Massive extranglandular aromatization of plasma androstenedione resulting in feminization of a prepubertal boy.

This report describes the mechanism of origin and the quantity of estrogen produced in a prepubertal boy who developed severe feminization at 8 yr of age as the result of a heretofore undescribed metabolic abnormality. The clinical findings were gynecomastia and accelerated linear growth and bone maturation. At the time feminization developed, there were no signs of growth or development of the otherwise normal prepubertal male external genitalia or any increase of muscle mass that normally accompanies male puberty. The hyperestrogenism was found to be the consequence of massive extraglandular conversion of plasma androstenedione to estrone. During a 6-mo period of study, the plasma production rate of androstenedione ranged from 1.2 to 1.6 mg/day. More than 55% of plasma androstenedione was metabolized by aromatization to estrone which, in turn, was extensively sulfurylated in the tissue sites of aromatization before its entry into the blood. Thus, estrone sulfate was the final product in the aromatizing sites, and the plasma production rate of estrone sulfate derived from plasma androstenedione was 782 mug/24 h. The extent of extraglandular conversion of plasma androstenedione to estrone measured in this boy was 50 times that observed in two normal prepubertal boys. Moreover, 94% of the extraglandular aromatization occurred in extrahepatic sites. The metabolic clearance rate of plasma androstenedione, 2,380 liters/day per m(2), was markedly increased in this boy. Approximately 1,500 liters of plasma androstenedione clearance was accounted for by extrahepatic, extraglandular aromatization. The fractional conversion of testosterone to estradiol, 0.16, was 50 times greater in this boy than that observed in normal young adult men. The total extent of aromatization of plasma prehormones was even greater in this boy inasmuch as evidence was obtained that aromatization of 16-hydroxysteroids, e.g. 16alpha-hydroxy androstenedione and 16alpha-hydroxy dehydroisoandrosterone (sulfate), resulted in estriol formation independent of estrone formation. Thus, extensive extrahepatic, extraglandular aromatization resulted in advanced feminization in this prepubertal boy by a previously undescribed metabolic abnormality.

Sulbactam/ampicillin for treatment of polymicrobial pelvic infections.

The increasing number of beta-lactam antibiotic-resistant bacteria observed in many strains of aerobic and anaerobic Gram-positive and Gram-negative bacteria, including Bacteroides species, has been well documented. Semisynthetic synthesis of penicillins and cephalosporins with increased resistance to beta-lactamase enzyme hydrolysis has not solved the problem. An alternative to therapy with newer agents is combination of an irreversible, suicide-type, beta-lactamase enzyme inhibitor such as sulbactam with a beta-lactam antibiotic such as ampicillin. Women with a variety of acute polymicrobial pelvic infections have been treated with the above combination, metronidazole or clindamycin combined with aminoglycoside, or cefoxitin in prospective trials. The clinical efficacy of 92.4%, in vitro bacteriological efficacy of 96.6%, and safety of sulbactam/ampicillin were comparable to that observed in women given comparative therapy. Penetration of pelvic tissues by sulbactam and ampicillin was excellent. Sulbactam/ampicillin is a viable alternative for the treatment of women with acute pelvic infections.

Sulbactam/ampicillin versus cefoxitin for uncomplicated and complicated acute pelvic inflammatory disease.

In this study, 17 women were treated for uncomplicated acute pelvic inflammatory disease requiring hospitalisation for therapy, and 5 women were treated for the same infection complicated by pelvic abscesses. Treatment regimens were sulbactam 1g plus ampicillin 2g (14 women) or cefoxitin 2g (8 women) given by intravenous infusion every 6 hours. On the third day of therapy, a rash developed in 1 woman who was being successfully treated for uncomplicated disease with sulbactam/ampicillin. The other 21 women were cured. No other adverse clinical reactions and no significant abnormal laboratory results were observed with either regimen. Bacteriological efficacy, 98% for sulbactam/ampicillin and 94% for cefoxitin, closely paralleled clinical efficacy. Sulbactam, a suicide-type beta-lactamase inhibitor, appears to have restored and expanded the antibacterial activity of ampicillin.

The use of ultrasound in multiple gestations.

A retrospective study of 20 multiple pregnancies and a prospective study of 13 multiple pregnancies were done to determine the accuracy of ultrasound in the diagnosis and dating of multiple pregnancy and in predicting intrauterine growth retardation (IUGR). The diagnosis of 1 multiple pregnancy in our study was missed. In another case triplets were erroneously diagnosed as a twin gestation. Fetal biparietal diameter correlates well with gestational age, particularly when the characteristic growth pattern of twins is taken into account. Ultrasound was noted to be of only limited use in antenatal diagnosis of IUGR, with a significant number of false positives and false negatives noted.

