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Biomedical subjects

W J Ledger

Publications and source records attributed to W J Ledger.

At least 73 records · Page 4Linked to original sources

The next 10 years in the treatment of pelvic infections.

The future developments in the treatment of pelvic infections in women are based on recent changes. There is an expanded knowledge of the complex multibacterial nature of pelvic infections, the clinical view of salpingitis has radically changed, and there have been great modifications in antibiotic treatment strategies with particular emphasis on anaerobes and Chlamydia. In the next 10 years, the following new developments may be expected. In the diagnosis of pelvic infection, there will be new efforts to have better clinical tests and the use of nonspecific and specific laboratory tests. The rapid identification of Neisseria gonorrhea, group B beta-hemolytic Streptococcus, Chlamydia, and Bacteroides fragilis would be an important laboratory aid. The treatment of pelvic infection will not be significantly altered by the introduction of new antibiotics. There will be an emphasis on new combinations of currently available antibiotics and studies that focus on the long-term follow-up of treated patients. In the understanding of the pathophysiology of pelvic infections, the importance of the spermatozoa as a carrier of bacteria and the potent immunosuppression due to seminal fluid will be investigated in detail, along with a greater emphasis on treatment of the male.

Anti-Bacterial Agents↗

Imipenem/cilastatin in the treatment of obstetric and gynecologic infections.

Fifty-five patients with soft tissue pelvic infections were treated with imipenem/cilastatin 500 mg intravenously every six hours for a minimum of four days. Six patients were unevaluable, one because of protocol non-compliance and five because no pathogen was isolated. At enrollment, mean temperature was 39.5 degrees C and the mean white blood cell count was 14,700. Of 49 evaluable patients, 43 (87.8 percent) had complete clinical cures. In three of the six patients with clinical failures, subsequent alternative antibiotic treatment also failed and they required operative intervention for pelvic abscess. In two of the patients with failures, antibiotic-associated pseudomembranous colitis developed after three days of imipenem/cilastatin therapy, requiring discontinuation of the medication. At the time of discontinuation, both patients had clinical failures. All microbiologic isolates were susceptible to imipenem/cilastatin, although at least one pathogenic organism persisted in two patients with clinical failures despite apparent in vitro susceptibility of the organism to imipenem/cilastatin. Imipenem/cilastatin is a promising agent for the empiric treatment of serious obstetric and gynecologic infections although surgery often remains a necessary treatment for pelvic abscess regardless of initial antibiotic choice.

Adolescent↗

Antibodies to the neutral glycolipid asialo ganglio-N-tetraosylceramide: association with gynecologic cancers.

As part of our efforts to define subpopulations at increased risk for gynecologic malignancies, sera from 145 women were obtained prior to diagnosis and analyzed for antibody to asialo ganglio-N-tetraosylceramide. This neutral glycolipid is present on the surface of thymocytes and natural killer cells, and asialo ganglio-N-tetraosylceramide antibody has been shown in animals to block natural killer cell activity and promote tumor cell proliferation. With the use of an enzyme-linked immunosorbent assay and with a value of 2 SD above the mean for healthy women designated as the boundary for a positive response, antibody to asialo ganglio-N-tetraosylceramide was detected in only one of 30 (3%) healthy women, none of 16 pregnant women, none of 18 women with benign masses, and two of 24 (8%) women with microbial infections. All of the above samples that contained antibodies were barely over the 2 SD limit. In marked contrast, 19 of 35 (54%) women with gynecologic malignancies had asialo ganglio-N-tetraosylceramide antibodies, with positive values ranging to greater than 10 SD above the control mean. Asialo ganglio-N-tetraosylceramide antibody was found in six of eight (75%) patients with cervical cancer, five of eight (63%) with endometrial cancer, and seven of 15 (47%) with ovarian cancer. Of the eight patients with Stage I gynecologic cancer at any site, five (62%) had asialo ganglio-N-tetraosylceramide antibodies. Four of 22 (18%) women with Hodgkin's disease also had antibodies, with values just exceeding 2 SD above control levels. The presence of these antibodies may contribute to an impaired immune surveillance system in these women and so increase their susceptibility to malignancy.

Antibodies↗

Contraceptive efficacy of bioabsorbable pellets of norethindrone (NET) as subcutaneous implants: phase II clinical study.

