Attitudes of the public to medical care: Part 8, "Non-Medical" Practitioners. A random sample of respondents in Dunedin and Auckland was surveyed to obtain details of utilisation of various aspects of health services and also opinions and knowledge of these services: a section of the survey dealt with "non-medical doctors". A miniority of respondents or their families had made use of such services (13.2 percent) in the previous five years, compared to 47.1 percent utilising medical specialist services and almost 100 percent utilising general practitioner services in the same period. The number of items of services for one patient with one consulting cause was high. The mean being just under eight and in one fifth of cases was 15 or more. Most respondents considered that the services of non-medical practitioners could sometimes be useful and one-third would consider consulting such practitioners themselves, although most would consult an orthodox doctor first. Only one-fifth of respondents were willing to see Government financial support for non-medical practitioners.


Drug-induced sclerosing peritonitis.

Drug-induced sclerosing peritonitis. The records and case reports of 20 patients presenting with practolol induced sclerosing peritonitis have been reviewed revealing striking similarities: symptoms and signs of bowel obstruction or the presence of a vague abdominal mass in a patient who is currently taking or has previously taken practolol should alert one to the possibility of sclerosing peritonitis as the cause. Skin or eye reactions attributed to practolol provide further strong support for the diagnosis. Although practolol has now been discontinued in New Zealand its effects may become manifest months or years later.


Special Unit and Medical School Laboratory Technicians in New Zealand. A follow-up review and survey of training and qualifications 1970-1975. In 1970 a survey was undertaken to ascertain the training opportunities and career prospects of laboratory technicians employed in medical research and special unit laboratories. After an interval of five years a follow-up survey was undertaken in an attempt to reassess numbers of technicians employed, qualifications, and training course preferences. This 1975 survey has revealed an increase from 26 to 49 departments undertaking laboratory investigations. There was also a 100 percent increase in the number, 150 to 290, of technicians employed. Heads of departments and senior staff responsible for employment have indicated a concern for and a high degree of satisfaction with technical institute courses and the certification authority's qualifying system in the field of technician training.


Carcinoma of the lung presenting as Cushing's syndrome. A case of bronchial carcinoma of the lung presenting as Cushing's syndrome is described. The clinical features and laboratory investigations leading to the diagnosis are outlined. The autopsy findings, histology and the ultrastructure of the tumour are illustrated and the literature is reviewed.


Clinical assessment of a new local anesthetic agent-carticaine. The combination of 4 per cent carticaine 5 mug per milliliter with epinephrine is an effective agent acting in the standard lidocaine-epinephrine-mepivacaine-epinephrine range. Like lidocaine, it is of no clinical value without the addition of epinephrine and its vasodilator properties are greater than those of mepivacaine or prilocaine. Its onset time is reasonably rapid, its duration and extent are satisfactory for clinical purposes, and no toxic reactions were noted in the 100 injections given. However, its predictability for +4 anesthesia is poor, and there is wide variation in the onset time. Finally, the success rate compared with that for lidocaine, mepivacaine, or prilocaine for the same dosage and areas, with the use of the same criteria, is not good enough in my opinion to qualify carticaine as a general-purpose anesthetic on a par with standard lidocaine.


Histologic changes following the grafting of connective tissue into human gingiva. Grafting connective tissue from the palate to partial-thickness sites prepared in patients with an inadequate width of attached gingiva resulted in an increased width of keratinized mucosa. Biopsies of these grafts at the newly created mucogingival junction at 24 weeks showed the epithelium to be keratinized with a normal architecture, except over scar tissue at the edges of the grafts, where rete-peg formation was absent. The results support the concept that morphodifferentiation of gingival epithelium is influenced by the underlying connective tissue.


Plasma-cell granuloma of the gingiva.

Plasma-cell granuloma of the gingiva. A case of plasma-cell granuloma of the attached gingiva has been presented. The lesion was pedunculated and, clinically, resembled a traumatic fibroma. The microscopic picture was that of plasma-cell granuloma. Serum electrophoresis and radiographs were normal. A diagnosis of plasma-cell granuloma confirms a benign lesion of the oral cavity which must not be confused with the plasmacytoma, a possible precursor to multiple myeloma. This case emphasized the need for biopsy of lesions in order to establish a diagnosis. Only by biopsy and histologic study can rare lesions be diagnosed and their incidence studied.


An epilogue to plasma-cell gingivostomatitis (allergic gingivostamtitis). Sixteen cases of plasma-cell gingivostomatitis were studied at the University of California San Francisco between 1966 and 1971. Twelve women and four men made up the group, with ages ranging from 15 to 70 years. Prior to treatment, the duration of the disease ranged from 5 to 60 months. Each of the sisteen patients manifested a homogeneous, diffuse, erythematous gingivitis associated with a cheilitis, and fifteen also had a marked glossitis. Each subject was symptomatic, and nine also complained of bleeding. Every biopsy specimen demonstrated a characteristically diffuse and dense plasma-cell infiltrate. There were no spontaneous remissions. Six patients completely responded to systemic corticoids alone, two to discontinuation of gum chewing or the use of their dentifrice, one to antifungal therapy, and the other seven to a combination of the preceding modalities. After completion of therapy, fifteen patients were followed for 2 to 55 months without any evidence of recurrence. Of interest, 69 per cent were gum chewers. The therapeutic benefit of discontinuing gum chewing by itself was not clear. It is assumed that the now nonexistent plasma-cell gingivostomatitis syndrome was a hypersensitivity response to an unidentifiable antigen used in various substances.


The odontogenic keratocyst. A clinicopathologic study of 312 cases. Part II. Histologic features. The histopathologic features of 312 odontogenic keratocysts are described. These features are discussed in relation to their pathogenesis and behavioral characteristics, including recurrence factors and neoplastic potential. In addition, a discussion and comparison of the histologic features found in solitary keratocysts, keratocysts associated with the basal-cell nevus--bifid rib syndrome, multiple keratocysts in patients with no other syndrome manifestations, and recurrent kerocysts is presented.


Ultrastructure of eosinophilic bodies in the degenerative surface epithelium of chronic hyperplastic oral lesions. Eosinophilic bodies were located extracellularly in the dilated intercellular spaces of degenerative epithelial cells. They consisted of electron-dense amorphous material with many scattered mature fibrin fibers. Eosinophilic bodies were PAS positive, mucicarmine negative, alcian blue negative. A large number of lysosome-like bodies with homogeneous electron-dense content were present in the cytoplasm of the surrounding degenerative epithelial cells. The plasma membrane of these cells was intact and there was no outpouring of tonofilaments or keratohyaline granules into the intercellular spaces. With the results of the present study, it is suggested that eosinophilic bodies are probably an exudate of plasma fluid accumulated in the dilated intercellular spaces of superficial degenerative cells.


Dentine dysplasia with sclerotic bone and skeletal anomalies inherited as an autosomal dominant trait. A new syndrome. Patients with teeth showing all of the clinical, radiographic, and histologic features of radicular dentine dysplasia (type I) have been found to have dense sclerotic bone and skeletal anomalies of the wrists and hand bones. The association of these defects of teeth and bone was found to be transmitted as an autosomal dominant trait over four generations. Review of theliterature failed to disclose a previous description of this disorder.


Evaluation of dental radiology students in Canadian dental schools. Evaluation involves the worth of an experience, idea, or process and is an integral part of dental education. The current article discusses a survey of dental radiology evaluation in Canadian dental schools. It appears that in Canada students are evaluated formally in didactic aspects of radiology, interpretation of radiographs, and clinical aspects of dental radiology.


Osteomyelitis with proliferative periostitis (Garré's osteomyelitis). Report of a case affecting the mandible. A case of chronic osteomyelitis with proliferative periostitis of the mandible is reported. This is a unique form of osteomyelitis characterized radiographically by localized thickening of the periosteum and deposition of laminated subperiosteal bone.


Acute measles encephalitis in children with immunosuppression. Four cases of encephalitis occurring in children treated for lymphatic malignancies by immunosuppressive drugs are reported. Measles virus was isolated from the brain in one case and identified immunologically in another. Nucleocapsids identical to those seen in subacute sclerosing panencephalitis were demonstrated in three cases. Severe immunosuppression was evidenced in two patients by failure of rosette formation and low phytohemagglutinin tests. Pathologically, the inflammatory reaction was absent in one brain and moderate in two. Clinically, epilepsia partialis continua was a prominent feature in three patients. A history of measles or of contact was elicited in three cases, five weeks to three months before onset. All cases ran an acute fatal course. Measles virus can behave as an opportunistic invader of the central nervous system in children and the diagnosis of measles encephalitis should be considered in immunosuppressed patients.


Current concepts in acute leukemia.

Current concepts in acute leukemia. Using chemotherapeutic agents in combination instead of separately has significantly improved the outlook for patients with acute leukemia. The rate and duration of complete remission have both increased substantially. Immunotherapy, recently introduced for use with chemotherapy, appears to prolong survival.


A novel prostaglandin is the major product of arachidonic acid metabolism in rabbit heart. The prostaglandins (PGs) released from the heart have generally been characterized as resembling PGE by bioassay techniques. The major PG formed from [14C]arachidonate (C20:4) by the isolated perfused rabbit heart has chromatographic mobility similar to that of PGE2 in most solvent systems. However, additional analysis of this radioactive "PGE" peak suggests that two substances are formed by the heart and migrate like PGE2: one has chemical properties similar to those of authentic PGE2 and the other is a novel PG. The unknown compound is the major PG formed by the heart from either exogenous arachidonate or hormonal stimulation of PG biosynthesis. The novel PG produced by the heart may be identical with either 6(9)-oxy-PGF or 6-keto-PGF1 alpha.


Synthesis of a 19-residue peptide with alamethicin-like activity. This paper describes the chemical synthesis of a compound with voltage-gating characteristics similar to those observed in nerve membranes. For alamethicin (ALA), a natural antibiotic that induces such properties in lipid bilayer membranes, there are two proposed structures, one a cyclic and the other an open chain peptide. The open chain sequence (ALA-o) proposed by Martin and Williams [(1976) Biochem. J. 153, 181-190] was synthesized by stepwise solid-phase condensation of four fragments prepared by solid-phase synthesis. The product, purified to homogeneity, was not identical with the main component of natural ALA. Nevertheless, in lipid bilayer membranes the exponential dependence of conductance on voltage and the dependence of conductance on a high power of the peptide concentration were qualitatively similar for ALA-o and for natural ALA. Like ALA, ALA-o showed the characteristics of a channel-former, although the single-channel conductances were less well defined for the synthetic compound. This work establishes that a cyclic structure is not a necessary condition for a peptide to induce voltage-dependent conductances in membranes and that ALA-o possesses all the structural elements required for such an activity.


