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Diagnostic use of muscle markers in the cytologic evaluation of serous fluids.

Differentiating reactive mesothelial cells from malignant mesotheliomas and from adenocarcinomas can be diagnostically challenging when based solely on the morphologic examination of serous fluids. The diagnosis even after the use of standard immunohistochemical stains may at times be inconclusive because of the variable reactivity of mesothelial cells for these markers. Pathologists and cytologists underutilize reactivity for desmin, a feature of mesothelial cells apparently not shared by adenocarcinomas. The purpose of this study was to evaluate the extent to which mesothelial cells express muscle differentiation and to assess the diagnostic utility of muscle markers in distinguishing reactive mesothelial cells from malignant mesotheliomas and adenocarcinomas. Archival paraffin-embedded cell blocks of serous fluids from 24 cases of reactive mesothelial cells, 14 cases of malignant mesothelioma, and 56 cases (14 cases from each) of metastatic adenocarcinoma from the lung, breast, ovary, and gastrointestinal tract were retrieved. Five cases of omentum with unremarkable mesothelial cells were also included in the study. All cases were stained for desmin, actin, myoglobin, and myogenin and evaluated independently by two observers. Strong cytoplasmic reactivity for desmin was noted in 22 of 24 cases (92%) of reactive mesothelial cells. The reactive mesothelial cells did not express actin, myoglobin, or myogenin. All cases of malignant mesothelioma and metastatic adenocarcinoma were negative for the four muscle markers. The mesothelial lining and scattered subserosal cells in the omental sections were positive for desmin. Because desmin was expressed only in benign mesothelial cells, it may serve as a reliable marker in distinguishing reactive mesothelial cells from mesothelioma or from adenocarcinoma. Awareness of this staining pattern is also important to avoid pitfalls when evaluating body fluid specimens from patients with a history of tumors expressing muscle differentiation.

Adenocarcinoma↗

Analyses of TT virus full-length genomic sequences.

Since the identification of TT virus, only one full-length and two near full-length sequences representing a single subtype of the virus have been reported. In order to understand further the nature of the TT virus genome, nine of the most divergent TT virus sequences have been extended to full-length or near full-length. Phylogenetic analysis demonstrated that these sequences represent three distinct TT virus genotypes and two subtypes. A high degree of nucleotide sequence variability (approximately 30%) was observed across the genomes with several significantly more divergent regions. Three conserved ORFs were identified, none of which shared significant amino acid sequence identity to sequences present in public databases. Additionally, sequence motifs, such as those necessary for protein translation and for rolling circle replication, were found to be partially conserved between all TT virus isolates.

DNA Viruses↗

Problems with curriculum implementation in in-service clinical education.

We report a hitherto poorly documented cause of failure of curriculum implementation. The case of the clinical training of foreign medical graduates (externs) in Hong Kong is used to illustrate problems that may arise in professional education where in-service work in institutions is part of the educational process. The example is particularly relevant to health professional education which generally involves a significant in-service component. We used participant observation, questionnaires and brief interviews to obtain data from 97 externs and 48 supervisors. The results indicated that between a third and a half of the externs did not receive experiences as designated in the curriculum. Apart from age, individual characteristics of the externs did not show statistically significant relationships to the kind of experience obtained. The major significant variable (P less than 0.01) was the type of hospital where the exposure was gained. In one type of hospital the externs shared the work-load, whilst in the other type they were largely used as observers with minor technical duties. The supervisors' perception of the externs' professional capabilities varied according to the hospital. We believe that the failure of curriculum implementation was related to conflict between institutional needs, which must be safeguarded by the supervisors, and the educational needs of the learners. This conflict affects the perceptions of the supervisors and without their full cooperation the curriculum cannot be delivered. The roles and perceptions of supervisor and learner must overlap sufficiently for the system to be effective and this must be taken into account by curriculum planners.

Attitude of Health Personnel↗

The genetics of children's oral reading performance.

Measures of reading achievement and verbal ability have been shown to be heritable. Additionally, recent evidence has been suggestive of a major gene effect on reading disability and for problem reading in a sample of normal readers. We report on the etiology of individual differences in oral reading performance, the Slosson Oral Reading Test (SORT), for which biometrical analyses have not been reported in the literature previously. Oral reading performance was measured in a large population-based sample of twins of the Virginia Twin Study of Adolescent Behavioral Development. Biometrical analyses of the SORT suggested that, in both males and females, 69% of the phenotypic variation was due to heritable influences and 13% of the variation due to shared environmental effects. While the relative importance of genetic and environmental influences is equivalent for males and females, males showed greater phenotypic variability than females.

