Early detection of complications in amebic liver abscess. A retrospective analysis of 140 cases with amebic liver abscess (ALA) seen at the AUNL University Hospital was done to see if patients with complications can be identified earlier in order to decrease morbidity and mortality. Sixteen patients (11.4%) presented complications and six patients died (4.2%). Patients with complications presented jaundice, large or multiple abscesses, acute abdomen, liver failure and sepsis more often than patients without complications. Hemoglobin, hematocrit, prothrombin time, total proteins, albumin, LDH, and BUN were more altered in patients who presented complications. The titer of antibodies against E. histolytica was higher in this group of patients. The six patients who died had been operated on. The causes of death were septic shock in two, sepsis in one, peritonitis in one, liver failure in one and colon perforation in one patient. Pleural effusion, jaundice and acute abdomen were seen in three patients, respectively (50%), two cases had multiple abscesses (33.3%), one patient had a ruptured abscess (16.7%). Patients who died exhibited more alterations in six laboratory examinations at admission: partial prothrombin time, total bilirubin, albumin, BUN, LDH, and leukocytes. Clinical data together with the severe alterations in laboratory examinations at admission for patients with ALA should alert the clinician to suspect complications earlier in order to decrease morbidity and mortality.


Molecular characterization of IgG and IgE antigens of Entamoeba histolytica. Several surface IgG antigens of E. histolytica have been characterized. We isolated two novel cDNAs by screening a library of pathogenic E. histolytica with rabbit antiserum against a membrane preparation of pathogenic amebas. cDNA K15 encodes a large protein > 220 kDa with sequence homology to myosins and K18 encodes a protein of around 40 kDa. Serum IgG from patients suffering from amebiasis binds to both antigens. Some IgE antibodies are able to recognize homologous proteins in all eukaryotes investigated. We demonstrate that IgE antibodies from pollen allergic patients bind to plant, human, as well as E. histolytica profilins.


IgA reactivity in patients with intestinal or hepatic amebiasis. The antigens of E. histolytica recognized by IgA antibodies in sera from patients with either amebic liver abscess or intestinal amebiasis, as well as saliva from the latter, were determined in immunoblots of whole native trophozoite proteins. Results show that sera of patients with amebic liver abscess reacted mainly with amebic proteins of more than 200 kDa, whereas those of individuals with intestinal amebiasis recognized a protein of 145 kDa. The saliva of the latter detected a protein of 210 kDa which is not always seen when using the sera of patients with intestinal or hepatic amebiasis.


Amebiasis in Nicaragua: class specific serum antibody responses. With the aid of the indirect hemagglutination (IHA) test and IgG ELISA the antibody profile against E. histolytica in León, Nicaragua was investigated in 562 sera from individuals belonging to various age groups. The highest reactivity was invariably recorded in the age group 6-15 years where 48% were seropositive. Several sera reactive by either one of IHA and IgG ELISA were negative by the other test. The main reason for this seems to be reactivity in different Ig classes. Treatment with 2-mercaptoethanol reduced the titre level in 63 of the 66 sera tested. Immunofluorescence using an anti-IgM conjugate showed that 26 of 43 sera contained specific IgM-antibodies, indicating that also unspecific reactions are involved in the IHA test. A comparison was made between class-specific reactivity in three population groups: healthy residents, healthy cyst carriers and patients with recent or acute liver abscess. No significant difference in the prevalence of reactions above the diagnostic significance level was recorded between cyst carriers and healthy residents. However, among the cyst carriers 33% had IgA and/or IgM antibodies but no demonstrable specific IgG. Most patients with recent and all with acute liver abscess reacted significantly above the diagnostic limit in all three tests.


A survey of Entamoeba histolytica and Entamoeba dispar (Brumpt) infections on Mahé, the Seychelles. E. histolytica, pathogenic, and E. dispar, non-pathogenic, being morphologically identical are, when recovered as cysts in feces, diagnosed as E. histolytica. A survey on The Seychelles demonstrated that when culture and zymodeme characterization was used to compare against microscopy alone, the risk of overdiagnosis of E. histolytica infections was drastically reduced. From a total of 313 subjects tested 21 cultures grew amebas. By zymodeme analysis eight were E. histolytica, 40 were E. dispar and the remainder were various species of non-pathogenic intestinal amebas. Two further small comparative surveys confirmed these findings.


Increased frequency of HLA-DR3 in Mexican mestizo pediatric patients with amebic liver abscess (ALA). Mexican mestizo pediatric patients with ALA revealed a significantly increased frequency of HLA-DR3 alone, or in its haplotype form HLA-A2, DR3, which confirms our previous observation in adult patients with ALA in the same ethnic group. However, the relative increase in these HLA specificities in pediatric ALA patients when compared to adult patients was not statistically significant, and calls for an enlargement of the population studied.


Recombinant expression, purification and biochemical characterization of a superoxide dismutase from Entamoeba histolytica. A recombinant iron-containing superoxide dismutase (recFeSOD) of Entamoeba histolytica was produced in a prokaryotic expression system. Purified recFeSOD was found to be enzymatically active as determined by (i) inhibition of ferri-cytochrome c reduction, (ii) dismutation of superoxide anions generated by human neutrophils and (iii) inhibition of nitroblue tetrazolium reduction. The enzymatic properties of recFeSOD were similar to those of the native protein in trophozoite extracts. In an ELISA using recFeSOD as antigen, 96% of sera from patients having invasive amebiasis were reactive whereas none of the healthy controls or of patients suffering from malaria, bacterial or viral infections were reactive. Only sera of Toxoplasma-, Leishmania- or Trypanosoma-infected individuals exhibited partial cross-reactivity to recFeSOD.


A DNA probe specific to pathogenic Entamoeba histolytica. A DNA sequence, IE-gen1 (3.1 kb), was isolated from the pathogenic strain of E. histolytica NIH-200. IE-gen1 was identified by the subtractive hybridization of a genomic library to a cDNA probe prepared from NIH-200 trophozoites. The IE-gen1 probe specifically detected pathogenic E. histolytica in slot blots of genomic DNA and Northern blots, but not other Entamoeba species and additional human parasites. This genomic probe could detect with complete specificity DNA from about 10(3) organisms. The IE-gen1 probe could be related to highly specialized loci in pathogenic E. histolytica, and is likely to be a valuable DNA reagent for clinical diagnosis and epidemiological investigations.


Use of polymerase chain reaction and nonradioactive DNA probes to diagnose Entamoeba histolytica in clinical samples. E. histolytica parasites in Mexican children's stools were identified and typed as pathogenic or non-pathogenic using the polymerase chain reaction (PCR) and nonradioactive probes. PCRs were performed with primers specific for 145 base pair (bp) pathogenic or 133 bp non-pathogenic DNA sequences, which are highly repeated in E. histolytica parasites with pathogenic or non-pathogenic isoenzyme patterns, respectively. Dot-blotted PCR products were identified with a horseradish peroxidase-conjugated oligonucleotide probe specific for either the 145 bp pathogenic or 133 bp non-pathogenic sequences. The PCR and the 145 bp pathogenic probe correctly identified eight cultures with pathogenic isoenzyme types and none of nine cultures with non-pathogenic isoenzyme. The PCR and 133 bp non-pathogenic probe identified all of the non-pathogenic cultures, none of the axenized pathogenic cultures, and three of five xenic cultures with pathogenic isoenzymes. The two probes together identified all 49 stools containing E. histolytica by light microscopy (sensitivity = 1.0), which represented the entire set of the E. histolytica-positive stools diagnosed at the Hospital Infantil over a 10 week period. Most patient isolates were positive with both 145 bp pathogenic and 133 bp non-pathogenic probes, suggesting that these children, 60% of whom were dysenteric, are infected with mixed populations of amebas.


Further diagnostic use of an invasive-specific monoclonal antibody against Entamoeba histolytica. Genotypic differences between invasive and non-invasive E. histolytica could explain the 1:10 ratio of symptomatic/asymptomatic infection worldwide. Currently, zymodeme analysis is used to differentiate invasive from non-invasive E. histolytica strains but the technique is cumbersome and expensive. In accordance with the WHO research priorities for amebiasis we report here the further use of an invasive-specific monoclonal antibody against E. histolytica in immunofluorescence, to identify isolates cultured from stool samples of patients from three geographically distant endemic regions: Bangladesh, Colombia and Mexico. We tested 107 E. histolytica isolates and the correlation between zymodeme characterization and the immunofluorescence assay was 100%.


Serodiagnosis of invasive amebiasis using a recombinant Entamoeba histolytica antigen-based ELISA. Amebic serology remains a critical component in the diagnosis of invasive amebiasis. A recombinant serine rich-Entamoeba histolytica-protein/maltose binding protein (SREHP/MBP) fusion protein was evaluated as the target antigen in an ELISA test to detect acute invasive amebiasis. Retrospective analysis of 65 serum samples from patients with amebic liver abscess and 40 asymptomatic control patients showed the SREHP/MBP ELISA test had a sensitivity of 74% and specificity of only 55% for the diagnosis of amebic liver abscess. This study was repeated under identical conditions using a purified recombinant SREHP cleaved from the MBP component. The purified recombinant SREHP-based ELISA had a sensitivity of 79% and specificity of 87%. Our data suggest a purified recombinant SREHP-based ELISA could prove useful in the serodiagnosis of acute invasive amebiasis.


Low risk of invasive amebiasis in cyst carriers. A longitudinal molecular seroepidemiological study. A seroepidemiological study of a household cohort, using both clinical observational and molecular criteria was conducted in a periurban area endemic for E. histolytica infection. This longitudinal study was undertaken to determine the risk of asymptomatic cyst carriers to develop invasive illness. Zymodeme patterns of strains isolated from these patients were correlated both with the clinical presentation of disease and with the serological response against the M-17 ameba antigen and further compared with that found in 16 proven cases of amebic liver abscess. From a total of 163 housewives screened, 39, (24%) were asymptomatic cyst carriers; 31 of them (index cases) and 114 members of their households remained in the study over an 8 month follow-up period to detect ameba infection and illness. Of the household members at risk, 46 (40%) became infected within 6 weeks. None of the index or secondary cases developed ameba-related symptoms and cyst excretion followed a chronic persistent, intermittent, or transient pattern over the period of the study. Amebas were recovered and zymodemes determined in 19 of 71 (27%) cyst carriers. Ameba shed from each of these 19 carriers exhibited nonpathogenic zymodeme 1, except for one index case where zymodeme 2 was recovered in one sampling, and returned to zymodeme 1 in subsequent samples. Of 48 of 71 cyst carriers studied, antibodies to crude E. histolytica antigen were detected by ELISA in 16 (31%); antibodies to the M-17 fusion protein were found in 8 (16%) by ELISA and in 2 (4%) by Western-Blot (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Primary structures of alcohol and aldehyde dehydrogenase genes of Entamoeba histolytica. Ethanol is the major metabolic product of glucose fermentation by the protozoan parasite E. histolytica under the anaerobic conditions found in the lumen of the colon. With the goal of finding new targets for anti-amebic drugs, the E. histolytica NADP(+)-dependent alcohol dehydrogenase gene (EhADH1; EC 1.1.1.2) and an aldehyde dehydrogenase gene (EhALDH1; EC 1.3.2) were cloned. The EhADH1 alcohol dehydrogenase gene encoded -39 kDa protein with 62 and 60% amino acid identities, respectively, with NADP(+)-dependent alcohol dehydrogenases of anaerobic bacteria Thermoanaerobium brockii and Clostridia beijerinckii. In contrast, EhADH1 showed a 15% amino acid identity with the closest human alcohol dehydrogenase. An EhADH1-glutathione-S-transferase fusion protein showed the expected NADP(+)-dependent alcohol dehydrogenase and NADPH-dependent acetaldehyde reductase activities. The enzymatic activities of the EhADH1 fusion protein were inhibited by pyrazole and 4-methyl pyrazole. The E. histolytica aldehyde dehydrogenase EhALDH1 gene encoded a 60 kDa protein, which showed a 36% amino acid identity over a 451 amino acid overlap with the human stomach aldehyde dehydrogenase (ALDH3).