Actin microheterogeneity in chick embryo fibroblasts. Secondary chick embryo fibroblasts contain three distinct actin species--alpha, beta, and lambda, in the approximate ratio of 1:6:3--with the same molecular weights but different isoelectric points. The most acidic of these components, alpha, comigrates on isoelectric focusing gels with the major actin of cardiac and skeletal muscle, while lambda, the most basic of the actins, comigrates with smooth muscle actin. The three components have overlapping methionine-containing tryptic peptides. All three actins are found to be present in actomyosin and cytoskeleton preparations from chick embryo fibroblasts. Identification of alpha-actin as the major actin from sarcomere-containing cells is confirmed by comparing embryonic chicken pre- and post-fusion myoblast cultures. Following myoblast fusion, the relative amount of alpha-actin increases until it changes from a minor actin component to the predominant actin species in the culture.


Mutational analysis of developmental control in Caulobacter crescentus. The relationship between the cell cycle and control of development has been studied by a genetic analysis of Caulobacter crescentus. The behavior of conditional cell division mutants showed that cell cycle events, such as DNA replication and cell division, are organized into a dependent pathway(s), i.e., later steps cannot preceed until earlier ones are completed. The ability of these strains to develop normally under nonpermissive conditions suggested that flagellin synthesis and stalk formation are dependent on the completion of different cell-cycle steps: the periodicity of flagellin synthesis is achieved by coupling it to either DNA chain elongation or completion, and stalk formation is dependent on a later step in the cell-division pathway. These developmental events are not themselves required for cell division, however.


Stable conformations of aliphatic disulfides: influence of 1,4 interactions involving sulfur atoms. The present state of knowledge of the stable conformations of the XCCSSCCX fragment (in which X is any saturated group) of aliphatic disulfides is examined. In particular, the evidence for the existence of attractive 1,4 interactions between CH groups and S atoms across C-S bonds and their influence on the potential function for rotation about C-S bonds is discussed. The effects of similar attractive interactions between NH groups and S atoms on the potential function for rotation about C-C bonds also are considered. It is concluded that weak attractive interactions between CH groups and S atoms are capable of stabilizing rotamers with unusually low (about 30 degrees) values of the SS-CC dihedral angle.


Enzymatic conversion of proteins to glycoproteins. The enzymatic transfer of the oligosaccharide moiety from an oligosaccharide-lipid to denatured forms of three secretory proteins--ovalbumin, alpha-lactalbumin, and ribonuclease A--has been demonstrated utilizing a membrane fraction from hen oviduct. Based on a survey of 10 proteins denatured by sulfitolysis, the presence of the tripeptide sequence -Asn-X-Thr-Ser- (X represents a variable amino acid) appears to be necessary but not sufficient for the protein to serve as acceptor in vitro. The results of this investigation also suggest that unfolding of the polypeptide chain is required in order to expose sites for carbohydrate attachment.


Distinctions between the two-state and sequential models for cooperative ligand binding. The two-state and sequential models for positive cooperativity in ligand binding can produce significantly different theoretical binding curves when presented in a Scatchard plot. The conditions that produce the greatest differences have been examined. The theoretical differences have been used to select the two-state model as the best model for describing the binding of acetylcholine to acetylcholine receptors that have been solubilized by Triton X-100 and sodium cholate.


Inside-out model for self-assembly of tobacco mosaic virus. Incompletely reconstituted particles of tobacco mosaic virus treated with moderate concentrations of dimethylsulfoxide prior to electron microscopy have two visible tails of unencapsidated RNA, a long one and a short one. The short tail has a constant length of 720 +/- 80 nucleotides in incomplete particles of diverse size and probably corresponds to the 3'OH end of the RNA. The length of the long 5' tail is inversely related to the length of the unfinished rod. Surprisingly, both tails appear to protrude from the same end of the particle. These observations suggest that the strand of RNA coming out of one end of the particle loops back along the length of the rod so as to appear at the opposite end. The "looped-back" tail almost certainly passes down the empty central channel of the incomplete rod. The findings are compatible with a model of tobacco mosaic virus assembly in which the RNA inserts itself beneath layers of incoming protein from within the central channel.


Relationship between the soluble glutathione-dependent delta 5-3-ketosteroid isomerase and the glutathione S-transferases of the liver. Soluble, glutathione-stimulated delta 5-3-ketosteroid isomerase (EC 5.3.3.A) activity of human and rat liver resides in very basic proteins with molecular weights of about 45,000 which are present in high concentrations in these tissues. Physiochemical and immunological evidence is presented for the identity of the proteins responsible for this enzymatic activity with the glutathione S-transferases (RX:glutathione R-transferase, EC 2.5.1.18) that conjugate glutathione with a variety of electrophilic compounds. In the rat, the steroid isomerase is associated principally with the major transferase (B), which is also known as ligandin, and has the versatility to bind various hydrophobic compounds such as bilirubin, corticosteroids, and metabolites of a number of carcinogens. Other rat liver-glutathione S-transferase species are far less active in the steroid isomerization reaction. The delta 5-3-ketosteroid isomerase activity of human liver is more uniformly distributed among the five glutathione S-transferases that have been described. Steroid isomerization differs fundamentally from other reactions promoted by glutathione S-transferases in that glutathione is not consumed in the reaction. However, because the transferase enzymes promote nucleophilic attack by glutathione on a variety of largely foreign organic substrates, a similar mechanism may be involved in the isomerase reaction. Delta 5-3-ketosteroids are among the few known naturally occurring substrates for these enzymes.


Protein-sugar interactions: preparation, purification, and properties of rabbit antibodies against di-N-acetylchitobiose. Antibodies against di-N-acetylchitobiose (CB) were raised in rabbits after injection of CB-bovine serum albumin conjugates and were fractionated by columns into two classes: the first bound to a column of Sepharose covalently coupled with N-acetylglucosamine (GlcNAc); the second bound to a column coupled with CB. Active antibodies were eluted by a moderate concentration of a chaotropic agent, but not by high ionic strength buffers or acidic buffers. The active fractions were identified as IgG by ultracentrifugation and immuno-electrophoresis. These antibodies gave precipitation bands with CB-protein conjugates and this reaction could be reversed in the presence of free CB. The GlcNAc-bound fraction quantitatively quenched the fluorescence of O-(4-methylumbelliferyl)-glucosides of GlcNAc and CB, while the CB-bound fraction quenched only the glycoside of CB; other O-(4-methylumbelliferyl)-glucosides were not quenched. Among eleven monosaccharides and oligosaccharides, only GlcNAc, CB, and tri-N-acetylchitotriose were able to inhibit the precipitation of antibodies against CB with CB-protein conjugate. These antibodies failed to agglutinate erythrocytes from various species but did agglutinate transformed cells and mouse lymphocytes. The binding of these antibodies on cell lembranes was reversed by free CB and by CB-protein conjugates. The properties of these antibodies are related to those of lectins with similar specificities and to the structure of glycoconjugates.


Activation of histone gene transcription by nonhistone chromosomal proteins in WI-38 human diploid fibroblasts. The regulation of histone gene expression was examined after confluent, nondividing WI-38 human diploid fibroblasts were stimulated to proliferate. Histone mRNA sequences were assayed by hybrid formation with an 3H-labeled single-stranded DNA complementary to histone mRNAs. Histone mRNA became associated with polyribosomes concomitant with the activation of DNA synthesis. The ability of chromatin from WI-38 cells to serve as a template for in vitro transcription of histone mRNA sequences parallels the onset of DNA replication. A role for nonhistone chromosomal proteins in the control of histone gene readout is suggested because, when chromatin from confluent WI-38 cells was dissociated and then reconstituted in the presence of S phase nonhistone chromosomal proteins, a 500-fold activation of histone mRNA sequence transcription was observed.


Purification of a putative precursor of globin messenger RNA from mouse nucleated erythroid cells. Nucleated erythroid cells were incubated for 10 min in the presence of [5-3H]uridine, and the total RNA was isolated by three different extraction procedures. RNA containing globin messenger RNA sequences was purified from other cellular RNAs by selective hybridization to globin complementary DNA cellulose. Depending upon the extraction procedure employed, 0.4-0.6% of the radioactively-labeled total cellular RNA applied to the column annealed to globin complementary DNA cellulose. The annealed RNA was treated with formaldehyde and analyzed by formaldehyde/polyacrylamide gel electrophoresis. Mature globin mRNA and an RNA migrating at approximately 15 S were observed. No globin mRNA containing sequences larger than 20 S were present. The 15S RNA was partially resolved from mature globin mRNA by neutral sucrose density gradient centrifugation. The RNA isolated from the heavy region of this gradient migrated as 15 S in the formaldehyde/polyacrylamide gels and retained its ability to quantitatively anneal to globin complementary DNA cellulose. On the basis of these observations, we conclude that nucleated erythroid cells obtained from the spleens of anemic mice have a 15S RNA which contains globin mRNA sequences. The 15S RNA is not an aggregate and is a good candidate for a globin mRNA precursor.


Mutagen-nucleic acid intercalative binding: structure of a 9-aminoacridine: 5-iodocytidylyl(3'-5')guanosine crystalline complex. 9-Aminoacridine forms a crystalline complex with the dinucleoside monophosphate, 5-iodocytidylyl(3'-5')guanosine. We have solved the three-dimensional structure of this complex by x-ray crystallography and have observed two distinct intercalative binding modes by this drug to miniature Watson-Crick double helical structures. The first of these involves a pseudosymmetric stacking interaction between 9-aminoacridine molecules and guanine-cytosine base-pairs. This configuration may be used by 9-aminoacridine when intercalating into DNA. The second configuration is an asymmetric interaction, largely governed by stacking forces between acridine and guanine rings. This type of association may play an important role in the mechanism of frameshift mutagenesis.


