Vertical transmission of Citrobacter freundii.
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Anti-Bacterial Agents↗
Biomedical subjects
J J Munoz
Publications and source records attributed to J J Munoz.
Intrathoracic gastric volvulus mimicking pyloric stenosis.
A 5-week-old-infant presented to hospital following the acute onset of non-bilious vomiting with clinical and acid-base features suggestive of pyloric stenosis. A chest radiograph obtained because of intercurrent infection unexpectedly revealed a left-sided congenital diaphragmatic hernia. A barium meal demonstrated the presence of an intrathoracic gastric volvulus, requiring urgent surgical management. We discuss the presentation and management of this rare surgical cause of non-bilious vomiting in infancy.
Abdomen, Acute↗
The retained penile prosthesis reservoir: a risk.
Complications associated with penile prostheses include malfunction, infection, and patient dissatisfaction. We present a rare complication of a retained abdominal reservoir eroding into the bladder and causing irritative voiding symptoms several years after the removal of the penile components of a three-piece penile prosthesis.
Aged↗
Effect of preoperative aspirin use on mortality in coronary artery bypass grafting patients.
BACKGROUND: Discontinuing aspirin use in patients before coronary artery bypass grafting (CABG) has focused on bleeding risks. The effect of aspirin use on overall mortality with this procedure has not been studied. METHODS: We performed a case patient-control patient study of the 8,641 consecutive isolated CABG procedures performed between July 1987 and May 1991 in Maine, New Hampshire, and Vermont. Patients included all 368 deaths. Each case patient was paired with approximately two matched survivors (control patients). Aspirin use was defined by identification of ingestion within 7 days before the operation. RESULTS: CABG patients using preoperative aspirin were less likely to experience in-hospital mortality in univariate (odds ratio [OR] = 0.73, 95% confidence interval [0.54, 0.97]) and multivariate [OR = 0.55, (0.31, 0.98)] analysis compared to nonusers. No significant difference was seen in the amount of chest tube drainage, transfusion of blood products, or need for reexploration for hemorrhage between patients who did and did not receive aspirin. CONCLUSIONS: Preoperative aspirin use appears to be associated with a decreased risk of mortality in CABG patients without significant increase in hemorrhage, blood product requirements, or related morbidities.
Aged↗
Upper tract urothelial neoplasms: incidence and survival during the last 2 decades.
PURPOSE: Upper tract urothelial cancer is rare but studies in the 1970s showed that its incidence was increasing. We evaluated national trends of the incidence and survival of upper tract urothelial neoplasms from 1973 to 1996. MATERIAL AND METHODS: We obtained information on upper tract urothelial neoplasms from 1973 to 1996 from the National Cancer Institute Surveillance, Epidemiology and End Results program. To provide a time comparison we evaluated upper tract urothelial cancer from 1973 to 1984 and 1985 to 1996. We also calculated overall disease specific survival stratified by cancer stage, patient race and gender for the study period overall. RESULTS: A total of 9,072 cases of upper tract urothelial cancer were identified in the Surveillance, Epidemiology and End Results program from 1973 to 1996, including 5,379 of the renal pelvis and 3,678 of the ureter. Comparing age adjusted annual incidence rates revealed an increase in ureteral neoplasms from 0.69 to 0.73/100,000 person-years but no change in the incidence of renal pelvic tumors, while the rate of in situ neoplasms increased from 7. 2% to 23.1%. Overall disease specific 5-year survival was significantly different in regard to tumor stage (95.1% in situ, 88. 9% localized, 62.6% regional and 16.5% distant lesions). Disease specific annual mortality was greater in black than in white individuals and in women than in men (7.4% versus 4.9% and 6.1% versus 4.4%, respectively). CONCLUSIONS: There appears to have been a slight increase in the national incidence of ureteral tumors in the last 23 years. Fortunately we also detected a slight improvement in the overall disease specific survival of patients with upper tract neoplasms.
Aged↗
Trends in rates of reexploration for hemorrhage after coronary artery bypass surgery. Northern New England Cardiovascular Disease Study Group.
