Alpha2-macroglobulin polymorphisms in Alzheimer's disease and dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is the second most common cause of dementia in the elderly after Alzheimer's disease (AD). The apolipoprotein E gene (APOE) is a major risk factor, but can only account for approximately 50% of AD cases. Whole genome scanning in late-onset AD families has suggested that a locus on chromosome 12 may contribute significantly to disease development. Recently the alpha2-macroglobulin gene (A2M) on chromosome 12 has been suggested as a candidate locus for AD. We therefore determined the influence of two polymorphisms in A2M, a pentanucleotide deletion 5' to the bait domain exon, and a valine to isoleucine polymorphism in the thiolester site of the protein, in AD and DLB cohorts. No evidence was observed for an association between the thiolester or deletion polymorphisms and AD or DLB alone or when accounting for the APOE epsilon4 allele. We did, however, identify a non-significant excess of deletion homozygotes in the AD and DLB groups. This genotype accounted for 4% of disease cases but was absent in the control population. Given that the A2M deletion polymorphism is non-functional, the chromosome 12 AD/DLB locus may be situated elsewhere and not with these A2M polymorphisms.

Pelvic abscess. A sequela of first trimester abortion.

First trimester therapeutic abortions were performed in 6790 patients from January 1, 1972, through December 31, 1973. The infectious morbidity during an 18-month concurrent time period which required readmission to the hospital was 0.52 per 100 women. Four of these women were ultimately diagnosed as having a pelvic abscess thought to be related to the procedure. The cause was probably related to undiagnosed or inadequately managed uterine perforation. Initial management should consist of systemic antibiotics and, if possible, surgical drainage via colpotomy. Two special precautions which should be taken are the use of antibiotics specific for Bacteroides fragilis and the investigation of the possibility of bowel injury. Laparotomy should be considered in unresponsive cases because of the possibility of bowel injury and the necessity of adequate surgical drainage even with appropriate antibiotic coverage.

Laparoscopic tubal sterilization coincident with therapeutic abortion by suction curettage.

PIP: This is a report of the first 100 patients undergoing laparoscopic tubal sterilization concurrent with therapeutic abortion by suction curettage. Operations were performed between May 15, 1971, and August 3, 1972, at the Women's Hospital, Los Angeles County Medical Center. Average age was 30.28 years. 58% were Spanish-speaking, 28% were Caucasian, and 14% Negro. 33% were single; 18% divorced. Mean gravidity was 6; parity was 4. Average period of gestation was 10-11 weeks. 17 had a history of prior abdominal-pelvic surgery. Patients were admitted to the hospital 1 day before operation for history and laboratory tests and the operations were performed by resident doctors supervised by senior obstetric-gynecologic residents. After general anesthesia was administered, Berkeley suction apparatus was used for therapeutic abortion. After suction curettage a cannula or Hega dilator was left in the uterine canal to manipulate the uterus for the laparoscopy. A pneumoperitoneum of 3-4 liters of carbon dioxide was created. The laparoscope was positioned through a small transverse incision and the oviducts coagulated until a distance of 2 cm was well blanched on either side of the grasping forceps. Then the tubes were severed. Subsequently a mild elevation of temperature occurred in most patients. Usually patients were discharged the next morning. Some required postoperative medication for pain. Subsequent pregnancies have not occurred. Bleeding required emergency laparotomy in 1 patient, bowel perforation with the Verres needle during carbon dioxide insufflation occurred without further complication in 1 patient, and endometritis was diagnosed in 2 patients 4 days after operation. Failure to establish pneumoperitoneum occurred 2 times, requiring laparotomy to accomplish sterilization. A patient with a history of pelvic inflammatory disease had adhesions which prevented visualization of both adnexa so a laparotomy was done. An unrecognized burn in an obese patient is presumed to have caused clear yellow fluid to exude from the puncture site, but this resolved spontaneously. The method is considered safe and as free of complications as laparoscopy in the nonpregnant patient.^ieng

Bladder training after surgery for stress urinary incontinence: is it necessary?

