The synthesis of 2-acetamido-2-deoxy-4-O-beta-D-mannopyranosyl-D-glucose.

Condensation of 4,6-di-O-acetyl-2,3-O-carbonyl-alpha-D-mannopyranosyl bromide with 2-amino-2-N,3-O-carbonyl-5.6-O-isopropylidene-D-glucose diethyl acetal gave, unexpectedly, 2-amino-2-N,3-O-carbonyl-2-deoxy-4-O-(4,6-di-O-acetyl-2,3-O-carbonyl-alpha-D-mannopyranosyl)-5,6-O-isopropylidene-D-glucose diethyl acetal, futher transformed, by de-esterification followed by acetylation, into the previously known 2-amino-2-N,3-O-carbonyl-2-deoxy-5,6-O-isopropylidene-4-O-alpha-D-mannopyranosyl-D-glucose diethyl acetal and its tetra-O-acetyl derivative. Benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-beta-D-glucopyranoside was condensed with 2-O-acetyl-3,4,6-tri-O-benzyl-beta-D-glucopyranosyl bromide to give benzyl 2-acetamido-4-O-(2-O-acetyl-3,4,6-tri-O-benzyl-beta-D-glucopyranosyl)-3,6-di-O-benzyl-2-deoxy-beta-D-glucopyranoside. Removal of the 2-O-acetyl group, followed by oxidation with acetic anhydridedimethyl sulfoxide, gave a beta-D-arabino-hexosid-2-ulose (25). After reduction with sodium borohydride, removal of the benzyl groups gave crystalline 2-acetamido-2-deoxy-4-O-beta-D-mannopyranosyl-D-glucose (27). The anomeric configuration of the glycosidic linkage was ascertained by comparison with the alpha-D-linked disaccharide.


Synthesis of prumycin and related compounds.

Prumycin (1) and related compounds have been synthesized from benzyl 2-(benzyloxycarbonyl)amino-2-deoxy-5,6-O-isopropylidene-beta-D-glucofuranoside (4). Benzoylation of 4, followed by deisopropylidenation, gave benzyl 3-O-benzoyl-2-(benzyloxycarbonyl)amino-2-deoxy-beta-D-glucofuranoside (6), which was converted, via oxidative cleavage at C-5-C-6 and subsequent reduction, into the related benzyl beta-D-xylofuranoside derivative (7). Benzylation of 3-O-benzoyl-2-(benzyloxycarbonyl)-amino-2-deoxy-D-xylopyranose (8), derived from 7 by hydrolysis, afforded the corresponding DERIVATIVES (9,11) of beta-and alpha-D-xylopyranoside, and compound 7 as a minor product. Treatment of benzyl 3-O-benzoyl-2(benzyloxycarbonyl)amino-2-deoxy-4-O-mesyl-beta-D-xylopyranoside (10), formed by mesylation of 9, with sodium azide in N,N-dimethylformamide gave benzyl 4-azido-3-O-benzoyl-2-(benzyloxycarbonyl)amino-2,4-dideoxy-alpha-L-arabinopyranoside (13), which was debenzoylated to compound 14. Selective reduction of the azide group in 14, and condensation of the 4-amine with N-[N-benzyloxycarbonyl)-D-alaninoyloxy]succinimide, gave the corresponding derivative (15) of 1. Reductive removal of the protecting groups of 15 afforded 1. Prumycin analogs were also synthesized from compound 14. Evidence in support of the structures assigned to the new derivatives is presented.


Methylation studies of the polysaccharides resulting from sequential Smith-degradations of the galactan from the snail Strophocheilus oblongus.

When the galactan from the albumen glands of the snail Strophocheilus oblongus was submitted to three Smith-degradation, the degraded polysaccharide, isolated in 6% yield, was much more linear. Methylation analysis showed that the Smith-degraded polysaccharide gave an increased percentage of 2,4,6-tri, decreased percentages of 2,3,4,6-tetra-and 2,4-di, and a large variation in the amount of 2,3,4-tri-O-methyl-D-galactose. The sugars in the polysaccharide which result in the formation of 2,3,4,6-tetra- and 2,3,4-tri-O-methyl-D-galactose are destoryed in subsequent degradation procedures. The above observations suggest that the degradation by periodate oxidation proceeds via non-reducing end-groups and though some internal residues that are exposed as the degradation proceeds. As a result of the overall process, new non-reducing end-groups are formed and new (1 leads to 6)-linked D-galactose residues are then exposed. The  isolation of glycosides of low molecular weight supports the suggestion that the molecule, in the main, is sequentially degraded from the external layers.


Synthesis of O-beta-D-galactopyranosyl-(1 linked to 4)-O-(2acetamido-2-deoxy-beta-D-glucopyranosyl)-(1 linked to 2)-D-mannose and its interaction with various lectins.

2-Methyl-[3,6-di-O-acetyl-2-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-alpha D-glucopyrano]-[2,1-d]-2oxazoline (4) was prepared from 2-acetamido-3,6-di-O-acetyl-2-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-alpha-D-glucopyranosyl chloride. Condensation of 3,4:5,6-di-O-isopropylidene-D-mannose dimethyl acetal with 4 in the presence of a catalytic amount of p-toluenesulfonic acid afforded O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1 linked to 4)-O-(2-acetamido-3,6-di-O-acetyl-2-deoxy-beta-D-glucopyranosyl)-(1 linked to 2)-3,4:5,6-di-O-ispropylidene-D-mannose dimethyl acetal (6) in 8.6% yield. Catalytic deacetylation of 6 with sodium methoxide, followed by hydrolysis with dilute sulfuric acid, gave O-beta-D-galactopyranosyl-(1 linked to 4)-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1 linked to 2)-D-mannose (7). The inhibitory activities of 7 and related sugars against the henagglutinating activities of various lectins were assayed, and 7 was found to be a good inhibitor against Phaseolus vulgaris hemagglutinin.


Chemical modification of aminocyclitol antibiotics.

The aminocyclitol antibiotic neamine has been chemically modified at the hydroxyl group on C-6 of the 2-deoxystrepatamine moiety. The partially acetylated neamine derivatives, 6,3,4-tri-O-acetyl- (3) and 5,3-57,4-tri-O-acetyl-1,3,2,6-tetra-N-(ethoxycarbonyl)neamine (4), were prepared by random hydrolysis of the 5,6-O-ethoxyethylidene derivative (2), followed by chromatographic purification. Condensation of 4 and 2,3,5-tri-O-benzoyl-D-ribofuranosyl chloride led to 6-O-(beta-D-ribonfuranosyl)neamine (7). Analogous condensation of 4 with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide or 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide afforded the corresponding 6-O-(D-hexopyranosyl)neamines.


Changes in carbohydrate content of surface membranes of human erythrocytes during ageing.

The carbohydrate content (neutral hexoses, fucose, sialic acid, and hexosamine) of human erythrocytes is significantly higher in young than in old erythrocytes. The differences observed in the carbohydrate content of surface glycopeptides, obtained after incubation with either Pronase or trypsin, is still more striking, suggesting important modifications of the carbohydrate moeties of the erythrocyte membrane during in vivo ageing.


Venous pressure and exercise tolerance.

Compared to the number of contractions obtained when a blood pressure cuff on the upper arm was at zero pressure, inflation of the cuff to pressures ranging between 5 and 40 mm Hg resulted in an augmentation of the number of hand contractions that could be performed prior to the development of ipsilateral severe fatigue or intolerable pain. Cuff pressures of 60 mm Hg reduced the number of contractions below the control level. These results are consistent with the concept that exercise during venous congestion facilitates the washout of the toxic catabolite presumed to be produced during muscular contraction.


Factors affecting the transvalvar pressure difference in a hydraulic model of aortic stenosis.

Mechanical factors that can modify the peak transvalvar pressure differences (delta P) in aortic stenosis were evaluated in a model. A latex rubber sac simulated the ventricle. Expansion of the walls of the sac by means of a negative pressure applied to its outer wall introduced a measure volume into the sac and placed the wall materials under tension. The stretched sac was then permitted to contract and to expel its contents through "aortic valvar" orifices of various severities of stenosis, into an aortic standpipe of selected diameters (compliances). Factors that increased the peak delta P included the strength (thickness) of the ventricular wall, the rate at which it mobilized and applied its tensile force to compress the sac contents, the unstressed volume of the sac, the total volume in the sac at onset of contraction, the severity of the valvar stenosis, the compliance of the aorta, the rate of arterial run-off, and the aortic diastolic pressure. Loss of forward stroke volume due to mitral regurgitation lowered the peak delta P. Elevations in diastolic arterial pressure also lowered delta P. All of these mechanical factors should be considered in the analysis of the severity of clinical aortic valvar stenosis and in decisions for medical therapy and surgical correction. The several factors which do not depend directly on the orifice area or on the forward stroke volume vitiate the sole use of the orifice formula in the analysis of the dynamics of aortic stenosis. The application of this approach in related problems is indicated.


Effect of ischemia and infarction on regional content of adenine nucleotides and derivatives in canine left ventricle.

Samples of myocardium from four areas of ischemic and infarcted canine ventricle were examined over a 20-day period for content of the three adenine nucleotides as well as inosine, hypoxanthine, adenosine, and inosine monophosphate. The adenosine triphosphate (ATP) content of central and peripheral areas within the infarct fell to 11% and 8% of control, respectively, 1 day after coronary occlusion. The total adenine nucleotide (TAN) content in these areas fell to 17% of control and showed no significant recovery during the period of study. In the functional myocardium immediately surrounding the infarct the ATP content was depressed to 58% control after 1 day, and the TAN content was also depressed. In the healthy myocardium near the apex, the ATP content was significantly depressed only at the 3-day sample period. Adenine nucleotide derivatives were detected only at 30 min in the central ischemic area. The absence of the nucleoside and nucleobase compounds formed during adenine nucleotide degradation is attributed to their high membrane diffusibility. Loss of these compounds is considered a contributing factor in the prolonged depression of adenine nucleotide content in both ischemic and non-ischemic regions.


Massive left atrial thrombus: a case report.

This case report describes a patient with aortic and mitral valvular disease who had a massive left atrial thrombus. The left atrial thrombus produced a disappearance of signs of mitral stenosis and a reversed pan diastolic mitral valve gradient. This gradient occurred in the absence of any diastolic mitral insufficiency and may have been due to artifactual lowering of the left atrial pressure by an organized left atrial clot.


