Toxins, test tubes, and tampons.
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Humans↗
Biomedical subjects
J K Todd
Publications and source records attributed to J K Todd.
Preterm birth and infection: pathogenic possibilities.
Preterm delivery remains the preeminent problem in perinatal care worldwide. Recent data suggest that cervical/vaginal microflora, and/or the inflammatory responses they engender, produce factors which can cause or predispose to preterm labor and rupture of membranes. Microorganisms mediating such processes may not be "recognized pathogens" and are often considered normal flora. These microorganisms may act singly, additively, or synergistically with host factors released during an induced inflammatory response. Both qualitative and quantitative aspects of cervical/vaginal microflora are likely important. Multiple cervical/vaginal microorganisms produce IgA proteases, neuraminidases, and mucinases which may facilitate passage of these and other agents past cervical barriers and into the lower uterine segment. Multiple microflora also produce phospholipases A2 and C, each of which can locally augment production of eicosanoids within the uterus which are important in cervical ripening and labor. Similar microflora produce various proteases, including collagenase, which can focally weaken the amniochorion and predispose to premature rupture of membranes and cervical ripening. Intrauterine microorganisms induce inflammatory reaction and may engender local release of similar proteases, phospholipases, oxygen radicals, as well as platelet activating factor (PAF), and lymphokines which can also initiate or further potentiate labor-inducing mechanisms. Roles for uteroplacental or systemic release of tumor necrosis factor (TNF) and various interferons are beginning to be understood. Recognition of microbe-induced pathogenesis of some cases of preterm birth offers the hope of specific treatment and prophylaxis. In recent studies, administration of erythromycin and tocolytic agents was associated with an improved outcome in selected women. "Just why so many gravidas go into labor prematurely and hence give birth to infants who often are unable to cope with extrauterine conditions is one of the great unsolved problems of obstetrics."
Female↗
Toxic shock syndrome.
In the past 10 years, we have learned much about TSS and S. aureus and its toxins. A number of important biologic principles have been reemphasized in this first decade of TSS research: S. aureus is a very complex organism, one not likely to yield quick answers; in vitro observations must always be confirmed in the patient; animal models may not always be reliable replicates of human disease; and epidemiologic associations cannot be equated with causation. Toxic shock is an intricate phenomenon with many interesting scientific facets. Unraveling its mysteries will undoubtedly teach us more about the complex interaction of patients and microorganisms.
Female↗
Test selection for the pediatric office laboratory.
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Child↗
The sore throat. Pharyngitis and epiglottitis.
Sore throat can be caused by different microorganisms and diseases. Most cases of acute pharyngitis are caused by group A streptococcus or viruses; however, uncommon organisms may be suggested by other clinical information or the persistence of symptoms. A thorough history and physical examination are essential for the appropriate selection of diagnostic tests for sore throat. Routine testing for the uncomplicated case should consist of a pharyngeal culture in most patients, with rapid streptococcal antigen testing only for the more severe cases. Those with positive streptococcal tests should be treated to prevent rheumatic fever and mitigate symptoms in severe cases. Sore throat caused by viruses usually resolves spontaneously. Cases that persist should be thoroughly re-evaluated, with alternative causes being considered. Acute epiglottitis is a medical emergency and requires treatment with appropriate antibiotics for Hemophilus influenzae type b and intubation.
Adolescent↗
Toxic shock syndrome, Staphylococcus aureus, and influenza.
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Humans↗
Influence of focal growth conditions on the pathogenesis of toxic shock syndrome.
Patients with toxic shock syndrome (TSS) had sequestered focal sites colonized or infected with Staphylococcus aureus significantly more frequently than did patients with scalded skin syndrome. Growth conditions within the infected foci of four patients with TSS included nearly physiological levels of pH, pO2, pCO2, protein, calcium, and magnesium. Two strains of S. aureus had typical TSS phenotypes (production of TSS toxin-1 [TSST-1] and protease), which were optimally expressed in vitro under conditions similar to those documented in vivo (6% CO2, pH 7.0, aerobic, high levels of protein). Altering any one of these growth factors significantly decreased production of TSST-1. In protein-containing media, depletion of divalent cations had a less-profound effect on organism growth and TSST-1 production. The unique in vivo environment in patients with non-menstrual TSS is similar to conditions associated with tampon use during menstruation. Growth conditions may play an important role in the expression of S. aureus phenotype and the pathogenesis of TSS.