Eighty-nine consecutive patients with a clinically and urodynamically proved diagnosis of genuine stress urinary incontinence entered this study. Forty women had a revised Pereyra procedure and 49 had a Burch retropubic urethropexy. All had a suprapubic Bonnano catheter for postoperative bladder drainage. Postoperatively, patients were randomly allocated to "bladder training" (N = 44) or "nonbladder training" (N = 45) protocols. "Bladder training" consisted of scheduled clamping and unclamping of the catheter, whereas the "nonbladder training" patients had continuous bladder drainage throughout their postoperative period. Postvoiding residual urine volume was measured twice daily after the patient had voided with a symptomatically full bladder. The catheter was removed once residual volume was 50 mL or less. The bladder training protocol had no effect on resumption of spontaneous voiding after surgery. There was no significant change in length of postoperative bladder catheterization or in urinary tract infection rate among women with or without bladder training.

Suprapubic versus transurethral bladder drainage after surgery for stress urinary incontinence.

Fifty-one patients with clinical and urodynamic diagnoses of stress urinary incontinence were randomly allocated to either suprapubic (N = 24) or transurethral (N = 27) bladder drainage after vaginal surgery for stress incontinence (revised Pereyra procedure). Postoperative use of suprapubic bladder drainage significantly reduced febrile morbidity (calculated as fever index; P less than .01) and length of hospitalization (P less than .05). Postoperative normal bladder functions resumed more quickly when suprapubic drainage was used (P less than .05), so that most patients did not need bladder catheterization upon discharge, as opposed to more than half of those with Foley catheters, who left the hospital with a catheter in place (P less than .05). We conclude that it is both beneficial and cost-effective to use suprapubic bladder drainage after a Pereyra operation for stress urinary incontinence.

Early secondary repair of third- and fourth-degree perineal lacerations after outpatient wound preparation.

Research has shown the feasibility of early secondary repair of third- and fourth-degree perineal laceration dehiscence after a short period of inpatient wound preparation; therefore, we evaluated the feasibility of early closure after outpatient wound preparation. In this case series, 23 patients underwent early repair of third- or fourth-degree perineal laceration after outpatient wound preparation. Twenty-one patients (91%) had a fourth-degree dehiscence, whereas two (9%) had a third-degree dehiscence. We repaired the defects after 4-10 days (mean 7) of outpatient debridement and wound preparation. All repairs were successful (95% confidence interval 85-100%), and no subsequent breakdowns occurred. One patient developed a small rectal-perineal fistula which, after irrigation, closed spontaneously within 3 months. Early repair of third- or fourth-degree dehiscence after outpatient wound debridement and preparation is both practical and effective. Forcing patients to wait the traditional 3-4 months before repairing such defects may be both cruel and unnecessary.

Low urethral pressure and stress urinary incontinence in women: risk factor for failed retropubic surgical procedure.

Nineteen women with stress urinary incontinence (SUI) and low urethral pressure were compared with 106 patients with SUI and normal urethral pressure. All underwent either a revised Pereyra procedure or Burch retropubic urethropexy, and all had detailed clinical and urodynamic evaluations before their operation and one year postoperatively. Surgical procedures effectively stabilized the bladder base and enabled adequate abdominal pressure transmission to the urethra in both groups of women. In spite of these urodynamic findings, the failure rate in women with stress urinary incontinence and low urethral pressure was significantly higher compared with women with good urethral pressure (50% vs 23% for the Pereyra procedure and 33% vs 12% for the Burch procedure [p less than 0.05]), indicating an etiology for their incontinence other than poor support to the urethrovesical junction; therefore, the need for another approach to cure stress incontinence.

Role of ultrasound in urinary incontinence evaluation.

Transrectal ultrasound was used to assess anatomic support of the urethrovesical junction (UVJ) in continent and stress incontinent women. UVJ drop on straining of less than 1 cm as assessed by transrectal ultrasound correlated well with good support to the UVJ. Drop of UVJ of more than 1 cm on straining correlated with poor support to bladder neck and stress urinary incontinence. The transrectal technique is quick and easy to perform and interpret.

First and midtrimester abortion with intramuscular injections of sulprostone.