Selection of temperature-sensitive CHL asparagyl-tRNA synthetase mutants using the toxic lysine analog, S-2-aminoethyl-L-cysteine.

We developed a procedure, using the toxic lysine analog S-2-aminoethyl-L-cysteine (thialysine) as the selective agent, to obtain mutant Chinese hamster lung (CHL) fibroblasts with temperature-sensitive defects affecting protein synthesis. The procedure is efficient, rapid, and simple. Using this selective system, we isolated six temperature-sensitive mutants that fail to grow (plating efficiencies less than 10-5) and synthesize protein at 39 degrees C. The temperature-sensitive phenotype of five of the six mutants is suppressed in vivo by exogenous asparagine. In the mutant studied in the greatest detail, asparagyl-tRNA synthetase activity is extremely thermolabile in vitro. Asparagine-suppressible, temperature-sensitive mutants are induced at a high frequency by the mutagen ethylmethane sulfonate (EMS), and they can be efficiently recovered using the proper selective conditions. Our results suggest that CHL cells have only one functional copy of the gene encoding for asparagyl-tRNA synthetase.


Control of lysozyme induction in the differentiation of myeloid leukemic cells.

A system has been developed with clones of mouse myeloid leukemic cells in culture to study the induction of synthesis and secretion of lysozyme in relation to other steps in myeloid cell differentiation. Lysozyme was initially absent in all the clones studied. The different clones can be divided into three types according to their ability to be induced to undergo normal cell differentiation by the protein inducer MGI (macrophage and granulocyte inducer). One type of clone that can be induced by MGI to form Fc and C3 receptors and differentiate to mature macrophages and granulocytes (MGI+D+) was also induced by MGI to synthesize and secrete lysozyme. Lysozyme was induced after Fc and C3 receptors, and labeling with 35S-methionine has shown that the induced lysozyme was newly synthesized. MGI+D+ clones were also induced to synthesize and secrete lysozyme by dexamethasone, prednisolone, cytosine arabinoside, or thymidine and in one of four clones by dimethylsulfoxide but not by sodium butyrate. Inhibition of cell multiplication by itself was not sufficient to induce lysozyme synthesis. A second type of clone which can be induced by MGI to form Fc and C3 receptors but not mature cells (MGI+D-) was more weakly inducible by MGI for lysozyme and was not inducible by any of the other compounds. A third type of clone (MGI-D) MGI for receptors or mature cells. One of four MGI-D- clones was induced to synthesize but not secrete lysozyme by dexamethasone together with sodium butyrate, but there was no lysozyme induction by MGI or any of the other compounds separately. The different clones maintained their different properties for at least 6 months in culture. The results indicate that clones with different hereditary blocks in the ability to be induced to differentiate by specific compounds can be used to dissect the process of myeloid cell differentiation, that the sequence of differentiation is induction of Fc and C3 receptors leads to lysozyme leads to mature cells, and that there are separate controls for these developmental steps.


The expression of three abundance classes of messenger RNA in mouse tissues.

Using the technique of mRNA-cDNA hybridization, we have shown that there are between 11,500 and 12,500 different mRNAs in three different mouse tissues:kidneys, brains, and livers. Several experiments suggest that in each tissue the mRNAs are organized into three abundance classes rather than as a continumm with respect to concentration. Cross-hybridization experminets show that the most abundant class of mRNA in each tissue is characteristic, and that a high proportion of the total sequences are common between tissues. For a more complete analysis, cDNA was fractionated into three classes. Studies using isolated abundant cDNA show that some abundant sequences of liver and kidney are present in other tissues, but among the lower frequency classes. Thus tissue-specific differences in mRNA populations may be related to abundance as well as qualitative differences. Using isolated middle frequency cDNA of the kidney, it was shown that of the 550 or so sequences in this class, approximately 500 are shared with the liver. Similarly, between 9,500 and 10,500 of the low frequency kidney cDNAs are shared with the brain and liver, respectively, suggesting that the majority of mRNAs may be involved with "housekeeping" activities. In an attempt to see whether abundance of mRNA is related to repetition of the sequence in the genome, it was shown that abundant and middle frequency cDNA of the liver and kidney contain a component that anneals with DNA repeated approximately 100 fold. However, the low frequency cDNA of the kidney contains no repeated sequences.


A radiological analysis of the transcription units for heterogeneous nuclear RNA in cultured murine cells.

Ultraviolet irradiation of cultured murine cells damages chromosomal DNA, thus causing premature termination of synthesis of hnRNA chains. We have utilized this effect for measuring the sizes of transcription units for the various classes of hnRNA. Target size analyses of the loss of synthesis of hnRNA species suggest that hnRNA, through its entire size range, constitutes mostly primary transcripts-that is, the shorter RNA molecules are not processed from longer precursors. Polyadenylated hnRNA appears to be a primary transcript as well. Our data, however, are also consistent with processing of precursors to poly(A)+ hnRNA from the 5'termini of larger hnRNA molecules. They are not consistent with models which postulate that poly(A)+ hnRNA sequences originate at the 3' termini of precursors which are considerably larger (greater than 30%) than the polyadenylated hnRNA molecules themselves. Finally, we have found that the process of polyadenylation is not measurably affected by ultraviolet irradiation of cells.


Identification and characterization of multiple forms of actin.

Multiple forms of actin have been found in a variety of mammalian cell lines and tissues by the use of high resolution, two-dimensional gel electrophoresis. One form (alpha actin) was found only in differentiated muscle cells, and its synthesis is induced during myogenesis in culture. Two other forms (beta and gamma actin) are present in all nonmuscle cell types examined, and they continue to be synthesized in cultured muscle cells after fusion. Tryptic peptide comparisons have shown that muscle actin is distinguished from the two "nonmuscle" actins by several peptide differences, and that the two non-muscle actins are nearly identical. All three forms contain equimolar amounts of N-methylhistidine, and extensive controls have shown no evidence of artifactual heterogeneity. In addition to the three major actins, two other proteins were identified as probably forms of actin by affinity for DNAase I-agarose. These proteins are similar in charge and molecular weight to the major actin forms, but are unstable and have lifetimes in the cell of less than 2 hr.


The effect of ecdysterone on nonhistone proteins in salivary gland chromosomes of Sciara coprophila.

Synthesis and transport of proteins to the cell nucleus during puff induction was studied in S. coprophila. Changes in grain distribution along chromosomes (L-methionine [35S] incorporation into protein) were correlated with puffs induced by ecdysterone in vitro; A pattern of specific labelling at the sites of incipient puffs was noted within 2 h after the addition of the hormone, i.e. grains on the chromosomes were in clusters, characteristic for this time point and not seen in the controls (where only non-specific labeling was noted 0-4 h). Characteristic chromosomal puffs appeared between 3-4 h after the addition of ecdysterone. It was concluded that during ecdysterone-induced puff formation in salivary gland chromosomes, proteins which had been previously synthesized were selectively transported from the cytoplasm to specific sites on the chromosomes.


Changes in type of collagen synthesized by chick fibroblasts in vitro in the presence of 5-bromodeoxyuridine.

Chick embryo fibroblasts cease to synthesize their normal collagen product when grown in the presence of the thymidine analogue, 5-bromodeoxyuridine (BrdU). The drug causes an alteration of synthesis from the normal Type I collagen (alpha1 (I)2alpha2) to a mixture of Type I and Type I trimer (alpha1(I)3). While the significance of the synthesis of Type I trimer is unclear, it has been noted that chondrocytes synthesize this collagen type following in vitro senescence and in the presence of BrdU. Since BrdU may cause a switching in the temporal pattern of collagen biosynthesis in chondrocytes and in fibroblasts it is proposed that BrdU may alter the normal regulatory controls acquired by the cells during the course of their differentiation. The synthesis of type I trimer might provide a marker for such a break-down in a wide variety of cell types.


Recombination of embryonic haemoglobin chains during the development of the chick.

Embryonic differentiation is at present interpreted as the expression of variable gene activity. It is commonly thought that derepression of operator gene groups is the main cause of progress during development. However it is equally possible that gene repression plays a role in the appearance of new phenotypic characteristics. This paper illustrates such a possibility. It is known that in chickens embryonic haemoglobins exist which are replaced by other haemoglobins at about the sixth day of incubation. Analyses of globin chain composition of these haemoglobins by chromatography and urea/starch gel electrophoresis as well as TLC-fingerprinting and amino acid analyses of the individual globin chains showed that the haemoglobin switch was not associated with appearance of new globin chains but rather with disappearance of a number of embryonic chains. Moreover the relative proportion of the various chains changed at that time. From these findings we conclude that new haemoglobins arise from a recombination ('hybridization in vivo') of those globin chains which remain after the repression of a gene coding for embryonic chains.


Evidence of hormonal control of the nucleolar activity in Sciara ocellaris.

The nucleolus organizing region in the salivary gland of Sciara ocellaris becomes gradually less active as the larvae approach pupation. The cytological visible condensation of the nucleolar puff is paralleled by a decrease in the incorporation of [3H]-uridine into the ribosomal RNA. Alterations in the nucleolar behavior were brought about by extirpation of the neuroendocrine glands at six stages of development. There is a 'critical stage' during the 7th day of the 4th instar when the hormonal stimulus for pupation occurs. If the ligature is performed before this stage the NOR remains expanded and the larval-pupal ecdysis is inhibited; if done later on the NOR condenses at a normal rate and the ligated larvae mount to head-less pupae. These results suggest that inhibition of rRNA synthesis and consequent condensation of the NOR is under the control of the moulting hormone.


[Pseudocysts of the pancreas. (Personal cases)].

After reviewing all the various procedures for surgical treatment of pseudocysts of the pancreas, the Authors, analysing the advantages and disadvantages of each method, present a set of nineteen personal cases treated by simple cystogastrostomy, simple cystojejunostomy and cystojejunostomy combined with entero-entero-anastomosis according to Braun, or cystojejunostomy on defunctionalised loop according to Roux. After stading the overall criteria for selection of the technique to be applied individually, the Authors conclude by stressing the advantages that cystojejunostomy on defunctionalised loop according to Roux offers as compared with all the other procedures.


[Arteriovenous fistulas in hemodialytic treatment].

