase-activity with restriction of the energy metabolism following: consequently the effect of Solcoseryl was interpreted as an activation of the disturbed energy metabolism.


[Increased regional hepatic blood circulation and bile flow following application of peloid paraffin packs on rat abdominal wall].

In Sprague-Dawley rats anaesthetized with pentobarbital-Na and breathing spontaneously, regional hepatic blood flow (rHBF) is measured in the liver in situ and during application of peloid paraffin packs on the abdominal wall. Blood flow measurements are performed by means of the 85Kr(beta)-clearance technique after slug injection of the dissolved indicator into the thoracic aorta. Mean arterial blood pressure is monitored continuously. After exposing the liver surface by an incision at the right costal margin, rHBF is measured, 5, 15, 35 and 45 min later. The results of a control series clearly show that there exists a time-dependent decrease of rHBF at comparable M ABP values and normal respiratory gas parameters. If peloid paraffin packs are applied on the abdominal wall 25 min after the surgery, this time-dependent decrease of rHBF ceases and rHBF then increases to initial values. In comparison to the control series the application of peloid paraffin packs on the abdominal wall causes a significant increase in rHBF of about 20--39%. Experiments on bile flow of rats show that under normal conditions and after insertion of a cannula into the common hepatic duct, a time-independent mean flow of 0.053 ml bile/kg body weight/min occurs. The application of peloid paraffin packs 45 min after the suture of the abdominal wall yields a significant increase in bile flow of 18% within 15 min.


Inhibitory effect of 1,4-dimorpholino-7-phenylpyrido[3,4-d]-pyridazine (DS-511) and its 4'-hydroxy derivative on antidiuretic action of vasopressin in rats.

The water-diuretic features of 1,4-dimorpholino-7-phenylpyridol[3,4-d]-pyridazine (DS-511) and its water-soluble 4'-OH derivative [DS-511(4'-OH)] were investigated. In saline-infused rats the minimum i.v. diuretic dose of DS-511(4'-OH) was 1.0 micrograms/kg/min, while in water-diuretic rats the minimum dose was 50 micrograms/kg/min. Intravenous infusion of DS-511 or DS-511(4'-OH) at rates of 1 to 10 micrograms/kg/min caused a dose-dependent inhibition of the ADH-induced antidiuresis in water-diuretic rats, and a decrease in urinary osmolality. However, hydrochlorothiazide even at 500 micrograms/kg/min did not alter the antidiuresis, but increased the osmolality. Furosemide at a rate of 10 micrograms/kg/min increased urinary excretion of water and sodium in both saline-infused and water-diuretic rats, but the same dose did not inhibit the ADH-induced antidiuresis. These findings indicate that the specific anti-ADH action at relatively low doses of DS-511 and DS-511(4'-OH) is partly involved in the diuretic mechanism of these agents.


Collection of control data from teratological experiments on mice, rats, and rabbits. A group study.

A joint study was undertaken in the laboratories of five pharmaceutical companies to evaluate accumulated data on the progeny of mice, rats and rabbits of various strains or breeds. The recorded morphological deviations from normal were classified according to the time of their occurrence during embryonic and foetal development, and three categories were differentiated. Comparison of the data from the various laboratories in general revealed similar results, and the variations observed are presumed to be due to differences in experimental conditions.


[Distribution volume and elimination of triamterene and its active metabolites in the rabbit (author's transl)].

In rabbits the volumes of distribution of triamterene (TA) and its metabolites hydroxytriamterene (OH-TA) and hydroxytriamterene sulfuric acid ester (OH-TA-ester) were determined after i.v. administration of the agents. Both TA as well as its metabolites distribute in at least 2 compartments, OH-TA exhibiting by far the greatest volume of distribution, followed by TA and then by OH-TA-ester. TA and its phase-II-metabolite are eliminated at practically equal rate, whereas the elimination of OH-TA is relatively slow.


[Pharmacological effects of phase-I- and phase-II-metabolites of triamterene (author's transl)].

