Controlled degradation and macrophage responses of a fluoride-treated polycaprolactone.

We have developed a new bone replacement material based on polycaprolactone (PCL), which can act as a suitable matrix for monomer transfer molding of degradable composites. A boron trifluoride catalyst with glycerol additive was used to produce PCL with a degradation rate that can be altered by treatment with fluoride ions. The effect of cations on the degradation of the polymer and macrophage cell responses are discussed. We found that treatment with fluoride ions reduced the degradation rate. No significant difference between these three fluorides was observed although a general trend was seen where KF-treated PCL appeared to degrade slower than NaF-treated PCL which was slower than NH(4)F-treated PCL. Variation in solubilities of the salts was observed where the K(+) cation had the highest solubility and the Na(+) cation had the lowest solubility, which suggests that NaF was able to degrade the polymer more efficiently than the other fluorides. No significant macrophage activation was observed after culture on the polymer surfaces as determined by peroxide and IL-1 beta release, whereas some activation occurred after culture in degradation products.

Levonorgestrel contraceptive implants in female patients 14 to 21 years old.

OBJECTIVE: To determine which factors are associated with duration of use of a levonorgestrel implant (Norplant) for contraception in adolescents and young adults. DESIGN: We retrospectively studied 144 young women (14 to 21 years of age) who chose a levonorgestrel contraceptive implant at Mayo Clinic Rochester between April 1990 and December 1993. MATERIAL AND METHODS: The following information was obtained at the time of insertion of the implant and from any follow-up visits: demographics, prior contraceptive experiences, frequency and management of complications, complications noted at removal of the implant, and subsequent contraceptive choice. The duration of use was examined. RESULTS: Of the 144 young women who underwent insertion of a Norplant system, 75 telephoned or made a medical appointment because of implant-related side effects. During the follow-up period, 64 patients had the Norplant system removed. The Kaplan-Meier estimate of the probability of the Norplant system remaining in place for at least 12 months was 83 % and for at least 24 months was 63 %. Duration of Norplant use was not found to differ with respect to age, prior contraceptive use, or timing of insertion, but it was significantly shorter among those with a prior pregnancy than in those who had never been pregnant. CONCLUSION: These findings suggest that a group of young women who are likely to continue use of a contraceptive implant (with or without treatment for side effects) are those who have never been pregnant.

PIP: A retrospective study of 144 US women 14-21 years of age who requested and received the Norplant contraceptive implant system at the Mayo Clinic (Rochester, Minnesota) in 1990-93 analyzed the factors associated with duration of method use. Of the 124 women who reported past use of contraception, 94 (76%) had been pregnant at least once. The method most commonly used before Norplant was oral contraception (57%). The reasons for Norplant selection were its convenience (86%) and problems tolerating the pill (14%). Of the 130 Norplant users who either telephoned or made a clinic appointment after insertion, 60% reported side effects such as breakthrough bleeding, headache, and depression or mood swings. 64 women had the implants removed. The median duration of Norplant use was 29 months. The Kaplan-Meier estimate of the probability of the Norplant system remaining in place for at least 12 months was 83% and 63% for at least 24 months. Age, prior contraceptive use, and timing of insertion had no impact on duration of Norplant use. Multivariate analysis indicated that women with at least 1 prior pregnancy had a two-fold increased risk of Norplant removal compared to those who had never been pregnant. Larger studies are needed to identify additional factors associated with long-term use of injectable contraception among young women and to suggest interventions that would improve compliance with routine follow-up.

Pregnancy after pancreatic-renal transplantation because of diabetes.

In this article, we describe two pregnancies in the same patient after pancreatic-renal transplantation. Severe, labile hypertension necessitated delivery at 35 weeks during the patient's first pregnancy and at 30 weeks (associated with renal graft obstruction) during her second pregnancy. Women with insulin-dependent diabetes mellitus who undergo pancreatic-renal transplantation can have a successful pregnancy if adequate multidisciplinary, specialized medical care is rendered.

Endometrial neoplasia: prognostic significance of ploidy status.