In view of the necessity for patients under periodical dialysis to preserve in operating condition the artero-venous fistulas performed on them, so that the application of the dialytic processes is extended as much as possible, particular technical suggestions are put forward, also taking into account the requirements of immediate dialysis for acute uremia and endeavouring to recover any artery and vein that may be used for external by-passes.


[Use of the femoral artery for chronic hemodialytic treatment].

In 4 patients subjected to periodical haemodialytic treatment a new route of access to the vessels was used; the common femoral artery and the large saphena to the outlet into the femoral vein. All four patients presented serious problems with regard to application of a new shunt in view of the previous reiterated use of the vessels commonly utilized. At the maximum distance of 46 months from implantation, only one of the four by-passes is still in use; 2 were removed for obstruction and the fourth, still operating at the time, was removed for a renal transplant performed on the patient. In view of the frequency  of troubles and the use-months of the femoral by-pass compared with the traditional ones, the femoral route of access may be considered favourably when the traditional shunt implantation or fistula creation procedures are precluded.


[Retroperitoneal liposarcoma].

The various aspects of this comparatively rare neoplasia are discussed on the basis of two cases of retroperitoneal liposarcoma and an analysis of the literature. Consideration are expressed on the clinical symptoms, the pathological anatomy, its marked tendency to evolve with repeated local relapses and the need to properly localise the mass and the feeding peduncles prior to the operation, so that radical exercise can be performed, since this leads to a more favourable long-term prognosis. The utility of radiotherapy, which leads to a lengthened period of freedom from the disease and to an increased  survival time, is also stressed.


[Senile dysplasias of Vater's ampulla].

Adenomiosis of Vater's papilla is an organospecific dysplastic process, clearly linked to age and not dependent on other pathological processes of the biliary axis. The reasons for which it is diagnosed in preoperative biopsies with a frequency lower than should be expected on the basis of investigations performed on cadavers are stated. In particular, pathogenetic weight is stressed as a cause of Vaterian stenosis, especially in elderly subjects cholecystectomized many years earlier.


Pharmacokinetics and effects of propranolol in terminal uraemic patients and in patients undergoing regular dialysis treatment.

Propranolol blood and plasma levels were measured after a single oral dose of 40 mg in patients with chronic renal failure, in patients undergoing regular dialysis treatment, and in healthy volunteers. Peak levels were observed in all cases within 1.5 to 3 hours. However, peak blood and plasma concentrations of propranolol in the chronic renal failure group were 2- to 3-fold higher (161 +/- 41 ng/ml) than those observed in the dialysis patients (47 +/- 9 ng/ml) and in the healthy volunteers (26 +/- 1 ng/ml). The apparent plasma clearance was also significantly reduced in the patients with chronic renal failure. The data suggest a reduced hepatic extraction in chronic renal failure patients. A significant increase in the fraction of the dose available to the systemic circulation was also found, together with a modification of apparent plasma half-life and volume of distribution in regular dialysis patients during the dialysis day as compared with the after-dialysis day. No extraction of propranolol by the dialyzer was noticed. Marked fluctuations in propranolol blood concentrations were also observed in patients on regular dialysis following continuous propranolol treatment. The suppressive effect of propranolol on plasma renin activity did not fully correlate with the hypotensive effect of the drug. On the basis of the reported data, propranolol should be used with great caution and at low doses in chronic renal failure.


Clinical pharmacokinetics in infants and children.

Wide variations in drug dose recommendations for children of the same or different ages reflect the inadequacy of data on pharmacokinetics and pharmacodynamics in children. Selected aspects of available literature on pharmacokinetics of drugs used in older infants and children has been reviewed with special attention to calculation of an age-appropriate dose. During the neonatal period and early infancy the elimination of many drugs that are excreted in the urine in unchanged form is restricted by the immaturity of glomerular filtration and renal tubular secretion. On the other hand, in late infancy and/or in childhood, a similar or greater rate of elimination from plasma than in adults has been observed for many drugs, notably digoxin, phenobarbitone, phenytoin, carbamazepine, ethosuximide, diazoxide, clindamycin and propoxyphene. Consistent with this, it has been shown that some drugs exhibit a lower plasma level/dose ratio in infancy and early childhood as compared with the adult. This is true for phenobarbitone, phenytoin and ethosuximide. Some age groups of children remain uninvestigated with regard to pharmacokinetics, even for the drugs reviewed. Therefore, pediatric therapy remains empirically based for many drugs.


Photoepicutaneous testing with the chamber method.

The chamber test, so far successfully applied to epicutaneous testing, proved to be suitable for photoepicutaneous testing as well. A simple and reliable method was developed by dividing the test areas (after removing the tests from the skin) into two equal parts, one for ultraviolet irradiation and the other for dark control. Variations in the amounts of the test substances had a slight influence on the size but not on the strength of the reactions.


Allergic contact dermatitis from propellants in deodorant sprays in combination with allergy to ethyl chloride.

Allergic contact eczema from the use of deodorant sprays is sometimes caused by sensitization to the propellants. Positive reactions were seen in three patients when patch testing to Freon 11 (trichloromonofluoromethane). One patient also reacted to Freon 12 (dichlorofluoromethane). Another patient had an eczematous eruption after ethyl chloride was sprayed on the skin prior to taking biopsy. The two other patients showed strongly positive patch tests with this compound. Further investigations of the sensitizing capacity propellants with chemical resemblance have to be carried out to solve the problem of cross-sensitization.


Rejection of metal to metal prosthesis and skin sensitivity to cobalt.

Metal to metal prostheses give satisfactory results in 90% of patients. About half of the failure rate may be due to allergic reaction to the metals involved, particularly cobalt. A total of 35 patients in this unsatisfactory group have been patch-tested; 16 were positive to metals, 13 to cobalt, 4 to nickel, and 2 to chromate. Only two patients showed any skin lesions - one a localized dermatitis round the knee joint from nickel sensitivity, and one to cobalt who had a widespread scattered circular erythematous lesion suggestive of a generalized allergic vasculitis. Patients requiring a metal/metal prosthesis should have a careful history taken for metal sensitivity and be patch-tested with the metals. All the patients in this investigation had metal/metal prostheses and no reaction was seen after metal/high density polyethylene implants. Titanium 318 may be a satisfactory substitute for cobalt chrome alloy if reactions are encountered.


Phytophotodermatitis from Heracleum mantegazzianum.

Five individuals developed striate bullous dermatitis two days after exposure on a clear day to Heracleum mantegazzianum, Umbelliferae (Parsnip) family. Photopatch testing confirmed phototoxicity from the plant. This and 28 other Heracleum species yield linear furanocoumarins.


Cement burns.

Four cases are presented of men who sustained burns after contact with premixed concrete. The pathogenesis of the condition is discussed.


Sensitization to propantheline bromide, trichlorocarbanilide and propylene glycol in an antiperspirant.

Out of 14 patients with axillary dermatitis due to an antiperspirant, and with positive patch test reactions to the product, the sensitizer could be demonstrated in 12. Of these, 11 were positive to propantheline bromide, 3 to trichlorocarbanilide and one to propylene glycol. The antiperspirant contains 90% propylene glycol, which is an irritant under occlusion. When applied in the axillae, where occlusive conditions usually prevail, an irritant effect of propylene glycol may have promoted sensitization to the ingredients of the antiperspirant.


Contact hypersensitivity to sesquiterpene lactones in Chyrsanthemum dermatitis.

In six persons with contact allergy to chrysanthemum of florists, patch tests were performed with 25 sequiterpene lactones. Positive responses were observed to 15 lactones. The most frequently encountered positive responses were to alantolactone (positive in all cases) and to arbusculin A, 8-deoxycumambrin, ambrosin, damsin and psilostachynin. The findings corroborate the assumption that an alpha-methylene group attached to the gamma-lactone ring is an essential prerequisite for allergenic activity of sesquiterpene lactones. Pyrethrum produced a positive reaction in one of the patients, pyrethrins gave negative reactions in all. Some of the chrysanthemum patients were also hypersensitive to turpentine and colophony and to garlic, primin and tars.


Results of routine office patch testing.

The results of patch testing over the past 18 months in a general dermatology clinic are presented and compared with the data recently reported by the North American Contact Dermatitis Group. Good correlation exists between the results of the two studies for all the reported allergens except nickel sulfate and potassium dichromate. The increased incidence of sensitivity to these allergens reported in our series probably reflects the tendency for all metal related contact dermatitis to be referred to our clinic, even though recognized as such by the referring physician. The 16.8% reactivity to a dye mix used in our screening kit, and not reported by others, proved most interesting. In the light of continuing reports of dye related allergic contact dermatitis, our experience prompts us to suggest that a dye mix of some sort should be evaluated in future large-scale studies of patch test screening kits.


Squaric-acid-diethylester - a strong sensitizer.

A patient developed a circumscribed contact dermatitis after a single contact with squaric-acid-diethylester (SADE). Patch tests with low concentrations of SADE were positive. Based on these observations, experimental studies on the sensitizing capacity of SADE were performed on guinea-pigs. The results disclosed that this compound is a strong sensitizer. Derivatives of SADE, such as the nearly insoluble squaric acid, squaric acid-1,2-diamide and dithio-N,N'-dicyclohexyle-1,2-diamide were not able to produce allergic skin reactions in the sensitized patient nor in guinea pigs. The chemistry and the range of uses of squaric acid and its derivatives are briefly mentioned. A hypothesis on the molecular mechanism of conjugation of SADE to human proteins and thereby on sensitization is discussed. A warning is given for taking precautionary measures before handling this substance.


Allergic contact dermatitis to a salicyclic acid plaster.

We report two patients who developed allergic eczematous contact dermatitis to a salacid plaster used to treat plantar warts. Both patients were subsequently shown to be allergic to dehydroabietic acid, a resin contained in the plaster.


Computer-derived exposure lights for common contact dermatitis antigens.

An established computer file was searched for lists of products containing 45 antigens recognized as causes of allergic contact dermatitis. The final lists included over 8000 products. The problem, ptoential and limitations of such lists are discussed.


Histological differences between irritant and allergic patch test reactions in man.

The results of a study of the histological aspects of the application of DNCB on the skin of unsensitized and sensitized persons are discussed. The nature of the histological changes in primary irritant and allergic reactions to DNCB in human skin appeared to be identical. The differences appeared to be primarily of a quantitative character. It is furthermore concluded from data in the literature that the skin of some persons may react with a primary irritant reaction to concentrations of a compound thought to cause only allergic reactions. In these persons histological examination of the patch test result may give insufficient clues as to the nature of the reaction. The practical consequences of the data presented are discussed.


