Necrotizing pulmonary aspergillosis with oxalosis.
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Biomedical subjects
Publications and source records attributed to K H Wilson.
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Three courses of thiabendazole therapy, including one course given directly into a blind loop of the bowel, failed to eradicate Strongyloides stercoralis from a 55-year-old man who had undergone a Roux-en-Y operation. The patient responded to 1.5 g/day of mebendazole for 14 days, and the infection did not recur. Our case illustrates the difficulty of eliminating S stercoralis from a blind loop of the bowel and indicates that mebendazole therapy used in adequate doses is effective treatment for strongyloidiasis. The lack of toxicity of mebendazole makes it a desirable drug for Strongyloides infestation resistant to thiabendazole therapy.
Cefoxitin-treated hamsters were first colonized with a nontoxigenic strain of Clostridium difficile, and then a toxigenic strain of C. difficile was administered. Toxigenic C. difficile was suppressed to a mean cecal population level of less than 0.2% of that found in control animals given only toxigenic C. difficile after cefoxitin treatment. Colonization with nontoxigenic C. difficile before toxigenic C. difficile was associated with 93% survival, as opposed to 21% survival of the control animals. Simultaneous administration of nontoxigenic and toxigenic C. difficile did not lead to suppression of toxigenic C. difficile and conferred no protection. These results are in keeping with previously established concepts of bacterial interactions on body surfaces and may have therapeutic implications.
Survival of Clostridium difficile in an aerobic environment is possible because of spore formation. When sodium taurocholate is substituted for the egg yolk of a selective medium, cycloserine-cefoxitin-fructose-agar (CCFA), enhanced recovery of C. difficile spores is shown. This selective medium (TCCFA) does not improve recovery of vegetative forms. In this study, dry and saline-moistened swabs, adhesive paddles, and Rodac plates containing CCFA and TCCFA were compared in their ability to recover C. difficile spores from an inoculated surface. Rodac plates grew 20 to 25 times as many spores on TCCFA as on CCFA. Saline-moistened swabs recovered fewer organisms than Rodac plates. Dry swabs and adhesive paddles rarely recovered spores. Prereduction of agar in an anaerobic chamber was not necessary for optimal spore recovery. Optimal growth of vegetative C. difficile required prereduced media. Agar prereduced for 2 h supported the growth of 12 C. difficile isolates as well as agar prereduced for 18 h. Vegetative cells of C. difficile survived for only 15 min in room air. Use of Rodac plates containing TCCFA is preferred for detection of C. difficile spores in the hospital environment.
Taurocholate, desoxycholate, and cholate stimulated germination of Clostridium difficile spores in broth medium and enhanced recovery of C. difficile spores on a selective agar medium. Desoxycholate and some crude taurocholate preparations also inhibited multiplication of vegetative cells. At a concentration of 1.2 X 10(-2) M, sodium cholate inhibited multiplication of vegetative cells, but at concentrations of 1.2 X 10(-3) to 2.4 X 10(-3) M, it stimulated germination without inhibiting cell multiplication. Thus, pure sodium taurocholate and sodium cholate may effectively be incorporated in cefoxitin-cycloserine-fructose agar, whereas some crude preparations of sodium taurocholate decrease recovery on this medium.
Amniotic fluid clearance of 133xenon was measured in pregnant baboons near term during a control period of spontaneous uterine activity and during induction of contractions with oxytocin or PGF2 alpha and inhibition of activity by a beta-adrenergic agent, berotec. There was no significant change in the clearance of 133xenon from the amniotic fluid during moderate uterine activity induced by oxytocin or PGF2 alpha. The clearance rate decreased five-fold during infusion of berotec, compared with the control infusion periods, simultaneous with a decrease in uterine activity. When the berotec infusion was discontinued, the clearance of 133xenon immediately returned to the previous level, while the return of uterine activity was more gradual.
Vaginal administration of prostaglandin analogues resulted in cervical changes that facilitated dilatation and evacuation in 80 patients in the late first trimester and the second trimester of pregnancy. When 0.5 mg and 1.0 mg of 15(S)-15-methyl-prostaglandin F2 alpha (15-ME-PGF2 alpha) was compared to 30 and 60 mg of 9-deoxo-16,16-dimethyl-9 methylene prostaglandin E2 (PGE2 analogue), the PGE2 analogue appeared to have more cervical ripening effect than did the 15-ME-PGF2 alpha. Overall, the 30 mg PGE2 vaginal suppository seemed to offer the most optimal combination of effectiveness, sufficient cervical dilatation, and minimal side effects. With the prostaglandins, maximal cervical effect was observed at 4 to 5 hours; this rapid effectiveness allows administration of the prostaglandin to accommodate a 1-day stay for surgical evacuation. The preoperative cervical priming results with the prostaglandins were compared to those obtained with the use of laminaria tents. Although the number of patients who needed further dilatation at the time of operation was less with the laminaria, the incidence of complications and the time for adequate dilatation were higher in that group.