Evaluation of cefamandole nafate for the treatment of acute gonococcal salpingitis.

Eighty-six women with suspected acute salpingitis were treated with parenteral cefamandole. From 53 (62%) of these Neisseria gonorrhoeae was recovered from an anogenital site(s) at admission. These women were younger, of lower parity, had pain for a shorter period of time, responded more rapidly to therapy, and required less antimicrobial agent for clinical cure than those from whom N gonorrhoeae was not recovered. The clinical success observed in these women was 94%, and only 2% of 122 gonococcal isolates were resistant to cefamandole in vitro.

Cefoxitin for prophylaxis in premenopausal women undergoing vaginal hysterectomy.

To determine the unbiased incidence and types of postoperative infection and their alteration(s) by antimicrobial prophylaxis, a prospective double-blind study was performed using perioperative intramuscular cefoxitin or placebo given to premenopausal women undergoing vaginal hysterectomy at Parkland Memorial Hospital. The clinical and surgical profiles of the 2 groups of women were similar, but there were marked differences in their postoperative clinical courses. Only 8% of the 50 women given cefoxitin had major postoperative infection, compared to 57% of the 49 women given placebo (P < .001); this was associated with a 2.8-day reduction in the hospital stay for those given cefoxitin (P < .001). No clinically significant side effects were observed.

Cefoxitin serum and uterine concentrations following a two-gram intramuscular dose.

Two grams of cefoxitin was administered intramuscularly to 31 premenopausal women when they were called to the operating room for a scheduled vaginal hysterectomy. Serum and tissue samples were obtained to determine cefoxitin concentration. The mean concentration of cefoxitin at the reported peak in serum after an intramuscular injection (30 minutes) was 25.3 micrograms/ml. The mean serum concentration at the time of uterine excision (a mean of 143 minutes after the on-call dose) was 18.0 micrograms/ml. The mean concentrations of cefoxitin in the uterine fundus and the lower uterine segment at the time of uterine excision were 1.1 and 1.8 micrograms/g tissue, respectively.

Sexual assault in pregnancy.

Little is known about the acute effects of sexual assault on pregnant victims and the outcome of their gestations. A retrospective review of sexual assault victims in Dallas County from 1983-1988 revealed that 114 of 5734 (2%) were pregnant. There were 0.55 and 0.75 gravid sexual assault victims per 1000 deliveries for Dallas County and Parkland Memorial Hospital, respectively. The purposes of this study were to examine patient demographics, forensic evidence and patterns of injury in pregnant victims compared with 114 matched nonpregnant sexual assault victims, and to compare pregnancy outcome with that of the Parkland Memorial Hospital obstetric population. The typical victim was a black, parous gravida in her twenties at a mean gestational age of 15 weeks, without previous prenatal care. Vulvar (95%), oral (27%), and anal (6%) penetration were reported with similar frequency in both groups. The detection of whole and motile sperm from the vaginal specimens was similar in pregnant and nonpregnant women. Physical trauma was more common in nonpregnant victims (63 versus 43%; P less than .004), especially genital trauma (21 versus 5%; P less than .001). Injury was more common to the head and neck or extremities than to the abdomen, chest, or back in both groups. There was no difference in the pattern of trauma by gestational age, but there were no truncal injuries in women at 20 weeks' gestation or greater. There were no spontaneous abortions or deliveries within 4 weeks of the assault, but low birth weight delivery (24%) and preterm delivery (16%) were common.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in lower reproductive tract flora after single-dose piperacillin and triple-dose cefoxitin at vaginal and abdominal hysterectomy.

There are no current data regarding the effect of a newer, broad-spectrum penicillin on lower reproductive flora at hysterectomy. To identify any existing differential effect on species and their susceptibilities, we obtained pre- and postoperative lower reproductive tract culture material from 209 women who were given single-dose piperacillin, then placebo or triple-dose cefoxitin, intravenously for prophylaxis at vaginal and abdominal hysterectomy in a prospective, randomized, blinded clinical trial. Significantly more preoperative endocervical bacteria were susceptible to piperacillin. Piperacillin caused less alteration in the numbers of lower reproductive tract flora when preoperative species were compared with postoperative species. More resistance to cefoxitin was identified postoperatively in bacteria recovered from the vaginal cuff of women who remained uninfected.