The development of metal hypersensitivity in patients with metal-to-plastic hip arthroplasties.

Sixty-six patients who had to undergo total hip replacement by means of a metal-to-plastic Stanmore prosthesis, were patch-tested prior to and 6 to 12 months after surgery with the standard ICDRG all allergens series and with acrylic monomer 5% in acetone. In 62 patients the history of metal allergy as well as the patch tests to all tested allergens were negative. One patient with a history of metal allergy reacted negatively before surgery; about 6 months after surgery the patch test to nickel sulphate was positive (2 plus). Three other patients developed positive patch test reaction after surgery: two reacted positively to nickel sulphate (2 plus) and one to cobalt chloride (2 plus). In none of the 66 patients have local side effects of the prostheses been found to date.


Phototoxicity of methoxsalen in various vehicles.

Methoxsalen (8-methoxypsoralen) was used as the photoxic substance in the study of the properties of various vehicles in photoepicutaneous testing. Macrogols as such were relatively poor bases, and positive reactions were seen only occasionally at a concentration of 0.05% methoxsalen. Increasing amounts of water in macrogols brought forth more numerous and stronger reactions. The photoxicity also increased when ethanol was added. The reactions were, however, weaker than to those with aqueous bases. Wool fat and glycerol as vehicles usually reacted in the same way as polyethylene glycols when water was added. An explanation of the mechanism of the changes in the properties of vehicles due to the addition of water/ethanol requires further investigation.


Incidence of neomycin and framycetin sensitivity.

A total of 450 consecutive patients were patch-tested to both neomycin and framycetin (20% in petrolatum). Thirteen patients were sensitive to both preparations, 10 to neomycin alone and four to framycetin alone. The significance of these results is discussed, with particular reference to the constituents of the preparations and the allergenic groups involved.


The place of irradiation in the treatment of malignant tumors of the salivary glands.

1. Radiation therapy is not indicated after surgical removal with adequate margins of low-grade tumor. 2. Radiation therapy is indicated with a) Inadequate surgical margins in low-grade tumors b) All high-grade tumors c) All recurrent malignant tumors 3. Irradiation of nerve pathways is indicated with demonstrated nerve and perineural invasion and/or with adenoicystic carcinoma. 4. Irradiation of the entire ipsilateral neck is indicated a) Wtih high-grade tumors unless radical neck dissection shows negative nodes b) In the place of radical neck dissection.


The "vanilla fudge" cyst.

A white cyst, partially covered by jet black splotches and streaks, had a surface appearance of vanilla fudge ice cream. Histologically, the cyst was lined with two distinctly different types of follicular epithelium--one identical to that of the infundibulum and the other to that of the matrix. The black pigment was melanin, produced by numerous dendritic melanocytes that were situated only in the region of the epithelium-resembling matrix.


The systolic click-murmur syndrome: clinical recognition and management.

The midsystolic click-late systolic murmur syndrome is a complex entity with variable manifestations that involves a primary process causing myxomatous degeneration of the mitral valve leaflet(s) and subsequent systolic mitral valve leaflet prolapse. Other cardiac diseases may cause mitral valve prolapse and regurgitation associated with a midsystolic click that mimics this primary syndrome. The prolapsing mitral valve leaflet(s) syndrome occasionally may be familial. Most patients are asymptomatic but some complain of chest pain, palpitation, dyspnea or fatigue. Prolapsing mitral valve leaflet(s) can be distinguished from other causes of systolic clicks and mitral regurgitation murmurs by the characteristic movement of the clikmurmur complex in systole with various hemodynamic interventions. The clinical diagnosis usually can be confirmed by echocardiography, which demonstrates the abnormally prolapsdrome usually is minimal but can be progressive and lead to the need for prosthetic valve replacement. Most symptomatic patients can be managed medically but some require cardiac catheterization to evaluate the possibility of coexistent coronary artery disease, to assess the degree of mitral regurgitation and to evaluate other associated cardiac lesions. All patients with this syndrome should receive antibiotic prophylaxis prior to any surgical or dental procedures. Those patients suspected of having arrhythmias should be evaluated by continuous ambulatory ECG monitoring and dangerous arrhythmias probably should be treated. The prognosis usually is excellent, but sudden death and rapidly progressive mitral regurgitation due to ruptured chordae tendineae have been reported. Although more than a decade has elapsed since the midsystolic click-late systolic murmur syndrome was first recognized, much remains to be learned about this common but complex clinical entity.


Cutaneous bilharzial granulomas: a histopathologic study.

Histopathological studies were done on seven cutaneous lesions; all but two were clinically diagnosed as cutaneous bilharzial granulomas. Epidermal, dermal, vascular, sweat and sebaceous gland changes were demonstrated. The purpose of this paper is to present the pathogenesis of these granulomas.


Update: seabather's eruption and swimmer's itch.

Swimmer's itch and seabather's eruption, while similar in morphology, differ in important aspects. Seabather's eruption occurs chiefly in salt water and involves covered parts of the body. Swimmer's itch occurs chiefly in fresh water and involves uncovered parts. The cause of swimmer's itch is definitely known to be schistosome cercariae, while the cause of seabather's eruption is for the most part unknown. Algae, coelenterates and schistosomes as well as other organisms found in seawater have been suggested. Control of swimmer's itch is best accomplished by decreasing the snail population.


Cutaneous Hodgkin's disease.

A case of specific cutaneous Hodgkin's disease, which is sparsely mentioned in the literature, is reported. The lesion was nodulo-ulcerative and corresponded to the Grosz-Hirschfield type. It was confirmed by biopsy and the pattern was similar to that of an excised supraclavicular node examined two years previously. The lesion responded to treatment with gentamicin topically, clindamycin orally and 500 r of cauterizing X-ray. There has been no recurrence to date and no other new cutaneous lesions. This report further confirms what Ferdinand von Hebra implied one hundred years ago--that a dermatologist should not only know skin diseases but also the cutaneous manifestations of visceral diseases.


Trichloroacetic acid peeling.

Trichloroacetic acid peeling refers to a system whereby a corrosive chemical is applied to the skin. The resultant good effect is due to epidermal regeneration, as well as the regenerating of new collagen in the dermis. The technique of deep chemical peeling in treatment of actinic degeneration and acne scarring is presented.


Cutaneous manifestations of hypothyroidism including purpura and ecchymoses.

Hypothyroidism has distinctive cutaneous manifestations which may be diagnostic. Biopsy and histologic study of the skin may provide a simple and useful tool for diagnosing hypothyroidism. Purpura and ecchymoses, although not often mentioned among cutaneous manifestations of hypothyroidism, occurred in nine of 222 hypothyroid patients at Ochsner Clinic between 1958 and 1972.


Herpes zoster: a cause of acute detrusor muscle paralysis.

The essence of this report is to apprise the dermatologist of this fascinating but unusual complication of herpes zoster and to underscore the help he may give in establishing the diagnosis along with assisting in the management of this disorder.


Photoallergy induced by quinidine.

An 82-year-old woman presented with a lichenified dermatitis over light-exposed areas. The eruption cleared upon withdrawal of quinidine and recurred on re-administration of the drug. Though quinidine has not been recognized as a photo-sensitizing agent, upon review of the literature we have uncovered other cases which meet the criteria and justify including this drug among those capable of causing such reactions.


Coexistence of discoid lupus erythematosus and porphyria cutanea tarda.

A case of coexistent porphyria cutanea tarda and discoid lupus erythematosus is presented. Abnormal urinary porphyrins, the presence of liver fluorescence, chronic alcoholism, fatty metamorphosis of the liver and histologically typical LE with the demonstration of basement membrane fluorescence were present in the patient. Awareness of the possible coexistence of these two conditions is of practical significance for the practicing dermatologist. The nature of the relationship between these conditions remains obscure. Is it coincidental or does it represent a common pathophysiological mechanism? Further work on this unique pair of diseases seems indicated.


Porphyria precipitated by hydroxychloroquine treatment of systemic lupus erythematosus.

This case report emphasizes the fact that patients presenting with photosensitivity could have lupus erythematosus or porphyria or both; and since the therapy for one may aggravate the other, extreme caution is indicated.


Radiotherapy of skin cancer: modern indications and techniques.

Skin cancer is the most frequent indication for radiation therapy in dermatology. X-ray treatments are particularly valuable in cutaneous neoplasms in special anatomical locations. Advantages and disadvantages of dermatologic radiation therapy are outlined, and modern indications, radiation methods and the selection of physical radiation factors are discussed.


Geographic lip: a variant of geopgraphic tongue.

The following aspects of the classic geographic tongue are discussed: clinical polymorphism with the appearance of annulus migrans, histological appearacne of the spongiform pustule, frequent association with pustular psoriasis and related diseases, and its relationship to psoriasis buccalis. Two cases of geographic lip are described in which annulus migrans was present. In one case, the geographic lip was associated with a plicated lip, a labial form of plicated tongue.


Lichen spinulosus: response to therapy.

Two cases of lichen spinulosus and the response to therapy with Keralyt under occlusion are presented. It is evident that Keralyt under occlusion for two consecutive weeks will clear these lesions. However, twice weekly application of Keralyt must be used in order to keep these areas free of lesions. An undesirable side effect in the two patients presented was a burning, stinging sensation immediately following application of Keralyt.


Common warts: immunity as a result of therapy.

Warts that don't regress frequently have wart cell specific immune globulin M(IgM), but no wart virus specific Immune Globulin M (IgM) in the circulatory system. Warts that regress spontaneously have multiple circulating antibodies-wart cell specific IgM, IgG, and IgA. When the antibodies of IgG class appear in the circulation, the warts will commonly disappear. Topical application of cell toxic, irritant materials will elicit discernible amounts of virus specific IgM and IgG. Those B Cells which produce IgG have a "computer bank memory" and IgG should be recalled if wart virus antigen reappears as a result of reinfection. Therefore, persistent, consistent, topical application of irritant modalities to warts that will cause them to regress and disappear, should confer immunity on the individual through the production of wart virus specific IgG. Over a seven-year span 150 cases of wart were cleared in our office by an irritant method. In that group of cases there were eight recurrences. Two cases cleared spontaneously within two weeks, and four cleared with an acute inflammatory response within a few days of reirritation.