Achievement↗

Familial aggregation of multiple myeloma and central nervous system diseases.

Degenerative central nervous system diseases such as Alzheimer's disease and lymphoreticular malignancies such as multiple myeloma occur with increased frequency with advancing age. Relatives of early-onset Alzheimer's disease patients may have an increased risk of lymphoreticular malignancies. This led us to evaluate the family history of central nervous system diseases in a case-control study of multiple myeloma. Thirteen of 439 multiple myeloma cases had one or more first-degree relatives with degenerative or demyelinating central nervous system disease. In comparison, there were nine "positive" family histories in 1,317 matched hospital controls (relative risk = 4.4, 95% confidence interval = 1.9-10.3). Relative risks for the component categories of Parkinson's disease, multiple sclerosis, and miscellaneous degenerative central nervous system diseases were 3.0, 4.0 and 11.9, respectively. Our findings suggest that the degenerative and demyelinating central nervous system diseases and the lymphoreticular malignancies may comprise an etiologically related group of "protean diseases." These diseases may have a shared genetic susceptibility, possibly an immunologic abnormality. The varied disease manifestation in family members suggests a second necessary etiologic step of a variable and possibly environmental nature.

Aged↗

Exposure of black youths to cigarette advertising in magazines.

OBJECTIVE: To estimate the potential exposure of black adolescents to brand specific advertising in magazines. DESIGN: A probit regression analysis was conducted of pooled 1990 and 1994 data on brand specific advertising in 36 popular US magazines to examine the relationship between the presence or absence of advertising in each magazine for each of 12 cigarette brands, and the proportion of each magazine's youth (ages 12-17 years) readers who were black. MAIN OUTCOME MEASURES: The presence or absence of advertising in each magazine in 1990 and 1994, for each of 12 cigarette brands. RESULTS: After controlling for total magazine readership and the percentage of young adult, Hispanic, and female readers, black youth cigarette brands (those whose market share among black youths exceeded their overall market share) were more likely than other brands to advertise in magazines with a higher percentage of black youth readers. Holding all other variables constant at their sample means, the probability of a non-black youth brand advertising in a magazine decreased over the observed range of percentage black youth readership from 0.65 (95% confidence interval (CI) 0.55 to 0.75) for magazines with 5% black youth readers to 0.33 (95% CI 0.00 to 0.69) for magazines with 91% black youth readers. In contrast, the probability of a black youth brand advertising in a magazine increased from 0.40 (95% CI 0.17 to 0.62) at 5% black youth readership to 1.00 (95% CI 0.97 to 1.00) at 91% black youth readership. CONCLUSIONS: Black youths are more likely than white youths to be exposed to magazine advertising by cigarette brands popular among black adolescents.

Adolescent↗

Genetic diversity of Carica papaya as revealed by AFLP markers.

Genetic relationships among Carica papaya cultivars, breeding lines, unimproved germplasm, and related species were established using amplified fragment length polymorphism (AFLP) markers. Seventy-one papaya accessions and related species were analyzed with nine EcoRI-MseI primer combinations. A total of 186 informative AFLP markers was generated and analyzed. Cluster analysis suggested limited genetic variation in papaya, with an average genetic similarity among 63 papaya accessions of 0.880. Genetic diversity among cultivars derived from the same or similar gene pools was smaller, such as Hawaiian Solo hermaphrodite cultivars and Australian dioecious cultivars with genetic similarity at 0.921 and 0.912, respectively. The results indicated that self-pollinated hermaphrodite cultivars were as variable as open-pollinated dioecious cultivars. Genetic diversity between C. papaya and six other Carica species was also evaluated. Carica papaya shared the least genetic similarity with these species, with an average genetic similarity of 0.432; the average genetic similarity among the six other species was 0.729. The results from AFLP markers provided detailed estimates of the genetic variation within and among papaya cultivars, and supported the notion that C. papaya diverged from the rest of Carica species early in the evolution of this genus.

Carica↗

Risk factors for extracranial carotid artery atherosclerosis.