Cefazolin for hysterectomy prophylaxis.

Efficacy data for single-dose cefazolin prophylaxis at hysterectomy are meager, and there are none evaluating the impact of route of administration on efficacy. For these reasons, 772 women undergoing elective abdominal or vaginal hysterectomy for benign diseases were given 1 g cefazolin either intramuscularly or intravenously in a randomized clinical trial. Preoperative diagnoses and clinical, surgical, and outcome variables were similar by route of administration for each surgical approach. Risk factors for infection after abdominal hysterectomy included younger age, lower postoperative hemoglobin concentration, and pelvic hematoma; women who developed infection after vaginal hysterectomy were heavier than those who remained uninfected and were more likely to have a pelvic hematoma. The overall incidence of major operative site infection requiring parenteral antimicrobial therapy in evaluable women was 7.2%: 7.6% for 539 women undergoing abdominal hysterectomy and 6.3% for 207 women undergoing vaginal hysterectomy. Postoperative infection was unrelated to route of cefazolin administration.

Single-dose cefoxitin prophylaxis for premenopausal women undergoing vaginal hysterectomy.

A prospective randomized blinded study was conducted comparing a single 2-g preoperative dose of cefoxitin with three 2-g doses of cefoxitin over 12 hours given to premenopausal women scheduled for vaginal hysterectomy in Parkland Memorial Hospital. The incidence of major pelvic infection in 58 women given one dose was 1.7%, and it was 3.7% for 54 women given three doses. The mean hospital stay (4.5 days) was similar for both regimens; for those who developed major infection it was eight days. More aerobic bacteria with altered species dominance and fewer anaerobic bacteria were recovered from the vaginal cuff at discharge from the hospital when compared with those recovered from the endocervix preoperatively. There was a trend toward increasing minimal inhibitory concentrations to cefoxitin in bacteria isolated after surgery, which was more frequent in women given three doses. There was not a statistically significant intergroup difference in the recovery of bacteria resistant to cefoxitin in vitro after surgery. A single preoperative dose of cefoxitin was as effective in preventing major infection as were three perioperative doses, while providing other real and theoretic benefits.

Bacteriology and treatment of malodorous lower reproductive tract in gynecologic cancer patients.

OBJECTIVE: To determine the bacteriology of lower genital tract cancers to direct potential treatment modalities and to determine the impact of treatment on quality of life. METHODS: Gram stain, saline preparations, tumor pH determinations, and anaerobic and aerobic tumor cultures were obtained from 13 consecutive patients with malodorous gynecologic cancers and 13 patients (controls) with nonmalodorous tumors. All patients with odor were treated with topical metronidazole for 7 days. Odor assessment questionnaires were administered daily in the treatment group. Quality-of-life evaluation was assessed using the Functional Assessment of Cancer Therapy questionnaire before and after treatment. RESULTS: Cancer of the cervix (n = 21) was the most common primary site and accounted for 81% (95% confidence interval 61%, 93%) of malodorous gynecologic cancers. Eight of 13 (62%) patients with malodorous tumors had bacterial vaginosis compared with four of 13 (31%) of those without odor (P =.11). Aerobic and anaerobic bacteria were isolated with equal frequency from malodorous gynecologic cancers. Results of odor assessment questionnaires showed a graded improvement with topical antibiotic therapy (P <.001). The Functional Assessment of Cancer Therapy questionnaire indicated improved quality of life after therapy (P =.02). CONCLUSION: Most patients with odor had bacterial vaginosis and had an improvement in odor with topical metronidazole. Therefore, this treatment might be useful for patients with malodorous pelvic tumors.

Cefotaxime sodium therapy for endomyometritis following cesarean section: dose-finding and comparative studies.

One hundred eighteen women who developed endomyometritis after cesarean section in Parkland Memorial Hospital were treated with parenteral cefotaxime sodium. The requirement for additional antimicrobial therapy was significantly higher at an initial daily dose of 3 g/day (16.4%) than when the dose was 6 g/day (4.8%) (P less than .05). The latter clinical efficacy and the observed in vitro susceptibility of 88% of isolates indicate that cefotaxime is well suited for single-agent parenteral therapy for this polymicrobial pelvic infection. Subsequently, 120 women with the same diagnosis were randomly treated with cefotaxime or clindamycin and gentamicin. Patient populations, surgical variables, in vitro microbiologic data, and side effects were similar for both groups. Clinical success observed was also similar: it was 97.5% for women given cefotaxime and 95% for women given clindamycin and gentamicin.