Partial nucleotide sequence of the enzyme pyruvate, orthophosphate dikinase of Entamoeba histolytica HM1:IMSS. We isolated a clone from a lambda gt11 cDNA library of E. histolytica, subcloned its insert in the vector pTZ18R and sequenced it by the method of Sanger. Sequence comparison with Genbank and of the corresponding amino acid sequence with the NBRF/PIR data bank using the FastA program, showed homologies between 54.9 and 58.5% for the nucleotides and between 48.6 and 49.4% for the amino acids with pyruvate, orthophosphate dikinases from maize, Flaveria trinervia and Bacteroides symbiosus. The sequence obtained for E. histolytica represents about 20% of the complete gene or protein sequence.


Identification of a myosin heavy chain gene from Entamoeba histolytica. The myosin heavy chain gene A, mhcA, from E. histolytica was identified by polymerase chain reaction. There is only one copy of this gene on the ameba genome. The mhcA gene encodes a 6 kb messenger RNA. The predicted protein sequence is homologous to myosin II from both, Dictyostelium discoideum and Acanthamoeba castellanii. Specific areas of the N-terminal region of myosin II are highly conserved reflecting a similarity in functional domains, like the ATP or the actin binding sites.


Chromosome walk in Entamoeba histolytica: the gene encoding for ribosomal protein L21 neighbors one of the actin genes. Actin is one of the most abundant proteins in the motile intestinal protozoan parasite E. histolytica. A number of actin gene copies have been detected. The cDNA and genomic sequences of two of the actin genes have been independently reported (1,2). Almost complete homology was detected between the coding regions of the two genes; however, significant differences were observed in the sequences of their 5' untranslated regions. Using the coding region of actin as the focal point, we performed a chromosome walk to identify the neighboring genes and the intergenic regulatory domains. A genomic library containing large fragments of DNA was screened with the coding and non-coding regions of the actin gene. An insert of 8.5 kb reacted on Northern blots with actin and two additional transcripts. The large (approximately 2.5 kb) transcript has not yet been identified, but the smaller one (600 bp), was shown to encode for the ribosomal protein L21. Both the cDNA and genomic sequences of this gene were determined. The RP-L21 gene was found to be physically connected to the actin gene by a 2.1 kb intergenic stretch. The actin gene on this DNA fragment contained a 5' untranslated region that was identical to the sequence described by Edman et al. The actin gene isolated by Huber et al. was located by PFGE on another chromosomal band that did not contain the RP-L21 gene.


Axenic massive cultivation of Entamoeba histolytica trophozoites in spinner flasks and in a microfermentor. A medium, PEHPS, whose main components are extracts of ox liver, and ox and swine pancreas (EHP) was used to develop two alternative methods for axenic cultivation of trophozoites in suspension: with magnetic stirrer and with a 14 l capacity microfermentor, giving the first technic yields of 2.36 x 10(5) to 3.08 x 10(5) and the second in a 14 l capacity microfermentor, which produced 1.65 x 10(5) amebas/ml in one batch and 2.94 to 3.65 x 10(5) of such parasites/ml at semicontinuous flux.


Effects of albendazole on Entamoeba histolytica and Giardia lamblia trophozoites. Albendazole, a benzimidazole carbamate commonly used for the treatment and control of intestinal helminthic infections, is also useful for the treatment of giardiasis. Therefore, it is of interest to determine whether the drug has activity against other intestinal protozoa, such as E. histolytica. The present results demonstrate that albendazole inhibits the growth of E. histolytica trophozoites in axenic cultures and induces fine structural changes such as polyribosome aggregation and loss of cytoplasmic vacuoles at concentrations up to 10 micrograms/ml. The viability of E. histolytica trophozoites was not affected by the drug. In contrast, lower concentrations of albendazole showed dramatic effects on G. lamblia trophozoites. These included loss of adhesiveness, striking modifications of the overall morphology of giardias, disassembly of the ventral disk, and loss of viability after prolonged treatment. The results provide further evidence on the potent antigiardial activity of albendazole and indicate that, at the concentrations used, the drug has no antiamebic activity.


Further studies on the in vitro activity of gossypol as antiamebic agent. Gossypol has an in vitro antiamebic effect, which is 11,39, and 980 times more potent than emetime, metronidazole and diiodohydroxyquinolein, respectively, on five Entamoeba histolytica axenic strains. The trophozoite NADP-dependent malic enzyme and alcohol dehydrogenase are inhibited by (+/-)-gossypol, in a noncompetitive manner with respect to the substrate. From the (-)- and (+)- enantiomers, which integrate the natural gossypol mixture, the first one is three and four times more active in inhibiting both the amebic culture growth and the mentioned oxidoreductases, respectively. The above results justify the analysis of gossypol as an antiamebic drug in experimentally infected animals.


Improved molecular karyotype of Entamoeba histolytica. Different electrophoretic conditions were used to improve the molecular karyotype of Entamoeba histolytica clone L6 derived from the heterogeneous strain HM1:IMSS. Eleven to 17 bands ranging between 0.3 and over 3 megabases (Mb) were resolved by transverse alternating field electrophoresis (TAFE). Amebic chromosomes presented similar pattern when they were TAFE separated at 72, 90 or 120 h running time, but resolution of the bands was increased at 90 h, and the best electrophoretic pattern was obtained at 120 h. Bal 31 digestion of DNA in the plugs suggested that most of the bands are lineal molecules and that pMD, an amebic DNA fragment, hybridizes with both lineal and nonlineal DNA molecules.


The fine structure of Entamoeba histolytica processed by cryo-fixation and cryo-substitution. Recently, the use of cryo-fixation followed by freeze-substitution has been shown to produce a better ultrastructural preservation of cellular components due to the rapidity of the fixation procedure and the lack of distortion during dehydration. When these techniques are applied to study the fine structure of axenically cultured trophozoites of E. histolytica, an improved preservation of cytoplasmic and nuclear components was found. The surface coat of the parasite appears much thicker and uniform than in conventionally treated samples. Also, the ground substance of the cytoplasm is packed with fibrogranular material, which is usually extracted by chemical fixation. The extremely fast fixation procedure allows the visualization of fusion and/or fission processes of cytoplasmic vacuoles and vesicles. Nuclear microtubules and cytoplasmic microfilaments are clearly identified. Low-temperature techniques allow not only a better preservation of the cell structure of E. histolytica parasites, but will also facilitate considerably future immunoelectronmicroscopical studies.


Entamoeba histolytica: electrophoretic analysis of isolated caps induced by several ligands. Caps induced by several ligands including sera from patients with amebic liver abscess (ALA) were isolated by differential centrifugation. Purification was verified by scanning and transmission electron microscopy. Electrophoretic profiles obtained by SDS-PAGE and Western blots were compared when probed with the ligand used to induce capping. It was confirmed that sera from different patients recognize different proteins. Indeed, electrophoretic profiles reveal that capped membrane proteins vary according to the ligand used to induce capping. This would agree with the supposition that E. histolytica might use this process as a mechanism to evade the host's immune response, by clearing the cell surface from recognized antigens.


Variation of proteins and proteinases in Entamoeba histolytica lysates containing a protease inhibitor. Sodium dodecyl sulfate (SDS)-lysates of E. histolytica trophozoites were analyzed by electrophoresis in simple and gelatin-containing ("substrate") SDS-polyacrylamide gels. In simple gels, boiled lysates with para hydroxymercuribenzoate (pHMB) had a complex pattern of apparently undegraded proteins; boiled lysates without pHMB showed a major 30 kDa and four minor (43, 46, 63 and 117 kDa) proteins, whereas unheated lysates displayed only the 117 kDa protein. Using substrate gels no gelatinases were detected in heated lysates; unheated lysates without pHMB showed a major 30 kDa and three minor (33, 46 and 68 kDa) gelatinases, whereas those with pHMB presented a major 56 kDa and two minor (70 and 105 kDa) gelatinases. Three caseinase peaks were separated by Sephadex G-75 chromatography from unheated lysates: peak I contained 46, 56 and 117 kDa pHMB-sensitive gelatinases and peaks II and III contained smaller pHMB-resistant caseinases. We conclude that proteins remaining in lysates after SDS-induced proteolysis appear to be mainly proteases relatively resistant to self-digestion whose type and amount changes with the conditions of lysis and the presence of inhibitors; this is exemplified by the finding of the major gelatinase of lysates with pHMB being larger (56 kDa) than in lysates lacking the inhibitor (30 kDa).


The effect of axenic versus xenic culture conditions on the total and secreted proteolytic activity of Entamoeba histolytica strains. Proteolytic activity was measured in lysates of four axenic and five xenic cultures of different strains of pathogenic E. histolytica, and in five non-pathogenic strains ("E. dispar") growing in xenic culture. There was no significant difference in total proteolytic activity, using either gelatin or albumin as substrate, between the two sets of xenic cultures; the axenic pathogens however had significantly higher levels of activity than the xenic pathogens, the levels appearing to correlate with virulence. An axenic strain (NIH 200) reassociated with mixed bacterial flora reverted to close to xenic levels of activity. There was no evidence of secretion of an elevated proportion of the total enzymic activity by pathogenic strains, and expression levels may owe more to culture conditions than to genotype.