We related risk factors, cardiovascular symptoms, and coronary status to the extent of extracranial carotid atherosclerosis as measured by B-mode ultrasonography in 376 volunteers hospitalized for elective coronary angiography. In a first analysis, we correlated risk factors and cardiovascular symptoms with carotid atherosclerosis. Univariate analysis showed that relations between many continuous risk factors and carotid atherosclerosis were graded and consistent for men and women. Multivariate analysis identified 6 significant variables (age, hypertension, pack-years smoked, and inversely, plasma concentrations of high density lipoprotein cholesterol and uric acid, and Framingham Type A score) that together accounted for 35% of the variability in extent of carotid atherosclerosis. In a second multivariate analysis, addition of coronary status (presence or absence of coronary stenosis as evaluated by coronary angiography) to the roster of candidate independent variables produced a new equation that accounted for an additional 5% of the variability in carotid atherosclerosis extent. Although much of the variability in extent of carotid atherosclerosis remains unexplained, these data define an association between coronary and carotid atherosclerosis that depends partly on shared exposure of both arteries to the same risk factors. They are also consistent with the concept that as yet undiscovered risk factors and/or genetic (e.g., arterial wall) factors common to both arterial beds also contribute to the relation between coronary and carotid atherosclerosis in human beings.

Age Factors↗

Drug design and the CAS ONLINE substructure search system.

CAS ONLINE, the chemical substance search and display system available directly from Chemical Abstracts Service, is a new service which is particularly useful in drug design studies. In CAS ONLINE chemists search by structures to identify chemical substances, for example, derivatives or analogs of a drug or its pharmacologically active fragment, which share user-defined features. Search questions are phrased in terms of one or more structure diagrams, each of which can include variable atoms, bonds, or positions of substitution as required by the searcher. CAS ONLINE provides access to the world's largest (more than 6 million substance records) and most current chemical structure information data base. CAS ONLINE is updated weekly with 7,000-10,000 new substance records. Substance information available from searches in CAS ONLINE include structure diagrams, systematic and common names (including trade names) for substances, molecular formulas, and the widely cited CAS Registry Numbers. The searcher may optionally request for each substance bibliographic information for the ten most recent literature references which have been cited in Chemical Abstracts since 1967.

Chemistry, Pharmaceutical↗

Mixed cryoglobulinaemia: a cross-road between autoimmune and lymphoproliferative disorders.

Mixed cryoglobulinaemia (MC) is a systemic vasculitis, secondary to the deposition in small and medium-sized blood vessels of circulating immune complexes, mainly the cryoglobulins, and complement. MC is characterised by a typical clinical triad (purpura, weakness, arthralgias) and by one or more organ involvement: chronic hepatitis, glomerulonephritis, peripheral neuropathy, skin ulcers and diffuse vasculitis. In a limited number of MC patients, a malignancy, that is B-cell non-Hodgkin's lymphoma or hepatocellular carcinoma, may also develop. Hepatitis C virus (HCV) infection has been found in the majority of patients with MC; the frequency of HCV markers (91%) was significantly higher than other rheumatic diseases (6.4%), namely systemic lupus, Sjögren's syndrome, rheumatoid arthritis and systemic sclerosis, or healthy controls (1.2%). The HCV infection of lymphoid tissues may represent the remote event leading to B-lymphocyte proliferation responsible for autoantibodies and immune-complex production. In a similar way, HCV infection may also be involved in the pathogenesis of other autoimmune (glomerulonephritis, thyroiditis, lung fibrosis, autoimmune hepatitis, porphyria cutanea tarda) and lymphoproliferative disorders (monoclonal gammopathies, B-cell lymphomas). MC shares numerous clinico-serological and pathological features with the above disorders. HCV seems to be their common etiological agent; however, a variable combination of unknown co-factors (infectious, genetic, environmental) should be determinant for the appearance of different clinical patterns.

Autoimmune Diseases↗

Human pheochromocytoma: different patterns of catecholamines and chromogranins in the intact tumour, urine and serum in clinically unsuspected cases.

Clinically unsuspected pheochromocytoma is usually discovered either at autopsy or during surgical intervention for unrelated conditions, despite often enormous neoplastic masses producing and storing catecholamine (CA). In order to assess whether these tumours share some common features we have compiled data for six patients admitted to hospital without previous diagnosis of their pheochromocytoma. The clinical variables and the morphological and immunohistochemical characteristics of the tumours revealed that these cases represented quite different expressions of adrenomedullary neoplasms. They differed not only with respect to nuclear ploidity and overall cytoplasmic morphology but also in catecholamine storage and expression of immunoreactive chromogranin A sequences in the intact tissue. In two of the patients hypertension had been overlooked as a diagnostic indicator of their CA-producing tumours. There was no clear relationship between the mean arterial pressure, the tumour content of CA and the serum levels of CA. Processed chromogranin A dominated in the serum of the two hypertensive cases. The 24-h urine values of CA and its main metabolite (vanillin mandelic acid) were, together with the serum values of chromogranin A and B, proportional to tumour mass and provided the most reliable diagnostic indicators for the non-hypertensive as well as the hypertensive cases.

