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Biomedical subjects

W J Ledger

Publications and source records attributed to W J Ledger.

At least 55 records · Page 3Linked to original sources

Interferon-gamma in the diagnosis and pathogenesis of pelvic inflammatory disease.

Serologic markers were evaluated to determine if they could aid in the differential diagnosis of pelvic inflammatory disease in 48 consecutive women seeking evaluation for pelvic pain. On the basis of clinical and microbiologic parameters, 29 patients (60.4%) were diagnosed as having pelvic inflammatory disease. Neisseria gonorrhoeae only was isolated from the cervix of eight (27.6%) patients with pelvic inflammatory disease, five (17.2%) had only Chlamydia, and two (6.9%) had Neisseria and Chlamydia, whereas in 15 (48.3%) patients no pathogen was isolated. Interferon-gamma was present in significantly more sera (p less than 0.025) from patients with pelvic inflammatory disease (65.5%) than from women without pelvic inflammatory disease (15.8%). Sera from 10 healthy women lacked detectable interferon-gamma. In patients with only Neisseria, seven (87.5%) had circulating interferon-gamma; three (60%) of the women with only Chlamydia, one (50%) woman with Neisseria and Chlamydia, and eight (57.1%) with no identified pathogens were also positive for interferon-gamma. Sera from 11 of 28 patients with pelvic inflammatory disease (39%) but only one of 19 sera from women without pelvic inflammatory disease (5%) also inhibited the Candida-induced proliferation of control lymphocytes. This immunosuppressive activity was prevented by immunoprecipitation of interferon-gamma by anti-interferon-gamma antibody but not by treatment with anti-interferon-alpha antibody. The persistence of interferon-gamma in the sera of patients with pelvic inflammatory disease may aid in the differential diagnosis of this disease and increase our understanding of the pathogenesis of microbial-mediated tubal damage.

Antibody Specificity↗

Contraceptive efficacy of norethindrone encapsulated in injectable biodegradable poly-dl-lactide-co-glycolide microspheres: phase II clinical study.

Contraceptive efficacy of injectable norethindrone (NET) microspheres of 90 day duration was evaluated for 6 months: nine women received two injections of 65 mg each and eight received two injections of 100 mg each with 90 days between each injection. Average serum NET levels were 5 to 9 ng/mL on the day after injection and subsequently remained at 1 to 3 ng/mL. With 65 and 100 mg doses, respectively, 36% and 25% of cycles had normal bleeding patterns, 36% and 48% were amenorrheic, and the remaining 28% and 27% had prolonged bleeding. Also, 56% and 40% of cycles showed increased spotting for the 65 mg and 100 mg dose, respectively. There was no incidence of pregnancy or serious side effects. The mean serum NET concentration returned to RIA nonspecific basal levels 100 days after the second injection. Women returned to ovulatory cycles between days 100 to 115 after the second injection.

Adult↗

Infection and premature labor.

The possibility that infection can cause premature labor is appealing. If true, antibiotics treat the cause, in contrast to tocolytic agents, which treat symptoms. There is strong evidence that infection is a factor in premature labor. Historical data from the preantibiotic era in patients with pyelonephritis and pneumonia support this. Vaginal bacterial colonization studies and amniotic fluid studies indicate that a portion of women with preterm labor have an identifiable microbiologic profile. Preliminary reports on antibiotic intervention in asymptomatic women and women in premature labor are encouraging. This may be the dawn of a new era in the diagnosis and treatment of preterm labor.

Bacterial Infections↗

Vaginal eosinophils and IgE antibodies to Candida albicans in women with recurrent vaginitis.

Eosinophils were identified in 31 of 121 (25.6%) vaginal smears obtained from women with recurrent vaginitis. The presence of eosinophils correlated (p less than 0.005) with the occurrence of IgE antibodies to Candida albicans in vaginal fluid. Localized allergic responses to C. albicans or other allergens may contribute to the pathogenesis of recurrent vaginitis in sensitized women.

Antibodies, Fungal↗

Total complement activity in maternal sera, amniotic fluids and cord sera in women with premature labor, premature rupture of membranes or chorioamnionitis.