Immediate autoproteolysis and new proteinases in Entamoeba invadens and Entamoeba moshkovskii trophozoites. We have examined the sodium dodecyl sulfate (SDS)-induced autoproteolysis of E. invadens (PZ and IP101) and E. moshkovskii (FIC and Laredo) trophozoite lysates. Heat-treated lysates containing parahydroxy-mercuribenzoate (pHMB) of all four strains had undegraded protein patterns. Unheated pHMB-lacking lysates of PZ had two (99 and 90 kDa) and IP101 lysates had three (45, 99, 90 kDa) major proteins, whereas FIC and Laredo lysates had only one (90 kDa). Heat-treatment changed the remaining proteins to smaller ones: 37 in PZ and IP101, 33 and 37 kDa in FIC and Laredo. Unheated lysates run on gelatin-containing "substrate" gels had gelatinases whose sizes were higher in lysates containing pHMB and allowed us to detect a 200 kDa gelatinase in E. invadens strains. Our results indicate that SDS induces immediate autoproteolysis by CPs in non-histolytica trophozoites, whose proteinases appear to be processed by self-digestion, and Entamoeba proteinases vary considerably under the various conditions used to obtain and characterize them.


Phenotypic heterogeneity in the expression of a 30 kDa cysteine proteinase in axenic cultures of Entamoeba histolytica. A polyclonal antibody raised against a purified approximately 30 kDa cysteine proteinase derived from extracts of axenically grown trophozoites of E. histolytica strain HM-1:IMSS was used to stain 72 h cultures of the same amebas by indirect immunofluorescence. Fluorescence was limited to the outer membrane of the parasite and was either uniformly distributed or more condensed on a segment, at times on a single point of the membrane. In relation to the intensity of fluorescence staining, three distinct amebic populations were present: negative, weakly stained and intensely stained. The relative numbers of these three groups remained quite constant for at least one year under the same culture conditions. Flow cytometry was used to quantitate simultaneous variations in amebic size and intensity of fluorescence at various times after different treatments. Amebic size was registered in three levels: small (< 7 microns), medium (7-20 microns), and large (> 20 microns). Staining intensity was measured in arbitrary units. Exposure to 100% fresh hamster serum, phagocytosis of erythrocytes, exposure to cysteine proteinase inhibitors E-64 and cystatin, and to calmodulin antagonist W-7, resulted in various modifications of the phenotype of amebas in very short time periods. We conclude that the expression of the membrane approximately 30 kDa cysteine proteinase in axenic amebic cultures is phenotypically heterogeneous, and that such heterogeneity is modulated and not constitutive.


Study of factors that influence the clinical response to ciguatera fish poisoning. A one-year observational study of all standardized medical records of ciguatera fish poisoning notified cases was conducted in French Polynesia. The objective was to determine the factors that influence the clinical response to ciguatera fish poisoning. During the year 1991, there were 551 cases notified on standardized code sheets by physicians (notification rate 276 per 100,000). The mean age was 36.6 years (SD 15.6). The largest age group was the 30- to 39-year-old one (138 cases, notification rate 970 per 100,000). Sex ratio (M/F) was 1.6. A clinical score was calculated to assess the outcome for each case. The adjusted odds ratio (OR) for a severe disease (33.2% with a score > 5) were significantly increased when the fish ingested was carnivorous (OR = 1.62, 95% Confidence Interval (CI): 1.07-2.45) and when a history of a previous attack was reported (OR = 1.71, 95% CI: 1.17-2.5). Men aged 30-39 years are at a higher risk to get ciguatera fish poisoning, whatever its severity. Severe diseases were observed when the ingested fish was carnivorous and in patients experiencing their second or more attack. This later finding could be related to an accumulation of toxin in the human organism.


Ciguatera fish poisoning in the Solomon Islands. Ciguatera fish poisoning may have existed in the Solomon Islands long ago though there has never been any ciguatera fish poisoning tests been carried to confirm its presence. Suspected occurrences are infrequent and seasonal. Most cases of ciguatera fish poisoning are undocumented that when cases do occur they depend largely on traditional-knowledge and anecdotal information. Areas suspected to have ciguatoxic poisoning problem in the Solomon Islands includes Santa Cruz, Rennell and Bellona, Indispensable reefs, Ontong Java and Wagina island. Fish species considered ciguatoxic includes red emperor, red snapper, roundfaced batfish, barracuda and blue lined sea-bream. In any way ciguatera fish poisoning is as yet not a big health problem in the Solomon Islands.


Review of the clinical use of intravenous mannitol with ciguatera fish poisoning from 1988 to 1992. Intravenous mannitol was introduced as an effective treatment for ciguatera in 1988. Clinicians have used intravenous mannitol with success in several geographic areas. However, there remains a general skepticism and reluctance to use mannitol to treat ciguatera amongst clinicians. The possible reasons for the clinician's reluctance to use intravenous mannitol to treat ciguatera are reviewed.


Clinical experience with i.v. Mannitol in the treatment of ciguatera. To assess the effectiveness of i.v. Mannitol treatment for Ciguatera Poisoning, 35 patients were treated from the Miami-Caribbean area with symptoms of acute and chronic Ciguatera Poisoning. Information was collected on demographics, fish type and location, timing and type of symptoms, and response to treatment. Iv Mannitol (1 g/kg infused 3-4 hours) given within 48 hours dramatically decreased the acute morbidity of Ciguatera Poisoning without serious side effects. Treatment also appears to be safe and effective in chronic cases up to eight weeks from ingestion of toxic fish.


Socioeconomic impacts and management ciguatera in the Pacific. The inshore fisheries resource is important to the health and culture of many of the inhabitants of Pacific Island countries (PIC). Ciguateric fishes (mainly demersal reef fishes) cause a range of distressing and often debilitating gastrointestinal neurological and cardiovascular disturbances. Consequently, ciguatera limits the utilisation of this otherwise over-exploited resource. For many victims, the symptoms suffered during the chronic phase of ciguatera (lasting weeks, months and occasionally years) are exacerbated upon consumption of certain foods, particularly non-toxic fishes. After each outbreak, victims and members of their social-network experience a transient increase in perception of the risk of eating reef fish. The impact of ciguatera is greatest in atoll island countries where fish is the primary source of protein (it also has a major impact and to facilitate the management of ciguatera in PIC, regular information is required that quantifies: (i) the true incidence of ciguatera; (ii) the extent and way in which different communities avoid ciguatera; and (iii) the adverse impact ciguatera has on health, the workforce, trade and tourism. Over the last 15 years (based on SPEHIS data to 1990), some countries recorded a decrease in the ciguatera problem (New Caledonia, Marshall Is.), other countries an increase (Kirbati, Tuvalu, French Polynesia), while still other countries recorded an increase followed by a decrease in ciguatera (Tokelau, American Samoa, Western Samoa, Fiji and Vanuatu). There may also be seasonal trends in the incidence of ciguatera in some countries e.g. Fiji. Management options presently implementable in PIC include: (i) treatment with i.v. mannitol; (ii) provision of timely advise on the location and status of ciguatera "hot spots" in each country that would allow affected communities to react objectively to the risk posed by ciguatera; and (iii) modification of human behaviour and aspirations to reduce the impact of increasing population, pollution and development (e.g. causeways) pressures.(ABSTRACT TRUNCATED AT 250 WORDS)


Ciguatera fish poisoning and fisheries development in the South Pacific Region. Ciguatera fish poisoning represents an impediment to the development of fisheries based on shallow water reef fish stocks and to the food security of islands where agriculture is limited. Although fisheries development initiatives in the past 20 years in the Pacific have focused on the development of deep slope fisheries and fisheries for large pelagics such as tuna, shallow reef fisheries continue to be a major animal protein source for Pacific Islanders and a source of commercial revenue for fishermen. Statistics on ciguatera outbreaks in the Pacific are limited to local databases in Hawaii and French Polynesia, and to the compilation by the South Pacific Commission of "fish poisonings" reported by the medical departments of the countries of the region. A new database was established at the South Pacific Commission during 1990 to serve as a focus for detailed reporting of fish poisoning and ciguatera in the South Pacific. Some preliminary results from this database are presented and the importance of such information to the development of coastal reef fisheries is discussed.


Benthic dinoflagellates from the coral reef lagoon of Mayotte Island (S-W Indian Ocean); identification, toxicity and preliminary ecophysiological study. The community of benthic dinoflagellates of Mayotte Island is similar to those of other regions. Four clones of Gambierdiscus toxicus and of other benthic dinoflagellates species (Prorocentrum spp., Ostreopsis sp., Amphidinium spp.) have been isolated and screened for their crude toxicity using mouse-test. The toxigenic reservoir seems moderated. One toxic clone of G. toxicus has been studied for factors governing growth and photosynthetic activity of this species: salinity, temperature, light intensity and nutrients with bioassays.


Role of associated bacteria in growth and toxicity of cultured benthic dinoflagellates. Clonal cultures of the toxic benthic dinoflagellate Ostreopsis lenticularis isolated from the coastal waters of southwest of Puerto Rico show peak toxicities during the stationary phase of growth, correlated with significant increases in bacteria directly associated with these cells. The specific toxicity (MU/mg) of dinoflagellate extracts in control cultures increased 340% during the static phase of culture growth, while those cultures treated with antibiotics that inhibit prokaryote protein synthesis showed no significant increase in toxicity during this phase of culture growth. There was a significant decrease in the diversity of dinoflagellate associated bacterial strains in antibiotic treated cultures. These data indicate that associated bacteria play a role in toxin production by dinoflagellate-bacteria consortia when grown in laboratory culture.


Bursts of ciguatera and endo-upwelling process on coral reef. We propose a significant relationship between bursts of ciguatera following disturbance on a reef area and seepages of endo-upwelled interstitial waters, rich in nutrients. Such waters cannot continue to be used by a stressed or eliminated algal-coral ecosystem and are taken up by epibenthic planktons i.e. Gambierdiscus toxicus, of which population increases sharply.


Progress on chemical knowledge of ciguatoxins. The chemical data setted up on the ciguatoxins responsible for ciguatera fish poisonings are summarized and discussed. The multiplicity of the toxic compounds isolated from fish and algal material is described. A tentative screening of the principal toxins still on process in the two laboratories has shown that (1) CTX is dominant in carnivorous fish, (2) less polar toxins are dominant in herbivorous fish, (3) CTX precursors are produced by G. toxicus in natura and in culture conditions. The increasing polarity of the toxins in step with the food chain levels supports the hypothesis of an oxidative modification of the precursors during the bio-accumulation in fish.


Partial structures and binding studies of maitotoxin, the most potent marine toxin. Partial structures of maitotoxin (MTX) were deduced by extensive two-dimensional NMR measurements, showing that the toxin had carbon-carbon double bonds in both termini of the molecule, and a primary alcohol group at the end. These functionalities were used for preparation of a radioligand of MTX; [3H]H-MTX and [3H]benzoyl-MTX. Both radioligands had high levels of non-specific binding to tissues. The binding of [3H]MTX to rat glioma C6 cells was inhibited by a didesulfo-MTX, suggesting the presence of the specific site for MTX-binding on the external surface of the cell membrane.