Bacterial Toxins↗
Identification of streptococcal pharyngitis in the office laboratory: reassessment of new technology.
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Antigens, Bacterial↗
Comparison of three latex agglutination kits and counterimmunoelectrophoresis for the detection of bacterial antigens in a pediatric population.
Three commercial latex agglutination kits (Bactigen, Wampole Laboratories, Cranbury, NJ; Directigen, Hynson, Westcott & Dunning, Baltimore, MD; Wellcogen, Wellcome Diagnostics, Dartford, England) used for the detection of bacterial polysaccharide antigens (Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis) were compared with counterimmunoelectrophoresis and Gram stain for the identification of systemic bacterial disease in children. Urine and (when available) cerebrospinal fluid specimens were saved for all patients. Positive blood or cerebrospinal fluid culture isolates included 36 with H. influenzae type b, 11 with S. pneumoniae, 3 with N. meningitidis and 6 with other organisms. All latex kits performed similarly for the detection of H. influenzae type b antigen with a sensitivity range of 91 to 100%. The four methods performed poorly for the detection of S. pneumoniae (23 to 50%) and N. meningitidis (0%) antigen. Gram stain of cerebrospinal fluid appeared to be equally sensitive to the antigen detection methods for patients with meningitis. The false positive rates for the latex kits and counterimmunoelectrophoresis ranged from 2.8 to 9.2%, with Wellcogen having the lowest rates. The false negative rates ranged from 6.5% to 12% with Directigen having the lowest rate.
Child↗
Bacterial protease-induced reduction of chorioamniotic membrane strength and elasticity.
We demonstrated that in vitro exposure to bacterial collagenase and collagenase-producing microorganisms significantly reduces measures of strength (bursting load), elasticity, and work to rupture of human amniochorion in a dose-dependent fashion. An attenuated noncollagenase-producing stain did not alter these measures. These findings support previous suggestions that infection within the lower uterine segment adjacent to the cervix may mediate some instances of premature rupture of membranes.
Amnion↗
Detection of group A Streptococcus: comparison of solid and liquid culture media with and without selective antibiotics.
Eight hundred thirty-seven consecutive throat cultures from pediatric patients were cultured comparatively on conventional sheep blood agar and selective agar containing 1.25 micrograms/ml trimethoprim and 23.75 micrograms/ml sulfamethoxazole. In two sequential studies the sheep blood agar-sulfamethoxazole-trimethoprim plates were significantly (P less than 0.01) more sensitive for Group A Streptococcus (Strep-A) detection than conventional sheep blood agar plates or Todd-Hewitt broth using the fluorescent antibody-antigen detection technique. The selective plates inhibited normal upper respiratory flora but not Strep-A. An incubation time of 18 hours was significantly better than one of 4 hours for the detection of Strep-A antigen in cultures incubated in Todd-Hewitt broth alone or Todd-Hewitt-sulfamethoxazole-trimethoprim broth, resulting in a 24% increase in positives. These studies demonstrate that Strep-A detection in throat swab specimens, by either culture or antigen detection, will be influenced by the use of selective antibiotics and incubation time.
Anti-Bacterial Agents↗
Adjunctive erythromycin treatment for idiopathic preterm labor: results of a randomized, double-blinded, placebo-controlled trial.
Pathogenesis and optimal treatment and prevention of preterm labor remain incompletely understood. Entry of cervical/vaginal microorganisms into lower uterine tissues has been implicated in preterm labor and may be amenable to specific therapy. Fifty-eight women with less than 34 completed weeks of gestation and without other obstetric complications, who were receiving intravenous tocolytics because of uterine contractions and who had cervical alteration (less than 5 cm dilated), were enrolled in a prospective randomized, double-blinded evaluation of 7 days of adjunctive therapy with enteric-coated erythromycin base (333 mg three times daily by mouth) versus placebo. Microbiologic examination included cultures for Neisseria gonorrhoeae, Chlamydia trachomatis, and group B streptococcus. Fifty-eight women with singleton pregnancies (29 erythromycin; 29 placebo) completed the protocol. Among women with cervical dilatation greater than or equal to 1 cm at the beginning of treatment, mean time until delivery was 32.5 days with erythromycin and 22.4 days with placebo treatment (p = 0.027). Of the erythromycin-treated women, seven of eight were delivered at greater than or equal to 37 weeks and only three of nine placebo-treated women were delivered at greater than or equal to 37 weeks (p = 0.035). Orally administered enteric-coated erythromycin as adjunctive treatment of pregnant women in labor less than or equal to 34 weeks is well tolerated. Adjunctive erythromycin given to women treated for preterm labor less than or equal to 34 weeks is associated with prolongation of pregnancy and delivery at 37 weeks only in women with cervical dilatation at the beginning of treatment.