Total hemolytic complement activity (CH50) was determined in maternal sera, amniotic fluids or cord sera, or all, from 119 patients with preterm uterine contractions, premature rupture of membranes or chorioamnionitis, or all, at 24 to 40 weeks of gestation. The mean CH50 of maternal sera exceeded the mean CH50 of both amniotic fluids and cord sera. The mean CH50 of amniotic fluids exceeded that of cord sera and increased significantly at 32 weeks. This rise preceded that of the mean CH50 of cord sera, which occurred at a fetal weight of approximately 2,500 grams. The mean CH50 of amniotic fluids varied significantly and inversely with that of cord sera. The levels of CH50 in these three fluids did not distinguish between patients with preterm uterine contractions who delivered prematurely and those who delivered at term. The CH50 in patients with premature rupture of membranes did not differ from a control population of women with uncomplicated pregnancies. The mean CH50 of maternal sera was increased in patients with chorioamnionitis but was not predictive of chorioamnionitis. The mean CH50 of maternal sera was decreased in patients who smoked cigarettes and in patients who received intravenous ritodrine.

Amniotic Fluid↗

Comparative effectiveness and safety of cefotetan and cefoxitin as prophylactic agents in patients undergoing abdominal or vaginal hysterectomy.

In a multicenter, randomized clinical trial, 282 women who underwent abdominal or vaginal hysterectomy were given a single preoperative 2 g dose of cefotetan (171 evaluable patients) or three perioperative 2 g doses of cefoxitin (84 evaluable patients) as antibiotic prophylaxis. A successful clinical response occurred in 92 percent of those receiving cefotetan and 90 percent of those receiving cefoxitin who underwent abdominal hysterectomy, and in 94 percent of those receiving cefotetan and 93 percent of those receiving cefoxitin who underwent vaginal hysterectomy. The incidence of vaginal cuff cellulitis was 3.4 percent and 5 percent for cefotetan and cefoxitin patients, respectively, who underwent abdominal hysterectomy, and 4.8 percent and 4.5 percent, respectively, for those who underwent vaginal hysterectomy. The incidence of major wound infection was 3.4 percent and 2.5 percent for cefotetan and cefoxitin, respectively, in the abdominal hysterectomy group. Postoperative changes in oral body temperature, duration of hospitalization, and postoperative grading of surgical wounds were similar. Both drugs were well tolerated. These results suggest that a single dose of cefotetan is equally effective and as safe as multiple-dose cefoxitin for prophylaxis in patients undergoing hysterectomy.

Adult↗

Recurrent vaginitis as a result of sexual transmission of IgE antibodies.

The role of the man in the etiology of recurrent vaginitis was examined in three women who reported an association between coitus and the initiation of clinical symptoms. The patients' disorders consisted of vaginal pruritus, burning, a white discharge, and painful coitus. Vaginal pH in each case was 4.5. Microscopic examination of wet mounts of vaginal secretion had no clue cells and no organisms other than lactobacillus. One culture was positive for Candida albicans; however, successful treatment of the C. albicans vaginitis did not eliminate the patient's symptoms. Semen samples from the patients' partners were negative for C. albicans. One of the seminal fluids had highly elevated concentrations of total IgE. The other two semen samples contained IgE antibodies that were reactive with a particulate fraction of vaginal fluids obtained from their wives. In contrast, vaginal fluids from the patients were all negative for IgE antibodies to their partner's semen. Use of a condom during coitus ended the recurring cycles of vaginitis in all three women. Vaginitis may be induced by an allergic reaction initiated by the transfer from men to women during coitus of IgE antibodies reactive either to antigens of the female genital tract or components of semen. Men allergic to female vaginal secretions, to vaginal microbes or their products, or to semen represent a previously unrecognized noninfectious vector for this disorder.

Adult↗

A localized vaginal allergic response in women with recurrent vaginitis.

In women with recurring vaginitis, treatment of a vaginal Candida infection is not always accompanied by an alleviation of symptoms, and infection frequently reappears after termination of the chemotherapeutic agent. To determine whether an allergic reaction might be involved in symptom prolongation and susceptibility to reinfection, sera and vaginal washes from patients were examined for specific IgE antibodies. With RAST modified to ELISA, anti-Candida albicans IgE was identified in 18.8% of saline vaginal washes, but in only 6.1% of sera, obtained from 64 patients. Similarly, 25% of 16 patients were positive for vaginal fluid IgE, but only 6.3% had serum IgE to their partners' seminal fluid. The detection of specific IgE antibodies vaginally but not in the peripheral circulation suggested the occurrence of a localized vaginal hypersensitivity response. Vaginal fluid-derived IgE antibodies reactive with contraceptive spermicides or present in the particulate fraction of saline vaginal washes were also identified. Vaginal fluids with IgE antibodies also contained detectable levels of prostaglandin E2. A vaginal allergic response can predispose to recurrent Candida infection by inducing prostaglandin E2 synthesis that suppresses cell-mediated immune responses.