Toxicity of French Polynesian strains of Gambierdiscus toxicus in cultures. Seven clonal strains of Gambierdiscus toxicus isolated from three ciguateric areas around Tahiti island were mass cultured and extracted for ciguatoxins and maitotoxin. CTX analogs were detected only in one clone (GTP1), suggesting that CTX production may be strain-dependent. However, this in vitro production of CTXs, which remains fairly poor with regards to the toxicity levels encountered in wild G. toxicus, is not a stable temporal characteristic. On the other hand, maitotoxic compounds were detected in all 7 strains in copious amount, especially in clone GTH2.


Isolation of analogues of okadaic acid from cultures of Prorocentrum lima. A chloroform extract of cultured Prorocentrum lima was analyzed for carboxylic polyethers related to okadaic acid (OA). The extract was derivatized with 1-(bromoacetyl)pyrene to give the fluorescent pyrenacyl esters of OA and other carboxylic acids. The resulting mixture was subjected to preparative high performance liquid chromatography with fluorescence detection. Positive chemical ionization mass spectrometry indicated that four OA-related compounds were present, including two methylated analogues. The fragmentation pattern of at least one of these suggests it is not the previously reported 35-methylokadaic acid.


Molecular properties of the sodium channel: a receptor for multiple neurotoxins. Sodium channels are the receptors for more than 10 distinct classes of biological toxins which act at five or more receptor sites. Brevetoxins and ciguatoxins act at neurotoxin receptor site 5. This receptor site is located on the alpha subunit of the sodium channel, and peptide segments in domain IV of that subunit are important in brevetoxin binding.


Ciguatoxin-induced changes in acetylcholine release and in cytosolic calcium levels. In this communication we summarize our current knowledge concerning the mode of action of ciguatoxin (CTX) on acetylcholine (ACh) release either from motor nerve terminals or from pure cholinergic synaptosomes. The results obtained indicate that CTX affects Ca(2+)-dependent ACh release via distinct actions mediated by Na+ which alter presynaptic excitability and Ca2+ influx through both voltage-sensitive channels and the reversed operation of the Na+/Ca2+ exchange system. The external calcium-independent ACh release induced by CTX in motor terminals seems to be due to a Na(+)-dependent and tetrodotoxin-sensitive mechanism which mobilizes Ca2+ from intraterminal stores, as determined by fluorometrical recordings in single mouse neuroblastoma x rat glioma NG108-15 cells.


Purified ciguatoxin-induced modifications in excitability of myelinated nerve fibre. The effects of external applications of 0.22-1.12 nM of purified ciguatoxin (CTX-1B), extracted from the moray-eel, were studied on frog current and voltage clamped node of Ranvier. CTX-1B induced spontaneous action potentials at a frequency of 70-100 Hz, suppressed by 50 microM lidocaine, which resulted from a toxin-induced maintained (late) inward Na current representing about 5.5% of peak Na current. Peak and late currents showed different voltage characteristics but were similarly affected by 50-500 microM lidocaine. It is concluded that the effects of CTX-1B are qualitatively but not quantitatively similar to those previously studied of partially purified toxin (2).


Preliminary results towards ciguatoxin immunodetection. Due to the lack of purified ciguatoxin (CTX), monensin was used as a model for developing an enzyme immunoassay to detect CTX. Specific antibodies directed against monensin have been produced in rabbits and mice using a monensin-protein immunogen obtained in bulk quantities. Rabbit polyclonal and mouse monoclonal (MAb) antibodies of high specificity and affinity have been produced. Using MAb 2H8, in a competitive micro-ELISA performed in Terasaki plates, the detection limit for free monensin was 75 pg. No cross-reactivity was detected against CTX but a procedure requiring only 100 micrograms of hapten is under current investigation with a brevetoxin (PbTx-3), another marine toxin with a polyether backbone structure similar to CTX and recently commercially available.


Rapid facile solid-phase immunobead assay for screening ciguatoxic fish in the market place. The precision of the solid-phase immunobead assay (Ciguatect) to detect toxins associated with ciguatera poisoning have been evaluated through analysis of toxic and non-toxic fish obtained from fishing areas around the Hawaiian Islands. The Ciguatect test kit has been optimized for application to field/marketplace screening of ciguatoxic fish. Twelve parrot, surgeon, and amberjack fish fillet and fish extract test portions containing various concentrations of toxins were distributed to participating laboratories for analysis. The presence or absence of ciguatera-related toxins is determined by binding the toxins to a membrane attached to a plastic strip and exposing the toxin ladened membrane to a monoclonal antibody-colored latex bead complex which has a high specificity for ciguatera-related toxins. The intensity of the color on the membrane denotes the presence of the toxins in the fish or fish extract. Toxic components in the fish were confirmed by extraction, column purification, and toxicity testing using the brine shrimp (Artemia sp.) assay. Okadaic acid was used to standardize both the S-PIA and brine shrimp assays. For determination of ciguatoxin and related polyether toxins in parrot, surgeon, and amberjack fish fillets, the relative standard deviations for repeatability (RSDR) were 13.5, 9.0 and 4.3%, respectively, and the relative standard deviations for reproducibility (RSDR) were 44.4, 29.7 and 14.3%, respectively, for concentrations ranging from 1-4 ng/test strip. For determination of ciguatoxin and related polyether toxins in parrot, surgeon, and amberjack fish extracts, the RSDR were 5.8, 4.8, and 3.7%, respectively, and the RSDR were 11.9, 9.9, and 7.6%, respectively, for concentrations ranging from 3-5 ng/test strip.(ABSTRACT TRUNCATED AT 250 WORDS)


A pilot study of a new ELISA test for ciguatoxin in humans. The major impediment to the thorough study of Ciguatera in human populations has been the lack of definitive diagnostic ability. However, recently an ELISA test was developed which can diagnose Ciguatera qualitatively and quantitatively in human fluids, as well as in contaminated fish tissue. This study proposes to evaluate this new ELISA test in human subjects with the clinical diagnoses of acute and chronic Ciguatera Poisoning. The contaminated fish from exposed subjects, and the blood and urine of exposed and controls, will be examined using the new ELISA. The ELISA performance will be compared to traditional bioassays for the fish testing. In addition, a distinct diagnostic profile will be developed using serial questionnaires, physical examinations, and nerve conduction tests. Ultimately this ELISA test can be used not only in establishing the correct diagnosis of Ciguatera Poisoning, but also in the treatment and clinical prognosis, and in epidemiologic studies of Ciguatera Poisoning in human populations. We hope that this protocol will serve as a model for the study of the effects of other marine toxins on human populations.


Ciguatera toxins in the food chain revealed by stable isotopes. The stable carbon and nitrogen isotope contents of the meat tissues of 27 identifiable fish found in the gut contents of 70 ciguatoxic and non-ciguatoxic barracuda caught along the southwest coast of Puerto Rico have been analyzed. The isotope ratios of those fish found in the stomach contents of ciguatoxic barracuda were significantly different than ratios determined in those fish found in the stomachs of non-ciguatoxic barracuda. The isotope ratios of the toxic dinoflagellate Ostreopsis lenticularis, a presumed vector of ciguatera in the Caribbean were found to be extremely light, particularly for nitrogen. The lightened nitrogen ratios of the herbivore (Doctorfish) and carnivore (Squirrelfish) fishes found in the stomach contents of ciguatoxic barracuda suggest that the dinoflagellate was in the food chain of these barracuda. Results indicate that the trophic pathway of ciguatoxins through the marine food chain from the presumed primary trophic level (dinoflagellates/bacteria) to ciguatoxic barracuda appears to be different than the pathway to non-toxic barracuda. Stable isotope ratios may be a very useful tool for tracing ciguatoxins in the food chain and the identification of ciguatoxic fish.


Liquid chromatographic mass spectrometric methods for the determination of marine polyether toxins. Experiments with novel nitrogenous coumarin-based reagents yielded moderately fluorescent derivatives of brevetoxin-3 and ciguatoxin-1. The diethylaminocoumarin-carbamic acid esters of brevetoxin-3 were resolved by high performance liquid chromatography into two derivative peaks that correspond to substitutions at the C-37 and C-41 hydroxyls. The derivatives produced intense molecular ions under fast atom bombardment ionization conditions, confirming derivative identity. Ciguatoxin-1 was also successfully derivatized, resolved, and identified by HPLC-fluorometry with an estimated lower limit of detection of 0.5 to 1.0 ng.


Methods for detecting brevetoxins in seawater, in biological matrices, and on excitable membranes. Although the toxins differ in each of the principal polyether marine seafood intoxication syndromes, developing technology is of general applicability. The brevetoxins can be readily detected in seawater, in dinoflagellate cells, and in shellfish using standardized mouse bioassay, isocratic high performance liquid chromatography, radioimmunoassay and enzyme-linked immunoassay...each possessing distinct advantages and disadvantages. Clinical diagnosis, pharmacokinetics, and membrane-receptor studies on the contrary require specialized radioligand technology and immunofluorescent and immunodense imaging. The applicability of brevetoxins assays towards predictive, detection, and molecular mechanism of action of ciguatoxin is presented.


[Cutaneous malignant melanoma in Rio Grande do Sul, Brazil: study of 101 cases]. Between 1985 and 1989, at the Hospital de Clínicas de Porto Alegre (HCPA), 101 cases of cutaneous malignant melanoma (CMM) were reviewed in order to evaluate the status of the disease at diagnosis. The cases were obtained from the records of the pathology service of the HCPA. Nodular Melanoma (ND) was the most frequent type (36.6%). In males, the predominant site was in the head, neck and trunk while in females it was in the lower limbs Clark level V was found in 35.6% of the cases. In 23.8%, the tumor was larger than 4mm in depth according to Breslow classification. These results clearly demonstrate that the diagnosis of CMM is established in later stages of the disease.


[Work situation of physicians graduating from medical residency programs in the State of São Paulo, Brazil]. The authors report on a study conducted to analyze the professional situation of physicians residing in the State of São Paulo, Brazil, five years after completion of a medical residency program. At least 50% of the professionals were interviewed in each specialty. A heavy work load was observed in physicians working both in the metropolitan area of the State capital and in other regions of the State. Male doctors had a higher income than female ones. The latter, however, had a higher proportion working in a single specialty, although 16.8% did not practice in the specialty in which they were trained. The most frequent working environment was a hospital, followed by an ambulatory facility and a private office. The metropolitan area physicians exceeded the remaining in teaching activities and public hospital appointments. They had also a higher tendency to work in a different specialty. This study offers significant information with respect to professional decisions as well as regarding the creation or expansion of residency programs.