Adrenal Gland Neoplasms↗

Confirmatory factor analysis of the Wechsler Memory Scale-Revised standardization sample.

A maximum likelihood confirmatory factor analysis was preformed by applying LISREL to the variance-covariance matrix obtained from standardization of the Wechsler Memory Scale-Revised (WMS-R) (N = 316). Analyses were designed to determine which of seven hypothesized factor solutions could best explain memory function as measured by the WMS-R. Competing latent variable models were identified in previous exploratory and confirmatory factor analytic studies. The measurement error matrix was set to remove method variance shared by the immediate and delayed trials of the same subtest. Hypothesized factors were fixed and allowed to correlate. Results indicated that a three-factor model, including Attention/Concentration, Immediate and Delayed Memory, explained 91% of the score variance and produced a significantly better fit than the Attention/Concentration--General Memory or Attention Concentration--Visual/Verbal Memory solutions. Findings support previous work suggesting that the WMS-R measures separate memory functions, and that the verbal/nonverbal Index distinction may not be a viable one.

Journal Article↗

[Complete sequence analysis on potato virus M infecting Solanum muricatum].

The complete sequence of Potato virus M from Solanum muricatum was determined. The liner, single-strand and positive sense genomic RNA was 8526 nucleotides long and six open reading frames were identified. The genome organization was typical feature of genus Carlavirus. Sequence analysis showed that PVM isolates shared 62.5% - 97.2% nucleotide and 60.9% - 97.4% amino acid identities. The coat protein gene was most conserved and TGB3 gene was greatly variable. Phylogenetic tree analysis suggested that the Idaho potato isolate (PVM-Id) was a distant strain, and other 4 isolates were grouped discriminatively based on CP and NABP amino acid sequences respectively. This is the first report of PVM from Solanum muricatum.

Capsid Proteins↗

Applicability of RAPD markers on silver-stained polyacrylamide gels to ascertain genetic diversity in Peripatus acacioi (Peripatidae; Onychophora).

RAPD (random amplification of polymorphic DNA) molecular markers can be utilized for analyzing genetic variability in populations for which only a few or no molecular markers are available. They were used in a study of an endangered species, Peripatus acacioi, found in the Tripuí Ecological Station, in Ouro Preto, MG, Brazil. The ecological station was specifically created to protect this velvet worm species, the first of this group found in Brazil. For an initial evaluation of the genetic diversity of this species, DNA samples from the lobopods of four individuals, collected at random, were analyzed using RAPD. Each reaction was run with a different primer (Operon RAPD 10-mer Kits), totaling 13 primers (OPC2, OPC3, OPC4, OPC6, OPC8, OPC10, OPC11, OPL2, OPL7, OPL11, OPL13, OPL18, and OPL19). Due to the low amplification yield, RAPD fragments were separated in polyacrylamide gels and stained with silver nitrate. Numerous bands were observed. Fifty-five of the amplified bands proved to be reproducible, both in terms of presence and intensity. Among these, 27 were variable and 28 were constant. The average number of bands per gel was 4.2. Nine of the 13 primers tested allowed the identification of constant and variable bands among these four individuals. RAPD analysis of genetic variation using silver-stained polyacrylamide gel electrophoresis provided measures of band sharing among the individuals, and therefore could be used in population genetics studies of P. acacioi.

Animals↗

[The surgical treatment of neoplastic colorectal occlusions].

The emergency treatment for neoplastic occlusions of rectum still needs debugging. While we finds perfect accord in to directly treat with a right hemicolectomy (more or less widened) the tumours from cecum to the first portion of the right colon, not the indications are likewise shared in presence of neoplastic stenosis of sigma-rectum. The treatment of urgency of these tumours is lent to so many variable and the tendencies too are constantly in evolution in relationship to the improvement of the technologies and the surgical devices. We have to chose from the two-three times intervention (now with less succession), or the total or subtotal colectomy otherwise the most used left hemicolectomy and anterior resection for sigmoid colon. Presenting our historical cases of 31 years of activity (Institute of Surgical Emergency Department--University La Sapienza of Rome), 564 neoplastic occlusions of the colon (75.7% sigma-rectum), the Authors describe their attitude both of approach and of surgical therapy in urgency that has brought them to practise in the 65.6% of the cases the anterior resection without protection colostomy, with extraperitoneal anastomosis and reconstitution of the pelvic peritoneum, in all the stenosis under descendant--sigma. In the last period it is frequent more and more the tendency to the positioning of a stent on the neoplastic stenosis: this treatment allows us to overcome the emergency to operate then under fitter conditions.