Accidental vaccinia of the vulva.

Vaccinia of the vulva in a 32-year-old married woman is described. The vaccination was apparently due to a heteroinoculation from her husband during sexual contact. Clinically it presented as an indurated ulcer with a few isolated umbilicated vesicles and was associated with an acute biological false-positive serological reactions.


Tinea pedis in children.

Many children have dermatoses involving the feet. Such problems are often misdiagnosed as tinea pedis, which is relatively uncommon in this age group. On the other hand, tinea pedis should not be ignored as a diagnostic possibility just because of its infrequent occurrence. Six cases are reported to demonstrate that this diagnosis will be missed if appropriate laboratory studies are not done as a part of the evaluation of these dermatoses.


Hormonal dependency in Darier disease.

Variation in the severity of keratosis follicularis relative to states of homonal change was noted in eight women with the disease. Observations included frequent onset near puberty, puberty, exacerbation during menses, and improvement while patients are pregnant or on oral contraceptive agents. It is proposed that states of relative estrogen excess are associated with quiescence of this skin disorder. In support of this hypothesis, three postpubertal women with Darier desease were observed to undergo significant improvement with the use of estrogen-dominant birth control pills.


Axillary and inguinal striae induced by systemic absorption of a topical corticosteroid.

A 21-year-old woman developed huge atrophic striae in the axillary and inguinal areas from the topical application, with occlusion, of potent corticosteroid preparation applied to the axillary or inguinal areas. It is postulated that the mechanism is systemic absorption of enough medication to produce a state of hyperadrenalism with subsequent striae formation as a sequela.


Lupus erythematosus exacerbated by griseofulvin.

Because griseofulvin is one of the safest systemic medications, its side effects are often forgotten. This paper serves as a reminder that griseofulvin can precipitate or exacerbate lupus erythematosus. Two patients are described: one had a photosensitivity reaction to griseofulvin which precipitated discoid LE skin lesions, without any previous evidence of LE. The other, who had known systemic LE, developed a systemic reaction, consisting of fever and malasise.


Immunologic mechanisms of infectious syphilis.

We believe that humoral and cellular immunity both are involved in the response of the host to infection with T. pallidum. A complex interaction between stimulation and suppression of cell-mediated immunity may be involved. This interaction may explain the unusual clinical course in which secondary syphilis waxes and wanes before culminating in immunity.


Lupus erythematosus and reactive tests for syphilis: update.

Sera of patients with lupus erythematosus can produce false-positive reactions in most serologic tests for syphilis, including the FTA-ABS test. False-positive reactions in the FTA-ABS test can exhibit beaded, borderline or reactive patterns of fluorescence. Beaded fluorescence is commonly associated with anti-DNA antibody and other correlates of lupus activity. Borderline and reactive results are common in both systemic and discoid lupus erythematosus, and are usually not associated with increased clinical activity. TPI and MHA-TP tests appear helpful in detecting false-positive FTA-ABS results.


Examination of the cerebrospinal fluid in syphilis.

In the diagnosis of neurosyphilis, a cerebrospinal fluid cell count or cerebrospinal fluid total protein are inconclusive by themselves, but together with a cerebrospinal fluid VDRL are of great diagnostic value. At present, the VDRL Slide Test on Spinal Fluid remains the serologic test of choice for the diagnosis of neurosyphilis. The significance and specificity of treponemal tests on spinal fluid remain to be established. Like all other laboratory tests, cerebrospinal fluid findings may be variable and an absolute diagnosis of neurosyphilis should not be made on the result of any one laboratory test alone, but should be viewed in light of all laboratory evidence, including serum serologic tests, and clinical findings.


Genital candidiasis: topical management with clotrimazole.

Clotrimazole was administered in the form of 100 mg tablets to patients with vaginal candidiasis, and in the form of a 1% solution to patients with cutaneous candidiasis of the genital and perigenital areas. The clinical and mycological response observed and the excellent tolerance and lack of side effects indicate that clotrimazole may be proposed as a treatment for candidiasis.


Familial malignant melanoma.

Two sisters simultaneously developed a superficial spreading malignant melanoma on their legs. Concurrently, a brother was affected with fatal metastatic melanoma. Several explanations for familial malignant melanoma are reviewed, including: 1. Genetically determined predisposition; ,2 Phenotypic and environmental factors; and 3. Infectious etiology (virus?). Relatives of patients who develop malignant melanoma spould be aware that they have a higher risk than the general population of developing this serious type of cancer.


Hidradenitis suppurativa occurring on the leg.

The case of a patient with a recurrent, painful ulceration on the lower leg, clinically and histologically resembling hidradenitis suppurativa, is presented. The fact that this site is devoid of apocrine glands supports the concept that apocrine involvement in hidradenitis suppurativa is coincidental and that these glands are involved secondarily. It is suggested that in this patient the pathogenesis of the disease is follicular occlusion rather than selective apocrine poral closure.


Photolocalized tinea facialis.

The case of a 34-year-old white woman with tinea facialis that persisted for nine months prior to diagnosis is presented. The confluent plaquelike erythematous eruption of the face with eyelid lichenification that flared outdoors was thought to represent polymorphic light eruption and was refractory to antibiotics, corticosteroids (topical and systemic), and antimalarials. A KOH preparation was positive when the dermatosis spilled onto the mandibular region, and restaining of the initial skin biopsy revealed fungal hyphae. Complete resolution was accomplished with griseofulvin and MicTin. Tinea cab be added to the list of infectious agents that have a photosensitivity component. The fungus possibly "photolocalizes" to sun-damaged areas, ie, areas of increased capillary permeability. This case illustrates the importance of including tinea in considering diagnoses of sun-exposed lesions of the face.


Acanthosis nigricans and wart-like lesions associated with metastatic carcinoma of the stomach.

A 63-year-old white man developed malignant acanthosis nigricans one year after a hemigastrectomy for adenocarcinoma of the stomach. Multiple "wart-like" lesions involving the dorsa of the hands, arms and trunk were also present. The malignant acanthosis nigricans in the patient appears to have paralledled the course of the metastatic gastric adenocarcinoma. Discrete verrucous lesions can occur in malignant acanthosis nigricans which histopathologically may show either squamous or basal cell hyperplasia.


Poikiloderma vasculare atrophicans.

A 46-year-old Negro man with poikiloderma vasculare atrophicans is described. The disease progressed graduall.y for 22 years, with lesions appearing over the neck, trunk and extremities in an asymmetrical distribution, but it did not become lymphoma or collagen disease. Treatment did not appear to influence the course of the disease.


Painful pigmented prosthesis pressure papules.

Two patients who presented with tender hyperkeratotic papules involving their weight-bear.ing amputation stumps were studied. Although these clinical findings are common in the experience of prosthetists, the author has been unable to find any documentation of these findings in the literature. All attempts at relining and reshaping the cups of the original offending prostheses by experienced prosthetists were unsuccessful. The eruption cleared only after entirely new prostheses were designed. It would appear that this condition is due to a poorly fitting prosthesis.


Erythema chronicum migrans.

Erythema chronicum migrans is characterized by an expanding erythematous band about an arthropod bite. While rare, it is an important disease to recognize because of its rapid response to even modest doses of antibiotics. This response and the association with arthropod bites suggest a microbial vector. Richettsial titers have been demonstrated in several cases but we were unable to show them in our patient, who we believe is the second reported case of erythema chronicum migrans incurred by an American without traveling abroad.


Superficial and deep granulomatous lesions caused by Trichophyton violaceum.

A patient with cutaneous and reticulo-endothelial lesions, lymphadenopathy and osteitis caused by Trichophyton violaceum is presented. Two types of skin lesions were found: 1. Erythematous, scaly plaques on the arms, chest and abdomen; 2. areas of diffuse infiltration, granulomatous ulceration, fistulation and destruction of the sternal bone. Long-term treatment with penicillin, streptomycin, sulfonamides, and griseofulvin, gave temporary improvement.


Insect sting allergy.

Allergy to insect stings may be quite serious, and occasionally lethal. Evaluation of these patients involves careful history taking. Skin testing for the stinging insects is helpful both for diagnosis and finding a beginning dose for hyposensitizing injections. According to many reports, these injections have been very effective in preventing subsequent severe reactions to insect stings. Prompt emergency treatment usually involves adrenalin injections. Insect avoidance procedures are effective.


Allergic reactions to molds.

Allergy to mold is common, and results from inhalation of mold spores or ingestion of mold related foods. Mold spores are complex, hardy organisms capable of eliciting diverse immune responses and illnesses which may be mild or severe. Diagnosis and treatment with mold antigens are outlined and environmental recommendations made. Mechanisms of reactions to treatment of mold allergy are postulated.


Psoriasis: treatment with a tar gel.

Crude coal tar has long been an effective and safe form of therapy for psoriasis. However, as compounded in an ointment base it has many objectional features and usually is limited to hospital use. A new tar gel has been studied which appears to equal the effectiveness of crude coal tar, is convenient to apply, and is cosmetically acceptable. This new tar preparation is a valuable addition to the therapy of psoriasis.


Nevoid basal cell carcinoma syndrome.

A case report of a young girl with nevoid basal cell carcinoma syndrome is presented. The patient showed cutaneous and skeletal findings characteristic of the syndrome. Multiple basal cell carcinomas, rib abnormalities, along with clinical evidence of frontal bossing and ocular hypertelorism were the primary features of the syndrome in this patient. It is suggested that other characteristics of the syndrome, such as jaw cysts, palmar and plantar pitting and calcification of the falx cerebri will develop as the patient grows older. Careful observation, particularly for medulloblastoma and malignant degeneration and invasiveness of basal cell carcinomas, will be an integral part of this young patient's care.


Erthropoietic protoporphyria: first report of cases in the American Nergo.

The first two cases of erthropoietic protoporphyria in the American Nergo are reported. The eruption was limited to the lips, subungual and periungual areas, which are relatively nonpigmented. Onset was at a later age and length of sun exposure required to produce symptoms was longer than that in most whites with the disease. The different presentation in Negroes is believed to be related to their increased pigmentation. Melanin appears to provide protection because of its free radical formation and absorption of 400 nm electromagnetic radiation.


The esthetics of hair transplantation.