[High mortality rates among Brazilian adult populations--an international comparison]. Adult disease in an increasingly important public health problem in Brazil. In order to compare adult mortality in Brazil to that in other countries, age-adjusted coefficients for adults aged 30-69 of the States of São Paulo and Rio Grande do Sul and of the city of Fortaleza (Ceará State) are compared to those of similarly aged adults in a series of 33, principally European, countries. The Brazilian population coefficients for overall, cerebrovascular and cardiovascular mortality are among the highest of the series; those for ischemic heart disease occupy median positions. These comparisons illustrate the precarious state of adult health in Brazil and, given the growing possibilities of preventing cardiovascular and other non-communicable diseases, help demonstrate the need for preventive programs in Brazil aimed at the major common and lethal diseases of the productive years of life.


[Lung cancer and the delay in the diagnosis: analysis of 300 cases]. This is a prospective study involving 300 persons with lung cancer admitted to the "Arnaldo Vieira de Carvalho" Cancer Institute (ICAVC). The intention of the survey was to detect delay in diagnosis after the initial symptoms. THe authors tried to identify causes of this delay and its implications. Patients were asked about the day that the symptoms started, medical care and specialists sought, number of physicians seen and their diagnosis, also examinations carried out and referrals. Results showed that 78% of cases were seen firstly by general practitioners and 69.6% looked for medical assistance at least 30 days after the clinical beginning of the disease. Chest X-rays could identify only 9 cases (3%) without symptoms. The most common clinical diagnoses were: pneumonia (20%), neoplasia (19%), bronchitis/emphysema (9.3%) and tuberculosis (8%). The number of first appointments seen by the Public Health Services and Contracted Private Hospital Network was 64.1% and the second appointment was 70%. Only 24 (8%) of the patients were referred to ICAVC just after their first appointment and 64.4% after the third. The time lost between the first appointment and the diagnosis was longer than 90 days in 55.7% of cases. These people needed to see 3 to 4 doctors (as an average) to obtain a positive diagnosis. The diagnostic techniques used more frequently were bronchoscopy (59.7%) and fine needle lung biopsy (18.4%) and the delay was 20 and 10 days on average, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


[Mycobacterium szulgai infection in a patient with hemophilia and AIDS]. Mycobacterium szulgai is a scotochromogenic species recently recognized as a human pathogen. Twenty-nine cases of disease caused by M. szulgai in humans have been reported. Pulmonary disease indistinguishable from that caused by M. tuberculosis was the commonest type of infection caused by M. szulgai. Olecranon bursitis was reported in 3 cases and disseminated infection was noted in 3 cases occurring in immunocompromised patients without AIDS. The authors report the first case of pulmonary disease caused by M. szulgai in Brazil and the first case in patient with AIDS in the world literature.


[Surgical treatment of fungal bolus in acute lymphoid leukemia]. Case report of a 24 year old female patient with ALL that developed pulmonary invasive aspergillosis during aplastic phase of induction chemotherapy. She was treated with antibiotics and amphotericin B. After recovering from neutropenia, she developed a mycetoma in the inferior lobe of the right lung, which required lobectomy. Nine months after surgery the patient is well, in complete remission of ALL and with no evidence of infection. One month after lobectomy, chemotherapy had been reintroduced. Attention should be called to this form of therapy of Aspergillosis, as a successful way to eradicate this fungal infection that responds poorly to antifungal drugs currently used.


[Acute cardiorespiratory insufficiency due to electric injury: invasive hemodynamic study]. Case report on right branch block, acute pulmonary oedema and enteritis caused by electric shock in a boy. The invasive hemodynamic study showed primary pulmonary hypertension, cardiogenic shock, and acute respiratory failure. The outcome was good, with total and progressive recovery of all lesions. The literature review revealed the rarity of pulmonary oedema and enteritis after an electric shock. The invasive haemodynamic data suggest physiopathological explanations for findings in the case and indicate therapeutic measures for similar situations.


[Vascular complications in intravenous drug addicts]. Twenty patients with complications of drug addiction were admitted to the Department of Vascular Surgery of the Santa Catarina University Hospital, from January 1986 to September 1990. Most of these patients were male, aged between 20 and 35 years. The most common drug used was propoxiphene, followed by cocaine. Swelling, ulcers and pain in the inferior extremities were the most common signs and symptoms. Six patients presented deep venous thrombosis, four had acute lymphangitis, all of them in the lower limbs. Five patients had acute arterial occlusions, one presented common femoral artery mycotic aneurysm and another had a false aneurysm of the superficial femoral artery. Venous and lymphatic complications were clinically treated with antibiotics, heparin and local care. Six patients were submitted to surgical procedures. One was treated by aneurysmectomy and vascular reconstruction, another with aneurysmectomy and arterial ligation. On one patient forearm fasciotomy was performed. Two amputations and one drainage of abscess were carried out.


[Course of pregnancy and puerperium in women with mitral valve stenosis]. To study pregnancy, delivery, puerperium and the newborn in cases of mitral valve stenosis, asymptomatic at conception. Sixty-two pregnant women, 30 with mitral valve stenosis (GE group) and 32 without cardiac disease (GN group) had their functional class, kind of delivery, anesthetic technique and newborn characteristics evaluated during gestation. In GE group 16 (53.3%) patients changed from functional class (FC) I/II to FC III and 10 (33.3%) to FC IV. In GN group 18 (56.2%) changed from FC I to II during the gestation. Delivery was vaginal in 21 patients (70%); anesthetic technique was regional block in 17 (56.6%). These findings were not statistically different between (p > 0.1) the groups. Premature (20.0%) and small babies for gestational age (36.7%) were higher (p > 0.001) in GE group. There were no cases of maternal death. The majority of GE women who started pregnancy in FC I/II changed to FC III/IV during gestation. Probably adequate medical treatment and valvoplasty in one case allowed fetal viability; but we had higher incidence of pre-term and small for gestation age babies in the GE group.


[Optimization of the use of cyclosporin in renal transplantation]. Strategies to optimize the use of cyclosporin A (CSA) in renal transplant were analysed retrospectively. Based on the incidence of acute rejection during the first 15 days of transplant, oral dosing achieved adequate immunosuppression earlier than constant intravenous infusion of CSA. The lack of CSA blood monitoring and the use of different steroid doses in this period could be responsible for these conflicting results. The differential diagnosis between acute rejection (AR) and CSA nephrotoxicity (NX) during the first year of transplant was made based on clinical findings, CSA levels and histological evaluation. Therapeutic CSA concentration range between 200 and 400 ng/mL, using radioimmunoassay with polyclonal antibodies, and between 100 and 250 ng/mL, using specific monoclonal antibodies, were found. A correlation of r = 0.82 between these two methods were obtained in 122 simultaneous dosages. Histological abnormalities found in biopsies from patients with AR were not different from those obtained from patients with NX, before and after 90 days of transplant. The conclusion was drawn that the therapeutic CSA monitoring associated with histological evaluation can reduce the incidence of renal dysfunction and promote a long-term and stable graft survival.


[Rheumatic fever: atypical joint manifestations]. The diagnosis of rheumatic fever (RF) continues to be a difficult one in Pediatrics, mainly because of the polymorphism of its clinical presentation and the lack of specific laboratory test. Among the Jones' major criteria, arthritis is the most frequent and the least specific. Ninety three children with RF who presented 117 flares of the disease were studied in the Department of Pediatrics, Escola Paulista de Medicina, between Dec. 1989 and Dec. 1991. The presence of arthritis was defined as an inclusion criterion. The diagnosis was based on history, physical and laboratory examinations (Modified Jones' Criteria). The mean age was 10 years and the sex ratio was 1 male: 1.4 female. In 45% of the flares, arthritis was the only major criterion. In 44% there were arthritis and carditis, in 7% arthritis and chorea and in 4% arthritis, carditis and chorea. In 64% of the flares the pattern of articular involvement was migratory and in 36% addictive. Polyarthritis and oligoarthritis were observed respectively in 64% and 36%. Monoarthritis was reported in 3%. The definitive diagnosis of RF with atypical articular involvement only was possible in the presence of carditis or chorea. The authors conclude that physicians should be aware of the atypical involvement observed in some cases of RF, specially when arthritis is the only major criterion.


[Incidence of hydatidiform mole at the Paulista Medical School]. Between January 1980 and December 1989, at Escola Paulista de Medicina, a referral centre, 75 patients with hydatiform mole were assisted. The frequency of the hydatiform mole was calculated in 65 patients, whose treatment was performed in our Hospital, out of 13,986 pregnancies, which had occurred in this period of study. Thus, the incidence was 1:215 pregnancies, similar to that found in Asian and African countries.


[Cutaneous melanoma: clinical versus anatomopathological diagnosis]. In order to estimate the ability of physicians to make the clinical diagnosis of cutaneous malignant melanoma, a retrospective study was carried out. A comparison between clinical hypothesis and histopathological diagnosis was assessed. The rate of diagnostic accuracy was only 51%. There were problems in the differential diagnosis between malignant melanoma and other pigmented skin lesions. The majority of the cases of melanoma was recognized in advanced stages of tumor invasion. These data point out toward the need of improving the skills of the general physicians in the clinical recognition of the cutaneous melanoma and its precursor lesions.


[Renal artery aneurysm].

[Renal artery aneurysm]. Patients with haematuria should be submitted to deep investigative protocol, for a more accurate diagnosis. Thus, we report a case of macroscopic haematuria and the set of complementary examinations that led to the diagnosis of this rare pathological entity. The classification (etiological or morphological), diagnosis, surgical intervention indications and therefore the treatment (embolization or surgical) were pointed out. Accurate diagnosis is obtained through Renal Digitalis Arteriography after the morphological assessment of the normal urinary tract (UGE and renal US) and the evidence of unilateral bleeding (cystoscopy).


Getting your research published: adapting the thesis style. Writing a research report is similar to the research experience; both are processes with many distinct steps. Break your research project into parts and write about key accomplishments as you complete each milestone in the project.


[Fournier syndrome: evaluation and initial treatment]. The records of 48 patients with Fournier's syndrome (FS) treated at the Emergency Surgical Service of the Hospital das Clínicas of the University of São Paulo Medical School in the period 1982-1991 were reviewed. Clinical and laboratory data at admission were analysed. The following factors were statistically significant when associated with bad prognosis: elevated serum creatinine, hypoxemia, metabolic alkalosis or acidosis, diabetes and age over 50 years. Based on these five criteria, the patients were divided into two groups: Group I, mild FS (32 cases) and Group II, severe FS (16 patients). This classification permits a better planning of therapy. In cases classified as severe, treatment should include wide débridement, with resection of all necrotic tissues, scheduled reoperations for further débridements, transverse colostomy, wide spectrum antibiotic therapy and total parenteral nutrition. In the mild cases, the patients may be treated with débridement and antibiotics only.