An intramuscular injection of a newer PGE2 analogue (Sulprostone) was given to fifty-seven patients for a late first or second trimester abortion. The drug was injected in doses of 500 microgram every 6 hours for a maximum of 24 hours. Fifty-two patients aborted. The incidence of gastrointestinal side effects was similar to patients receiving intramuscular 15-methyl PGF2 alpha and there were no serious complications.

PIP: A study was undertaken to assess the efficacy and side effect rate in induced abortion with Sulprostone, a newer analogue of PGF2 (prostaglandin). 57 healthy women between 10 and 16 weeks gestation were selected at random from the pregnancy termination clinic at Los Angeles County-University of Southern California School of Medicine to receive Sulprostone by intramuscular injection. The drug was administered in a 500 mcg dosage every 4 hours up to a maximum of 6 injections. The procedure was termed a failure if any therapy other than Sulprostone was needed or if the patient had not aborted 24 hours after the initial injection. 19 women (33%) aborted within 12 hours and 52 (91%) within 24 hours with a mean injection-abortion time of 14.1 hours and range from 2.7 to 24 hours. Primigravid patients required more time to abort than multigravida patients. 16 patients aborted completely, 36 required surgical removal of the placenta, and 5 required termination by other means. Abortion time was inversely correlated with gestation age; women over 16 weeks gestation had a higher failure rate. The incidence of side effects was similar to that in PGFalpha-aborted patients and there were no serious complications. The advantage of Sulprostone over 15-methyl PGF2alpha is the reduced number of injections required to produce an abortion. There was, however, a higher failure rate with Sulprostone.

The vaginal administration of 9-deoxo-16,16-dimethyl-9-methylene PGE2 for second trimester abortion.

9-Deoxo-16,16-dimethyl 9-methylene PGE2 was given as a vaginal suppository at 0 and 8 hours to 37 patients. Two different doses were given, a 75-mg and 60-mg dose. The larger dose achieved an 86% abortion rate at 24 hours and for the smaller dose it was 53%. When an intramuscular injection of 15-methyl PGF2 alpha Tham was added at 24 hours, the success rate was 91% and 80% at 36 hours. The incidence of gastrointestinal side effects were significantly reduced when compared to vaginal administration of either PGE2 or 15-methyl PGF2 alpha methyl ester. The incidence of temperature elevation was similar to that achieved with the use of vaginal PGE2 but higher than with the use of vaginal 15-methyl PGF2 alpha methyl ester.

PIP: A comparative study was conducted to assess the relative efficacy and side effects of 2 dosage schedules using 9-deoxo-16,16-dimethyl-9-methylene PGE2alpha (prostaglandin) for 2nd-trimester abortion. 37 healthy women received the PGE2alpha analog. 22 received an initial 75-mg dose in a vaginal suppository repeated at 8 hours; 15 recived a 60-mg dose which was repeated at 8 hours. If abortion had not occurred at 24 hours, an intramuscular injection of 250 mcg 15-methyl PGF2alpha was administered and repeated at 2-hour intervals for at least 6 injections. The success rate with the 75-mg dose was 86% at 24 and 91% at 36 hours. The mean time for abortion was 14.7 hours with a range of 5.5 to 36 hours. 6 of the women aborted completely and 14 required curettage to complete the procedure. The success rate for the 60-mg dose was 53% at 24 and 80% at 36 hours. The mean time was 21.9 hours with a range of 5.8 to 36 hours. 8 aborted completely and 5 required curettage. The lower dosage required a longer abortion time and produced slightly more side effects. The incidence of gastrointestinal side effects with this method of administration was significantly reduced when compared to vaginal administration of either PGF2 or 15-methyl PGF2alpha methyl ester. All of these PG abortifacients are preferable to saline solution.

Midtrimester abortion with intramuscular injection of 15-methyl-prostaglandin F2alpha.