Cefoperazone and cefoxitin prophylaxis for abdominal hysterectomy.

One hundred one women undergoing elective abdominal hysterectomy were given perioperative cefoperazone or cefoxitin in a prospective randomized blinded study. Both regimens were well tolerated and no significant toxic or allergic manifestations were observed. Interrelationships between antimicrobial concentration in serum and pelvic tissues, intraoperative cardinal ligament cultures, febrile morbidity, and major postoperative infection were determined. At uterine removal, mean cefoperazone concentrations in serum (56.1 micrograms/mL) and pelvic tissues (18.6 micrograms/g) were significantly higher than mean concentrations of cefoxitin, ie, 16.1 micrograms/mL and 8.1 micrograms/g, respectively (P less than .001). The incidence of major postoperative infection was 6% or less with both regimens. Perioperative prophylaxis significantly reduced the incidence of this infection. When it did develop, however, it continued to cause significant morbidity, prolonging hospital stay a mean of more than four days (P less than .001) and increasing the hospital bill a mean of almost $1500 (P less than .001).

Combination antimicrobial therapy for serious gynecological and obstetrical infections--obsolete?

The normal flora of the lower reproductive tract are the pathogens isolated from upper reproductive tract infections after cesarean section and hysterectomy and from intraperitoneal cultures taken from women treated for acute pelvic inflammatory disease. Because these infections are usually polymicrobial, traditional antimicrobial therapy has included various combinations of agents. During the last six years we used five different antimicrobial combinations to treat more than 600 women with one of the above infections. From 15% to 50% of cases required the addition of a third (anaerobic-specific) antimicrobial. Original therapy with clindamycin/gentamicin was unsuccessful in only 5% of the infections treated. Single-agent therapy with third-generation cephalosporins avoids most problems associated with combination therapy. Over the past 18 months we treated 237 women with cefotaxime; 94% required no further therapy.

Results of a double-blind, placebo-controlled clinical trial program of single-dose ceftizoxime versus multiple-dose cefoxitin as prophylaxis for patients undergoing vaginal and abdominal hysterectomy.

In a series of three double-blind, controlled, clinical studies, the efficacy and safety of a single 1 gram dose of ceftizoxime were compared with those of a standard regimen, three 2 gram doses of cefoxitin, for prophylaxis of perioperative infection in women undergoing abdominal or vaginal hysterectomy. Two hundred and twenty-seven patients received ceftizoxime prophylaxis and 234 patients received cefoxitin prophylaxis. Study 1 entered 110 patients in Dallas, Texas and Los Angeles, California. Study 2 entered 242 patients in Canada. Study 3 entered 109 patients in Denver, Colorado. Within studies, the distribution of surgical procedures was comparable between antibiotic groups. The groups were similar for demographic and medical factors at each center and overall. Analyses were performed within and across studies, applying consistent criteria to the selection of evaluable patients and to the definitions of prophylactic success and primary and secondary prophylactic failure. Three hundred and sixteen patients were evaluable, 160 who received ceftizoxime and 156 who received cefoxitin. Overall, complete prophylactic success occurred in 138 of 160 evaluable patients (86.3 percent) receiving ceftizoxime and 128 of 156 evaluable patients (82.1 percent) receiving cefoxitin. Prophylactic success rates differed by study as well as by type of hysterectomy. In studies 1 and 2, prophylactic success rates for ceftizoxime were 95.1 and 87.6 percent, respectively, versus 93.1 and 87.8 percent for cefoxitin. In study 3, success rates were lowest, 70.0 percent for ceftizoxime and 59.5 percent for cefoxitin. Among evaluable patients overall, prophylactic success rates after vaginal hysterectomy were 91.0 percent for those receiving ceftizoxime and 85.1 percent for those receiving cefoxitin. After abdominal hysterectomy, success rates were 78.3 percent for both groups. Febrile morbidity rates and duration of hospitalization were comparable for both groups across all studies and within individual studies. Ceftizoxime and cefoxitin were safe and well tolerated. The results of these controlled studies indicate that single-dose ceftizoxime is as effective and safe as multiple-dose cefoxitin when used as adjunctive chemoprophylaxis in patients at risk of postoperative infection after vaginal or abdominal hysterectomy.

Ceftriaxone or cefazolin prophylaxis for the prevention of infection after vaginal hysterectomy.