[Ectodermal dysplasias--a general view]. Ectodermal dysplasias comprise a group of about 150 diseases, in general of a genetic nature. The most common form--Christ, Siemens, Touraine's Syndrome--is characterized by high intermittent fever in infancy and, when the patient is not properly cared for, the hyperthermia may cause death. In Brazil, there are at least 400 men severely affected by this syndrome (such a number is not higher because approximately 50% of the patients die early) and 1,000 women. In women, however, the syndrome occurs in a mild form, and many go unnoticed. Disinformation renders difficult the diagnosis and treatment of patients. This was the reason that led us to create, in 1982, the Center for the Study of Ectodermal Dysplasias, the only specialized institution of such diseases in the world.


Strengthening your case study approach.

Strengthening your case study approach. A well-written case study has an important place in nursing literature because it describes new problems and techniques in clinical practice and helps identify researchable clinical questions. Do not be deceived into thinking that the case study manuscript is easy to write, because it is not. But, with the application of a few guidelines, the case study can be fun to write, exciting to edit, and enjoyable to read.


[Primary erythromelalgia].

[Primary erythromelalgia]. Erythromelalgia is a rare disease characterized by intense erythema, burning pain and increased temperature in the distal of the extremities. Primary forms and secondary forms have been described, most commonly with essential thrombocythemia and policythemia vera. The authors describe a fifteen year old patient with primary erythromelalgia and discuss the pathogenic, clinical and therapeutic features of this disease.


Soliciting hospital newsletter articles. I keep my newsletter fairly brief and publish it quarterly, so I have plenty of time to practice my author-finding techniques between editions. This also gives me more time to come up with something on my own, if necessary. Although this article is presented in jest, I am not above anything that works to get contributions for my newsletter. Sometimes we editors are just that desperate.


Is my book idea sellable? Writing the book proposal. Follow up on your book idea with a prospectus. Allow yourself to dream about what the book will look like and share these details with a publisher. We can tell you how well the book fits our needs.


[Postmortem chromosome analysis and its significance]. Cultivation of necroptic material taken by pathologist or obstetrician according to determined indicative groups was performed during the years 1986-1990. Cytogenetical evaluation was feasible in 157 cultivated samples from the total of 252. There were found 32 pathological karyotypes among them.


[69, XXY triploidy in a liveborn infant]. Triploidy 69, XXY was described in a liveborn foetus weighing 760 g. Diagnosis was based on postmortal cytogenetical analysis.


[Amyloid in articular cartilage--a new type of amyloid?]. Hip and knee joints from 48 randomly selected autopsies have been investigated for amyloid deposits by means of conventional histology and immunohistology. 45 of 48 hip joints (93.75%) and 28 of 32 knee joints (87.5%) contained amyloid deposits. Amyloid has been found in a thin layer along the surface as well as infissures of the cartilage and around chondrocytes with increasing intensity towards the articular surface. Amyloid characteristically showed apple green birefringence in polarized light after staining with alkaline Congo red and pretreatment with potassium permanganate did not change intensity of reaction in most cases. None of the usual constituents of amyloid could be demonstrated by immunohistological methods. P-component (when present) kept the distribution of the amyloid material. It is possible that articular cartilage amyloid represents a new class of amyloid but its identity is to be proved by chemical analysis.


[Theory of multistep lymphocyte transformation]. The transformation of B lymphocytes in lymph nodes proceeds from the specialized small (centrocytoid) blast cell of the lymphatic tissue germinal centre base. It runs three subsequent steps. The transformation stream of lymphocytes of the first step is derived from the basal matrix of germinal centres and is aimed towards its replica in the mantle zone. Therein the transformed cells are supplemented and qualitatively altered towards the prevailing monocytic cells of the second step. The monocytoid cells are squeezed through the mantle zone under the basal part of the germinal centres. The third step continues in the terminal medullary direction, functionally linking up to the T4 paracortical nodules. A hierarchic feedback mechanism operates between individual steps, but partial hyperplasia of one step is possible. Under adequate antigenic stimulation, effector cells of local significance are derived from the main stream of incompletely transformed cells. During the first step (germinal centres) it is the lymphoplasmacytoid cells, whereas immunocytes and autoaggressive clear cells are produced during the second (mantle zone) step. The third (medullary) step as the final one results in the development of committed blood lymphocytes and plasmacytes. Transformation depends on local structural conditions, but immediate generic relations are not always present. The theory may be useful for the understanding of hyperplastic and neoplastic conditions usually comprising mixtures of cells belonging to one transformation step.


[Flow cytometry in primary renal tumors in childhood]. A group of nineteen primary renal tumors in childhood was analyzed by flow-cytometry. All clinically important entities were included. Paraffin embedded material was used. Two anaplastic nephroblastomas and a case of renal rhabdomyosarcoma had an aneuploid DNA content. One Wilm's tumor showed a moderate DNA-hyperdiploidy. One of two rhabdoid tumors showed a marked right-sided shift of G1/G0 phase from that of a control and was considered as probably hyperdiploid. All other tumors including high grade neoplasms such as rhabdoid tumor and bone metastasizing tumors were found in the DNA-diploid range. Proliferation index was high in most tumors and in six it reached or exceeded 40. Mitotic index counted in the histological sections correlated with the percentage of G2 + M phase in most cases. Although small, the group of tumors under study shows that prognostic criteria cannot be based on the DNA content or on the proliferation index only. The only relevant result may be an overt DNA-aneuploidy in anaplastic nephroblastomas. Difficulties in interpreting the results of flow cytometry are discussed.


[Basal-squamous carcinoma of the hypopharynx and larynx]. Another case of a very rare type of carcinoma is presented which was introduced recently as occurring in hypopharynx, larynx and tongue. Macroscopical description of an exophytic tumour of aryepiglottic fold and piriform recess in a 41-year old man is the second one in literature. Main histological feature of the tumour is a biphasic cellular structure with closely related basaloid and squamous components. Immunohistochemical expression of the squamous component concerned carcinoembryonic antigen, whereas S-100 protein, desmin and neuron specific granules. The small group of one own case and of 11 cases from the literature seems to support the idea that the tumour is aggressive, tending to early regional and remote metastases, and with shorter survival than other subtypes of epidermoid carcinoma.


[Apoptotic gastrointestinal stromal tumor--AGIST]. Leiomyoma with a faint desmin positivity was identified among gastrointestinal stromal tumours. In addition to smooth muscle cells it was characterized by particular sausage-like strongly oxyphilic structures. The structures may have represented partially degraded tumour cells as well as insudative fibrinoid changes of intersititial collagen. Apoptotic bodies could be compared with Rosenthal fibres, Civatte bodies and other apoptotic phenomena. They were typical for described tumour and therefore it was recommended to classify it as "apoptotic gastrointestinal stromal tumour".


[Adenolipomas, lipomatosis and amyloidosis of the thyroid gland]. Adipose tissue in the thyroid gland was observed in 7 biopsies and 2 autopsies: in 3 cases of solitary adenolipoma, 3 cases of multiple adenolipoma, 1 case of pure lipomatosis and 2 cases of lipomatosis with multiple adenolipomas combined with amyloidosis of lobules as well of adenomas in one bioptic case. Pathogenesis of this unusual phenomenon was discussed.


[An ovarian tumor with structural gonadoblastoma, dysgerminoma and choriocarcinoma]. A 14 1/2-year old girl with menometrorrhagia followed by amenorrhea and abdominal pain had a pelvic resistance with limited mobility. Histology of a left ovarian tumour showed gonadoblastoma turning to dysgerminoma and associated with choriocarcinoma (M-9073/1, M-9060/3, M-90101/3). Genuine ovarian tissue was hypoplastic on both sides. In the right ovary, there were additional thecalutein cysts. The patient's karyotype was 46 XX. She has been without any relapse 2 1/2 years after chemotherapy and actinotherapy.


[Morphologic study of aneurysms of the thoracic aorta]. Aneurysm of thoracic aorta was found in 20 from 7175 autopsies (0.25%) of persons deceased at the age of more than 15 years. The aneurysm was localized in 4 cases, diffuse in 14 and combined in two cases. Its pathogenesis was related to medionecrosis in 6 cases, to chronic aortitis in 5 and to isthmic aortic coarctation in two cases. Left ventricle hypertrophy which was found in 17 cases was related to arterial hypertension in 10 cases but only twice to a diffuse aneurysm. The aneurysm was closely connected with the cause of death in 10 patients. In a control study of subsequent 100 autopsies the mean aortic circumference was 75 mm in men and 71 mm in women, 59 mm in patients under the age of 50 and 82 mm over the age of 71 years. Medionecrosis was found in 45 cases, mucodystrophy in 8 and chronic aortitis in two cases.


[The first public autopsy in the region which is now Czechoslovakia?]. An autopsy performed in 1600 by a Slovak Dr. Jesenius, professor of anatomy at the Charles University of Prague, was for long years taken for the first public postmortem in this country. According to our investigations, another autopsy for public was done by Dr. med. Simon Grynaeus 6 years earlier in Brno. The fact was verified by a notice in the Municipal Chronic of Brno preserved in basement of the Brno Municipal Archives. Its author was identified as Georg Ludwig von Liebeneck, official chronicler at that time.


Study of the effect of the state of reparative regeneration of normal hemopoietic tissue on the leukemic process. On the basis of the investigation of transplanted leukemia development in mice with induced reparative restoration of hemopoietic tissue, of the antileukemic activity of various components isolated from regenerating blood forming organs and of the underlying mechanisms of this action, it has been suggested that some growth regulator molecules in recovering hemopoietic tissue are a part of the natural antileukemic defence of the body and may be of special significance in leukemia treatment especially for residual leukemic cell inhibition as a strategy.


Activated charcoal for theophylline toxicity in a premature infant on the second day of life. A premature infant received an overdose of aminophylline on the 2nd day of life and was successfully treated with activated charcoal. The use of activated charcoal this early postnatally has never been reported.


Neonatal modulation of hepatic acid soluble sulfhydryls and xenobiotic metabolizing enzymes in suckling mice exposed translactationally to butylated hydroxyanisole. The present study examines the effect of butylated hydroxyanisole (BHA) exposure through mother's milk on some of the hepatic xenobiotic metabolizing enzymes in the F1 offspring. Lactating Swiss albino mice received either a 0.5 or 1% BHA diet during the lactation period. The acid-soluble sulfhydryl content and activities of glutathione S-transferase and glutathione reductase increased significantly (p < 0.01) whereas the activity of glutathione peroxidase decreased significantly (p < 0.01) in the liver of pups exposed to BHA via milk. The hepatic content of cytochrome b5 increased (p < 0.01) while that of cytochrome P-450 decreased (p < 0.01) in the pups of dams which received a 1% BHA diet during lactation.