Adult↗

The histologic and functional characterization of enzymatically dispersed intestinal mast cells of nonhuman primates: effects of secretagogues and anti-allergic drugs on histamine secretion.

Despite the apparent involvement of gastrointestinal mast cells in hypersensitivity reactions in the mucosa, remarkably little information is available concerning the characteristics of these cells from man and higher animals. To study the characteristics of gastrointestinal mast cells from nonhuman primates, a previously described technique which uses a combination of mechanical and enzymatic methods to obtain mast cells from the tissues of rodents required modification to permit the successful dispersion of normal gastrointestinal tissues of higher animals. This modified procedure, as described in this report, appears to be relatively selective for mast cells located in the mucosal site, and typically yields ca 9 X 10(5) mast cells per gram of tissue. The mucosal mast cells obtained comprised ca 2% of the total nucleated cells, contained approximately 1 pg of histamine per cell, and stained metachromatically with toluidine blue only at low pH. The cells exhibited a dose-dependent release of histamine on challenge with goat anti-human IgE or the ionophores A23187 and Br-x537A but were refractory to the action of compound 48/80. IgE-mediated histamine release from monkey intestinal mast cells differed from that observed from rat intestinal mast cells in that release was inhibited not only by quercetin but also by theophylline. Disodium cromoglycate gave variable results. The data indicate that viable nonhuman primate mucosal mast cells can be obtained for study, and that these cells, although sharing some characteristics of mucosal mast cells from lower species, have distinct and unique properties. The availability of this nonhuman primate model for the study of mast cell function in higher animals should contribute to the understanding of mast cell-mediated diseases in man.

Animals↗

Effect of donor age and sex on the outcome of liver transplantation.

We correlated donor and recipient factors with graft outcome in 436 adult patients who underwent 462 liver transplants. Donor variables analyzed were age, gender, ABO blood group, cause of death, length of stay in the intensive care unit, use of pressors or pitressin, need for cardiopulmonary resuscitation, terminal serum transaminases, and ischemia time. Recipient variables analyzed were age, gender, primary diagnosis, history of previous liver transplant, ABO blood group, cytotoxic antibody crossmatch, United Network for Organ Sharing (UNOS) status, and waiting time (except for the cross-match results, they were all known at the time of the operation). The endpoint of the analysis was graft failure, defined as patient death or retransplantation. Using multivariate analysis, graft failure was significantly associated with donor age, donor gender, previous liver transplantation, and UNOS 4 status of the recipient. The effect of donor age became evident only when they were older than 45 years. Livers from female donors yielded significantly poorer results, with 2-year graft survival of female to male 55% (95% CI, 45% to 67%); female to female, 64% (95% CI, 54% to 77%); male to male, 72% (95% CI, 66% to 78%); and male to female, 78% (95% CI, 70% to 88%). The only donors identified as questionable for liver procurement were old (> or = 60 years) women in whom the adverse age and gender factors were at least additive. However, rather than discard even these livers, in the face of an organ shortage crisis, their individualized use is suggested with case reporting in a special category.

Adult↗

Sequence variability of hepatitis C virus and its clinical relevance.

Chronic type C hepatitis is a potentially serious disease that can lead to cirrhosis and hepatocellular carcinoma. This complex disease is caused by the hepatitis C virus (HCV), a positive sense, single-stranded RNA virus. HCV has been assigned to a separate genus within the Flaviviridae, and shares a close relationship to the pestiviruses. Nucleotide sequence variation has been observed in genomes amplified from serum of patients with HCV infection, and cloning of RNA amplified from patients infected with HCV has confirmed the heterogeneity of the agent responsible for post-transfusion and sporadic hepatitis C. The variability of HCV is structured in a way that immediately suggests a two tiered classification: this nomenclature comprises 'types' corresponding to the major branches in a phylogenetic tree of sequences from genomic or subgenomic regions of the genome, and 'subtypes', corresponding to the more closely related sequences within some of the major groups. This genotyping designation has provided an epidemiological tool for studying geographical differences in hepatitis C infection. Clearly discernible patterns of genotype distribution have been found in those countries that have been studied so far. In many European countries genotype distributions vary with the age of patients, reflecting rapid changes in genotype distribution with time within a single geographical area. Unfortunately we know very little about modes of transmission within different communities. There is considerable interest in the clinical significance of different HCV genotypes, and the intriguing question of whether these differences may affect the spectrum of the disease associated with hepatitis C. These data also have implications for diagnosis and treatment of acute and chronic hepatitis C. A uniform typing scheme and nomenclature will facilitate our understanding of the disease caused by this virus worldwide.

Genotype↗