There are many potential candidates, and greater attention to esthetic considerations has accelerated the interest in the hair transplantation field. Although discriminatory selection is essential, there are few interested patients who could not benefit from this procedure. Successful hair transplantation and patient satisfaction depend on the physician's skillful sustained concentration on the frontal hairline, tenacious motivation of the patient to seek a sufficient number of transplants, and the choice of a pleasing hair style with utilization of recommended grooming aids.


Skin changes and lesions in our senior citizens: incidences.

One hundred and sixty-three community volunteers were interviewed and examined. After a decade, the 69 survivors were again interviewed and examined. The incidences of their skin changes and lesions were recorded and interrelationships sought relative to internal and external signs of aging. Asteatosis of moderate or severe degree, large numbers of scrotal angiomas in men, and retention of nevi appeared to be associated with a relatively shortened life expectancy and may be signs of decline and approaching death in older individuals.


Surgical management of herpes simplex keratitis.

The various surgical managements of herpes simplex keratitis are listed. Our management is "atraumatic" keratoplasty, if vision is reduced, if the disease is protracted, or if perforation occurs. Our preoperative care is aimed at the production of a quiet eye with no active virus infection, by the use of antiviral drops, steroids, antibiotics, and bandage contact lenses. Removal of all corneal disease is desirable, but not mandatory. Perforations are managed in the same manner, but the host window is started at the perforation. Postoperative management is characterized by the use of therapeutic modalities necessary to prevent or treat complications, including steroids and frequent observation to check for complications of treatment. Our understanding of herpes simplex virus infections as they relate to surgical management is presented. The results of treatment warrant continuation of our efforts--but lead to the conclusion that it would be most helpful if latent virus infection could be eradicated.


Pyoderma gangrenosum with carcinoid tumor.

A patient with the classic lesions of pyoderma gangrenosum was found on autopsy to have a carcinoid tumor of the ileum. The simultaneous occurrence of a carcinoid tumor with pyoderma gangrenosum is interesting because both conditions are associated with immunologic defects.


Synthesis of nuclear acidic proteins in mature and immature avian erythrocytes.

The synthesis of the nuclear acidic proteins in immature and mature avian erythroid cells was compared. Synthesis of these proteins was found to occur in both types of cells. However, there are quantitative and qualitative differences in incorporation of labelled amino acids into the electrophoretic patterns of these proteins. There was an overall decline in the specific activity of the proteins as erythrocyte maturation proceeds. In particular, one protein band of molecular weight 81,000 is predominantly synthesizied in the immature cells but not in the mature cells.


The DNA of Volvox carteri: a biophysical and biosynthetic characterization.

Various biophysical and biosynthetic characteristics of deoxyribonucleic acid (DNA) from Volvox carteri are examined. The DNA from three strains (HK-10,NB-7 and KA-1) is compared, and all strains are shown to contain at least two distinct DNA species which band at densities of 1.714-1.715 and 1.704-1.705 g/cm3 in neutral CsCl and correspond to nuclear and "cytoplasmic" DNA, respectively. Base compositions calculated from these densities, 55-56% G+C for nuclear DNA, and 45-46% G+C for cytoplasmic DNA, are in close agreement with % G+C values estimated from thermal denaturation data. DNA from strain KA-1 has a third component with a buoyant density of 1.693 g/cm3. DNA synthesis is analysed using radioactively labelled heterogeneously grown strains of Volvox carteri and profiles obtained following preparative CsCl density gradient centrifugation are presented. In addition, dissimilarities in patterns of DNA synthesis at various periods in the asexual life cycle are reported for synchronous cultures of strain HK-10. These differences in temporal patterns of DNA synthesis clearly indicate that while nuclear DNA is make to some degree throughout the life cycle, cytoplasmic DNA synthesis appears to occur only at discrete intervals.


Quantitative analysis of human chromosome segregation in man-mouse somatic cell hybrids.

The presumed random and independent process of human chromosome segregation in man-mouse somatic cell hybrids was studied. The results of chromosome analysis on 196 cells from 15 related hybrid strains have provided the first convincing evidence that segregation of human chromosomes can be nonindependent and often concordant. Different human chromosomes were not retained with equal frequency in these hybrid clones. Some were present in 80% of all the cells, whereas others appeared in less than 10% of the same cells. Linear regression analysis was used to test for correlation of the frequencies of all pair-wise combinations of human chromosomes present in these hybrid clones. Twenty-two of 136 possible correlations were statistically significant, indicating that concordant segregation of particular pairs of human chromosomes is a rather frequent occurrence.


Cytological demonstration of mitotic crossing-over in man.

Quadriradial (QR) configurations from four different human lymphocyte metaphase samples have been analyzed: a patient with Fanconi's anemia; normal female cells X-irradiated with 150 or 200 R in S or G2; spontaneous QRs occurring in 13,584 metaphases; and cells from two sibs with Bloom's syndrome. That mitotic chiasmata are caused by crossing-over rather than by random breakage and reunion was concluded from the following observations: (1) In the spontaneous sample, mitotic chiasmata are about as frequent as all other QRs together. (2) The frequencies of mitotic chiasmata and of other QRs are not correlated in the different samples. (3) The break points in other QRs are situated at random relative to chromosome length, whereas the distribution of chiasmata is highly nonrandom. (4) Although the centromeres of chromatid translocations occur in alternate and adjacent positions with approximately equal frequencies, there are very few adjacent counterparts to mitotic chiasmata. These can best be interpreted as a result of an abnormal U-type rejoining of chromatids in a chiasma. (5) Chiasmata found in heteromorphic chromosome pairs show that crossing-over has, indeed, taken place.


Chronobiology in the diagnosis and treatment of mesor-hypertension.

An elevation of systolic and diastolic bloodpressure to values regarded as abnormal ones on the basis of conventional criteria was recognized by self-measurement. For both systolic and diastolic blood pressure, the overall means adjusted for rhythms, the so-called mesors, also were elevated in the light of their response to treatment: these mesors were found to be lowered with statistical significance when values during treatment were compared by an objective test with values measured before treatment. Individualized rhythmometry quantitatively characterizes a predictalbe portion of the variability in human blood pressure and tests for the statistical significance of changes in blood pressure as a function of the treatment and also as a function of the  circadian timing of such treatment. The case report thus illustrates an individualized chronotherapy of systolic and diastolic mesor-hypertension, diagnosed retrospectively from the tested effect of hydrochlorothiazide. In the case reported, and perhaps routinely, computer-analyzed self-measurements can serve 1) to prescribe the right kind and amount with the right timing, for a given therapy, and 2) for diagnosis and prevention as well (Meyer et al.; Halberg et al.).


Evidence for a circadian oscillation in the gonadal response of the tropical weaver bird (Ploceus philippinus) to programmed photoperiod.

The effect of an asymmetrical skeleton photoperiod scheduleee was studied on the gonadal development in a tropical finch, the weaver bird (Ploceus philippinus). The schedul comprised a short nonstimulatory primary photoperiod of 6 hrs and a secondary  much shorter lightperiod given as a 15-min light pulse at different times in the dark period. The light pulse 11 hrs after the basic period resulted in gonadal stimulation, while light pulse in contimuation with the basic period or 8, 14 or 21 hrs after the basicperiod was not stimulatory. The "photoinducible phase" was much more precisely outlined by shifting the birds from an 8-h to a 10-h pulse, and from an 11-h to 12-h pulse and was found to be very short, lasting about an hour falling between 11 and 12 hrs after the primary light period. The short photoinducible phase may be of an adaptive value since in the tropics the difference between the shortest and the longest daylength is also rather small (3 hrs and 15 min at Varanasi, 25degrees N). Clearly the weaver bird possesses a fine time-measuring device involving an endogenous circadian rhythm in photosensitivity. In nature, spermatogenesis in this bird also begins in March when the daylength exceeds 11 hrs (thus perhaps coinciding with the photoinducible phase). In rather small, photoperiod may not serve as a cue to trigger seasonal reproductive periodicity, it seems that photoperiod can act as a Zeitgeber for the initiation of spermatogenesis in the weaver bird at least.


The role of pineal and eyes in the photoperiodic effect on the gonad of the medaka, Oryzias latipes.

Studies on gonadal development in the female medaka, Oryzias latipes, intact, blinded or blinded-pinealectomized, maintained on different lighting schedules, i.e. LD14:10 and LD 10:14 and under natural daylight conditions, revealed that: 1)blinded fish were capable of responding to annual photoperiodic shifts with alterations of gonadal development, if the pineal was left intact; 2)the mean gonosomatic index(GSI) was higher in blinded fish than in intact fish, during a period from October through April, under LD 14:10, LD 10:14 and the natural daylight conditions; 3)when reared under the natural daylight conditions, the mean GSI in blinded fish was approximately half of that in intact ones in May and June, although the values were significantly larger than those in fish examined during all the other seasons; and 4)in December, the mean GSI was larger in blinded-pinealectomized fish than in intact and blinded ones. These findings seem to indicate that, during the breeding season, the gonadal growth in the medaka is stimulated by the pineal blocking the inhibitory mechanism against the hypothalamo-hypophyseal gonadotropic system, whereas during non-breeding seasons, the gonadal involution is induced by an anti-gonadal factor released by the pineal. It is likely that the effects of photoperiods are exerted on the pineal through the eyes.


Antecedents of narcotic use and addiction. A study of 898 Vietnam veterans.

Previous studies of predictors of narcotic abuse have been retrospective and based on samples of long-term addicts obtained from legal or medical channels. There are several methodological problems in this approach. The present study is an attempt to test certain alleged predictors of narcotic use in a cohort of 898 Vietnam veterans. The design overcomes several of the methodological weaknesses of previous studies. Eight variables which have been reported as predictors of drug use or addiction in the drug literature were inquired about during a personal interview which included the premilitary life of each subject. The antecedent variables were socioeconomic background, inner city residence, psychiatric illness, broken home, race, employment history, education and antisocial history. Using information obtained from interviews and military records, we then tested the predictive value of each of these antecedents by comparing narcotic used and addiction in Vietman and use after Vietnam in men differing with respect to each antecedent. Results indicate that some of the variables were very poor, and others very good predictors of the various levels of narcotic involvement. The predictive value and overall importance of each of the variables we tested are discussed.


Treatment effectiveness as judged by successfully and unsuccessfully treated alcoholics.