BACKGROUND: While mortality rates associated with coronary artery bypass grafting (CABG) have been declining, it is unknown whether similar improvements in the rates of morbidity have been occurring. This study examines trends in reexploration rates for hemorrhage, one of the serious complications of CABG surgery. It also explores changes in patient characteristics and several surgeon practice patterns potentially related to bleeding risks that may explain variations in these rates. METHODS: We performed a regional observational study of all of the 12,555 consecutive patients undergoing isolated CABG surgery in northern New England between 1992 and 1997. The rates of reexploration and patient characteristics were examined between two time intervals: period I (January 1, 1992 to June 1, 1994) and period II (June 1, 1995 to March 31, 1997). All of the region's 23 practicing surgeons responsible for these patients were surveyed to assess changes in practice patterns potentially related to bleeding risks. RESULTS: The adjusted rates of reexploration for bleeding declined 46% between periods I and II (3.6% versus 2.0%, p < 0.001). All of the five cardiac centers in northern New England showed similar trends with adjusted risk reductions ranging from 32% to 48% between the two time periods. This decline occurred despite the patients in period II having higher percentages of risk factors for reexploration for bleeding compared to patients in period I. From the surgeon survey, the number of surgeons using antifibrinolytics markedly increased from period I to period II. More surgeons were also using preoperative aspirin and heparin up until the time of surgery in period II. CONCLUSIONS: Similar to the rates of mortality, the rates of reexploration for bleeding following CABG surgery are substantially declining. This decrease in the reexploration rates occurred despite higher patient risks.
Aged↗
Reexploration for hemorrhage following coronary artery bypass grafting: incidence and risk factors. Northern New England Cardiovascular Disease Study Group.
OBJECTIVE: To assess mortality and risk factors associated with reexploration for hemorrhage in patients undergoing coronary artery bypass grafting (CABG). DESIGN: Regional cohort study. Patient characteristics, treatment variables, and outcome measures were collected prospectively. SETTING: All 5 centers performing cardiac surgery in Maine, New Hampshire, and Vermont. PATIENTS: A consecutive cohort of 8586 patients undergoing isolated CABG between 1992 and 1995. MAIN OUTCOME MEASURES: Postoperative hemorrhage leading to reexploration, in-hospital mortality, and length of stay. RESULTS: A total of 305 patients (3.6%) underwent reexploration for bleeding. In these patients, in-hospital mortality was nearly 3 times higher (9.5% vs 3.3% for patients not requiring reoperation, P<.001) and average length of stay from surgery to discharge was significantly longer (14.5 days vs 8.6 days, P<.001). High rates of reexploration for hemorrhage were observed in patients with prolonged (> 150 minutes) cardiopulmonary bypass (39 [11.1%] of 351) and in those requiring an intra-aortic balloon pump intraoperatively (12 [8%] of 139). In multivariate analysis, older age, smaller body surface area, prolonged cardiopulmonary bypass, and number of distal anastomoses were associated with increased bleeding risks. The use of thrombolytic therapy within 48 hours of surgery was weakly but not significantly associated with the need for reexploration. Factors not significantly associated with reexploration included patient sex, preoperative ejection fraction, surgical priority, history of liver disease, myocardial infarction, prior CABG, renal failure, and diabetes mellitus. CONCLUSIONS: Hemorrhage requiring reexploration after CABG is associated with markedly increased mortality and length of stay. Patients predicted to have increased risks of bleeding may benefit from prophylactic use of aprotinin, aminocaproic acid, or other agents shown to reduce hemorrhage.
Aged↗
Action of pertussigen (pertussis toxin) on serum IgE and on Fc epsilon receptors on lymphocytes.
Pertussigen (pertussis toxin (PT] is one of the most effective stimulators of IgE production in mice and rats. Employing flow microfluorimetric analysis (FMF), we showed that PT increases the percentage of blood and spleen lymphocytes with IgE on their surface. The percentage of IgE-bearing cells in the spleen of normal untreated C57Bl/10SCN mice of various ages varied from 2.2 to 12.2%, with an average value of 6.1 +/- 5.4%. In mice treated with 400 ng of PT and 1 mg of chicken egg albumin (EA), the percentage of these cells increased, 14 days after immunization, to an average value of 31.1 +/- 2.2%. Immunization of mice with PT alone increase the percentage of IgE-bearing cells only slightly (13.1 +/- 2.2% of the splenic lymphocytes) while injection of 1 mg of EA alone did not have any detectable action. As little as 6 ng of PT, when given simultaneously with 1 mg of EA, increased the percentage of IgE-bearing lymphocytes. A booster dose of 10 micrograms of EA given on Day 14 induced a further increase in the percentage of these cells even when as little as 0.039 ng of PT had been given at the time of initial immunization. PT was effective when given 4 days before or 5 days after EA. EA was effective when given 4 days before or 4 days after PT, but not 8 days after. The increase in IgE-bearing cells was mainly due to cytophilic binding of IgE to receptors for the epsilon chain of IgE (Fc epsilon) on the surface of lymphocytes rather than to a greater number of IgE-producing cells. This was shown by removing the IgE from Fc epsilon receptors by acid treatment which reduced the percentage of IgE-bearing cells to nearly normal values. The antibodies of IgE class with specificity to EA were increased dramatically, while antibodies with specificity to PT were not detected.