Allergens↗

Comparison of cefotetan and cefoxitin prophylaxis for abdominal and vaginal hysterectomy.

The safety and efficacy of parenteral prophylaxis with either cefotetan or cefoxitin were evaluated in a prospective, randomized study of 355 subjects undergoing abdominal or vaginal hysterectomy. Each subject received either a single 1 gm dose of cefotetan intravenously 30 to 60 minutes before operation or three 2 gm doses of cefoxitin, the first 30 to 60 minutes before operation and subsequent doses 6 and 12 hours later. Prophylaxis was successful in 69 of 70 (98.6%) receiving cefotetan and 32 of 33 (97.0%) receiving cefoxitin who underwent vaginal hysterectomy. Prophylaxis was successful in 160 of 169 (94.7%) receiving cefotetan and in 79 of 83 (95.2%) receiving cefoxitin who underwent abdominal hysterectomy. Both drugs were well tolerated and without serious side effects or complications. On the basis of these findings, we conclude that a single 1 gm dose of cefotetan given before operation is as safe and effective as a multiple-dosing regimen of cefoxitin in subjects undergoing vaginal hysterectomy and in those undergoing abdominal hysterectomy at institutions where prophylaxis is indicated.

Abdomen↗

Antibiotic treatment for pelvic infection.

Antibiotic strategies for pelvic infections in the 1980s are much more complex, because of the variety of bacteria involved, aerobes, anaerobes and Chlamydia. There is a difference in the clinical response of patients treated with early or well-established infections. In well established infections, patients with a pelvic mass or symptoms greater than five days, the failure rate of antibiotic treatment is higher and operative intervention to drain or remove an abscess is more frequently needed. Physicians need to know the antibiotic susceptibilities of Bacteroides fragilis and the activity of antibiotics against this species when large numbers of bacteria are present. In patients seen early in the course of infection, antibiotics effective against gram-negative anaerobes are helpful, particularly in the patient with an endomyometritis following cesarean section.

Animals↗

Aminoglycosides in gynecologic infections.

Aminoglycosides have always had a major role in the treatment of gynecologic infections. This therapeutic emphasis has been based upon the bactericidal activity of the aminoglycosides against gram-negative aerobes. This group of organisms is important to the gynecologist because of their frequent isolation from soft tissue, urinary sites, and the bloodstream in women with nosocomial or community-acquired pelvic infections. In the past decade, there has been increasing clinical awareness of the multi-bacterial nature of these soft tissue pelvic infections. A major therapeutic change directed against gram-negative anaerobes has been the substitution of more effective agents like clindamycin or metronidazole for the penicillin arm of the older penicillin-aminoglycoside combination. The majority of intra-abdominal and pelvic infections treated by gynecologists occur in patients who are younger and usually healthier than those with similar infections who are treated by general surgeons. Consequently, in many instances, single drug therapy with a cephalosporin (usually cefoxitin) is adequate, if combined with surgical drainage when indicated. However, there is an increasingly larger group of patients who are significantly older and who may also have pelvic malignancies. In addition, they may be immunocompromised. Infections in this group mandate the use of the most effective antimicrobial agents that will cover the broadest spectrum. When anaerobic bacteria are involved, either clindamycin or metronidazole are acceptable choices; for aerobic gram-negative organisms, an aminoglycoside should be used. Recent studies suggest that amikacin may be the best choice, since it is associated with a low level of bacterial resistance and has been shown to reduce levels of resistance to other aminoglycosides. Amikacin has become the "gold standard" for comparisons with any new cephalosporins or penicillins. New developments will modify the use of aminoglycosides in the future. The expansion of oncology care with immune-system-modifying chemotherapy and radiation will expose patients to the dangers of gram-negative sepsis. Aminoglycosides are a logical part of the initial therapeutic regimen for these septic patients. On the other hand, the majority of gynecologic patients with pelvic infections are young and healthy. Recent studies have demonstrated that as many as 40 percent of these women will be underdosed by standard treatment regimens based upon ideal body weight. This means that patients receiving aminoglycosides will require monitoring of peak and trough levels to insure therapeutic drug levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Aminoglycosides↗

A macrophage defect in women with recurrent Candida vaginitis and its reversal in vitro by prostaglandin inhibitors.