Ligand kinetics of hemoglobin S containing erythrocytes. Oxygen uptake of fully deoxygenated sickle (SS) erythrocytes is slower than that of normal (AA) erythrocytes, as demonstrated by the half-times of the overall oxygenation reactions: at 25 degrees in an isotonic phosphate buffer the normal red cells have a t1/2 = 82 +/- 4.7 msec, as compared to sickle red cells where t1/2 = 135 +/- 17.6 msec. The effects of temperature, extracellular osmolality, and the presence of an antisickling agent (n-butylurea) on the rate of red cell oxygenation strongly suggest that the differences in oxygenation rates encountered with sickle red cells is directly related to the intracellular polymerization of deoxyhemoglobin S.


Bacterial flagella rotating in bundles: a study in helical geometry. Bacterial flagella are semi-rigid helices that undergo true rotation. In peritrichously flagellated bacteria (e.g., Escherichia and Salmonella) there are many flagella on each cell; during translational cell movement these operate as a coordinated bundle that actively disperses upon reversal of the rotation sense. The dynamic behavior of a set of helices originating on separate rotational axes is explored by a working model, geometrical analysis, and hydrodynamic calculations. A critical relationship exists between the interaxial separation and phase difference of parallel helices with overlapping domains; in the subcritical case the filaments are not intertwisted, whereas in the supercritical case they are intertwisted in the same sense (left-handed) as the helices, with one twist per helical turn. During counter-clockwise rotation (the sense operative in forward swimming) any preexisting twists of this kind are automatically cancelled and the helices brought progressively into phase. Hydrodynamic calculations suggest that some wrapping then occurs in a right-handed sense, opposite to that of the helices; this necessitates a distortion from true helical geometry which is minimized by maintaining a coaxial in-phase relationship. A highly coordinated helical bundle results that is capable of operating smoothly for an indefinite period, in agreement with the observed behavior of swimming bacteria. During reverse rotation, the supercritical case develops to cause jamming of the bundle, as has been observed with bacteria in high-viscosity medium. The explosive dispersal of the bundle during reversal in low-viscosity medium is a consequence of a complicating phenomenon, namely, a drastic change in flagellar quaternary structure. The overall conclusion is that bundle formation and function are perfectly compatible with a rotational mechanism for the individual flagella.


Role of cell surface carbohydrates and proteins in cell behavior: studies on the biochemical reversion of an N-acetylglucosamine-deficient fibroblast mutant. AD6, a mutant derived from 3T3 Balb/c cells, is characterized by low adhesion to substratum, round shape, increase in surface microvilli, increase in agglutinability by concanavalin A, and loss of directional motility. These properties are often observed in transformed cells. However, the mutant has normal growth properties and anchorage-dependence of growth, and it does not form tumors. In AD6, the biosynthesis of complex carbohydrates and glycoproteins is impaired because of a block in the acetylation of GlcN-6-P. This defect is responsible for all the surface alterations because feeding of GlcNAc to AD6 cells corrects the defects in the synthesis of complex carbohydrates and the exposure of glycoproteins at the outer surface of the plasma membrane. Parallel to this biochemical reversion, there is full restoration of the altered biological properties. In contrast, GlcNAc has no effect on the morphologic features of two lines of transformed cells. Our results suggest that the carbohydrate portion of cell surface proteins has an important role in adhesion and related aspects of cell behavior. The fact that a defined alteration of the cell surface induces many properties often encountered in transformed cells, without affecting control of cell division, strongly suggests that these alterations in properties are not sufficient to account for the loss of growth regulation.


Chromosome mapping of the genes that control differentiation and malignancy in myeloid leukemic cells. The chromosome banding pattern has been analyzed in clones of mouse myeloid leukemic cells that differ in their ability to be induced to differentiate by the protein inducer MGI (macrophage and granulocyte inducer). None of the clones had a completely normal diploid banding pattern. The clones studied were either MGI+ (that can be induced to form Fc and C3 rosettes), a stage in the differentiation of myeloid cells, or MGI- (that cannot be induced to form these rosettes). All six cultured clones of MGI- cells from myeloid leukemias independently produced in six separate animals showed a loss of a piece of one chromosome 2 and this abnormal chromosome was maintained in leukemias derived from the cultured cells. This loss was not found in MGI+ clones or lymphoid leukemias. Five MGI+ mutants, derived from an MGI- clone with a loss of a piece of one chromosome 2, one normal chromosome 12, and two translocated chromosomes 12, maintained the abnormal chromosome 2 but lost either the one normal or one of these translocated chromosome 12. These results indicate that chromosomes 2 and 12 carry genes that control the differentiation of myeloid leukemic cells and that inducibility by MGI is controlled by the balance between these genes. We suggest that these chromosomes also carry genes that control the malignancy of these cells.


Phosphorylation of membrane proteins at a cholinergic synapse. Endogenous membrane protein kinase activity and protein kinase substrates have been found in membrane fractions enriched in the acetylcholine receptor that were prepared from the electric organ of Torpedo californica. Phosphorylation of four polypeptides is stimulated 9-fold by K+. The specific cholinergic ligand, carbachol, inhibited phosphorylation of these four polypeptides by 72% in the presence of 1mM Na+ and 100 mM K+. The 65,000-dalton component of the acetylcholine receptor in the membrane fraction appears to be phosphorylated by the endogenous protein kinase. These results suggest that protein phosphorylation may play an important role in synaptic events at nicotinic cholinergic synapses.


Cell differentiation in Dictyostelium under submerged conditions. Hitherto it has not been possible to obtain spore and stalk cell differentiation of the cellular slime molds in submerged cultures. It is shown here that cells, when placed in roller tubes under an atmosphere of oxygen, will form clumps and differentiate in 48-72 hr into mature spores and stalk cells. Although differentiation occurs without the normal morphogenetic movements, there is the appearance of an anteroposterior polarity of the cells in the clump. In addition to oxygen we examined a number of other factors that affect differentiation.


Rejection by syngeneic mice of cell variants obtained by mutagenesis of a malignant teratocarcinoma cell line. Cells from the malignant teratocarcinoma line PCC4.azal were treated with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine. Fifty-five clones were isolated from the surviving cells. Twelve clones are unable to form tumors in the syngeneic 129/Sv mice. However, these "tum-" clones form tumors as readily as the original cells when they are injected into irradiated mice. Moreover, they stimulate the production of immune memory cells, which protect the injected animals and confer resistance by adoptive transfer. The tum- clones are therefore unable to generate tumors in syngeneic mice because they elicit an immune rejection response.


Cleavage map of linear mouse sarcoma virus DNA. Proviral DNA transcribed from the RNA of Moloney murine sarcoma virus was isolated from newly infected cells. Three forms of viral DNA were observed: (i) a linear double-stranded form of 3.4 X 10(6) daltons which constituted the major viral DNA species in the cell, and is thought to be a complete transcript (monomer) of viral RNA; (ii) a fast-sedimenting viral DNA bigger than the monomeric unit which can be either integrated provirls or concatamers; and (iii) covalently closed circles of monomer size representing 5% or less of the total viral DNA in the cell. The linear viral DNA was tested for its susceptibility to restriction endonucleases by electrophoretic analysis of the digestion products and their identification by hybridization with viral RNA or cDNA probes. The linear DNA is not cleaved by endonucleases EcoRI and BamHI. It is cleaved into two fragments by endonucleases HindIII and Hae II, and into three fragments by restriction endonuclease HincII. The fragments of the viral DNA added up to approximately 3.4 X 10(6) daltons; this and the uniform size of the linear DNA indicated that the viral DNA has unique ends and a complexity of 3.4 X 10(6) daltons. The different cleavage fragments were ordered with respect to each other and the 3' end of the viral RNA. It was observed that fragments from both ends of the linear DNA can be hybridized to sequence(s) at the 3' end of murine sarcoma virus RNA; this result suggested the possibility that a short redundant sequence exists at both termini of the genome.


Initiation of genetic exchanges in lambda phage--prophage crosses. When Escherichia coli K-12 (lambda) lysogens were infected with lambda phages, genetic exchanges between phage and prophage occurred at low frequencies (less than 0.1% between the markers P3 and P80), but at frequencies above 1% if the infecting phages were first treated with the photosensitizing agent 4,5',8-trimethylpsoralen and 360 nm light. Exchanges were induced by psoralen damage at about the same frequency in wild-type lysogens and in those carrying recB(-), recC(-), recF(-), or lexA(-), but at an intermediate frequency in a quadruple mutant carrying recB(-)recC(-)recF(-)sbcB(-). Few if any exchanges were induced in lysogens carrying uvrA(-), uvrB(-), or recA(-). The increase in the frequency of recombination was presumably due to the psoralen damage in the phage DNA molecules and the action of host cell repair and recombination enzymes. The production of crosslinks in the phage DNA by psoralen and 360 nm light was measured by sedimentation in alkali. It showed second-order kinetics indicative of a two-photon reaction. In contrast, first-order kinetics had been reported for monoadduct formation. Second-order kinetics, similar to those for crosslink production, were found for genetic exchanges in homoimmune crosses. Presumably, crosslinks, rather than monoadducts, cause most of the exchanges. Because the uvrA(-) gene product (UV-endonuclease) was required, it is likely that recombination was initiated by DNA molecules cut at crosslinks. This system has been used to show that after the crosslinked phage duplex has been cut, one or more of the subsequent steps-homologous pairing, cutting, and joining-require the recA(+) gene product.


Genetic control of mitochondrial malate dehydrogenases: evidence for duplicated chromosome segments. The genetic control of the major mitochondrial isoenzymes of malate dehydrogenase (L-malate:NAD+ oxidoreductase; EC 1.1.1.37) has been investigated in Zea mays. The mitochondrial isozymes are coded at four nuclear gene loci. Two of the loci (mdh1 and mdh2) are diallelic and tightly linked. The other two loci (mdh3 and mdh4) appear to have arisen by duplication of the chromosome segment carrying mdh1 and mdh2, but are not linked to them. The segregation of such a duplicate segment can explain anomalous backcross and F2 segregation ratios.