PIP: This study examines the efficacy and side effects of 15-methyl-prostaglandins F2alpha (PGF2a) free acid administered intramuscularly for midtrimester abortion. 50 healthy women aged 14 to 37 years and between 12 to 18 weeks gestation were randomly selected from the abortion clinic at the Los Angeles County/USC Medical Center, Women's Hospital to participate in the study. The prostaglandin preparation was supplied in ampules containing 1.1 mg. in 2.2 ml. of aqueous solution. The injection was given every 2 hours until the fetus was expelled or for a maximum of 12 injections. Vital signs of the patients were closely monitored. 46% (23) of the subjects aborted within 12 hours and 90% within 27 hours. Mean injection-abortion time was 13.5 hours (range, 5 3/4 to 27 hours). The effectiveness and rapidity of abortion was related with gestational age: the lower the gestational age, the shorter the abortion time. Women with more than 17 weeks gestation had a higher failure rate. Mean number of injections was 7.5. 5 patients failed to abort with prostaglandin alone, all of them primigravidas and weighing in excess of 150 lbs; supplemental therapy was provided. Side effects and complications associated with 15-methyl-PGF2a included: emesis (66%); diarrhea (76%); flushing (12%); chills (4%); fever of 100 degrees Fahrenheit (12%); pain requiring medication (16%); and blood loss (6%). The success of this method appears to be related to dosage; parity; gestational age; weight of patient; and frequency of administration. Although there were side effects, these were outweighed by rapid abortion time, mild contractions, and ease of administration. Asthma is the only medical contraindication to prostaglandin therapy.^ieng

The Ball-Burch procedure for stress incontinence with low urethral pressure.

Up to a 50% failure rate may be expected when genuine stress incontinence with low urethral pressure is treated with routine urethropexy. A combination of Ball and Burch procedures has been suggested as an acceptable alternative to a sling procedure for the condition. In this study, 18 women undergoing a Burch procedure and 48 undergoing a Ball-Burch procedure were available for follow-up urodynamic evaluation. The one-year objective failure rate of the Burch procedure was 38%, and that of the Ball-Burch procedure was 10%, for a statistically significant difference (P less than .05). The Ball-Burch procedure appears to be an effective means of curing women of genuine stress incontinence with low urethral pressure.

Negative Q-tip test as a risk factor for failed incontinence surgery in women.

Fifteen women with a clinical and urodynamic diagnosis of stress urinary incontinence had a negative Q-tip test (greater than or equal to 30 degrees Q-tip angle change on straining). All 15 had retropubic surgical procedures for stress incontinence in the form of a revised Pereyra procedure (n = 6) or Burch retropubic urethropexy (n = 9). Five of the nine patients undergoing the Burch procedure (55%) and three of the six undergoing the Peyreya procedure (50%) failed the procedure, for an overall failure rate of 53%. This rate was five times higher than that among women with stress urinary incontinence and a positive Q-tip test who underwent the same procedures (P less than .01). We conclude that women with stress urinary incontinence and no anatomic defect in the support of the urethrovesical junction should not undergo retropubic procedures because of their high failure rate. Other occlusive procedures, such as sling operations, should be considered for this group.

Prostaglandins for enhancing detrusor function after surgery for stress incontinence in women.

Sixty-nine women with a clinically and urodynamically proven diagnosis of genuine stress incontinence underwent urethropexy in the form of the revised Pereyra procedure (n = 28) or Burch colposuspension (n = 41). Postoperatively the patients were assigned randomly to one of three study groups. Group 1 received a daily saline injection to the bladder (control group, n = 24), group 2 received daily intravesical injections of 250 mg of prostaglandin F2 alpha (PGF2 alpha) (n =23), and group 3 received a daily 10-mg PGE2 (PGE2) vaginal suppository (n = 22). The patients' suprapubic catheter was removed once the postvoiding residual urine volume was less than or equal to 50 mL. Both PGE2 and PGF2 significantly reduced the length of time required for postoperative bladder drainage after both the Burch and Pereyra procedures as compared to that in the control group (P less than .05). Hospital stay and bacteriuria were reduced as well in women receiving postoperative prostaglandins as compared to the control group. Clinically there were no differences between PGE2 and PGF2 alpha. Both produced no side effects, were well tolerated by the patients and were effective in reducing both the number of days required for bladder catheterization and the incidence of significant bacteriuria when administered after the surgical procedures.

Detrusor instability. Is the bladder the cause or the effect?