Amniotic Fluid↗
Protease production by microorganisms associated with reproductive tract infection.
Factors influencing pathogenicity of various microbes found in the female lower genital tract remain incompletely understood. Protease production by cervico/vaginal microorganisms may alter or inactivate a variety of proteins important in host defense and structural-functional integrity including collagen-containing chorioamniotic membranes and uterine cervix. Host tissues may be made more susceptible to other organisms' virulence factors by protease-producing members of genital tract local flora. Microorganisms themselves may also be influenced by the presence of other microbial protease. Nonspecific protease, gelatinase, collagenase, and elastase production was examined for in vitro with use of aerobic (30) and anaerobic (25) strains of microorganisms typical of those isolated from the lower genital tract of women with premature rupture of membranes, chorioamnionitis, and puerperal infection. Microorganisms including Bacteroides bivius, Bacteroides melaninogenicus, Bacteroides fragilis, Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Proteus species, and Propionibacterium acnes produce various proteases. Protease production by both acknowledged pathogenic and commensal bacteria may contribute to the occurrence of reproductive tract morbidity including premature rupture of membranes and preterm labor.
Agar↗
Microtiter broth dilution method for yeast susceptibility testing with validation by clinical outcome.
There is no ideal laboratory procedure or culture medium in current use for susceptibility testing of pathogenic yeasts. Six candidate growth media (RPMI 1640 with L-glutamine, yeast nitrogen base, Casamino Acids medium, Mueller-Hinton broth, Sabouraud dextrose broth, and minimum essential medium-Eagle salts) were screened by spectrophotometric absorbance for nucleic acid and protein. From these, two media were selected: a chemically defined growth medium (RPMI 1640 with L-glutamine) and a chemically complex medium (Casamino Acids). MICs of four antifungal agents (5-fluorocytosine, miconazole, ketoconazole, and amphotericin B) for 84 clinical isolates of various Candida species were then determined with both media in agar dilution and microtiter broth dilution systems. The resultant MICs were correlated with clinical outcome for those isolates obtained from patients treated with single antifungal agents, and susceptibility cut points were calculated. Derived MIC cut points for susceptibility were validated in a murine model of systemic candidiasis. RPMI 1640 with L-glutamine was found to have the lowest absorbance values for both nucleic acid and protein, while Casamino Acids medium was highest in both categories. We found that RPMI 1640 with L-glutamine was superior to Casamino Acids medium in the yield of MICs which correlated with actual clinical and animal outcome data. While there were no significant differences in MICs when RPMI 1640 medium was used, the microtiter broth dilution technique was superior to agar dilution in efficiency and ease of performance. We conclude that a microtiter broth system containing RPMI 1640 medium with L-glutamine is a simple, precise, and economical technique for susceptibility testing of pathogenic Candida species. We also suggest that the validation of susceptibility cut points with patient and animal outcome data make this microtiter broth system a preferential method for yeast susceptibility testing.
Amphotericin B↗
Toxic shock syndrome. I. Clinical exclusion of other syndromes by strict and screening definitions.