Thirty-seven successfully and 46 unsuccessfully treated male alcoholics were asked to judge the effectiveness or ineffectiveness of six treatment methods routinely offered by a state hospital. For each treatment method, the total frequencies of judgments of most and least helpful, respectively, were as follows: detoxification (16%, 14%), lectures (16%, 20%), group therapy (54%, 7%), individual counseling (26%, 6%), work therapy (17%, 22%) and family therapy (13%, 14%). The two groups of subjects differed significantly in the frequencies of treatment methods judged to be "least helpful", but not in the frequencies of "most helpful" treatment. The similarity between the judgments of successfully and unsuccessfully treated alcoholics might reflect the positive effects of previous treatment in the unsuccessful group.


Addicts' attitudes toward drugs: a semantic-differential study.

The Drug Rating Scale, an adaptation of the Osgood semantic-differential technique, was devised to measure the connotative aspects of attitudes toward drugs. Sixty-two heroin-addict clients and fourteen staff members of the Haight-Ashbury Free Medical Clinic completed the Scale. The Addict group tended to regard heroin in a negative light, possibly consistent with their own lack of self-esteem. Amphetamines and LSD had the greatest distance from heroin in the addicts' "semantic space"; this was consistent with addicts' relative preference for alternative drugs to heroin. The evaluative and activity dimensions provided a plausible assignment of the eight drugs inquired about into four quadrants.


Reassessing the goal of drug education: diversity of preference among teachers and students.

Most of the proponents of drug education assume that the primary objective of such programs is to deter student drug use. To test this assumption, administrators, students and teachers from six public school districts were surveyed about what they thought the primary role of the school should be. While most administrators and teachers thought that the school's role should be limited to developing responsible attitudes or providing drug information, students selected a more diverse set of objectives for the schools. The policy implications of these findings are discussed.


Metabolic disposition of 2-phenylethylamine and the role of depression in methadone-dependent and detoxified patients.

We have now postulated that differences in the innate capacity of individuals to synthesize, store and utilize biogenic amines may provide the biological basis for human abuse of narcotic and other drugs, and that these drugs are used in an apparent unconscious effort to self-medicate against an inherent affective disorder. In this communication, we attempted a preliminary characterization of the narcotics withdrawal syndrome on biochemical and clinical parameters. Abstinence was found to be characterized by low urinary excretion of 2-phenylethylamine and depression. An indication for use of tricyclic drugs has been discussed.


Neurological assessment of patients on prolonged methadone maintenance.

Medical histories, neurological examinations and electroencephalograms of 25 methadone-maintained subjects were compared with those of 25 abstinent controls. Comparisons on all measures failed to show significant differences between groups. The incidence of abnormalities was low for all subjects. None of the observed conditions appeared to involve methadone in their etiology.


Clinical pharmacological studies with 6-azidomorphine.

The intravenous (i.v.) administration of 4 mug/kg 6-deoxy-6-dihydroazido-isomorphine (6-AM) base to healthy, young adult male volunteers caused no circulatory and relatively little, short-lasting respiratory depression. Of the ten volunteers all felt lightheaded, two became euphoric and when they became ambulatory at the end of the experiment, three vomited and two other became nauseated. The intramuscular (i.m.) administration of the same dose of 6-AM had considerable analgesic effect against various types of experimental pain. It was more effective against ischemic pain, than against pain induced by electrical stimulation of the earlobe or the tooth pulp and it effected severe pain more than mild or moderate pain. In the six subjects investigated, 6-AM produced significant myosis. Of the 16 subjects who received 4 mug/kg 6-AM i.m. five experienced mild euphoria, two felt lightheaded, six became pale and sweaty in the course of the experiments carried out in the sitting position. When they becam ambulatory after the completion of the experiments, two subjects vomited and six others became nauseated. The findings of this study indicate that 6-AM causes less circulatory and respiratory depression than is to be expected from equianalgetic doses of morphine. Its other side effects (e.g., nausea, vomiting) are also less frequent and severe than those encountered after the administration of comparable doses of morphine to ambulating volunteers.


Seven attitude scales used in assessing cannabis use amongst students.

A number of newly constructed attitude measures are described and correlated with two previously established measures, on a sample of 830 university students. Scales were devised to measure political orientation, permissive-restrictiveness, puritan ethic, parental congruence and extra-intra punitiveness. In addition a checklist concerned with degree of social and political activity, a modified (shortened) version of Crumbaugh's Purpose in Life Test, Srole's Test of Anomie (complete), and the shortened form of the E.P.I. were used. Item loadings on the main facotr in each scale and overall correlations between the scales are given.


Neuronal depletion in the globus pallidus of heroin addicts.

Decreased neuronal population densities are described in the globus pallidus of narcotic addicts. Toxicologic studies indicate mixed addiction to be frequent, but exposure to parenteral heroin is the only common factor. This permanent brain damage seems more likely to be caused by recurrent episodes of hypoxia during severe reactions to narcotics than to be related to direct neurotoxic effects of heroin. The lesion may account for some of the long term changes observed in addicts.


Motivation for alcohol in rats: position and bottle preferences do not cause drinking.

Position preference, i.e., the tendency to drink from onelocation rather than the other, was found to be relatively unimportant in determining the drinking behavior of rats presented with a choice between water and a 7% (v/v) ethanol solution in typical two-bottle choice situations. It accounted for essentially none of the variance in rats generally drinking more alcohol solution than water after prolonged previous alcohol experience, and in rats consuming very little alcohol; only in rats drinking slightly less alcohol solution than water was it found to have an influence. Similarly, bottle preference, i.e., the tendency to drink from one of the two bottles regardless of its position or contents, andposition preference were found to have almost no effect on heavy-drinking rats even on their first day of exposure and on low-drinking rats after about three days of access to alcohol.


The drinking habits of residents of a rehabilitation program with a controlled drinking option: a preliminary report.

Residents of an alcoholism rehabilitation program with a controlled drinking option were asked to give daily reports on their drinking. Program staff were also asked to report evide-ce of resident drinking. A comparison of information from these two sources showed, among other things, that residents were generally reluctant to report drinking which was proscribed the the program. Such drinking as was reported varied from isolated, non-problematic, small quantity drinking, to heavy, regular and problem-producing drinking. In general, residents' drinking did not prevent them from work while in residence. The men's reluctance to report proscribed drinking is seen as largely accounted for by the system of fines for intoxication and drinking without rights. It is concluded that it would be premature to recommend the program's drinking policies to other residential programs, but future experimentation is indicated.t is concluded that it would be premature to recommend the program's drinking policies to other residential programs, but future experimentation is indicated.


Radioimmunoassay of amphetamines in rat parotid saliva.

Amphetamines, a commonly abused class of drugs, have been detected in various biological specimens, in particular, urine and blood. However, little information is available concerning the detection of these drugs in saliva. This investigation, utilizing the rat salivary secretions, has been attempted to establish the ability of amphetamines to be secreted in saliva and to determine the feasibility of using radioimmunoassay (RIA) for drug detection in saliva. The results of this investigation showed that (1) d-amphetamine and methamphetamine decreased salivary flow, (2) after d-amphetamine RIA tests were demonstrated in both saliva and plasma for a period of fifty minutes, and (3) positive RIA reactions were obtained by the following metamphetamine metabolites: amphetamine, 4-hydroxynorephedrine and 4-hydroxyamphetamine. Methamphetamine and 4-hydroxy-N-methylamphetamine were found to be non-reactive in the radioimmunoassay procedure. The results indicate that saliva could be radioimmunoassayed for the detection of amphetamine or amphetamine derivatives after the administration of either d-amphetamine and methamphetamine.


A sociological theory of the diffusion and social setting of opiate addiction.

The theory presented here is intended to apply to socially deprived areas where heroin addiction is endemic, narcotics are available, and adolescents are not naive about the consequences of heroin use. In such settings rapid epidemic changes occur in which within a short period of time large numbers are involved. The transition of heroin use is a conversion-type phemonenon which is facilitated by the basic belief system, the network of social circles and the social and psychological inducements for compliance.


Experiences of a methadone detoxification programme for opium addicts.

The conduction of a new programme of methadone detoxification of opium addicts in a general hospital setting is described. A blind technique of dispensing methadone in a powdered form mixed with powdered aspirin to two groups of opium addicts was used: Group A were given a gradual reduction of the methadone over a period of ten days, while group B were maintained on the initial stabilising dose for the ten days and then abruptly withdrawn from methadone on the eleventh day. It was observed that the number of complaints and abstinence symptoms was markedly reduced in Group B. It is suggested that this technique is a major improvement over the standard progressive reduction method of methadone detoxification. A follow-up of these patients over a period of 1 1/2 years is reported.


The impact of methadone and drug-free treatment on criminal behavior.

The present study was initiated to evaluate the effect of methadone versus drug-free treatment on a series of criminal involvement measures. A 50% random sample of the 776 clients who had registered with the Central Intake Unit over a one year period was selected for intensive study. Data were collected through examination of intake and treatment files for pre- and post-admission time periods. Arrest, conviction and incarceration rates as well as correctional status were measured and compared across pre-treatment, intake and three month post-intake periods. The arrest rate for the total sample decreased radically from 92.8% upon entering treatment to 8% after three months in treatment. The subsequent rates at 6, 9 and 12 months decreased in a fairly consistent manner. This trend was similar in the methadone, drug-free, and methadone/drug-free groups for either arrests, convictions or incarceration rates with time in treatment. The relationship between arrests and employment and drug use was also examined. No association was found between use of opiates as measured by urinalysis results and frequency of arrest. Similarly, arrest rates showed no significant association with employment rates during the first nine months of treatment, although the comparison at twelve months was significant with only 16.7% of those employed clients being arrested.


Drug abuse: a manifestation of the cyclic nature of human behavior.

The authors conclude that a cyclic pattern of drug use behavior can be documented in a given population. While such a study provides a microcosmic view of such behavior, it is postulated that this same cyclic pattern was experienced in the macrocosm of society at large by drug-abusing populations over centuries past.


A study on the personality characteristics of Iranian addicts.

The present study was undertaken to investigate the personality characteristics of addicts in Iran and to investigate the applicability of the Persian version of the Manson Evaluation Scale in a sample of 107 hospitalized male addicts as compared with a group of 90 non-addicts. All MES values attained statistically significant t-value at or better than 0.01 level of confidence between the two groups. The study supports findings in Western socities except that our sample exhibits psychoneurotic traits more than psychopathic trends.