The contraceptive efficacy of norethindrone (NET) fused pellets was evaluated over 12 months in a Phase II clinical study with three and four pellets, each pellet containing 35 mg of NET. Volunteers were healthy, fertile, sexually active women. The release rate of NET from three and four pellets, respectively, was 150.3 +/- 7.2 micrograms and 212.5 +/- 8.6 micrograms NET/day. Following the implantation of NET pellets, serum NET levels did not show any 'burst effect' and were sustained at levels between 0.4 and 0.6 ng NET/ml serum with three pellets and 0.6-0.7 ng NET/ml serum with four pellets. With three and four pellets, respectively, 40% and 27% of the women had normal menstrual cycles; 20% and 14% were amenorrheic; 27% and 37% had mid-menstrual spotting or bleeding; and 13% and 22% had prolonged episodes of bleeding. Cardiovascular, hepatic, and renal functions were normal throughout the study. Ovulation was inhibited in 85% and 92% of the cycles with three and four pellets, respectively. In women using three pellets, two pregnancies occurred, one at the 6th cycle and another at the 12th cycle. In women using four pellets, no pregnancies occurred during the entire period of study.

Adult↗

Controlled, comparative study of moxalactam and cefazolin for prophylaxis of abdominal hysterectomy.

Moxalactam was compared with cefazolin and a control group to determine the efficacy and value of a third generation cephalosporin in abdominal hysterectomy antibiotic prophylaxis. One hundred patients were prospectively randomized in a double-blind manner between moxalactam and cefazolin. An additional 50 patients who were either allergic to penicillin or refused participation in this study were simultaneously observed to establish a base line level of infection on our service during this time period. Dosage for both antibiotic groups was 1 gram given intravenously or intramuscularly on call to the operating room followed by two 1 gram doses at six and 12 hours after the first dose. Standard febrile morbidity was 36, 30 and 42 per cent for moxalactam, cefazolin and control groups, respectively. Postoperative surgical infection requiring antibiotic treatment occurred in 8, 6 and 4 per cent, respectively; urinary tract infection or symptomatic findings, or both, requiring treatment occurred in 8, 10 and 10 per cent, respectively. No pelvic abscesses occurred in this series. In every statistical evaluation of postoperative morbidity, there were no differences noted among the three groups. Our results suggest no benefit from the use of prophylactic antibiotics in abdominal hysterectomy in terms of standard febrile or infectious morbidity or urinary tract pathologic findings. In addition, there was no difference between the two antibiotic groups.

Adolescent↗

Detection and characterization of immune complexes in the circulation of infertile women.

The incidence of circulating immune complexes (CICs) was evaluated in sera from 39 female partners of infertile marriages and from 38 fertile women. Fifteen (38%) of the infertile women had CICs, as determined by the Raji cell assay, in levels ranging from 300 to 8000 micrograms/ml; whereas only 1 (3%) of the fertile women displayed CICs (P less than 0.001). Analysis of the CICs from nine of the women following polyethylene glycol precipitation and acid dissociation revealed that four contained C1q and three contained an antigen reactive with rabbit antibody to human spermatozoa. These latter three women all lacked free sperm antibody, as determined by enzyme-linked immunosorbent assay and agglutination. Thus, CICs are not uncommon as a manifestation of infertility in females. Their presence may lead to an underestimation of sperm antibody levels and may be indicative of underlying infection or autoimmunity.

Agglutination Tests↗

Circulating immune complexes in sera of patients with gynecologic disorders.

Sera from 211 women seen in the Department of Obstetrics and Gynecology at the New York Hospital were assayed for CIC by the Raji cell enzyme linked immunosorbent assay. Only 9 per cent of healthy women (two of 21), 6 per cent of pregnant women (two of 34), 2 per cent of women with benign tumors (one of 39) and 5 per cent of women with vaginal and cervical infection (two of 37) had detectable CIC. CIC was present in low concentrations when it was found. In marked contrast, 80 per cent of the patients with Condylomata acuminatum infection (eight of ten), 46 per cent with acute salpingitis (11 of 24) and 39 per cent with gynecologic malignant diseases (13 of 33) had CIC, usually at high levels. In a patient with salpingitis, CIC was shown to be 19S and 14S, dissociable at acid pH and capable of activating complement.

Antigen-Antibody Complex↗

Use of amniocentesis in preterm gestation with ruptured membranes.