A prospective, double-blind, perioperative prophylactic antibiotic study was performed in 127 women undergoing vaginal hysterectomy. Patients were randomly given a preoperative 1 g dose of ceftriaxone and then placebo 8 and 16 hours later or three 1 g doses of cefazolin over 16 hours. At surgery, blood samples were collected from 81 women and vaginal mucosa samples, from 49 women. Respective antibiotic concentrations were determined by high-pressure liquid chromatography. During the 10 months of this study, 64 patients received ceftriaxone and 63 received cefazolin. Clinical and surgical profiles of the two groups were similar, and the incidence of postoperative pelvic infection was identical, being 1.6 percent. The mean concentration of ceftriaxone was significantly higher than that of cefazolin in serum (p less than 0.001) and vaginal mucosa (p less than 0.05). A single dose of ceftriaxone before surgery was as effective in preventing major pelvic infection and urinary tract infection as were three perioperative doses of cefazolin given over 16 hours. The safety and tolerance of the two regimens were equivalent.

Multicenter clinical trials comparing cefotetan with moxalactam or cefoxitin as therapy for obstetric and gynecologic infections.

The clinical efficacy and safety of cefotetan was assessed in two multicenter clinical trials involving 335 evaluable patients hospitalized with obstetric and gynecologic infections. In Study I, cefotetan was compared with moxalactam and in Study II, cefotetan was compared with cefoxitin. The clinical response rate in Study I was 67 of 70 patients for cefotetan (96 percent) and 33 of 34 patients (97 percent) for moxalactam. In Study II, the clinical response rate was 138 of 147 patients in the cefotetan group (94 percent) and 76 of 84 patients in the cefoxitin group (91 percent). For the patients with bacteriologic response data, 196 of 205 cefotetan patients (96 percent), 23 of 24 moxalactam patients (96 percent), and 70 of 75 cefoxitin patients (93 percent) had a satisfactory bacteriologic response. Cefotetan was well tolerated and produced no major adverse reactions. The mean amount of cefotetan given was lower than that of moxalactam or cefoxitin.

Infections after gynecologic surgery.

Infections observed after gynecologic surgical procedures are polymicrobial and require parenteral broad-spectrum antimicrobial therapy until the patient has been afebrile 24 to 72 hours. Therapy should be tailored to the specific infection and patient response thereto. When the infections are complicated by abscess or infected hematoma, combination therapy appears to be effective in a shorter period of time, and surgical drainage is infrequently necessary other than drainage of those in the supravaginal, extraperitoneal space. Administration of antibiotics immediately before surgery to women at high risk for postoperative infection has essentially eliminated pelvic infections. These infections range from cuff cellulitis through pelvic abscess and include pelvic thrombophlebitis. Pelvic infections and those in an abdominal, perineal, or vaginal incision can occur during the immediate postoperative period or after discharge from the hospital. As many as 50 per cent of these infections may occur after the patient is discharged from the hospital. Without question, the most appropriate means of objectively identifying infection rates, appropriate and inappropriate use of antimicrobials, and trends in morbidity is with an infection control program, usually consisting of an epidemiologist or specially trained nurses. Their contribution to appropriate patient care is significant. Information uncovered may put some clinicians on the defensive. This need not happen if gynecologic surgeons participate in and define criteria to be used for various infection diagnoses and similar situations. These diagnoses must be based on physical examination evidence, not "presumptive evidence." Antimicrobial administration and selection has an emotional component; objective evaluation avoids this bias. Optimal and efficient patient care is the goal and these programs should be established with that as their only goal. Several synergistic polymicrobial infections involve skin, subcutaneous tissue, and perhaps fascia; these are infrequently observed but require prompt recognition and antimicrobial therapy as well as wide surgical excision to healthy tissue to effect a cure. Clinical presentation extends to both ends of the spectrum with respect to degree of illness. These infections also occur spontaneously in gynecologic sites, and do so only in patients at high risk, such as those with diabetes, delibitating disease, advanced age, or evidence of arteriosclerotic disease. Another infection that was diagnosed and managed only surgically (that is, septic pelvic thrombophlebitis) can now be accurately diagnosed without surgery and can be adequately treated medically.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute pelvic inflammatory disease. Etiologic and therapeutic considerations.

Acute pelvic inflammatory disease (PID) is a community-acquired bacterial infection presumed to be initiated by sexual activity. The therapeutic goals in its treatment are to treat the symptoms, preserve fertility when desired and prevent the development of sequelae. PID should be diagnosed early and accurately, and appropriate antimicrobial therapy should be initiated immediately. Cost-effective parenteral therapy should include antibiotics that can be administered in as few daily doses as possible without sacrificing efficacy.