Microcell-mediated transfer of murine chromosomes into mouse, Chinese hamster, and human somatic cells. In this report, we describe the production and characterization of proliferating hybrid cell populations generated by fusion of murine microcells with intact mouse, Chinese hamster, and human recipient cells. The microcell hybrids so produced contained one to five intact murine chromosomes derived from the microcell donor. these transferred chromosomes were maintained as functioning genetic elements in the hybrid cells. Our results firmly establish subnuclear particle-mediated chromosome transfer as a valid somatic cell genetic tool.


Glucose homeostasis during prolonged suppression of glucagon and insulin secretion by somatostatin. Somatostatin was infused for 5-8 hr into five normal men and eleven normal, conscious dogs. This infusion resulted in a persistent decline in plasma glucagon (40-60%) and insulin (30-45%). Plasma gluccose fell 15-25% during the initial 1-2 hr, but subsequently rose to hyperglycemic levels (130-155 mg/100ml) by 3-6 hr, despite persistent hypoglucagonemia. Glucose production initially declined by 40-50%, but later rose to levels 15-20% above basal rates while peripheral glucose utilization fell to levels 20-30% below basal, thereby accounting for hyperglycemia. Infusion of exogenous insulin so as to restore plasma insulin to preinfusion values or cessation of the somatostatin infusion with restoration of endogenous insulin secretion resulted in a prompt reduction of plasma glucose to baseline values. Prevention of the initial somatostatin-induced hypoglycemic response by intravenous infusion of glucose failed to prevent the delayed hyperglycemia. We conclude that somatostatin caused only transient hypoglycemia in normal subjects and that hyperglycemia eventually developes as a consequence of insulin deficiency. These data indicate that basal glucagon secretion is not essential for the development of fasting hyperglycemia and support the conclusion that insulin deficiency rather than glucagon excess is the primary factor responsible for abnormal glucose homeostasis in the diabetic.


Beta-endorphin: stimulation of growth hormone release in vivo. Two micrograms of beta-endorphin (beta-lipotropin61-91) injected intraventricularly in rats that had been treated with antiserum against somatostatin led to a 6- and 10-fold stimulation of the concentration of plasma growth hormone (somatotropin) measured 10 and 20 min after injection of the peptide, whereas 400 mug of methionine-enkephalin led to a 4- to 6-fold increase of levels of plasma growth hormone at 10 min with a rapid return to basal levels at later time intervals. At doses of 5 and 25 mug, beta-endorphin led to a 20- to 30-fold stimulation of levels of plasma growth hormone, the maximal effect being measured between 20 and 30 min after injection. These data suggest the possible role of the endogenous opiate-like peptides in the control of growth hormone secretion.


Reduction of blood pressure and vascular collagen in hypertensive rats by beta-aminopropionitrile. beta-Aminopropionitrile, a specific inhibitor of lysyl oxidase prevented the rise in blood pressure induced by deoxycorticosterone-salt in rats. In addition, after the onset of hypertension, administration of beta-aminopropionitrile lowered the blood pressure. Concomitant with the lowering of blood pressure, there was a reduction in the more highly crosslinked form of vascular collagen. These findings would indicate that increases in vascular connective tissue are not only sequelae of hypertension, but may also contribute to the maintenance of elevated blood pressure.


Inhibition of erythrocyte sickling in vitro by DL-glyceraldehyde. Concentrations of DL-glyceraldehyde between 5 and 20 mM reduce the sickling of S/S erythrocytes even in the complete absence of oxygen; at 10 mM glyceraldehyde the increase in the number of normal cells ranges from 20 to 40%. The inhibition of sickling was both concentration- and time-dependent and was not reversed by repeated washings with buffer. Incubation of erythrocytes with increasing concentrations of glyceraldehyde resulted in only a small increase in the oxygen affinity, a moderate reduction in the Hill coefficient, a substantial increase in the minimum gelling concentration, and modification of up to two lysine residues per hemoglobin molecule.


Development of the nervous system of Aplysia californica. The ability to grow the marine molluse Aplysia under laboratory conditions allows a detailed study of the formation of the nervous system and of the development of specific identified cells. I have found that the ganglia develop in a specific temporal order. Cerebral and pedal ganglia develop at hatching, the abdominal, pleural, and osphradial ganglia 3 weeks after hatching, and the buccal ganglia at 4 weeks. The origin of the abdominal ganglion is complex; its anlage forms at 3 weeks from three larval ganglia that fuse to form the abdominal ganglion. Individual cells cannot be distinguished from one another by their location within the ganglion or by their appearance alone until metamorphosis at 5 weeks. After metamorphosis, the identified neuron, R2, suddenly becomes recognizable because of a significant increase in its size.


Measures of fitness and demographic stability. The concepts of entropy and reproductive potential of a genotype were introduced in a previous paper [Demetrius, L. (1974) Proc. Natl. Acad. Sci. USA 71, 4645-4647] and an analoge of the fundamental theorem of natural selection was derived. This paper relates to entropy of a population with the rate of convergence of the population to the stable age distribution. I show that (i) at maximal entropy, no oscillatory components exist and the birth sequence is unaffected by perturbations in the stable age distribution; and (ii) at zero entropy, oscillatory components occur and increase as rapidly as the real exponential component in the birth sequence. These results have implications towards (i) the relation between population fitness and adaptedness, (ii) modes of selection and the evolution of reproductive strategies, and (iii) the evolution of senescence.


Synthesis of two collagen types by embryonic chick corneal epithelium in vitro. To better understand the mechanisms involved in matrix development, we have analyzed the collagen synthesized by embryonic corneal epithelium, the tissue known to produce the collagenous component of the primary corneal stroma. Isolated epithelia were cultured in vitro in medium containing [oH]proline and the newly synthesized, labeled collagen was extracted, fractionally salt precipitated, and analyzed by carboxymethyl-cellulose chromatography and peptide mapping after cleavage with cyanogen bromide. The data show that the cornela epithelium produces at least two different types of collagen, one similar, if not identical, to the type I molecule of skin, and a second similar, if not identical, to the type II molecule of cartilage. Type II, heretofore, had been thought to be characteristic of cartilage extracellular matrix.


Selective and accurate transcription of the Xenopus laevis 5S RNA genes in isolated chromatin by purified RNA polymerase III. Chromatin isolated from immature oocytes was found to contain an endogenous RNA polymerase activity (RNA nucleotidyltransferase; nucleoside triphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) that synthesizes predominately 5S RNA. However, the levels of total RNA synthesis and 5S RNA synthesis in chromatin were each stimulated 10- to 50-fold by an exogenous RNA polymerase III purified from X. laevis oocytes. The 5S genes in chromatin were transcribed by the exogenous enzyme in a highly selective (3000-fold above random) and predominately asymmetric fashion. A significant fraction of 5S RNA sequences were also found in a discrete transcript, approximately 5S in size. Total RNA synthesis was significantly stimulated when chromatin was transcribed by oocyte RNA polymerase I, murine RNA polymerase II, and low levels of Escherichia coli RNA polymerase. However, these enzymes did not significantly stimulate 5S RNA synthesis above the endogenous levels. Both homologous oocyte RNA polymerase I and III and E. coli RNA polymerase transcribed the 5S genes in deproteinized DNA to approximately the same extent (severalfold above random) and both the sense and anti-sense strands of the gene were transcribed. It appears, therefore, that both chromatin-associated components and a purified RNA polymerase III are necessary and sufficient for the selective and accurate transcription of the 5S RNA genes in vitro.


A soluble ATP-dependent proteolytic system responsible for the degradation of abnormal proteins in reticulocytes. Reticulocytes, like other cells, selectively degrade certain abnormal proteins by an energy-dependent process. When isolated rabbit reticulocytes incorporate the valine analog 2-amino-3chlorobutyric acid (ClAbu) in place of valine, they produce an abnormal globin that is degraded with a half-life of 15 min. Normal hemoglobin, in contrast, undergoes little or no breakdown within these cells. Cell-free extracts from reticulocytes have been shown to rapidly hydrolyze these abnormal proteins. The degradative system is located in the 100,000 X g supernatant, has a pH optimum of 7.8, and does not appear to be of lysosomal origin. This breakdown of analog-containing protein was stimulated severalfold by ATP, and slightly by ADP. AMP and adenosine-3':5'-cyclic monophosphate had no significant effect on proteolysis. Experiments with ATP analogs suggest that the terminal high energy phosphate is important in the degradative process. Proteolysis in the cell-free system and in intact reticulocytes was inhibited by the same agents (L-l-tosylamido-2-phenyl-ethylchloromethyl ketone, N-alpha-p-tosyl-L-lysine chloromethyl ketone, N-ethylmaleimide, iodoacetamide, and o-phenanthroline). In addition, the relative rates of degradation of several polypeptides in the cell-free extracts paralleled degradatives rates within cells. Thus, a soluble nonlysosomal proteolytic system appears responsible for the energy-dependent degradation of abnormal proteins in reticulocytes.


Isolation of transcriptionally active chromatin from mammalian nucleoli. Nucleoli isolated from HeLa cells are functionally active but contain large amounts of RNA and proteins (RNA/DNA ratio 1:1; protein/DNA ratio 7:1). We have isolated from the nucleolus a DNA-protein complex that has the characteristics of nucleolar chromatin (RNA/DNA ratio less than 0.05:1; protein/DNA ratio 1.7:1). This nucleolar chromatin has most of the transcriptional activity of the intact nucleolus and, as assayed by circular dichroism and dye binding, has largely preserved its structure. The isolation of a transcriptionally active, fragment of chromatin, which constitutes only a small part of the total genome and codes for only one recognizable product, offers several advantages for the study of chromatin structure and function.


Ordering of cyanogen bromide peptides of type III collagen based on their homology to type I collagen: preservation of sites for crosslink formation during evolution. The order of the cyanogen-bromide-derived peptides from alpha 1 (III) chains of pepsin-solubilized calf skin collagen was found to be 3A-3B-3C-7-6-1,8,2-4-5-9A-9B. The amino-acid sequences of the NH2-terminal region of all peptides were determined by Edman's automated degradation procedure. The alignment of the peptides along the peptide chain was established by searching for the best homology between the partial sequences of the cyanogen bromide peptides from the alpha 1 (III) chain and the completely known sequence of the alpha 1 (I) chain. Characterization of three cyanogen-bromide-derived double peptides provided confirmation of the deduced order. A sequence Gly-Met-Hyl-Gly-His-Arg-Gly-Phe- was established near the NH2-terminus and a sequence Gly-Ile-Hyl-Gly-His-Arg-Gly-Phe near the COOH-terminus of the alpha 1(III) chain. Identical sequences have been found in the corresponding regions of the alph 1(I) chain. They include hydroxylysine, a site for intermolecular crosslink formation. Because these sequences are conserved during evolution of the collagen molecule, they are probably important for collagen structure and function.