[Possibilities for information processing and operations simplification in multidimensional tasks of morphokinetic synthesis].

The authors propose an iterative method for separating classes of objects by reduction of multidimentional space of sings, which describe objects by twodimentional space of two integral processings of the differences between sings. For this purpose the differences are evaluated by three steps rating: positive difference, negative difference and no difference. The proposed iterative algorhythm allows by finite and a small number of procedures to remove indeterminace which in the general case is contained in the so defined on the work integral processings. The application of the algorhythm does not require a special mathematical training. Represantation of the objects by integral characteristics is made in twodimentional space. In the paper the report the authors give a generalization for the case of M-steps rating for evaluation of the differences between the signs of the objects.


[Morphologic characteristics of carbon tetrachloride poisoned liver in the presence of iron loading].

The author examined the influence of abnormal amounts of iron on the development of early fibrosis (14th day), early and advanced cirrhosis (45th and 90th day) in liver esperimentaly damaged by carbon tetrachloride by means of morphological and histochemical methods. On the basis of the obtained data she could suggest that while at early stages iron did not have significant influence on the rate of development and gravity of the pathologic process, later (advanced cirrhosis) the changes were less manifested. She asumed that three valence iron, administered in the organism of the animals intoxicated by carbon tetrachloride, improved the course of the metabolic processes in the damaged liver cells, a manifestation of which was later and weaker development of the cirrhotic process.


[Structuro-functional parallels in several liver lesions in rats resulting from dietary protein deficiency].

The authors examined 60 white rats of the Wistar strain with initial age of four monts and weight of 200 -- 15 gm, subjected to deficient food regime with varous protein content (5.74%, 11.48%, but the control was 17.50% of protein) for a period of 16 weeks. After this period half of the animals were stimulated by an antigen -- 10% of human gamma globulin. They determined total protein and protein fractions in serum, histological changes in liver and some morphometric indices. It was established that there was a correlation between the level of serum proteins and the observed changes in liver parenchyma and mesenchyma, in which the factor "protein deficit" had significantly greater effect than the factor "heterologous serum protein" as an antigenic stimulus.


[Changes in myocardial activity of several enzymes of glycolysis, the tricarboxylic acid cycle and pentosephosphate shunt in rats with experimental hypertension].

The authors examined dynamicaly from the third day to the third month the activity of enzymes, participating in glycolysis (ALD, PK, LDH), pentosemonophosphate shunt (G6P-DH), citric cycle (MDH, INDH) in the myocardium of rats with hypertension, induced by the method of Selye, modified by Kolarova. There were phase changes in enzymatic activity in the myocardium, manifested at the first stages by lowering (LDH, ALD, INDH) or elevation (MDH, PK, G6-DH). The activity of all examined enzymes was over that of the control group on the thirteenth day, while there were also oscillations on the nineteenth day. Only the actimity of G6-DH revealed a progressive elevation during the whole experimental period. The changes in the enzymic activity of the myocardium at the first stages were interpreted as a sign of nonspecific adaptation to the changed conditions of heart activity. The later changes were manifestations of the disturbances at various metabolic links, which were unevenly involved in the processes of myocardial hypertrophy.


[Effect of preparation TB-68 on spermatopoiesis in rats (autoradiographic study)].

Male mature rats were treated per of with TB-68 and intraperitonealy with 3H-thymidine during 7 and 12 days. By means of statistical count of labelled cells in semi niferous tubules a considerable increase of DNA replicating cells in experimental animals was established. The higher percentage of labelled calls reveales an stimulating effect of TB-68 concerning the spermatogonial proliferation, some acceleration of the meiosis and positive influence of the spermatopoiesis as a whole.


[Effect of arpenal on the EMG-potentials of the anterior tibial muscle in cats during acute phosdrine poisoning].

The authors examined the changes in the nerve-muscular conductivit occuring after acute poisoning with phosdrine and treatment with arpenal and oximic reacytivators of HE-toxogonine and TMB-4 on 20 cats, anesthethised with urethane and atropine protection under the conditions of artificinal respiration. They found that there was a total nerve-muscular block cessation of the mediation in the myoneural synaptic zones, characterized by complete cessation also of the induced electrical responses after single and serial stimuli, during acute intoxications with phosdrine, used in lethal doses of 300 mg/kg intramuscularly. After treatment with H-cholinolitics (arpenal) there was a quick recovery of the muscle contractions as well as of the evoked myopotentials after stimulation with single electric stimuli. In contrast to the oximnic reactivators of He (toxogonine, TMB-4) during serial electric stimuli (10,20 and 30 per second after treatment with arpenal there was a quick contraction only after the first stimulus, after which a progresive weakening of the induced electric myopotentials followed till the appearence of a total nerve-muscular block. This phenomenon was explained by the lack of reactivating properties of H-cholinolitics to HE, inhibited by FOV.


Physiologic basis and interpretation of common indices of respiratory mechanical function.

Tests of pulmonary mechanical function may be used in determining the prominent site of pulmonary reaction to intervention. Responses may be localized from a knowledge of changes in lung resistance and compliance. A peripheral airway or parenchymal response is characterized by a decrease in lung compliance. A central airway reaction is characterized by an increase in pulmonary resistance. In mixed reactions both parameters may change. In this communication some of the physiologic determinants of pulmonary resistance and compliance are discussed and examples of localized responses given.


Role of metabolic activation in the pathogenesis of chemically induced pulmonary disease: mechanism of action of the lung-toxic furan, 4-ipomeanol.

Many xenobiotics produce hepatic injury due to their metabolism in the liver to highly reactive electrophile intermediates which form covalent conjugates with nucleophilic cellular constituents. This presentation describes studies indicating that the production of chemically reactive metabolites by pulmonary metabolism of xenobiotics can also play a fundamental role in the pathogenesis of chemically induced lung disease.


Paraquat toxicity: proposed mechanism of action involving lipid peroxidation.

The purpose of this study was to investigate the hypothesis that paraquat pulmonary toxicity results from cyclic reduction-oxidation of paraquat with sequential generation of superoxide radicals and singlet oxygen and initiation of lipid peroxidation. In vitro mouse lung microsomes catalyzed an NADPH-dependent, single-electron reduction of paraquat. Incubation of paraquat with NADPH, NADPH-cytochrome c reductase, and purified microsomal lipid increased malondialdehyde production is a concentration dependent manner. Addition of either superoxide dismutase or a single oxygen trapping agent 1,3-dipheylisobenzo furan inhibited paraquat stimulated lipid peroxidation. In vivo, pretreatment of mice with phenobarbital decreased paraquat toxicity, possibly by competing for electrons which might otherwise reduce paraquat. In contrast, paraquat toxicity in mice was increased by exposure to 100% oxygen and by deficiencies of the antioxidants selenium, vitamin E, or reduced glutahione (GSH). Paraquat, given IP to mice, at 30 mg/kg, decreased concentrations of the water-soluble antioxidant GSH in liver and lipid soluble antioxidants in lung. Oxygen-tolerant rats, which hae increased activities of pulmonary enzymes which combat lipid peroxidation, were also tolerant to lethal doses of paraquat as indicated by an increased paraquat LT50. Furthermore, rats chronically exposed to 100 ppm paraquat in the water had elevated pulmonary activities of glucose-6-phosphate dehydrogenase and GSH reductase. These results were consistent with the hypothesis that lipid peroxidation is involved in the toxicity of paraquat.


Secretory cells of the peripheral pulmonary epithelium as targets for toxic agents.

The extracellular lining of the pulmonary peripheral airways is of vital importance to the lung. In this report, some aspects of the pulmonary extracellular lining and the epithelial cells believed to be responsible for its formation and secretion have been briefly reviewed. The influence of a number of toxic agents on the extracellular lining either directly or via those cells involved in its formation indicates that the extracellular lining may be important in understanding numerous toxic agent interactions with the lung.


Inhalation exposure of animals.

Relative advantages and disadvantages and important design criteria for various exposure methods are presented. Five types of exposures are discussed: whole-body chambers, head-only exposures, nose or mouth-only methods, lung-only exposures, and partial-lung exposures. Design considerations covered include: air cleaning and conditioning; construction materials; losses of exposure materials; evenness of exposure; sampling biases; animal observation and care; noise and vibration control, safe exhausts, chamber loading, reliability, pressure fluctuations; neck seals, masks, animal restraint methods; and animal comfort. Ethical considerations in use of animals in inhalation experiments are also discussed.


An isolated perfused rat lung preparation.

An isolated perfused rat lung preparation (IPL) is described and its physiologic status is evaluated. The evaluation includes light and electron microscopy after perfusion and estimations of substrate utilization. ATP content, lactate production, and incorporation of glucose carbons into lipids and CO2. It is concluded that the IPL is useful for short-term metabolic and physiologic experiments and offers some unique advantages in evaluating effects of reactive gases upon lung function.


Studies on the uptake, metabolism, and release of endogenous and exogenous chemicals by use of the isolated perfused lung.

The isolated perfused lung is a valuable tool for studying many lung functions. The kinds of information one can obtain from the isolated perfused lung are illustrated by examples from our studies on the uptake, accumulation, and metabolism of endogenous and exogenous chemicals.


Use of tracheal organ cultures in toxicity testing.

Fragments of tracheal epithelium alone or in continuity with connective tissues, can be maintained in culture medium and used for short term or long term studies of toxicity of a variety of chemicals. Large numbers of uniform cultures are prepared with the aid of a slicing device or by application of simple method for dissecting sheets of epithelium free from underlying cartilage. The cultures may be placed in an exposure chamber-incubator mounted on a microscope stage and monitored continually for ciliostasis and exfoliation of cells. Morphology is further studied by fixation of selected specimens and preparation for light microscopy and electron microscopy. Synthetic functions are evaluated by autoradiographic measurement of incorporation of radioactive precursors into macromolecules and other dynamic features are indirectly assessed by histochemical and histoenzymatic methods. Short-term studies using these several techniques have shown that ciliostasis does not correlate with cell injury in all instances, and a long-term study has demonstrated dose dependence of a cytotoxic agent when duration of culture viability is measured. The method lends itself to a broad range of investigations in which dose, period of exposure, and role of cofactors must be independently and quantitatively assessed.