Acute effects of amiodarone on sodium currents in isolated neonatal ventricular myocytes: comparison with procainamide. Recent studies suggest that amiodarone's acute clinical effects in infants and children are related predominantly to its class I antiarrhythmic activity. However, the effects of amiodarone on Na+ currents have not been investigated directly in immature cardiac cells. Accordingly, the tight seal whole cell voltage clamp technique was used to measure time- and voltage-dependent Na+ currents in acutely isolated neonatal ventricular myocytes from 2- to 5-day-old rabbits, before and after addition of amiodarone (0.1-10 microM). To evaluate the class I antiarrhythmic activity of amiodarone in this age group, the effects of amiodarone on Na+ currents were compared with those of procainamide. Similar to procainamide, amiodarone significantly decreased peak inward Na+ current in neonatal ventricular myocytes. Moreover, both amiodarone and procainamide shifted the steady-state inactivation curve to more negative membrane potentials and delayed recovery of the Na+ current from inactivation. Thus, the effects of amiodarone on the Na+ current in immature myocardium are qualitatively similar to those of procainamide, suggesting that amiodarone may act acutely as a class I antiarrhythmic agent in the newborn heart.


Sedative/hypnotic effects of chloral hydrate in the neonate: trichloroethanol or parent drug? Although the metabolism and pharmacokinetics of chloral hydrate (CH) have been reported, there have been no attempts to correlate CH or its metabolite, trichloroethanol (TCE) with the sedative or hypnotic effects. In order to determine whether plasma concentrations of CH or TCE reflect the sedative/hypnotic effects, a sedation/agitation scale was developed. Based on the results of the present study, the sedative/hypnotic effects of TCE cannot be ruled out completely. However, in the neonate, the parent drug CH seems to have a more important role than has been previously suggested from human research.


Adrenal responsiveness in very-low-birth-weight infants treated with dexamethasone. This study was designed to investigate the effect of steroid administration in ill premature neonates. Twenty high-risk very-low-birth-weight (VLBW) infants [birth weight (BW) < or = 1,300 g] with a mean BW 948 +/- 220 g, gestational age (GA) 27 +/- 1.7 weeks underwent 1-hour ACTH (Cortrosyn) stimulation tests and determination of 17-hydroxyprogesterone (17OHP)/dehydroepiandrosterone sulfate (DHEAS) at 23.6 +/- 15.9 days poststeroid treatment for bronchopulmonary dysplasia (BPD)/airway obstruction. Metyrapone tests were also obtained in 18 infants. Baseline (nonsteroid-exposed) values for pre-/post-ACTH cortisol, 17OHP, DHEAS, and pre-/post-metyrapone compound S values were obtained in 5 infants. Eight of 18 (44%) infants had evidence of secondary (hypothalamic-pituitary) adrenal suppression based on abnormal metyrapone tests. No difference was found in BW, GA, time on O2 or AV, steroid dose/kg, or neonatal/postneonatal mortality between the suppressed and nonsuppressed groups. Two of 4 infants with borderline ACTH tests had subnormal compound S levels postmetyrapone. No relationship was found between steroid dose/kg and cortisol response post-ACTH. Additionally, corrected GA was not related to change in cortisol, 17OHP, and DHEAS pre-/post-ACTH. Two infants exhibited recovery of adrenal suppression documented by repeated metyrapone testing at 63 and 186 days poststeroid treatment. In conclusion, this study documents the apparent high incidence of secondary adrenal suppression in VLBW infants treated with dexamethasone. Clinical significance of these findings deserves further investigation.


Atrial natriuretic peptide in newborn piglets with a patent ductus arteriosus. Atrial natriuretic peptide (ANP) is a hormone involved in fluid and blood pressure homeostasis. We studied the effects of left-to-right shunting through a patent ductus arteriosus on blood pressure changes and plasma ANP concentrations in newborn piglets. In five experimental piglets, the ductus arteriosus was bathed with PGE1 and infiltrated with formalin to maintain its patency. In four age-matched control piglets, the ductus arteriosus was ligated. Plasma ANP concentrations and blood pressure determinations were obtained prior to (base-line) and 25 +/- 1 h (day 1), and 48 +/- 1 h (day 2) after surgery. Radionuclide-microsphere determinations of left-to-right patent ductus arteriosus shunts were performed on days 1 and 2 in the 5 piglets with a patent ductus arteriosus. Plasma ANP concentrations were significantly elevated in the left atrium on day 1 and the right atrium on day 2 in the PDA piglets. No correlation was demonstrated between plasma ANP concentrations and right or left atrial pressures. We conclude that left and right plasma atrial ANP concentrations are significantly elevated in newborn piglets with left-to-right patent ductus arteriosus shunts.


A possible 5-HT3 component of thyrotropin-releasing hormone-induced increases in gastric motility in developing rats. Intracisternal injection of thyrotropin-releasing hormone (TRH) increases gastric motility primarily via a vagal cholinergic mechanism. However, a serotonergic (5-HT) component may also exist. Rats (7, 10, 14, and > or = 50 days of age) were anesthetized and gastric motility monitored via an extraluminal strain gauge. Following baseline, ICS 205-930 which blocks 5-HT3 and 5-HT4 receptors (0.01, 0.10, or 1.0 mg/kg) was administered intraperitoneally, then 30 min later intracisternal TRH (5 or 10 micrograms). ICS 205-930 0.1 and 1.0 mg/kg blocked TRH-induced motility in 7-day-old rats. Results support a 5-HT3 or 5-HT4 receptor contribution to TRH-induced gastric motility stimulation, and suggest that receptor expression is dynamic during development.


Vasodilators in persistent pulmonary hypertension of the newborn: a need for optimal appraisal of efficacy. Tolazoline hydrochloride is usually the first choice pulmonary vasodilator in persistent pulmonary hypertension of the neonate (PPHN). The analysis of 26 articles including 467 tolazoline-treated infants has been hindered by many methodological drawbacks. Tolazoline has always been administered to infants suffering refractory hypoxemia, but, unfortunately, pulmonary hypertension has not usually been investigated. Moreover, 80% of the tolazoline-treated neonates had an underlying pulmonary parenchymal disease as a potential cause of severe hypoxemia. Noteworthy is that similar comments apply to all studies dealing with the use of other pulmonary vasodilators in PPHN. Pulsed Doppler echocardiography (PDE) should allow a qualitative and quantitative approach for PPHN and an analysis of both success and failure of vasodilator therapeutics. In the meantime, the use of PDE requires more intense investigation prior to wide application in PPHN.


Pregnancy alters the hemodynamic responses to cocaine in the rat. To test our hypotheses that the hemodynamic response to cocaine may be altered during pregnancy, cocaine (0.33 mg/kg/min) was infused intravenously to chronically catheterized pregnant and nonpregnant female rats. Cardiac output and regional blood flow were measured, and cocaine concentrations in plasma and tissues, as well as plasma cholinesterase activity were determined. Results were compared between pregnant and nonpregnant groups. Cocaine produced a significant decrease in heart rate, accompanied by a fall in cardiac output, and decreased cerebral, myocardial, and placental blood flow in pregnant rats. The plasma cocaine concentration in pregnant animals was lower than that of nonpregnant ones, but tissue concentrations were similar in both groups. These results indicate that pregnancy enhances cardiovascular responses to subtoxic doses of cocaine. There was little placental transfer of cocaine with a fetal to maternal plasma concentration ratio of 0.28.


Comparison of methods for prediction of nephrotoxicity during development. Drugs with nephrotoxic potential are continuously introduced into perinatal and pediatric medicine, and assessment of their relative toxicity is important. We compared different methods of assessment of renal damage during development in an attempt to establish their relative sensitivity, age and dose dependence. Newborn, 6- to 8-day-old and adult rats were treated for 7 days with intramuscular gentamicin (5, 10 or 20 mg/kg/day) or amikacin (5, 20 or 40 mg/kg/day). Renal damage was assessed by serum and urine creatinine, urine N-acetyl beta-glucosaminidase and beta 2-microglobulin, cortical sphingomyelinase in vivo and in vitro and morphologic changes in light and electron microscopy. As expected, there was a dose-dependent damage, with gentamicin being more nephrotoxic than amikacin, and with newborn rats more resistant. The light- and electron-microscopic assessment were more sensitive than all other methods, followed by urinary N-acetyl glucosaminidase and then by beta 2-microglobulin. Sphingomyelinase changes occurred only at the highest doses of gentamicin.


Oxygen-mediated regulation of neonatal and adult rabbit aortic tension. To determine the influence of oxygen on aortic tension in young and mature animals, we evaluated the response of neonatal and adult rabbit aortic rings to changes in oxygen tension. In 95% nitrogen/5% carbon dioxide, endothelium-derived nitric oxide was not a factor in the development or maintenance of low resting aortic ring tensions. However, the production of endothelium-derived nitric oxide increased in 21% oxygen/74% nitrogen/5% carbon dioxide and 95% oxygen/5% carbon dioxide, and attenuated a concomitant endothelium-independent mechanism of increasing vascular tension. A protein kinase inhibitor, 0.2 mM 1-(5-isoquinolinyl-sulfonyl)-2-methyl piperazine (H-7) inhibited oxygen-mediated constriction of neonatal vessels, but also significantly reduced the contractile response to 60 mM KCl. In conclusion, resting aortic tension is in part determined by oxygen-mediated control of the production of endothelium-derived nitric oxide and one or more opposing endothelium-independent mechanisms of constriction.


Pharmacokinetics of high-dose methylprednisolone in children. Disposition of methylprednisolone was characterized in 11 children receiving the high-dose therapy (26.0 mg/kg on average). After intravenous infusion, methylprednisolone hemisuccinate was rapidly converted to methylprednisolone with a half-life of about 20 min. Methylprednisolone in serum, eliminated monoexponentially in 8 patients and biexponentially in the remaining three, had the mean residence time of about 3 h, and a terminal half-life of 2.5 h. The volume of distribution at steady state, and the clearance were 1.3 liters/kg and 0.5 liters/kg/h, respectively. Although these average pharmacokinetic parameters were comparable to those determined in other studies with conventional low doses, the clearance values in our data were characterized by 5-fold interindividual difference, suggesting large variations in exposures to methylprednisolone among children on the high-dose pulse therapy.


[Electrophysiologic parameters of ion transport systems in early developmental stages of fish and amphibia]. It is shown that the membrane potential level, ionic current and membrane conductance depend on the cell cycle stage both in Misgurnus fossilis L. embryos and in Xenopus laevis Daudin embryos by the microelectrode technics. Allowing for the role of the adenylate cyclase system in the membrane potential oscillations and ion conductance of membranes, some series of experiments for analysis of the inhibitor have been carried out.