Animals↗
Is hexachlorobenzene human overload related to porphyria cutanea tarda? A speculative hypothesis.
After the epidemic outbreak of Porphyria Turcica from 1955 to 1961, the porphyrinogenic effect of hexachlorobenzene (HCB) on humans and animals has been fully confirmed. HCB is an environmental contaminant originated from its use as fungicide or obtained as a by product from industrial residues. Measurement of HCB levels in adipose tissue and maternal milk is a useful tool for monitoring its body stores which are clearly higher in Spain than in other European or American countries. At least in the Spanish area of Catalunya, the HCB fat tissue concentration decreased from more than 5 ppm in 1981-1982 to less than 3 ppm in 1986-1987. Porphyria cutanea tarda is a relatively frequent disease in Spain. More than 700 cases were observed in Madrid from 1964 to 1988. Before 1970, less than 10 cases were annually detected, a figure that rose up to 60-70 annual cases from 1977 to 1982 and decreased to less than 25 annual cases from 1985 to 1988. Based on all these previous data, a speculation is tempting: the high and variable incidence of porphyria cutanea tarda in Spain may be related to environmental contamination with HCB.
Body Burden↗
Expression of pertussis toxin correlates with pathogenesis in Bordetella species.
Pertussis toxin is a principal determinant of virulence produced by Bordetella pertussis in the disease whooping cough and is the primary toxinogenic component of the pertussis vaccine. This toxin is not produced by the closely related species Bordetella parapertussis. Toxinogenic strains of B. parapertussis were constructed by the conjugative introduction of cloned pertussis toxin genes. These and analogous toxinogenic and nontoxinogenic strains of B. pertussis were assayed for their toxicity and reactogenic activities. Expression of active toxin by either Bordetella sp. correlated with the induction of leukocytosis, anaphylaxis, and histamine sensitivity.
Anaphylaxis↗
Role of pertussigen (pertussis toxin) on the mouse protective activity of vaccines made from Bordetella species.
Pertussigen [pertussis toxin (Ptx)] from Bordetella pertussis, when detoxified, induces protection in mice to intracerebral challenge (ic) with virulent B. pertussis. In its native form, minute nonprotective doses promote the development of immunity induced by other antigens of B. pertussis. As little as 4 ng of Ptx, given with a nonprotective dose of 8 X 10(7) killed cells of the phase III Sakairi strain, promoted detectable protection to ic challenge. Native Ptx in doses of 0.4 to 400 ng did not protect mice, and vaccines made from strains not producing Ptx induced only weak protection. The marked enhancing action of Ptx was also observed with 5 micrograms of purified filamentous hemagglutinin and with vaccines made from other species of the Bordetella genus, such as B. parapertussis and B. bronchiseptica, but it was not observed with B. pertussis endotoxin. In addition, Ptx was still effective when given as late as 7 days after the vaccine. Antibodies to surface antigens of the challenge strain were demonstrated in sera of mice immunized with vaccines prepared with the different Bordetella species tested, but antibodies to Ptx were detected only in the sera of mice immunized with the wild-type B. pertussis strains. Glutaraldehyde detoxified Ptx does not have this action. Pretreatment of normal mice with Ptx, also enhanced the protective action of a mouse antiserum to a wild-type strain of B. pertussis. These observations show that antigens other than Ptx are responsible for the protection, and that Ptx acts non-specifically to enhance the mouse protective action of those antigens.
Adjuvants, Immunologic↗
ADP-ribosyltransferase activity of pertussis toxin and immunomodulation by Bordetella pertussis.
Pertussis toxin is produced by the causative agent of whooping cough, Bordetella pertussis, and is an adenosine diphosphate (ADP)-ribosyltransferase capable of covalently modifying and thereby inactivating many eukaryotic G proteins involved in cellular metabolism. The toxin is a principal determinant of virulence in whooping cough and is a primary candidate for an acellular pertussis vaccine, yet it is unclear whether the ADP-ribosyltransferase activity is required for both pathogenic and immunoprotective activities. A B. pertussis strain that produced an assembled pertussis holotoxin with only 1 percent of the ADP-ribosyltransferase activity of the native toxin was constructed and was found to be deficient in pathogenic activities associated with B. pertussis including induction of leukocytosis, potentiation of anaphylaxis, and stimulation of histamine sensitivity. Moreover, this mutant strain failed to function as an adjuvant and was less effective in protecting mice from intracerebral challenge infection. These data suggest that the ADP-ribosyltransferase activity is necessary for both pathogenicity and optimum immunoprotection. These findings bear directly on the design of a nontoxic pertussis vaccine.