Activation of cardiac adenylate cyclase: horminal modification of the magnesium ion requirement. Histamine and epinephrine stimulate the activity of guinea pig heart adenylate cyclase [ATP pyrophosphate-lyase (cyclizing) EC 4.6.1.1], in part, by decreasing the requirement for Mg2+ as an activator. This effect may represent an increase in affinity for Mg2+ and/or a decrease in sensitivity of the enzyme towards inhibition by free ATP. Both of these inotropic hormones also increase maximum velocity. Pretreatment of the membrane-bound enzyme with EDTA, to remove available divalent cations, almost eliminates persistent stimulation by guanyl-5'-yl imidodiphosphate [Gpp(NH)p]. Addition of Mg2+ to the preincubation medium restores the capacity of Gpp(NH)p to acutely activate the enzyme. These results indicate that Mg2+ interacts with the nucleotide (GTP) regulatory site. Persistent stimulation of the enzyme by either Gpp(NH)p or fluoride ion also involves a decrease in the requirement for Mg2+ and an increase in maximum velocity.


[The centric relation. III. Usefulness of 3 interocclusal registration materials during mounting of the models on an articulator]. 3 waxes commonly used to record interocclusal positions are tested on an articulator. All recordings are made at the same opening and the condylar variations are analysed with a Buhnergraph. Soft materials may induce errors and relining the interocclusal records allows a higher degree of accuracy.


[Model test on the change of position of the mandibular condyle after sagittal splitting of the mandible]. On two acrylic copies of a cranium with mandibular prognathy, the mandible was moved back by sagittal cut of the ascending ramus. It is shown that with both methods of immobilization, circumferential and screw-osteosynthesis, the segments cause a change in the position of the condyles. There are no clear advantages or disadvantages of either method. Observed cases of circumferential wiring showed practically no arthrotic symptoms after 2-10 years, which indicated that the t.m. joint has a large degree of adaptability. However, such a statement can be made definitely only after an observation time of 20-30 years.


[Dental care of prison inmates in Switzerland]. The dental status of inmates of 10 Swiss penitentiaries (capacity 50 to 245 persons) was investigated, and also organization and economic questions pertaining to dental treatment of penitentiary inmates. In all 10 institutions, the minimal claims of the UNO (1955) relative to dental treatment of penitentiary inmates are fulfilled. Nevertheless, there are significant differences between the 10 institutions. In some, practically only pain therapy is customary, while in others the whole spectrum of modern dentistry is used. Preventive measures are uniformly insufficient. Since the administering of punishment in Switzerland is cantonal, the differences in dental treatment will not be easy to eliminate.


An animal model for human osteosarcoma.

An animal model for human osteosarcoma. Osteosarcomas formed in antilymphocyte serum (ALS)-treated hamsters when 2x10(6) TE-85 human osteosarcoma cells (maintained in tissue culture) infected with M-MSV (RD-114) virus were injected adjacent to the femur or the scapula; undifferentiated sarcomas formed when 1 x 10(6) cells were injected subcutaneously. Tumors were palpable 10 to 14 days after the cells were injected and grew progressively until the animals died (mean survival time was 30 days). All animals had pulmonary metastases. Neither the subcutaneous sarcomas nor the metastases contained bone or osteoid; however, the osteosarcomas adjacent ot the femur and scapula contained collagen, osteoid and calcified bone when observed by light and electron microscopy. These results indicate that the TE-85-M-MSV cell-ALS hamster system is an animal model for the study of osteosarcomas of human cell origin.


[Irradiation of the spleen during malign diseases of the blood (author's transl)]. The results of splenic irradiation in 8 patients with neoplastic hematologic diseases are compared with those previously published. Although only 2 of our 8 cases showed a remission, 7 of the 8 patients showed a decrease in spleen size and a subjective improvement. The regularly observed and often severe pancytopenia after splenic irradiation was in no apparent relation to the dose applied. The indications and the dosage of radiotherapy of the spleen are discussed.


[Design and haemodynamic evaluation of the ellipsoid heart for total heart replacement]. Thromboembolism is a complication which represents a major limiting factor in animals with long-term postoperative survival periods following total artificial heart replacement. Thrombi are formed on the artificial valves, the biomaterials and in stagnation areas within the artificial ventricles. In design planning the stagnation areas should be avoided as well as major turbulences. The filling volume should be maximally used for the stroke volume and the epicenter of the membrane should be underneath the valve areas. The ellipsoid heart eliminates stagnation areas and the stroke volume is 82% of the filling volume. The maximum cardiac output is 15.8 l/min. The ellipsoid heart was implanted in 20 female calves; the maximum length of survival was 213 hours. There was no compression of the inferior vena cava and the heart fitted well into the chest of the animals. The cardiac output, self-regulated in the sense of Starling's law, was adequate to perfuse the animals and to allow moderate exercise such as standing. The arterial pressure curves show normal physiological activity. The curves in both atria are unphysiological, owing to relative insufficiency of the valves. The limiting factors were pulmonary insufficiency and surgical complications. The ventricles showed no thrombus formation -- except in one case, in which faulty material was the predisposing cause. It was possible to develop an automatic driving system on the basis of these experiments. Regulation occurred by means of gas flow control in the driving tubes, whereby the form of the gas flow curve provides information on position of the membrane. As soon as the membrane has reached the end-diastolic position, systole is triggered off and lasts until the end-systolic position is reached. If the venous return is increased, the ventricles are filled more rapidly and the heart is driven at a higher rate. One part of the ellipsoid heart is used as ventricle for assisted circulation. The left ventricle is cannulated via the left appendage or the apex. The ventricle relieves the left heart to a large extent and the cardiac output is taken over by the pump placed in a paracorporeal position. The blood is directed back into the thoracic aorta.


[Erythema annulare centrifugum as a symptom in acute myeloid leukemia]. Erythema annulare centrifugum occurred in a 68 year-old women suffering from acute myeloid leukemia. A "paraneoplastic" origin of the skin disease was most probable in this case.


The importance of complementary cytology and colposcopy in a detection program. Since 1956, we have used cytology and colposcopy routinely as complementary methods and the percentage of positive results has brought us much closer to the ideal 100 per cent. In order to achieve this, it is essential to put to good use the experience acquired by cytologists and colposcopists and to constantly update and improve the technique employed. The population must be made aware of the benefits of the simultaneous use of these detection methods through health education. The possibilities of diagnostic prediction of cytology are already well known. By means of colposcopy, we may classify the findings as follows: 1) normal, 2) with benign pathology, 3) suspicious, requiring additional frequent control, 4) highly suspicious of neoplasm, 5) malignant. Using the combined methodology, we were able to detect the flaws in use of both methods separately. Considering the carcinoma in situ and microcarcinoma, the results amounted to 16.6 per cent of cytologic false negatives and 12.9 per cent of colposcopic false negatives, whereas applying both methods simultaneously, we obtained only 2.7 per cent of false negatives. As we mentioned previously, this percentage of error may be attributable to technical faults, associated pathology and/or anatomic-histologic localization. We emphasize our reference to the simplicity of our method, making it possible to dispense with exaggerated human and material requirements and, at the same time, obtain highly successful results.


The identification of Paragonimus westermanii in bronchial washings. Case report. Ova of Paragonimus westermanii were identified on Papanicolaou stained slides prepared from bronchial washings of a 40 year-old Korean-American male. In addition to evaluation for neoplasia, a careful search of all cytological material for non-neoplastic conditions is mandatory in our routine practice, especially in this age of population mobility.


Cytologic diagnosis of herpetic esophagitis. A case report. A diagnosis of herpetic esophagitis was made in a patient with alcoholic liver disease by means of endoscopy and brush cytology. Herpetic esophagitis is a common cause of esophageal ulceration in severely debilitated or immunosuppressed patients especially when the esophagus is traumatized by nasogastric intubation. Dysphagia or odynophagia may occur in some but not all patients. Radiographic picture may resemble Candida esophagitis. Endoscopy, biopsy, cytology, culture and serological studies will help in making a diagnosis. Specific antiviral agents may be used for treatment but spontaneous resolution without any sequelae was documented in our patient.


Leiomyosarcoma of the lung. Primary cytodiagnosis in two consecutive cases. Two cases of primary leiomyosarcoma of the lung are described, in which primary cytodiagnosis of the tumor type was established prior to surgery. The cytologic features of the cell samples obtained and correlated histopathologic findings are described. The cytologic features of pulmonary leiomyosarcomas are sufficiently characteristic to allow definitive diagnosis, if representative cell samples are obtained.


Balantidium peritonitis diagnosed on cytologic material. Balantidium coli were detached in a routine cytologic smear of ascitic fluid. The morphologic features were clearly discernible in the Papanicolaou stained smears.


Intraduodenal sarcoma. A case report.

Intraduodenal sarcoma. A case report. A case of a duodenal and a pancreatic pleomorphic sarcoma which was diagnosed as a malignant undifferentiated neoplasm cytologically is described. Primary malignant sarcomas at this site are highly unusual. The importance of endoscopic brush cytology is emphasized.


X chromatin and aging.

X chromatin and aging. X chromatin analysis of 30 aged and 30 control women failed to confirm X chromosome loss as responsible for the increase in incidence of hypodiploid cells observed with increasing age in women. No evidence was found to support a previously suggested relationship between X chromosome loss and the loss of mental function (senility) as measured by psychological tests.


Cytologic diagnosis of Molluscum contagiosum of the mons pubis. Report of two cases. 1) Two cases of molluscum contagiosum diagnosed by cytologic examination were reported. 2) Cytologic findings of molluscum contagiosum are described. 3) The usefulness of cytologic examination in detection of unsuspected and/or suspected molluscum contagiosum is emphasized. 4) One molluscum contagiosum case showing coexistence of fungal organisms which seemed to be pityrosporum ovale is reported.