Since triamterene (TA) is rapidly metabolized to hydroxytriamterene (OH-TA) and then to its sulfuric acid ester (OH-TA-ester) the question arose whether the metabolites are still effective on ion transport as is triamterene. The effect of the metabolites was studied in microperfusion experiments on the rat submaxillary duct, which resembles the distal nephron and is considered the site of action of triamterene. Added to the lumen the phase-I- as well as the phase-II-metabolites decreased reabsorption of Na+, secretion of K+, and yielded an accumulation of HCO3-. These effects of the metabolites were produced by equimolar concentrations and are almost identical to those of native triamterene. In conclusion, the phase-II-metabolite must be considered to be essentially responsible for the natriuresis and antikaliuresis observed after oral administration of triamterene.


[Pharmacokinetics of triamterene and its active metabolites in renal insufficiency (author's transl)].

1. After one oral dose of 100 mg triamterene plasma levels of triamterene (TA) and its metabolites hydroxytriamterene (OH-TA) and hydroxytriamterene sulfuric acid ester (OH-TA-ester) were studied in patients with normal and impaired renal function and in patients submitted to hemodialysis. Triamterene and its metabolites were also determined in the urine and the dialysate, respectively. 2. Hydroxytriamterene sulfuric acid ester (OH-TA-ester) representing a phase-II-metabolite of triamterene was found to yield plasma concentrations which were always higher than those of native TA. 3. In decreased renal function the elimination half-lives (t 1/2) of TA and OH-TA-ester were increased yielding elevated plasma levels of TA and its metabolites. The data of t 1/2 for TA and OH-TA-ester correlated with the creatinine clearance in an almost hyperbolic fashion. 4. Dialysance values of about 2 to 4 ml/min were determined for TA and OH-TA-ester.


Plasma concentrations of isosorbide dinitrate after administration of increasing doses of a sustained-release formulation to human subjects.

Plasma concentrations of isosorbide dinitrate have been measured after administration of increasing doses in the range 20--100 mg as sustained-release tablets (Isoket retard) containing 20 mg to human subjects. Means of peak concentrations of 4.2 ng/ml, 13.1 ng/ml, 20.7 ng/ml, 36.8 ng/ml, and 34.9 ng/ml were measured after doses of 20 mg, 40 mg, 60 mg, 80 mg and 100 mg, respectively. In the plasma of individual subjects, peak concentrations of isosorbide dinitrate increased in proportion to the dose administered. Areas under the plasma isosorbide dinitrate concentration-time curves also increased in proportion to the dose administered. Bioavailability parameters were better correlated to the dose over the range 20--60 mg than over the range 20--100 mg.


[The toxicity of lincomycin. Two i.v. applications of 6 g. each to a 10 year old girl without toxic symptoms].

A 10-year old girl (34.5 kg) being treated at our clinic for osteomyelitis erroneously received an overdose of lincomycin. On a single day she was given 2 infusions containing 6 g of lincomycin each, which corresponds to a dose of 343 mg/kg of body weight. There was an interval of 10 h between infusions. Apart from fatigue and unpleasant taste sensation, she demonstrated no signs of intoxication. None of the laboratory parameters (GOT, GPT, gamma-GT, LDH, G-LDH, LAP, alkaline phosphatase and CK; furthermore, the concentrations of glucose, BUN, creatinine, uric acid and bilirubin) offered any evidence of toxic organ damage. Osteomyelitis in children demands extremely high doses of antibiotics. In view of this fact, the therapeutic range of a substance is of utmost clinical interest.


[Determination of azapropazone and 8-hydroxyazapropazone in urine by direct quantitative thin-layer chromatography (author's transl)].

A method for quantitative determination of 5-dimethyl amino-9-methyl-2-propyl-1H-pyrazolo[1,2-a] [1,2,4]benzotriazine-1,3-(2H)-dione (azapropazone) and 8-hydroxyazapropazone in urine has been described. The analysis is performed by quantitatively thin-layer chromatography. The method is selective with a standard deviation of about 5%. After daily oral administration of 3 x 300 mg azapropazone-dihydrate a mean excretion of azapropazone of 62% and a mean excretion of 8-hydroxyazapropazone of 14% was determined.


Influence of linseed oil on cholesterol-induced atherosclerosis in rabbits.