Sixty-one patients with preterm rupture of membranes were studied. Transabdominal amniocentesis was performed successfully in 42 patients (68.8%). Among these 42, 26 (61.9%) had a lecithin:sphingomyelin (L:S) ratio of 1.8 or greater and 16 (38.1%) demonstrated pulmonary immaturity. Amniotic fluid obtained from vaginal pooling was compared to fluid obtained transabdominally in seven patients and did not demonstrate any significant differences in L:S values. Gram stain and subsequent culturing of amniotic fluid obtained transabdominally was accomplished in 41 patients. Seven of the 41 patients (17.0%) had bacteria on Gram stain and/or subsequent amniotic fluid growth. All patients with either bacteria on Gram stain or a positive amniotic fluid culture developed clinical amnionitis or endometritis. Review of the neonatal morbidity and mortality in relation to gestational age of infants with preterm rupture of membranes suggests that: 1) In infants at less than 32 weeks' gestation, amniocentesis need not be done for pulmonary maturity as the morbidity of prematurity in this group is too high even in the presence of pulmonary maturity. 2) In infants at 32 to 34 weeks' gestation, amniocentesis for L:S ratio, Gram stain, and culture is helpful in selecting those in whom delivery should be instituted. 3) In infants at greater than 34 weeks' gestation, the neonatal morbidity is sufficiently reduced so that delivery should be considered except in cases of suspected delayed pulmonary maturation.

Amniocentesis↗

Subcutaneous bioabsorbable pellets of norethindrone for contraception in women: Phase I. Clinical study.

Ten healthy, normally menstruating female volunteers participated in a 1-year phase I clinical study in which subcutaneous pellet implants of norethindrone (NET) were employed as a low-dose and long-acting potential contraceptive. Two NET pellets were implanted subcutaneously by the aid of a trocar in the forearm of each volunteer on the fifth day after the start of menstrual bleeding. Serum levels of NET, follicle-stimulating hormone, luteinizing hormone, 17 beta-estradiol, and progesterone were determined weekly by radioimmunoassay. The daily NET release from the pellets, based on mean values (+/- standard error of the mean) in five subjects was 79.4 +/- 7.6 micrograms. The mean serum NET level was initially 1.0 +/- 0.34 ng/ml; thereafter, it gradually lowered during the 343 days of the study period to the level of 0.43 +/- 0.09 ng/ml. The ovarian response, days of bleeding, and cycle lengths with continuously sustained release of NET from the pellets were similar to those observed in women taking the daily oral "minipill" of 300 micrograms NET. The results of the phase I study suggest that NET pellet implants may provide a simple and acceptable approach to long-term contraception in women.

Absorption↗

Inhibition of Candida albicans--induced lymphocyte proliferation by lymphocytes and sera from women with recurrent vaginitis.

To investigate whether there was an immunologic basis for recurrent Candida albicans-induced vaginitis, peripheral blood lymphocytes were isolated from six women with this disorder and from six healthy control women. No differences were observed in the proliferative responses of peripheral blood lymphocytes to mitogens. However, only the control peripheral blood lymphocytes proliferated in response to a C. albicans extract. Furthermore, patients' lymphocytes or serum suppressed the proliferative response of control lymphocytes to C. albicans but not to mitogens. Women with recurrent C. albicans vaginitis appear to produce Candida-specific suppressor lymphocytes which block the cellular immune response to this organism.

Blood↗

Antepartum pneumonia in pregnancy.

Thirty-nine patients satisfying criteria for antepartum pneumonia in pregnancy were retrospectively reviewed. Twenty-one patients had culture-proved bacterial pneumonias. Streptococcus pneumoniae was the most common organism isolated (13/39). Significant anemia (hemoglobin less than or equal to 10 gm) was present in 49% of patients (19/37) on admission. In the patients presenting in the second and third trimesters (25 to 36 weeks) of pregnancy, 85% (11/13) were delivered at term. The perinatal mortality rate for the entire group was 40/1,000. There were no maternal deaths.

Adult↗

Laparoscopy in the diagnosis and management of patients with suspected salpingo-oophoritis.

There is a potential role for laparoscopy in the management of patients with suspected salpingo-oophoritis. It would be helpful in establishing the diagnosis in patients who are admitted with a clinical diagnosis of salpingo-oophoritis. Laparoscopy also would be beneficial in the long-term evaluation of fertility of patients treated for salpingo-oophoritis. Finally, this technique will delineate the microbiologic details of patients with endosalpingitis. How frequently laparoscopy should be employed will be dependent upon findings from prospective studies.

Diagnostic Errors↗

Three metronidazole-resistant strains of Trichomonas vaginalis from the United States.

Trichomonas vaginalis isolates were obtained in the United States from three women with trichomoniasis refractory to routine treatment with metronidazole. Cure was obtained in these cases with increased dosage of metronidazole. In experimental mouse infections, all three strains showed a significantly (about 10 to 20 times) lower susceptibility to metronidazole than did a number of control strains. In vitro, the lowered susceptibility could be detected only in an aerobic assay but not in the routine anaerobic assay. The conclusion is that T. vaginalis strains with lowered metronidazole susceptibility do exist. Such strains might be responsible for a certain, but as yet entirely unknown, number of failures in routine metronidazole therapy of human trichomoniasis.

Adult↗