[Restoration of peptidergic regulation in the kidney by exogenous polypeptide substances of renal origin]. Investigations, performed by high-effective liquid chromatography method have shown changes in the chromatographic spectrum of polypeptides, extracted from the cortex of the kidneys of rats with experimental pathology (autoimmune Haymann's nephritis). Injection of exogenous polypeptides substances extracted from kidney tissues caused normalization of the exogenous polypeptide substances in the kidneys of the experimental animals. A conclusion is made on the regulatory influence of renal exogenous polypeptides in terms of conception of the peptidergic regulation system.


[Lysosomal apparatus of some body tissues in hemorrhage-induced hypoxia ]. The experiments on 40 Wistar male rats with acute circulatory-hemic hypoxia induced by hemorrhage in amount of 15-20% of circulating blood volume were carried out to study the state of lysosomal apparatus of the liver and lung tissues as to changes in activity of acid phosphatase (AP), a marker enzyme of lysosomes. In the case of such a hemorrhage the common activity of AP decreased by 37% in the liver tissue and by 41% in the lung tissue, the free activity increased by 30% and 25%, and bound activity decreased by 84 and 70% in homogenates of the corresponding tissues. Under these conditions the activity of the above lysosomal enzyme in blood plasma became five times as higher as control. A conclusion is made concerning the circulatory-hemic hypoxia influence on the lysosomal membrane's structures of organ's tissues cells (as one can judge by the example of liver and lungs), which is observed in an increase of permeability of lysosome membrane and causes a sharp increase of AP enzymia in blood plasma.


[Interaction of the inotropic effect of norepinephrine and acetylcholine on the guinea pig's myocardium]. The experiments on guinea pig myocardium slices have been carried out to study the interaction of inotropic effects of different doses of norepinephrine (NE, from 10(-7) to 10(-5) mol/l) and acetylcholine (AC, from 10(-8) to 10(-6) mol/l). With an increase of NE concentration the negative influence of AC on the inotropic action is replaced by positive one. It is shown that there are optimal concentrations of NE and AC to exert a negative influence of AC on adrenergic inotropic effect (in these experiments--3 x 10(-7) mol/l for both influences). A decrease in frequency of contractions of AC on NE effect and positive influence of adrenergic myocardium stimulation on inotropic effect of AC, respectively. Such a type of relation of cardial effects of choline- and adrenergic influences is suggested to be designated by term "negatively accentuative antagonism" unlike the opposite type of choline-adrenergic interaction--"positive accentuative antagonism", under which AC increases inotropic effect of adrenergic myocardium stimulation, while adrenergic positive inotropic influences decrease AC effect.


[Role of the hypothalamic-hypophyseal-adrenocortical system in lysosomal reactions of neutrophilic leukocytes in stress immobilization]. The carried out investigation of the peripheral blood indices in one-month old rabbits against the background of reactivity suppression of the hypothalamic-hypophyseal-adrenocortical system in response to 12-hours immobilization has shown an interrelation between the activity of the hypothalamic-hypophyseal-adrenocortical system and the reaction of the lysosomal apparatus of neutrophilic leukocytes under stress conditions.


[Effect of lipine, a new antihypoxic agent on some respiratory indices in newborn infants after asphyxia]. Lipine, a new antihypoxic drug, has been studied for its effect on respiration and pulmonary gaseous exchange in 47 newborn children, health and with respiratory distress syndrome stresses (SRD) after perinatal asphyxia. It is shown that lipine inhalations cause a considerable increase in duration of respiratory cycle, decrease of respiration frequency, ratio of ispiration di time, to expiration time, increase of alveolar ventilation volume and decrease of respiratory dead space ventilation volume in all lung ventilation volume in newborns with SRD, to a larger degree pronounced in premature children. A conclusion is made on the positive effect of lipine on the state of respiration function and gaseous exchange in lungs in newborn children with symptoms of SRD.


[Experimental study on efficiency of enterosorbents in the combined treatment of iron-deficiency anemia in pregnancy]. Efficiency of anti-anemic drug Ferrum Lack when using it alone or together with enterosorbent Uvesorb has been studied on the model of iron deficiency anemia (IDA) in pregnant rats. It is stated that three-fold blood-letting in total volume of 6 ml carried out prior to pregnancy causes symptoms of IDA. Over a period of the whole pregnancy the concentration of hemoglobin and the concentration of erythrocytes were lower than in intact pregnant rats. Tissue hypoxia characterized by disturbance of terminal microcirculation, capillary tissue diffusion and oxygen utilization was observed in pregnant rats with anemia model. Dysfunctional shifts in the system lipid peroxidation (LPO)-antioxidant protection (AOP) as noncompensated process of free-radical oxidation of lipids were revealed in parallel. A comparative estimation of results from treatment in groups of animals which were given and not given enterosorbent Uvesorb together with anti-anemic drug Ferrum Lack permitted determining the presence of anti-anemic and antihypoxic effects in both groups, though the latter was more pronounced in animals which were given enterosorbent. Various results were revealed relative to changes in the LPO-AOP system. When using drug Ferrum Lack alone, the content of products of LPO-lipid hydroperoxides and malonic dialdehyde increased in blood, whereas in group of animals which were given enterosorbent the number of these products was observed to significantly decrease.


[Early hypoxic contracture of the myocardium in adult and newborn rats]. The effect of 30 min substrate free hypoxia (H) on isometric tension was studied in isolated myocardium (M) of adult (A) and newborn (N) rats. The perfusion with 50% Na+ H solution caused in AM the development of H contracture which was more than 50% higher than control contracture. H perfusion with 0.1 mM Ca2+, 1.0 mM La3+, and 10.0 mM of caffeine provides the discrimination of control and hypoNa+ contractures. It is assumed that early H contracture in AM is a result of inability of Ca-sequestering system to accumulate intracellular Ca2+ and Ca2+ influxing through the sarcolemma. In myocardium of N rats Na-Ca exchange is proposed as a main source of Ca2+ for H contracture development.


[Role of globus pallidus in mechanisms of antiepileptic caudate- cortical effects]. The experiments on rats have shown that striatal electrostimulation influences inhibiting cortex epileptic activity decrease under conditions of globus pallidus destruction. Besides, it is noted that globus pallidus lesion exerts a pronounced antiepileptic effect on development of the neocortical epileptic activity complexes. Globus pallidus stimulation enhanced the neocortex interictal seizure activity and transformed it to ictal discharges. The results are discussed in terms of the role of pale globe in mechanisms of caudate inhibitory action on neocortex epileptic activity.


[Characteristics of sleep structure in patients with sleep apnea]. The course of different sleep phases has been studied in group of patients. A decrease in duration of deep sleep phase and increase in the number of awakenings are found in them.


[Age dependent typology of central nervous system activity in school children]. The age peculiarities of higher nervous activity (HNA) have been studied in 777 1st-10th form pupils at school of general education. Heterogeneity and nonuniformity of changes in indices are peculiar to age dynamics of HNA. The most intensive changes are stated in junior and senior forms.


[Functional asymmetry of the brain and effectiveness of sensorimotor function of oral cavity organs]. It has been established that in healthy persons functional brain asymmetry positively influences the effective performance of sensomotor function of oral cavity organs. Individual brain asymmetry is of considerable importance, the higher it is, the quicker the final results of sensomotor function are achieved. The character of brain asymmetry (right hand or left hand) does not practically influence the performance of sensomotor functions.


[Systemic and cerebral hemodynamics and mental activity in marked neuro-emotional stress]. Changes in efficiency of mental activity and general and brain hemodynamics in students of physico-mathematical faculty when they solve problems on math analysis for 3 hours under conditions of pronounced neuro-emotional tension (NET) during examination have been experimentally studied. The results obtained from these studies are considered. It is shown that relation of higher nervous activity and general and brain hemodynamics is determined by efficiency of the activity, its energy provision (intensity), the level of NET and the rate of automated psychic reactions. A conclusion is made that efficiency of the activity is a basic system-forming factor in a relation arising between higher nervous activity, on the one hand, and general and brain hemodynamics, on the other hand. The higher is the efficiency, the lower are power requirements and the level of NET and the higher is the rate of automated psychic reactions: mental working capacity.


[Effect of the mineral water naftusy on some indices of water-electrolyte metabolism in man]. The clinic-physiological examination of patients with urolithiasis has revealed that single and course taking of medicinal water Naftusya induces shifts of water-electrolyte exchange in the organism, their expressivity and direction are determined, as a rule, by the initial value of indices. As a whole, the effect of water Naftusya can be characterized as "equilibratory" one effecting by the "law of the initial value".


[Role of the ventromedial nucleus of the rats thalamus in food-procuring movements]. The characteristics of ballistic food-procuring movements were studied in albino rats. After electrolytic destruction of ventromedial nucleus of thalamus (VM) of contralaterally preferred extremity the number of attempts and frequency of movements were determined to increase with a decrease of their duration. The restoration of parametres of movements took place during a week. A phase structure of movements also undergoes some modifications: in the case of invariance of initial ballistic components, conditioned by strict links of programme one-side switching off of VM tells on the following components, subject to correction. Re-teaching, requiring the modification of motor programme caused considerable difficulties in rats with switched off VM. The obtained results illustrate the significance of rats' VM in the formation and realization of motor programmes.


hu-li tai shao, a gene required for ring canal formation during Drosophila oogenesis, encodes a homolog of adducin. Drosophila females bearing mutations in a previously undescribed gene, hu-li tai shao [(hts) too little nursing], produced egg chambers that contained fewer than the normal 15 nurse cells and that usually lacked an oocyte. The cytoplasmic bridges (ring canals) interconnecting nurse cells and the oocyte appeared abnormal, and lacked associated actin rings. The hts locus was found to encode a homolog of the mammalian membrane skeletal protein adducin. During oogenesis, hts mRNA became localized at the anterior of the oocyte and was subsequently expressed in a variety of embryonic tissues. These studies suggested that Drosophila adducin is needed to assemble actin at specialized regions of cell-cell contact in developing egg chambers and may also function at other times during the Drosophila life cycle.


[Effect of hypoosmotic stimulation of the gastrointestinal mucosa on the activity of NA+, K+-atpase of epithelial cells in the small intestine and kidney in rats]. The experiments on Wistar rats have shown that intragestral injection with mannitol hypotonic solution (20 mmol/l) causes the significant activation of Na+, K(+)-ATPase of duodenum and distal intestine epithelial cells, kidney cortex cells, but does not affect the brain cortex of Na+, K(+)-ATPase activity. Simultaneously the activator of enzyme (AE) enters blood serum of rats, its activity is revealed by blood serum addition to homogenates of tissues of control rats. It is assumed that AE is produced in duodenal and intestinal mucosa released to blood after stimulation of mucosal surface by hypotonic solutions and included into the osmoregulation processes on the Na+, K(+)-ATPase level.