The possible involvement of a defect in cellular immunity in the etiology of recurrent vaginal candidiasis was explored. The mean and range of in vitro lymphocyte proliferative responses induced by mitogens were comparable in 65 patients and 36 control subjects. In contrast, Candida-directed proliferation was reduced at least 70% below the mean control value in 73% of the patients. Further analyses on selected patients demonstrated that lymphocytes of the patients responded in the normal range to Candida if incubated in the presence of control macrophages. Conversely, macrophages of patients inhibited the responses of control lymphocytes to Candida. These effects were independent of mixed leukocyte reactions between allogeneic cells. Addition of the prostaglandin inhibitors ibuprofen and indomethacin prevented macrophages of patients from inhibiting patient or control lymphocyte proliferation. In response to Candida, macrophages from some women with recurrent vaginitis produce prostaglandin, which blocks the lymphocyte proliferation response to this organism.

Candidiasis, Vulvovaginal↗

A double-blind, controlled comparison of piperacillin and cefoxitin in the prevention of postoperative infection in patients undergoing cesarean section.

Data are presented from a randomized, double-blind multicenter trial (six study sites, involving 346 patients) in which piperacillin was compared with cefoxitin as a prophylactic agent for patients undergoing cesarean section. One hundred and sixty-nine patients received piperacillin and 177 received cefoxitin; in each instance, the total dosage was 6 grams. Strict criteria were used to evaluate safety and efficacy. The courses of all of the patients were evaluable for safety and 183 courses were evaluable for efficacy (136 efficacy-evaluable courses were from patients treated with piperacillin and 147, from those treated with cefoxitin). Postoperative infection was prevented in 89 per cent of the patients treated with piperacillin and in 93 per cent of the those treated with cefoxitin. The difference was not statistically significant. The data from each of the individual study sites, as well as the pooled data, indicated that the short term perioperative administration of piperacillin in patients undergoing a cesarean section was as safe and effective as cefoxitin with regard to prophylactic response, duration of hospitalization and the usage of other systemic antibiotics.

Adolescent↗

Randomized, comparative trial of imipenem/cilastatin and moxalactam in the treatment of serious obstetric and gynecologic infections.

Thirty-four patients with pelvic inflammatory disease, postoperative, postabortal and postpartum infections were randomized to intravenous therapy with either 500 milligrams of imipenem and cilastatin sodium every six hours or 2 grams of moxalactam every eight hours for a minimum of four days. One patient in the moxalactam group was nonevaluable because of protocol noncompliance; three more patients had no bacteriologic pathogen isolated (two in the moxalactam group and one patient in the imipenem/cilastatin group). The two groups were similar with respect to age, diagnosis, etiologic agents and duration of therapy. Of the 17 evaluable patients in the imipenem/cilastatin group, all were complete clinical cures. Three patients in the imipenem/cilastatin group had persistence of at least one bacteriologic pathogen despite clinical cure and apparent laboratory evidence of susceptibility. Of the 13 evaluable patients in the moxalactam group, eight were complete clinical cures. Two more patients in that group were clinically improved enough to be discharged on oral antibiotics. There were three clinical failures in the moxalactam group, all of whom had group D streptococcus resistant to moxalactam. An additional three patients in the moxalactam group had other resistant organisms isolated despite clinical cure. Both drugs were well tolerated and no serious complications or side effects occurred in either group. Despite small numbers, our data suggest that imipenem and cilastatin is a more appropriate agent for initial treatment of obstetric and gynecologic infections than moxalactam.

Acute Disease↗

Nonintervention in premature rupture of the amniotic membranes.

One hundred and forty-one instances of premature rupture of the amniotic membranes (PROM), between 25 and 36 weeks gestation and with duration of PROM greater than six hours, were managed by bedrest, observation and no obstetric intervention. Delivery was allowed if the patient had spontaneous labor develop, and delivery was initiated for chorioamnionitis or fetal distress. The perinatal mortality was 25 of 148 infants delivered (168 of 1,000 births). The majority of neonatal deaths (64 per cent) were attributable to complications of prematurity. Neonatal sepsis was uncommon as a cause of death (0.16 per cent). Results indicate that the natural history of PROM is associated with a low incidence of serious maternal and fetal infections and that prematurity is the most serious problem.

Amniocentesis↗