Signet-ring cell stromal tumor of ovary cytologic appearances of fine needle aspiration biopsy. The cytologic appearances of fine needle aspiration biopsy from a benign signet-ring cell tumor of ovarian stroma are presented. The aspirate is characterized by the presence of many cells with large vacuoles in their cytoplasm giving them the signet-ring appearance. The lack of malignant criteria in the nuclei and the failure to demonstrate mucin or lipid by special stains helps to differentiate these cells from other sources of signet-ring cells such as mucinous cystadenomas and cystadenocarcinomas and Krukenberg tumors.


The results of some cytochemical reactions in metastatic malignant tumor cells in pleural and peritoneal effusions. The cytomorphologic and cytochemical investigation of 59 samples of pleural and peritoneal effusions with malignant tumor cells was performed and the results were compared. The diagnosis was confirmed histologically in most cases. The cytomorphologic method gave very good results not only in the determination of malignant tumor cells but also in the differentiation of various kinds of tumors. A diagnosis was made of differentiated carcinoma (adenocarcinoma and squamous carcinoma) in 40 cases, undifferentiated carcinoma in five, sarcoma or hemoblastosis in nine and undifferentiated malignant tumor in five cases. The results of cytochemical reactions investigated demonstrated a significant difference between the cells of carcinoma and sarcoma, and in various kinds of carcinoma the most important difference was found between the positive reaction of the alkaline phosphatase and negative reaction of the acid phosphatase in the cells of ovarina and uterine carcinoma. Although we consider the morphologic examination of effusions the most important for the diagnosis of malignancy, the cytochemical methods can sometimes be helpful in a more precise differentiation.


Decay of methyl green-pyroninophilia in Burkitt's lymphoma. The spontaneous decay of methyl green-pyroninophilia in Burkitt's lymphoma was studied at four temperatures (0 degrees C to 56 degrees C) in four biopsies using Kurnick's method. The decay is temperature and time related and is presumably due to intrinsic enzymatic action, probably ribonuclease. Imprints from tumor tissue preserved at 0 degrees C lose pyroninophilia by six hours; from tumor preserved at room temperature pyroninophilia, in most instances, would have been lost by three hours, from tumor tissue maintained at 37 degrees C, by two hours in most instances and by 15 minutes at 56 degrees C in most instances. The absence of pyroninophilia after these intervals at the appropriate temperatures should not detract from the diagnosis of Burkitt's Lymphoma.


Cytologic effects of adriamycin on human peripheral lymphocytes. Preliminary data show adriamycin (AM) induces chromosomal structural changes and division delay in human peripheral lymphocytes. Cells treated for one hour with 0.01, 0.03, 0.05 and 0.10 mug/ml AM show chromatid lesions mainly breaks and deletions. Chromosome type lesions and chromatid exchanges were less frequent even in cells with the highest percentage of aberrations. Dicentric chromosomes were very rare and were scored only in cells treated with higher concentrations (0.10 mug/ml) and recovered 24 hour post-treatment. Based solely on cytologic evidence G1 and S phase cells appear to be more sensitive to adriamycin than G2 phase cells.


Colon cytology simplified using enteric coated encapsulated polyurethane foam as a cellular collecting agent. A preliminary report. The advantage of the method lies in the relative ease of obtaining cellular material. The patient requires some instruction but need not be medically supervised. The major disadvantage is in fecal contamination and frequently cell preservation that may not be comparable to that of other cytologic approaches. The success of the test depends upon harvesting mucus. It is essential that the laxative action be as mild as possible and that after the initial clearing of the colon an adequate rest period is allowed to permit adequate mucus regeneration.


Cerebrospinal fluid cytology in patients with brain tumors; a simple method using the cell culture technique. A simplified cytologic method using the cell culture technique was employed in 71 cases with brain tumor. Neoplasitc cells were demonstrated in 17 cases (24%), that is in 11 out of 30 cases of glioma, four out of ten cases of metastatic brain tumor, and two out of 17 cases of meningioma. None of 14 other miscellaneous tumors proved positive. Identification of glioma cells could be easily made because they usually showed characteristic morphology and good proliferation in vitro. However, for other types of tumor, conventional methods were considered to be superior to the culture method because their exfoliated cells usually underwent rapid degeneration without showing characteristic morphology during the culture. Some of the illustrative cases were presented.


Vaginal cytology in the postmenopause. A study into some correlates. A considerable number of women continue to have proliferative vaginal smears indicating a certain level of endogenous estrogen production. Some correlates of this were studied. No significant correlation was found with age since menopause or with overweight. No correlation was found between the proliferation of the vaginal smear and climacteric complaints, circulatory or nervous. The implications of a proliferative smear for the postmenopausal woman and of the postmenopausal estrone production are briefly discussed. They appear at least to be ambiguous, because, although they protect against some facets of the estrogen deficiency syndrome, the factors which are correlated to a high level of endogenous estrone production are known as risk factors, predisposing for a higher incidence of uterine bleedings and perhaps malignant degeneration of some target cell tissues.


Vaginal cytology and the human menopausal gonadotropin-test (HMG-cytohoromonal-test) in cases of gonadal dysgenesis. Cytohormonal investigations and HMG-cytohormonal-test were carried out in 15 patients suffering from gonadal dysgenesis and the results were compared with the histology of the gonad, the karyotype and the clinical appearance. All patients were primary amenorrhoeic. According to the gonad histology and the phenotype the term "gonadal dysgenesis" was subdivided into Turner's syndrome, pure gonadal-dysgenesis and syndrome of ovarian hypoplasia. For the HMG-cytohormonal-test Humegon was administrated three times in weekly intervals (one amp. 75. i.u. in the first, two amp. in the second and three amp. in the third week). The gonadal response to Humegon was detected by vaginal cytology taken on the first, second, fourth and sixth days, after each injection of Humegon. Smears in patients with streak gonads irrespective of their phenotype were completely atrophic and did not change following Humegon administration. This finding seems to be characteristic and the HMG-cytohormonal-test is a simple way to diagnose the presence of the streak gonad. Cytohormonal patterns in the syndrome of ovarian hypoplasia accompanied by primary amenorrhoea consisted of mostly intermediate cells although superficial cells in five to 20 per cent and parabasal cells in five per cent also occurred. Following Humegon administration there were no or slight changes in the smears, much less marked than those in secondary ovarian failure.


Cytology of gynecologic condyloma acuminatum. The morphology of certain cell types often encountered in vaginal and cervical smears of condyloma patients are described. These cells, considered to be exfoliated from epithelium affected by condyloma virus, were found in 60 per cent of the smears obtained from 192 women with condylomatat acuminata. Dysplasia of the cervical and vaginal epithelium is frequently associated with condyloma. Structural features typical of the condylomatous epithelium were common in these dysplasias. These lesions are probably also due to infection by condyloma virus, yet their significance is unknown and the possibility of a precancerous status cannot be ruled out except by a very long term follow-up study which is in progress. It may be assumed that this virus may affect the cervical and vaginal epithelium without any typical papillary condylomatous lesions resulting. Even in the absence of typical condylomatous papillary formations, the cytologic findings may reveal condyloma infection.


Cytology of primary neoplasms of the central nervous system. The case histories of 273 patients with primary neoplasms of the central nervous system seen in The New York Hospital and Memorial Hospital during the years 1968 through 1973 were reviewed. Neoplastic cells were identified in cytologic preparations obtained from 76 patients. These include patients with meningioma, astrocytoma, glioblastoma multiforme, oligodendroglioma, ependymoma, medulloblastoma, neuroblastoma, retinoblastoma, pineoblastoma, and pituitary adenoma. It is concluded that there are certain suggestive cellular features of these neoplasms in cytologic preparations, but additional studies are needed to establish the cytomorphologic characteristics which may aid in the differential diagnosis of primary intracranial neoplasms from extracranial neoplasms which are metastatic to the central nervous system.


Rapid correction of anemia with partial exchange transfusion. Six pediatric patients have recently undergone eight partial exchange transfusions for anemias complicated by other clinical conditions. The procedure was well tolerated, and those patients who were in congestive heart failure exhibited good clinical improvement. This technique is particularly useful in situations where the patient is unable to tolerate the increased blood volume produced by other methods of RBC-transfusion therapy. We present a formula for estimation of partial exchange transfusion volume and suggest indications for partial exchange transfusion.


Neutropenia, fever, and infection in children with acute lymphocytic leukemia. In an attempt to determine the relationship between neutropenia (absolute granulocyte count less than 1,000/cu mm), infection, and disease status, 20 patients with acute lymphoblastic leukemia were observed for a total of 34 patient-years. Febrile episodes occurred with much greater frequency in patients during the course of treatment induction (0.9/mo), or while in relapse (2.46/mo) than while in remission (0.19/mo). A cause for fever was identified much more frequently in patients in remission, both when neutropenic and nonneutropenic. When absolute granulocyte counts fell below 200/cu mm, a cause for fever was generally identified regardless of disease status. We propose that the majority of febrile episodes in patients at the time of induction of treatment or in relapse with neutrophil counts of more than 200/cu mm are caused by the disease process rather than secondary to a diagnosable infection.


The cytologic diagnosis of gastric carcinoma related to the histologic type. In gastric smears obtained by direct vision fiberoptic brush technique from 78 patients with carcinoma of the stomach, an attempt was made to recognize cytologically the histologic type of the tumor with reference to Lauren's classification. The cytologic diagnosis of intestinal type carcinoma was made in 36/45 positive cases on the basis of an abundant cellularity and the presence of rather large pleomorphic cohesive cells often arranged in sheets with a moderately increased N/C ratio. One case of intramucous and two of "early" invasive carcinoma revealed malignant cells which did not differ from those of the advanced cases. In these cases as well as in some of the advanced ones, atypical epithelial cells were found in addition to the malignant ones; these cells could have derived from the histologic areas of atypical hyperplasia of the gastric mucosa surrounding the carcinoma. 14/15 cases of advanced diffuse carcinoma of the stomach could be cytologically identified on the basis of a scanty cellularity and the presence of rather small, monomorphic poorly differentiated cells with a high N/C ratio. The cytologic diagnosis of the mixed-type carcinoma was made in 2/5 positive cases on the basis of the presence of an admixture of both cell types described above. In two cases of the mixed-type carcinoma, only intestinal type cells were found. In the smears of nine cases of intestinal type carcinoma, one of which was intramucous, and of one case of mixed-type carcinoma, the tumor cells could not be specified. 13/78 cases (16.7%) showed negative cytology. The overall accuracy rate was 83.3 per cent. The statistical analysis of a number of cytologic parameters indicated that morphologic differences between Type I and Type D carcinomas of the stomach do exist and that they can be evaluated for differential diagnostic purposes.