Seventy-two patients had a clinical and urodynamic diagnosis of detrusor instability. All were given four weeks of anticholinergics (oxybutinin, 5 mg three times a day) and had their evaluation repeated. Forty-one patients (57%) responded favorably to the anticholinergics, and 31 (43%) did not. The 31 discontinued the anticholinergics and were placed on sympathomimetics (phenylpropanlamine, 25 mg two times a day) for another four weeks before repeating their evaluation. Based on urethrocystometry, two groups were identified: group I (n = 44) had bladder contraction that preceded any urethral pressure change, and group II (n = 28) had urethral relaxation that preceded bladder contraction. Most women in group I (38 or the 44 [86%]) responded favorably to anticholinergics. Most women in group II failed to respond to anticholinergics, while more than two-thirds of them (19 of 28 [68%]) responded favorably to sympathomimetics (P less than .001). Our results suggest that bladder contraction that precedes any urethral pressure change represents detrusor pathology as opposed to bladder contraction that follows urethral relaxation: it probably represents urethral pathology.

Diagnostic considerations in coexisting bladder and urethral leiomyomata. A case report.

BACKGROUND: Leiomyomata of the lower urinary tract in women are rare. Coexisting urethral and bladder leiomyomata have never been reported before. CASE: A 45-year-old woman, gravida 6, para 5, abortus 1, presented with a one-year history of increasing frequency, nocturia and hesitancy of up to 10-15 minutes at times. An intravenous pyelogram showed an extrinsic mass at the bladder neck. Urethrocystoscopy revealed a regular bulge at the level of the bladder neck on the right side without involvement of the bladder mucosa. Ultrasound showed a 5 x 4.7 x 4-cm mass of heterogeneous echogenicity, posterior to the bladder and anterior to the lower uterine area, with a normal-appearing uterus. The patient underwent surgery for vaginal excision of the tumor. Two separate masses were found at surgery. One small, firm, solid, 2-cm mass was found on the posterior proximal aspect of the urethra, and a larger, soft, 3 x 3-cm mass was found on the posterior lower aspect of the bladder. The masses clearly arose from the urethra and bladder, respectively. Rapid frozen section revealed smooth muscle cells consistent with leiomyomata. Both leiomyomata were entirely resected. CONCLUSION: Lower urinary tract leiomyomata should always be considered in the differential diagnosis of an anterior vaginal mass in premenopausal women.

Role of the Q-tip test in evaluating stress urinary incontinence.

The Q-tip test was applied on 105 patients. Fifty-one had stress urinary incontinency (SUI), 28 had bladder instability by clinical and urodynamic criteria, and 36 had mild or moderate pelvic relaxation without urinary pathology. More than 90% of the patients with SUI and no previous surgery had a positive Q-tip test, with 90% test sensitivity in this group. More than one-third of the patients with bladder instability and almost one-half of the patients with pelvic relaxation and no urinary incontinence had a positive Q-tip test, for low test specificity. The Q-tip test is a simple clinical tool for diagnosing pelvic relaxation, which at times leads to SUI. Almost all patients with primary SUI have pelvic relaxation. The Q-tip test alone does not stand as a diagnostic test. When it is positive, the diagnosis of genuine stress incontinence is possible although not absolute. A negative test should cause one to question the diagnosis of genuine stress incontinence, and sophisticated and more expensive tests should be ordered before establishing a final diagnosis.

Role of cystourethrography in the preoperative evaluation of stress urinary incontinence in women.

Thirty-two women with stress urinary incontinence and 27 control continent patients with pelvic relaxation underwent a detailed clinical and urodynamic evaluation of the lower urinary tract. All patients underwent a standard chain urethrocystographic evaluation to detect anatomic pathology of the lower urinary tract. Urethrocystographic study included an evaluation of the posterior and anterior urethral angle, funneling of the proximal urethra on straining, the position of the urethrovesical junction and flattening of the bladder base. No differences were seen in the incidence of radiographic findings in women with pelvic relaxation with or without stress urinary incontinence. All five cystographic criteria were similar in the continent and stress incontinence patients. Static urethrocystography cannot differentiate women with and without stress urinary incontinence from among those with pelvic relaxation and thus should not be relied upon in the evaluation of women with urinary incontinence.