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Isolation of Clostridium difficile from fecal specimens has been facilitated by the development of a selective and differential medium, cefoxitin-cycloserinefructose agar (CCFA). We substituted 0.1% sodium taurocholate for the 2.5% egg yolk in CCFA and compared the growth of 15 isolates of C. difficile on the resulting medium with growth on conventional CCFA. The taurocholate-containing medium (TCCFA) quantitatively recovered vegetative forms of C. difficile in the same numbers as CCFA medium. Recovery of spores was a mean 1.7 log(10) higher on TCCFA than on CCFA. Thirty-six of 60 patient stool specimens growing C. difficile gave a heavier growth on TCCFA than on CCFA, and 9 failed to yield C. difficile on CCFA. TCCFA detected spores of 75 colony-forming units per ml from artificially inoculated fecal specimens when conventional stool culturing techniques were used. Fluorescence of colonies of C. difficile was more intense on TCCFA than on CCFA. TCCFA was simpler to prepare and, overall, was more sensitive than CCFA.
We evaluated a direct fluorescent-antibody test to detect Clostridium difficile, the most frequent cause of antibiotic-associated colitis. C. difficile organisms were injected into the ear veins of New Zealand White rabbits to induce antibodies, and the globulin fractions of their sera were conjugated to fluorescein isothiocyanate. The resulting conjugate strongly stained all 40 isolates of C. difficile tested. It also stained isolates of C. sordellii, C. bifermentans, C. chauvoei, and C. sporogenes, but not 20 other clostridial isolates or 10 isolates from other species. Results of testing fecal smears with the direct fluorescent-antibody method were compared with results of testing stools for C. difficile toxin and of culturing for C. difficile on a selective medium. A total of 158 fecal specimens from patients with antibiotic-associated diarrhea were tested. In these patients, the fluorescent-antibody test agreed with culture and toxin testing in 93% of the specimens. However, in normal adults, 62% of the fecal specimens from which C. difficile could not be cultured were positive by the fluorescent-antibody test. Absorption of the conjugate with C. sordellii led to a loss of reactivity to other clostridia as well as to 18 of 20 isolates of C. difficile.
Fetal monitoring equipment that provided accurate external measurement of the interval between each fetal heartbeat permitted the evaluation of beat-to-beat fetal heart rate (FHR) variability as part of routine nonstress testing. Nonstress tests (NSTs) were performed on 350 high-risk patients over a 12-month period. The beat-to-beat FHR variability and the reactivity of the last NST within 7 days of labor were analyzed in relation to the appearance of fetal distress during labor as indicated by late decelerations. Beat-to-beat FHR variability combined with nonstress testing was more predictive of subsequent fetal distress than nonstress testing alone. In all instances, complete loss of beat-to-beat FHR was followed by fetal distress during labor. Fetal distress was present in only 39% of labors following nonreactive NSTs. The inclusion of beat-to-beat FHR variability in nonstress testing can significantly aid in the detection of fetal compromise.
Eight commonly used cephalosporins were evaluated in the hamster colitis mode. They were all found to cause hemorrhagic cecitis and death within 10 days of being given as subcutaneous or oral challenges. Necropsy findings were indistinguishable from clindamycin-induced cecitis. Bacteria-free cecal filtrate obtained from hamsters dying of cephalosporin-induced cecitis contained toxin similar or identical to hat produced by Clostridium difficile isolated from the cecum of a hamster. Daily oral administration of poorly absorbed cephalosporins protected hamsters from clindamycin-induced cecitis and death as long as the cephalosporins were continued. The absorbable cephalosporins were ineffective in protecting hamsters from clindamycin-induced cecitis. This difference probably relates to the lower concentrations of absorbable cephalosporins maintained in the ceca of the hamsters. The possible correlation of these findings to human cases of cephalosporin-induced pseudomembranous colitis is discussed.
Administration of normal cecal homogenates decreased numbers of viable Clostridium difficile and prevented cecitis in antibiotic-challenged hamsters. Cecal anaerobes appeared to suppress C. difficile.