Reliability of the cyto-radio-clinical triplet in breast pathology diagnosis. 1. Two hundred and twenty-two cases of cytologic breast specimens were correlated with clinical and radiological findings. 2. False negative and no-cell incidence were respectively 2.7 and 2.2 per cent. 3. By means of a thorough clinical and radiological approach the cytologic failures (misdiagnosed and acellular smears) could be corrected: no cancer escaped diagnosis. 4. Cytology diagnosed three clinical and radiological undetected breast cancers, an incidence of 1.3 per cent. 5. Any suspicion of malignancy, either on cytologic clinical or mammography examinations, must be further investigated by means of biopsy. 6. In our experience, evidence of necrosis, even without other cytologic evidence of malignancy, has proved coincidental with mammary cancer.


Trends in mortality from uterine cancer in relation to mass screening. Mortality rates from cancer of the cervix uteri, as well as for all uterine cancer, have shown a remarkable decrease in recent years in Louisville, Kentucky. For women ages 30-39 the decrease was 70.8 per cent, and for ages 50-59, 69 per cent. No change in rates was noted for women ages 70 years and over. These changes correlate well with the success of recruitment for screening of women according to age. The high degree of success in screening the low socioeconomic quartile is thought to be of prime importance. The average annual age adjusted mortality for uterine cancer other than cervix also fell impressively. In contrast to Louisville, mortality from cervical cancer in England and Wales, with the exception of the younger age group, has remained fairly constant over the past decade. Denmark showed no mortality decline between 1961 and 1971. Like England and Wales and unlike Louisville, screening there had not achieved high population coverage and the screening as does exist was not commenced as early.


The permeability of the lymphocyte membrane: applying a particle size analyzer and a hybrid computer to measure rapid changes in cell volume. In summary, this method is ten to twenty times more sensitive than the densimeter method as presently employed. This is not to say that densimeter methods may not be feasible if suitably modified. For example, modern flow systems such as those used at Los Alamos Scientific Laboratories, which measure light transmittance and scattering on an individual cell-by-cell basis, could probably be modified and adapted to summate individual pulses as the population responds to an osmotic gradient prior to entry into the analyzer. Nevertheless, with our present method, we are able to measure the permeability profile of lymphocyte populations from peripheral blood. It should be readily applicable to isolated populations from aspirated bone marrow.


Scanning electron microscopy of cotton swab smears from ectocervix. A methodological study. A method for scanning electron microscopic examination of exfoliated ectocervical cells smeared with a cotton swab is described. It is concluded that this technique has advantages over techniques in which cell samples are collected from the portio by washing, scraping, or adherence to membranes.


The borderline patient and conservative treatment in the late mixed dentition. 1. The possibilities for successful conservative treatment of mild lower arch length deficiencies (2 to 5 mm.) are explored for twenty growing patients in the late mixed dentition. 2. Methods of case selection and treatment particulars are presented. 3. Each patient should be considered as an individual with regard to cephalometric norms for the optimal position of the incisors, in determining the size of the leeway space at the lower second deciduous molar position, in evaluating the feasibility of distal uprighting the lower first permanent molars, and in formulating a reasonable treatment plan. 4. It is postulated that oversized lower second deiduous molars may be an etiologic factor in some mild lower arch length deficiencies (r = 0.4; P less than 0.05). 5. The amount that the lower first premolars and lower canines can be distally retracted into the leeway space in these conservatively treated cases is directly related to retraction of the lower incisors (r = 0.7; P less than 0.01). In the present cases uprighting the lower incisors allows the upper teeth to be treated well and together this enables functional and esthetic improvement and tooth stability.


Thumb- and pacifier-sucking habits.

Thumb- and pacifier-sucking habits. The prevalence of thumb- and pacifier-sucking children was studied in two "kibbutz" settlements and city nurseries. The variables considered were age, sex, duration of breast feeding, and family size. Data on 333 children were collected by interviewing the parents, and nurses (in kindegartens and nurseries). Differences in prevalence were found between the three groups. Among the city children, 95 per cent sucked and 89 per cent and 69 per cent of the kibbutz children had sucking habits. In Group A, from whom pacifiers were withheld, most children sucked their fingers. With the increase in age, the prevalence was lower in all groups. No difference was found between the sexes. A reverse association was found between finger and pacifier sucking. No association was found between the habit and the duration of breast feeding. The prevalence was highest in single children. It is suggested that the pacifier may be a substitute of choice for thumb sucking.


The use of methylphenidate and imipramine in Gilles de la Tourette's disease in children. The authors treated two children with Gilles de la Tourette's disease and one child with a probable combination of Gilles de la Tourette's disease and minimal brain dysfunction with methylphenidate, which resulted in exacerbation of symptoms. One child was briefly treated with imipramine, with similar results. The authors suggest that these pharmacologic agents should be used cautiously in treating patients with possible movement disorders (tics) and conclude that their findings lend support to the catecholamine hypothesis of the etiology of Gilles de la Tourette's disease.


An electron microscopic study of the spleen of the rat in an acute myelogenous leukemia. The spleens of rats were studied by light and electron microscopy during the course of an acute myelogenous leukemia, with special reference to infiltration of leukemic myeloblasts in the spleens and to the correlation of leukemic cell infiltration with splenic hematopoiesis and splenomegaly. Leukemic myeloblasts infiltrated the cordal space of the red pulp. Many of them appeared in groups. Even in spleens which were heavily infiltrated, leukemic myeloblasts did not penetrate the while pulp. Massive infiltration and proliferation of the leukemic myeloblasts in the red pulp resulted in splenomegaly. The spleen increased its hematopoietic activity, while the medullary hematopoiesis diminished due to the invasion of leukemic myeloblasts in the bone marrow. Compensatory splenic hematopoiesis occurred in most of the leukemic spleens, but diminished in spleens which were very heavily infiltrated with leukemic myeloblasts. Thus, the degree of splenomegaly and splenic hematopoiesis did not necessarily correspond to the percentage of leukemic myeloblasts in the bone marrow, but rather related to the number of leukemic myeloblasts present in the spleen. A possible role for the splenic sinus walls in promoting compensatory hematopoiesis in the spleen is discussed. A consistent association of type "C" virus particles with leukemic myeloblasts was observed.


Thyroid radiation dose during panoramic and cephalometric dental x-ray examinations. Radiation exposure from panoramic equipment can be reduced significantly by use of smaller film, adjustment of the beam height to the height of the smaller film, and careful positioning of patients. These techniques have no adverse effect on the quality of the diagnostic information needed in dentistry. In addition to describing methods of reducing exposures from panoramic machines, this study demonstrates that the use of a barrier collar during static, cephalometric examinations can appreciably reduce thyroid exposure. Since the objective is to obtain diagnostic information from the film without irradiating the thyroid, the application of a lead-impregnated collar is a minor inconvenience, easily borne by the patient and operator. It should be noted that the use of the collar during panoramic examinations affords little or no protection since the relative motion of the panoramic machine places the axis of movement inside the head and neck of the patient. While the evolution of diagnostic radiology may have reached a high level of technical refinement of equipment and film the clinician still must avoid unnecessary exposure for X-ray examinations and must carefully select the best type of examination to be used for each patient. For example, a complete panoramic examination to determine the position of a known unerupted third molar tooth is probably not an exercise of good judgment since other examinations, such as periapical, could yield the same information with less exposure. Decisions must be made with good judgment, value being placed on relative risks versus the benefits of diagnostic yield.


The effect of bite plane use on terminal hinge axis location. The effect of bite phase therapy on the location of hinge axis was observed and compared in a sample of normal subjects and a group of individuals with TMJ dysfunction. The normal group displayed a mean change of 1.0 mm with a range of 0.3 mm to 3.4 mm between bite plane use and its absence. The direction of change with bite plane use was anterior with a tendency for superior component. The same group utilized the bite plane a second time and the axis location was compared with the original determined with bite plane use. This procedure was done to test the reproducibility of hinge axis on normal subjects. The mean change between the two bite plane uses was .87 mm with a range of 0.0 mm to 3.0 mm. The symptomatic patients changed a mean of 1.46 mm with a range of 0.0 to 3.3 mm. The direction of change was definitely posterior following therapy with a strong tendency for a superior component. This study seems to emphasize the need for a relaxed and asymptomatic muscular pattern for individuals on whom occlusal adjustments are to be made. In the presence of erroneous maxillomandibular skeletal relationships inaccuracy is inherent for occlusal equilibration.


Effects of Von Langenbeck palatoplasty on facial growth. The conclusion derived from this study is that the Von Langenbeck palastoplasty as performed on the cleft individuals evaluated here did not produce gross discrepancies in the dento-facial structures or relations examined. On the average, the skeletal and profile relations of the maxilla to the mandible can be considered within the acceptable range. With this in mind, speech becomes a more crucial parameter in evaluating the over-all results of this procedure. Other dental parameters, e.g., incidence of crossbite, arch collapse, etc., need to be examined if a complete evaluation of the results of palatal surgery is described. This should be done after all orthodontic treatment has been completed and all retainers removed.


The saddle angle: constancy or change?

The saddle angle: constancy or change? Serial cephalometric radiographs of 165 children have been used to analyze age-associated changes in the saddle angle (Ba-S-N). There are mean decreases in this angle of about 5 degrees from birth to 2 years in those with either a Class I or a Class II occlusion; later changes are slight. The mean values tend to be slightly smaller in Class I boys than in those with Class II. Generally, the means are slightly larger in boys than girls but in adults this sex difference is in the reverse direction while remaining slight. It is reasonable to conclude that change is dominant in the first two years. Even after pubescence the angle is not constant but the changes are much smaller. The variability of the angle is greater for Class II than Class I individuals and its variability is greater in girls than boys after 12 years. Almost all the median increments are negative; that is, the flexure of the cranial base decreases with age particularly if the increments begin at the first available radigraph. This tendency is more marked in Class II then Class I occlusion. The increments are markedly variable in each occlusion group with large changes occurring in some individuals. Correlations between the saddle angles at different ages are high; this shows a marked constancy of the relative levels for individuals. The correlations between increments are small; presumably this reflects the small sizes of these increments relative to error terms. In the present group the saddle angle is positively correlated with Ba-N length, but the correlation between the saddle angle and either cranial vault length of stature are near zero. These findings show that there is marked constancy within individuals after the age of 2 years although, as noted earlier, there is marked variability in the size of the angle at particular ages and the serial data for some unusual individuals show large changes that are generally decreases.