Four groups of rabbits were studied to determine the effect of linseed oil on cholesterol-induced atherosclerosis. Group C received cholesterol alone; group CL received cholesterol and linseed oil, group L were given linseed oil alone, while group N were fed the normal stock diet for 18 weeks. Cholesterolemia was marked in groups C and CL but not in groups L or N. Cholesterolemia was significantly greater (P less than 0.001) in group CL (462 mg/dl) than in group C (318.6 mg/dl). Thus, the addition of linseed oil to cholesterol led to greater hypercholesterolemia than with the cholesterol diet alone. There was no significant change in the serum triglyceride level in either group. Atherosclerotic lesions (mostly fatty streaks but some fibrous plaques) were present only in groups C and CL and were absent in groups L and N. The percentage of atherosclerotic intimal involvement was significantly greater in group CL than C (P less than 0.001). The severity of atherosclerosis correlated with serum cholesterol levels (r = 0.79, P less than 0.001), but not with serum triglyceride levels.


Deuterium nuclear magnetic resonance investigation of dimyristoyllecithin--dipalmitoyllecithin and dimyristoyllecithin--cholesterol mixtures.

Deuterium nuclear magnetic resonance (NMR) spectra of 1,2-dimyristoyl-3-sn-phosphatidylcholines (DMPCs) specifically deuterated in the 2-chain at one of positions 2', 3', 6', or 14' have been obtained by the quadrupole-echo Fourier transform method at 34.1 MHz (corresponding to a magnetic field strength of 5.2 T) or the pure material as a function of temperature, and in the presence of either 1,2-dipalmitoyl-3-sn-phosphatidylcholine (DPPC) or cholesterol as a function of temperature and composition. The results with pure DMPC and DMPC--DPPC mixtures indicate that a sharp, intense deuterium resonance is characteristic of fluid-phase lipids, whereas a broad resonance is characteristic of solid-phase lipids. There is shown to be good agreement between the deuterium NMR derived DMPC--DPPC phase diagram and that derived by using other techniques. The deuterium NMR results obtained with the DMPC--cholesterol system are not interpreted in terms of a phase diagram. They do indicate, however, that the transition breadth is increased considerably and the temperature at which the lipid chains "solidify" is depressed by the addition of cholesterol to the DMPC bilayer. The particular nature of the increase and the depression is found to be dependent on where the label is located on the lipid.


The physical properties of an effective lung surfactant.

It is suggested that the phospholipids at the alveolar/air interface exhibit both thermodynamic (equilibrium) and kinetic forces during the course of a respiratory cycle. The alveolae are kept open at full expiration by a residue of nearly pure dipalmitoyl phosphatidylcholine which is condensed and therefore, incompressible at 37 degrees C.


[Do children take their milk at the dilution that you indicated].

The experiment was plotted with the purpose of discovering the variability of the measurements of powder milk and refined cane sugar. With this idea in mind, a plastic measurement contained in a commercial lactic product and teaspoon were used. With the results obtained from the dehydrated milk measured by 3 groups of 25 mothers and one of 25 nurses and those corresponding to 10 mothers and 5 nurses who measured the cane sugar, a speculation arose on the eventual significance these findings might have on the state of nutrition of the infants.


[Heterogeneity of phospholipid membranes detected by the fluorescent probe method].

The measurements of fluorescence polarization index within the emission spectra of the fluorescent probes 4-dimethylaminochalcone (DMCh) and 3-methoxybenzantrone (MBA) have indicated that probes are distributed in liposomes prepared from synthetic dipalmitoyl lecithin (DPL) between binding sites of two types. By the method described in the present paper the spectra measured experimentally have been divided into two spectral components. The shape and position of this componential spectra were independent of the probe:lipid concentrations ratio.


HLA and sexually transmitted diseases in prostitutes.

The HLA profile of 148 unrelated, Chinese prostitutes (56 with repeated gonococcal infection, 31 with syphilis, 31 with gonorrhoea and syphilis, and 30 with no evidence of infection) was compared with that of 238 unrelated, healthy, Chinese control subjects. The joint occurrence of AW19 B17 was observed in 25.8% of prostitutes with double infections compared with 6.7% of control subjects, while that of A11 B15, on the other hand, was associated with a resistance to syphilis and gonorrhoea. The latter profile was observed in 46.7% of prostitutes in business for more than two years who were resistant to disease, in 30% of prostitutes with an overall disease resistance, in 13.4% of control subjects, and in only 3.2% of prostitutes with combined syphilis and gonorrhoea. Because of the statistical uncertainty when multiple variables are being analysed these studies should be repeated in other groups of prostitutes of the same and different ethnic origins.