The 15-methyl analog of prostaglandin F2 alpha (15-ME-PGF2 alpha), administered in a 3-mg dose via a single vaginal suppository and supplemented at 24 hours by intramuscular injection(s) of 250 micrograms, successfully induced abortion in 80 of 81 patients in the midtrimester of pregnancy. The mean abortion time was 19.6 hours. Two thirds of the patients aborted after treatment with the suppository alone in a mean time of 14.6 hours; the remaining 27 patients required intramuscular injections of 15-ME-PGF2 alpha to effect expulsion of the products of conception. Twenty-six of these 27 patients subsequently aborted in a mean total abortion time of 29.6 hours. Fifty-eight patients aborted within 24 hours of the initial prostaglandin administration, and 78 aborted by 36 hours. Parity and length of gestation did not significantly affect abortion time in this series, although the mean abortion time for parous patients and patients with gestations earlier than 17 weeks tended to be somewhat shorter than that of nulliparous patients and those with more advanced gestations. The placenta was spontaneously expelled in the majority of patients. Abortion was incomplete in 3 patients and required curettage. Uterine activity, as measured via an intraamniotic catheter in 6 patients, developed very gradually with the suppository, peaking at 3 hours after insertion, and was characterized by regular contractions with low intrauterine baseline tonus. The gastrointestinal side effects that occurred in 59% of patients who received the suppository were also most frequently observed at 3 hours after administration. In contrast the gastrointestinal disturbances elicited by intramuscular injections of the analog immediately followed the administration.
Intravenous ethanol infusion significantly reduced oxytocin-induced uterine activity in pregnant patients at term. The dose response to oxytocin was linear when plotted log2 x in all patients studied, and the line was shifted to the right by alcohol, but the slope remained essentially unchanged. These results suggest that alcohol directly inhibits the effect of oxytocin on the myometrium, although the possibility of some central inhibition of oxytocin release cannot be discounted.
The recent Food and Drug Administration's approval of prostaglandin E2 (PGE2) vaginal suppositories provides the clinician with a technique for the immediate management of missed abortion and intrauterine fetal death (IUFD). During a 4-year period at our institution, 78 of 80 patients with gestations ranging from 13 to 42 weeks had pregnancy successfully terminated with PGE2 suppositories with a dose schedule of 20 mg every 2 hours. The mean interval from induction to delivery of the fetus was 8.9 hours. Fifty percent of the patients spontaneously expelled the placenta; active intervention to remove the placenta within 2 hours of delivery of the fetus is recommended to avoid excessive vaginal bleeding. The most frequently encountered side effect was a temperature elevation, which was managed by less frequent administration of the prostaglandin. Gastrointestinal side effects were minimized by premedication with antidiarrheal and antiemetic agents, which also were administered during the induction period when indicated by the patient's symptoms. A concomitant oxytocin infusion was utilized in 38 patients. In gestations of less than 24 weeks the oxytocin was administered via intravenous drip at a rate of 10 U/hour. In the case of a patient with IUFD and a gestation of 24 weeks or more, oxytocin should be administered only with a constant-rate infusion pump starting at a dose schedule of 1 mU/minute with careful titration of the dose against the monitored uterine activity. The availability of the vaginal PGE2 suppositories for missed abortion and IUFD makes it important for the clinician to fully acquaint himself with the drug, its administration, effects, and side effects.
Vaginal administration of 15-ME-PGF2a suppositories successfully terminated pregnancy, as determined by a negative pregnancy test at 14 days following insertion, in 34 of 39 patients with gestations of 34 to 51 days of amenorrhea. Fifteen of 20 patients who received a single long-acting 3-mg suppository had negative pregnancy tests at follow-up, while all 19 patients in whom the 3-mg suppository was preceded by a rapidly acting 1-mg suppository successfully aborted. This two-suppository regimen resulted in a more rapid onset of uterine activity and vaginal bleeding, as well as a slight decrease in gastrointestinal side effects. Peripheral plasma levels of 15-ME-PGF2a as detected by radioimmunoassay were also more consistent with two suppositories. It appeared that the rapidly acting 1-mg suppository provided a "prostaglandin impact" which significantly enhanced the abortifacient effectiveness of the technique. Nine patients on the 2-suppository regimen had the procedure performed on an outpatient basis. Expanded studies are indicated to determine the practicality of this technique as a valid pharmacologic alternative to surgical interruption of very early pregnancy.
Vancomycin protects hamsters from the development of Clostridium difficile colitis after treatment with clindamycin, and vancomycin is useful in treatment of humans with the disease. Relapses have occurred in both hamsters and humans when vancomycin is discontinued. Vancomycin appears to enhance susceptibility to colonization with C. difficile by eliminating competing intestinal organisms. The nature of these organisms is not known, but various tools are now available to aid in identifying them. Cancer chemotherapeutic agents should be added to the list of factors such as surgery and antibiotics that may predispose to emergence of C. difficile. The number of organisms required for colonization of antibiotic-treated hamsters is low and cross-infection seems to play a role in the disease in hamster colonies. The organism can be detected on surfaces in rooms of patients with the disease, and on the hands of personnel caring for them. Outbreaks of the disease have been recognized. Our results suggest isolation precautions should be used to prevent spread of the organism from patients with the disease to others being treated with antibiotics.