Effects on lower third molars after extraction of second molars. The material consisted of 78 cases, 44 males and 34 females of the ages of 10-15 years. The orthodontic treatment followed the diagnosis of Class II malocclusion with crowding in the lower jaw. In addition to extraction of lower second molar the treatment consisted of distal driving of lower first molars in different ways. The treated cases were assessed by use of study models and lateral oblique X-rays. No third molars were treated in any cases. The results showed that in the majority of cases the third molars were adequate substitutes for the extracted second molars.


Caries experience in orthodontically treated individuals. The caries ecperience in 26 girls and 26 boys living on an island outside. Bergen, who had received orthodontic treatment with fixed appliances, was examined 1.5 to 2 years after the end of treatment. The children were then between 1l and 17 years old. The remaining children of the same age group, 58 girls and 53 boys, served as controls. The orthodontic patients had received repeated hygiene instructions during the treatment period and were expected to rinse their mouth with 0.05% sodium fluoride daily. The percentage distribution of DMF-surfaces indicated somewhat less caries experience in the treated group. A chi-square test showed significantly more intact surfaces on the maxillary first molars, second premolars, canines and central incisors, and mandibular molars and second premolars in treated than in untreated children, and also demonstrated significantly fewer new lesions in the upper second molars at the time of examination in the treated groups. A comparison of the caries experience of the different surfaces revealed significantly more intact surfaces in the treated group and significantly fewer new lesions on the mesial and distal surfaces in treated in untreated children at the time of examination.


Amphotericin B induction of sensitivity to adriamycin, 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) plus cyclophosphamide in human neoplasia. Seven patients with metastatic tumors resistant to therapy with adriamycin, BCNU, plus cyclophosphamide received the same chemotherapy combined with amphotericin B. One complete response (acute myelomonocytic leukemia), two partial responses (carcinoma of the breast and multiple myeloma), and one case with objective improvement (carcinoma of the breast) were observed in seven evaluable trials. Myelosuppression was not consistently changed by addition of amphotericin B. Fever and chills were common after amphotericin B. Bronchospasm and hypotension occurred twice. Amphotericin B reverses resistance to adriamycin-containing chemotherapy regimens in some patients.


Myelomonocytic leukaemia with a preleukaemic syndrome and Ph1 chromosome in monozygotic twins. A case of monozygotic twins with a preleukaemic phase of 3 1/2 years is reported. The final haematological picture was that of myelomonocytic leukaemia. The karyotype investigated in one twin during the final period of the disease showed a Ph1 chromosome.


Anesthesia and postoperative care for cardiac operations. Almost three decades have passed since the establishment of open-heart surgery, and in such a short life span the specialty has established itself scientifically and reached a certain maturity. New techniques, better understanding of the pathophysiology of cardiac problems, and the effective use of new drugs constantly improve the results of operation. Greater experience in anesthetic management and improved postoperative care will contribute much to the success of this youngest surgical specialty. This review outlines the current principles of anesthesia and postoperative care of patients undergoing cardiac operations. Preanesthetic evaluation provides guidance for anesthetic management, supportive techniques, and postoperative care. During operations, light anesthesia is usually sufficient for patients with cardiac disease and minimizes myocardial depression. Monitoring must provide data on the physiological changes that are taking place from moment to moment during and after operations. Perfusion produces a highly abnormal state, and the severity of complications varies with its duration. Introduction of new drugs has also facilitated hemodynamic management during and after operations. Postoperative care is based on careful observation of the patient and early detection of trends, both of which lead to preventive rather than curative treatment wheneven possible.


Does allergy play a role in fibrositis?

Does allergy play a role in fibrositis? Twenty patients with active fibrositis and no underlying disease (and with normal electromyographic findings) were evaluated for the possible role of an active allergic process in their conditions. A definite atopic history was obtained in just fewer than 50% of the patients, and an allergic diathesis in slightly more than 50% of the patients' families. Serum immunoglobulin E levels and eosinophil counts for all 20 patients fell within the normal range. Thus the traditional allergic reaction (type I hypersensitivity) would seem unlikely as a mediator of fibrositis.


Electrolyte and acid-base disturbances in the management of leukemia. Electrolyte disturbances in leukemia can be the result of the disease process or drug therapy. One group of electrolyte abnormalities is related to the stage of the leukemic process. Included in this group are newly diagnosed patients who may show elevated serum potassium, phosphorus, and magnesium--a result of their release from malignant cells after cytotoxic therapy or their accumulation due to urate nephropathy. Patients in remission usually have normal serum electrolyte concentrations, but acute leukemia patients during relapse may have hypokalemia, hypophosphatemia, and hypomagnesemia. This imbalance may be related to cellular uptake of these electrolytes in the presence of inadequate dietary intake. Other factors contributing to electrolyte derangements, and related to the leukemic process, include hyponatremia and hypochloremia secondary to the SIADH, hypokalemia in acute monocytic or acute myelomonocytic leukemia due to lysozyme-induced tubular damage, hypercalcemia possibly secondary to leukemic infiltration of bone or parathyroid glands (with PTH release), or production of a PTH-like substance by leukemic cells. Nonspecific factors related to the disease process which may aggravate the electrolyte imbalance include gastrointestinal loss through nausea, vomiting, and malnutrition. The drug-related electrolyte abnormalities include cyclophosphamide- and vincristine-induced SIADH; decreased serum sodium, chloride, potassium, and calcium concentrations as a result of polymyxin B nephrotoxicity; hypokalemia and hypomagnesemia secondary to amphotericin B; hypocalcemia, hypophosphatemia, and hyperphosphaturia due to L-asparaginase-induced hypoparathyroidism; hypokalemia due to a nonreabsorbable anion effect of antibiotics in the distal tubule or changes in membrane ionic transport of all cells by large doses of antibiotics. Electrolyte disturbance in leukemia thus have a multifactorial pathogenesis which can best be delineated according to the stage of the leukemic process and the drugs being used. Recognition of the cause or causes in a particular patient is essential for an effective approach to management. This review emphasizes the need for routine measurement of serum electrolytes during all phases of the leukemic process.


Changing erythrocyte populations in juvenile chronic myelocytic leukemia: evidence for disordered regulation. Fetal and adult erythrocyte characteristics were studied serially in a 30-mo-old female with juvenile chronic myelocytic leukemia. On presentation the erythrocytes exhibited predominantly fetal characteristics as indicated by 69% hemoglobin F (HbF), 1.1% hemoglobin A2 (HbA2), absent I antigen, and fetal levels of the erythrocyte enzymes, carbonic anhydrase I and II, glucose-6-phosphate dehydrogenase, hexokinase, pyruvate kinase, and lactate dehydrogenase; 100% of the erythrocytes present contained HbF. However, Orskov-Jacobs-Stewart hemolysis demonstrated that at least one adult characteristic was present. Seven months later HbF was 17%; I antigen and carbonic anhydrase I had increased to adult levels. The number of cells containing HbF had decreased to 30%. Further studies indicated that at least three new populations of red cells were present after 7 mo which had not previously been detected. Two of these populations exhibited a mixture of both fetal and adult characteristics. Such findings suggested that an ongoing disturbance of regulatory mechanisms was responsible for the variable expression of fetal versus adult erythrocyte characteristics.


The Philadelphia chromosome in human macrophages. Three patients with chronic myelocytic leukemia in different phases of the natural history of the disease were studied. Their bone marrow cells were cultured under conditions favoring macrophage proliferation, and parallel cytogenetic and cytochemical studies were performed. All cell metaphases examined contained the Ph1 chromosome at a time when more than 80% of these metaphases were in identifiable macrophages. We conclude that the mononuclear phagocyte cell line contains the abnormal chromosome in Ph1-positive chronic myelocytic leukemia.


Repeated chlorpromazine administration increases a behavioural response of rats to 5-hydroxytryptamine receptor stimulation. 1 The hyperactivity syndrome produced in rats by administration of tranylcypromine (20 mg/kg i.p.) followed 30 min later by L-tryptophan (50 mg/kg i.p.) is generally considered to be due to increased 5-hydroxytryptamine (5-HT) functional activity. It is inhibited by chlorpromazine (30 mg/kg i.p.) injected 60 min before the tranylcypromine. However, chlorpromazine injection for 4 days either at a dose of 30 mg/kg once daily or 5 mg/kg twice daily results in an enhanced hyperactivity response to tranylcypromine and L-tryptophan administration 24 h after the final dose of chlorpromazine. 2 One injection of chlorpromazine (30 mg/kg) did not produce enhancement 24 h later and the inhibition of the tranylcypromine/L-tryptophan hyperactivity observed after acute chlorpromazine injection was seen if the rats were given tranylcypromine and L-tryptophan 1 h after the fourth chlorpromazine (30 mg/kg) dose. 3 Chlorpromazine (30 mg/kg) once daily or 5 mg/kg twice daily for 4 days resulted in rats displaying enhanced behavioral responses to the suggested 5-HT agonist 5-methoxy N,N-dimethyltryptamine (2 mg/kg) on day 5. 4 Chlorpromazine (30 mg/kg) once daily for 4 days produces a slight increase in brain 5-hydroxytryptamine (5-HT) concentration on day 5, but no difference in the rate of brain 5-HT synthesis or the rate of 5-HT accumulation after tranylcypromine and L-tryptophan administration. 5. There is some evidence that chlorpromazine blocks 5-HT receptors. It has also been observed that several other neuroleptic drugs do not produce enhanced 5-HT responses after repeated administration. It is suggested therefore that the enhanced behavioural response to 5-HT receptor stimulation following repeated chlorpromazine administration may be because this drug blocks 5-HT receptors.