ADP Ribose Transferases↗
Heterogeneity of familial porphyria cutanea tarda.
The concentration of immunoreactive uroporphyrinogen decarboxylase has been measured in erythrocytes from 17 patients with porphyria cutanea tarda (PCT) from 10 families, from 74 of their relatives, and from 47 control subjects. The 10 families were divided into two groups according to their erythrocyte enzyme concentrations. Group A contained four families in which at least two subjects had overt PCT. All members of these families, including seven patients with overt PCT, had normal erythrocyte uroporphyrinogen decarboxylase concentrations and activities. Apart from their family history, patients in group A were clinically and biochemically indistinguishable from cases of type I (sporadic) PCT. Group B contained six families with the only previously described form of familial PCT (type II PCT) in which decreased erythrocyte uroporphyrinogen decarboxylase segregates as an autosomal dominant trait. These findings show that familial PCT is heterogeneous and suggest that inheritance contributes to the pathogenesis of at least some cases of type I PCT.
Adult↗
Anaphylaxis or so-called encephalopathy in mice sensitized to an antigen with the aid of pertussigen (pertussis toxin).
Sensitization of mice with 1 mg of bovine serum albumin (BSA) or chicken egg albumin (EA) given intraperitoneally and 300 to 400 ng of pertussigen (pertussis toxin [Ptx]) given intravenously (i.v.) induced a high degree of anaphylactic sensitivity when the mice were challenged i.v. with 1 mg of antigen 14 days later. Regardless of H-2 haplotype, all of the strains tested (CFW, BALB/cJ, DBA/2J, and C3H.SW/SnJ) were susceptible to anaphylaxis. Sensitization of mice by a multiple-dose procedure that has been reported to induce fatal encephalopathy in mice (L. Steinman, A. Weiss, N. Adelman, M. Lim, R. Zuniga, J. Oehlert, E. Hewlett, and S. Falkow, Proc. Natl. Acad. Sci. USA 82, 8733-8736, 1982) (1 mg of BSA on day -1, 100 to 400 ng of Ptx on day zero 1 mg of BSA on day +1, 100 to 400 ng of Ptx on day +2, and 1 mg of BSA on day +6) induced shock in BALB/cJ, DBA/2J, and C3H.SW/SnJ mice, but not in CFW mice. When EA was used instead of BSA, CFW, BALB/cJ, and C3H.SW/SnJ mice did not develop fatal shock, whereas DBA/2J mice did. When dose 3 of antigen (BSA or EA) was postponed to day +21, all mouse strains sensitized by the multiple-dose procedure were found to be susceptible to shock. The fatal shock induced by this procedure, as well as that induced by giving a single sensitizing dose of antigen and Ptx, could be prevented by one to three 1-ml doses of saline given i.v. at the time signs of severe shock appeared. Although only one dose of saline was often sufficient to save the mice, two or three doses were usually needed. Microscopic changes were not found in midsagittal sections of the brains of mice sensitized by either procedure. This was true of mice that died from shock or were saved from shock by injections of saline. From these results, we concluded that the proposed model for encephalopathy induced in mice by Ptx and BSA demonstrates only the well-known anaphylactogenic effect of Ptx or pertussis vaccine. Since there are many other more sensitive methods to detect Ptx, induction of anaphylaxis is not of much value for detection or quantitation of Ptx in pertussis vaccine.
Anaphylaxis↗
Detection of subunits of pertussis toxin in Tn5-induced Bordetella mutants deficient in toxin biological activity.
Monoclonal antibodies with specificity for pertussis toxin subunits S1, S2, and S4 were used in Western blots to show that the subunits were not secreted into culture medium from Tn5 insertion mutants. The mutants are deficient in toxin biological activities due to an insertion in the S3 subunit structural gene. The Western blots demonstrated that each of the respective subunits was exported in a wild-type strain. Anti-S1 and anti-S2 monoclonal antibodies were capable of detecting subunits in solubilized whole-cell material from a wild-type strain and from the Tn5 mutants lacking only in biologically active toxin (Tox-). Another Tn5 insertion mutant, lacking all known B. pertussis virulence factors (Vir-), did not produce any of the subunits either in whole cellular extracts or in culture supernatants. The data demonstrate that Tn5 Tox- insertion mutants, though defective in toxin activity, synthesize some toxin subunits. The presence of the S3 subunit is most likely a necessity for transport of the toxin from cells. Alternatively, a nonstructural gene coding for a protein involved in transport of the toxin across the membrane may be affected by the Tn5 mutation.