For several decades, clinical and histologic assessment of various phenotypic properties has provided a basis for treatment planning. However, it is recognized that, preoperatively, clinical assessment identifies only 20% of patients with advanced disease. Furthermore, the variability in intraoperative sampling, the subjectivity and limitations of histologic interpretation, and the variability in response to standardized treatment modalities represent concerns associated with the current treatment of endometrial carcinoma. Presumably, early dissemination, early recurrence, treatment refractoriness and, ultimately, compromised survival are reflections of the inherent biologic characteristics of the tumor. A reasonable assumption is that proscribed molecular events determine various behavioral characteristics of tumors that become manifested at the time of transformation rather than evolving as the tumor volume increases. Therefore, the identification of one or more of these quantifiable molecular variables that directly or indirectly assess tumor biology would assist clinicians in determining patient risk status and in selecting treatment options. As noted, DNA ploidy is an independent, broadly applicable, quantifiable predictor of progression-free survival in patients with endometrial cancer and, therefore, warrants designation as a major prognostic factor or therapeutic determinant. Aneuploidy implies the presence of an abnormal quantity of genomic material and imparts a progressively less favorable prognosis as the DNA index increases. These assayable aberrancies of cellular DNA content presumably reflect the more extreme alterations at the molecular level. Because neoplastic transformation is generally a multistep process, aberrations in several proto-oncogenes or tumor suppressor genes (or both) presumably must be realized before a clinical malignancy develops. A number of genes that encode for various regulatory proteins are overexpressed in endometrial cancer. Whether these aberrancies are fundamental to the pathogenesis of this disease process is unclear. Nevertheless, there appears to be an association between DNA ploidy and the overexpression of several regulatory genes, such as c-fms, K-ras, HER-2/neu, and p53. Although overexpression of these oncogenes and tumor suppressor genes harbor prognostic significance in endometrial cancer, the ploidy status of the tumor appears to represent the most cogent objective variable. As the etiopathogenesis of endometrial carcinoma becomes more discernible, one can envision a limited number of tissue-specific molecular-genetic indices characterizing the risk status of patients. Because the estimated number of deaths from endometrial cancer has doubled since 1987, reassessing of the therapeutic determinants for this disease process is important. The management objective for endometrial cancer by the turn of the century should be the identification of patients at high risk for advanced disease or post-treatment recurrences (or both) at the time of clinical declaration of symptoms and diagnosis. Such pretreatment identification would afford patients at high risk for advanced or recurrent disease access to physicians with special expertise and would facilitate the evaluation and application of new or modified therapeutic modalities. Equally important would be the identification of patients at low risk for untoward outcome, thereby avoiding the cost and morbidity of excessive therapeutic measures.

Urinary incontinence in the elderly population.

OBJECTIVE: To describe the causes, evaluation, and management of urinary incontinence in the elderly population. DESIGN: We reviewed pertinent articles in the medical literature and summarized the types of incontinence and contributing factors. RESULTS: Urinary incontinence is common in elderly patients and often has a major role in determining whether a person can remain independent in the community or requires nursing home placement. Urinary incontinence is not a single entity but rather several different conditions, each with specific symptoms, findings on examination, and recommended treatment. Thus, accurate classification is important for appropriate management. Because of the complexity of urinary incontinence, many physicians are uncomfortable with undertaking assessment and treatment. Hence, many patients are not asked about incontinence, and the condition remains untreated and often considered a natural consequence of the aging process. Urinary incontinence can be treated and either cured or alleviated with treatment. CONCLUSION: Elderly patients should be asked about symptoms of urinary incontinence because appropriate assessment and treatment can usually provide relief.

Hormone replacement therapy: management of common problems.

OBJECTIVE: To describe common pitfalls associated with hormone replacement therapy (HRT) and recommendations to prevent or ameliorate them. DESIGN: After pertinent articles and texts were reviewed, we outlined the available regimens of HRT, the commonly encountered side effects, and the management options. RESULTS: HRT is frequently prescribed for elderly women. Vaginal bleeding, nausea, breast tenderness, migraine headaches, mood alterations, and abdominal bloating are common occurrences with HRT. These problems often can be managed by changing the dose, using another preparation or regimen, or altering the route of administration. For example, transdermal administration of estradiol may be tolerated better than oral therapy in patients with nausea. Irregular bleeding warrants endometrial biopsy to rule out hyperplasia. CONCLUSION: With simple measures, common side effects of HRT can easily be managed by primary-care physicians. Gynecologic referral is recommended when endometrial biopsy is necessary or when symptoms fail to respond to adjustments in hormone therapy.

DNA ploidy of ovarian granulosa cell tumors. Lack of correlation between DNA index or proliferative index and outcome in 40 patients.

BACKGROUND: Most cases of granulosa cell tumor of the ovary are characterized by relatively good outcome; however, some tumors behave aggressively, and some tend to recur many years after the initial diagnosis. Because DNA ploidy has been shown to predict biologic behavior better than conventional prognostic variables in many types of genitourinary tumors, the DNA ploidy of granulosa cell tumors was studied to determine if this test correlates with recurrence or survival. METHODS: Paraffin embedded tissue blocks were available from the primary ovarian tumors of 40 patients. DNA ploidy, percent S-phase fraction, and proliferative index were determined for each sample and were compared with patient outcome. RESULTS: Of the 40 tumors, 33 were DNA diploid, 5 were DNA near diploid/aneuploid, and 2 were aneuploid. The Kaplan-Meier estimate of the probability of tumors not recurring within 5 years postoperatively was 0.907 (95% confidence interval: 0.811, 1.00). CONCLUSIONS: There is insufficient evidence to claim that the DNA pattern is associated with morphology, stage of disease at diagnosis, or tumor size or that either survival or progression free survival differs with respect to any of the conventional prognostic factors considered. However, progression free survival tends to be shorter for those whose maximal tumor dimension was at least 10 cm (borderline significance, P = 0.0597), and survival time tends to be shorter for those with a high proliferative index (P = 0.0008).

A comparative study of alternative bone-conduction calibration methods.

The accepted instrument for calibrating the bone-conduction section of an audiometer is the artificial mastoid. For a variety of reasons, alternative calibration methods are in general use. Three common methods are: (1) the input voltage method; (2) the real-ear threshold method using normal-hearing listeners; and (3) the real-ear threshold method using subjects with sensorineural hearing loss. The present investigation compared these methods for both accuracy and efficiency. There were no significant differences in accuracy found among the three calibration methods. Substantial differences in efficiency were noted, however. When accuracy and efficiency are considered, the input voltage method appears to be the best alternative method for calibrating the bone-conduction system of an audiometer.