Several clinical definitions of toxic shock syndrome have been proposed and used in extensive epidemiologic and clinical studies. Most of these definitions suggest (but usually do not require) that there be sufficient laboratory studies to exclude other potentially similar syndromes. Simplified definitions which broaden the spectrum of toxic shock syndrome illness have also been proposed but not validated. In this study, clinical findings of consecutive hospitalized patients were compared: nine with toxic shock syndrome (confirmed by a modification of the collaborative strict case definition) and 120 with potentially similar diagnoses (bacteremia with shock, meningococcemia, Staphylococcus aureus bacteremia, scarlet fever, toxic epidermal necrolysis, acute rheumatic fever, leptospirosis, Rocky Mountain spotted fever, rubeola, Kawasaki syndrome, erythema multiforme, and Stevens-Johnson syndrome). None of the 120 controls satisfied the clinical criteria of the modified strict definition of toxic shock syndrome, demonstrating its exclusionary properties even in the absence of additional laboratory data. A "simplified" screening definition was constructed which might be applied early in illness (i.e., at admission) and this definition distinguished all the patients with toxic shock syndrome from all but three (2.5%) of the 117 analyzable patients with other mucocutaneous or potential infectious shock syndromes. Applied prospectively in the state of Colorado passive/active reporting system, the screening definition identified 24 potential toxic shock syndrome cases of which 19 (76%) eventually were confirmed as toxic shock syndrome. Before being adopted and widely used, clinical syndrome definitions should be documented to exclude other potentially overlapping syndromes or should require additional mandatory exclusionary laboratory data.
Adolescent↗
Toxic shock syndrome. II. Estimated occurrence in Colorado as influenced by case ascertainment methods.
Medical records for hospitalized patients between 30 days and 30 years of age at two hospitals, one in each of two Colorado counties, were reviewed for possible cases of toxic shock syndrome conforming to one or both of two clinical case definitions. Patients with toxic shock syndrome were detected in each year from 1970 through 1982. Fifty patients with possible toxic shock syndrome were identified; 14 were males, five were premenarchal females, and the remaining 31 were females of menstrual age of whom 21 (42% overall) were menstruating at the time of illness. The combined annual toxic shock syndrome incidence rate ranged between 0.8/100,000 population less than or equal to 30 years of age (1974) and 9.1/100,000 (1980) with a maximum of 15.8/100,000 (1980) in females between the ages of 10 and 30. Incidence curves for males, females less than or equal to 30 years of age, and females of menstrual age (10-30 years) fluctuated in a statistically (p less than 0.02) nonrandom fashion, each peaking in 1979-1980 and declining in 1981. In a separate statewide voluntary case reporting system, 103 cases of toxic shock syndrome of all ages were reported by health care providers with onset from 1970-1982. A minimum estimate of 26 (26%) of these were not menstrually-associated, occurring in five females prior to menarche, three following menopause, three postpartum, and 15 males. Total cases reached an annual peak in 1980, declined somewhat in 1981, and increased during 1982 to levels comparable to 1980. Less than half (46%) of the strictly defined cases actively ascertained in the retrospective hospitalized population study had been reported voluntarily to the statewide system. Jurisdictions depending primarily on passive toxic shock syndrome case ascertainment techniques, even with periodic active solicitations, may not be reliably detecting the majority of cases, and those cases which are so reported may be limited by physician perception of syndrome spectrum.
Adolescent↗
Staphylococcal toxin syndromes.
Staphylococcus aureus produces many extracellular products often referred to as toxins, some with definite disease-causing potential. The enterotoxins A through E are common causes of acute food poisoning characterized by a short incubation period after ingestion of performed toxin followed by nausea, vomiting, abdominal pain, and diarrhea. The epidermolytic toxins (A, B) are absorbed from a local site of colonization or infection and affect the granular cell layer of skin to cause the painful erythroderma and desquamation of the scalded skin syndrome. Other unique S. aureus strains produce one or more products that appear to be formed at sites of focal infection (wound infection, vagina during menstruation and tampon use) with systemic absorption and generalized effects resulting in toxic shock syndrome.
Bacterial Toxins↗
Corticosteroid therapy for patients with toxic shock syndrome.
A comparative retrospective analysis of 45 patients with toxic shock syndrome (TSS) was designed to evaluate the effect of corticosteroid therapy on outcome. All patients satisfied the collaborative strict case definition for TSS, were hospitalized, had shock or postural hypotension, had a potential focus of Staphylococcus aureus infection, and received appropriate antistaphylococcal antimicrobial therapy. Twenty-five patients received corticosteroid therapy during the acute phase of illness and 20 did not. The groups were comparable for age, sex, weight, year of admission, day of illness hospitalized, minimum systolic and diastolic blood pressure, severity of illness, co-intervention with antimicrobials and antipyretics, and amount of intravenous fluid received. Corticosteroid-treated patients had a significantly reduced severity of illness and duration of fever if treated within two to three days of onset of TSS.
Adolescent↗