Antibodies, Monoclonal↗
Molecular cloning of pertussis toxin genes.
We have cloned a 4.5 kb EcoRI/BamHI DNA fragment from Bordetella pertussis which contains at least two genes responsible for expression of pertussis toxin. The S4 subunit of the toxin was isolated by high pressure liquid chromatography and the NH2-terminal amino acid sequence determined. Using a mixed synthetic oligonucleotide probe designed by reverse translation of a portion of the protein sequence, a cloned DNA fragment was identified which contains the coding information for at least the S4 structural subunit of the toxin. Sequence analyses indicate that the mature protein is derived by proteolytic cleavage of a precursor molecule. Southern blot analyses of Tn5-induced B. pertussis toxin-deficient mutants show that the Tn5 DNA is inserted 1.3 kb downstream from the S4 subunit gene. This second gene could code for another subunit required for assembly of the mature toxin or a non-structural transport protein, possibly in the same polycistronic operon. The molecular cloning of pertussis toxin genes provides the basis for development of a safer recombinant "new generation" vaccine for whooping cough.
Amino Acid Sequence↗
Pertussis toxin as a probe of neutrophil activation.
In reviewing our own and other work, it is clear that pertussis toxin treatment of neutrophils causes a time- and concentration-dependent inhibition of granule enzyme secretion induced by formylmethionylleucylphenylalanine (fMet-Leu-Phe), C5a, leukotriene (LT) B4 and platelet-activating factor (PAF). Chemotaxis, O2- generation, aggregation, and arachidonic acid production induced by fMet-Leu-Phe are also inhibited by pertussis toxin. Granule enzyme release caused by A23187 or phorbol 12-myristate 13-acetate is not inhibited. The inhibition of neutrophil function correlates closely with the NAD-ribosylation of a 41,000-dalton protein in the neutrophil plasma membrane, presumably the GTP-binding regulatory protein Ni. Pertussis toxin treatment prevents or obtunds the increased influx of Ca2+ induced by fMet-Leu-phe and LTB4, but not that caused by stimulation of neutrophils with PAF. Pertussis toxin prevents the receptor-induced breakdown of polyphosphoinositides in intact neutrophils and isolated membrane and prevents or decreases the production of inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol. The hypothesis advanced by us and others is that pertussis toxin interacts with a GTP-binding regulatory protein identical or similar to Ni, which couples receptor-chemotactic factor interaction to phospholipase C activation. Inhibition of the activation prevents the production of IP3 and the resulting release of Ca2+ from intracellular stores and of 1,2-diacylglycerol and thus, the activation of protein kinase C. The lack of these two mediators is the immediate cause of the depression of neutrophil activation resulting from pertussis toxin. Some of the limitations and uncertainties of our present knowledge with respect to this hypothesis are discussed.
Animals↗
Immunoreactive uroporphyrinogen decarboxylase in the liver in porphyria cutanea tarda.
Immunoreactive and catalytic uroporphyrinogen decarboxylase were measured in liver from 15 patients with sporadic porphyria cutanea tarda (PCT) and 4 patients with familial PCT at different stages of the disorder. In sporadic PCT, catalytic activity was lowest and immunoreactive enzyme concentration was highest when active skin lesions were present; this pattern was also seen in the one familial PCT patient who had skin lesions. During remission, the ratio of catalytic activity to immunoreactive enzyme concentration returned towards normal. Immunoreactive enzyme was increased by comparison with controls in sporadic patients with skin lesions; in familial PCT mean concentration was 59% of the overall sporadic value. In 4 sporadic patients in prolonged (4-8 years) remission (following venesection) enzyme activity and immunoreactive enzyme concentrations were normal. It is suggested that clinically overt PCT is precipitated by an iron-dependent process which inactivates the active centres of uroporphyrinogen decarboxylase molecules in the liver. Treatment by venesection eventually leads to complete reversal of this biochemical defect in at least some patients with sporadic PCT. The findings are consistent with the view that sporadic PCT is an acquired disorder.
Adult↗