[More optimism for nursing].
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Biomedical subjects
Publications and source records attributed to J Rieder.
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OBJECTIVE: To identify continuation rates of depot medroxyprogesterone acetate (Depo-Provera) and characteristics of long-term users in a population of inner-city, minority adolescents with high pregnancy rates. DESIGN: Retrospective medical record review. SETTING: An inner-city adolescent clinic and an adolescent pregnancy program. METHODS: A review of the medical records of 250 females aged 13 to 20 years (mean +/- SD, 16.8 +/- 1.1 years), 62.9% Hispanic and 34.2% African American, receiving a first depot medroxyprogesterone acetate injection for contraception between August 1993 and June 1996 was conducted using a standardized form. The mean +/- SD age at menarche of the subjects was 11.6 +/- 1.4 years, and the mean +/- SD age at first intercourse was 14.1 +/- 1.3 years; the mean number of lifetime sex partners was 2.4. Of the subjects, 73.6% had used condoms, 32.0% used oral contraceptives, and none used implants. Of the 201 subjects for whom there were data in the medical records regarding prior fertility, 172 (85.6%) had been pregnant, and 145 (72.1%) had a child. Life table analysis was used to measure depot medroxyprogesterone acetate continuation rates and to compare subgroups of adolescents. RESULTS: Depot medroxyprogesterone acetate continuation rates were found to be 70.3% at 6 months, 48.3% at 9 months, 31.5% at 12 months, and 12.8% at 24 months. The most common reason for depot medroxyprogesterone acetate discontinuation was missed appointments (41.7%). Subjects were followed up for a mean +/- SD of 1.3 +/- 0.7 years after discontinuation of depot medroxyprogesterone acetate use; 46.7% became pregnant. Among those 156 adolescents who discontinued depotmedroxyprogesterone acetate use, 40.0% restarted the method at some later time. Continuation of depot medroxyprogesterone acetate use was more likely if age at first intercourse was younger than 13 years (P = .04). Continuation rates were not related to age, ethnicity, age at menarche, number of sex partners, use of other contraceptives, prior pregnancy, or having a child. CONCLUSIONS: In this study, just less than one third of the adolescents continued depot medroxyprogesterone acetate use for 1 year or longer. This suggests that depot medroxyprogesterone acetate does not function as a long-term method for most inner-city adolescents. The only characteristic that was associated with successful continuation of depot medroxyprogesterone acetate use was young age at first intercourse, implying that experience may be the main determinant of continuation.
Although the 1990s have seen a reduction in unintended pregnancy rates and improved contraceptive-use rates, the negative consequences of unintended pregnancy and STD acquisition continue to plague our youth. Primary health care providers, including pediatricians, play an essential role in further reducing unintended teen pregnancy and STD acquisition rates through the promotion of effective and consistent contraception. Pediatricians need to be aware that now, more than ever, nonhormonal contraceptive methods should be used by every sexually active youth, and counseling of both boys and girls should be routine. Although not as effective at preventing pregnancy as hormonal methods of contraception, many nonhormonal methods provide excellent STD protection. Condoms plus spermicide continue to be a very popular and effective method of pregnancy and STD prevention. The newer polyurethane male and female condoms provide alternative, safe barrier protection, although their efficacy at preventing HIV in vivo needs further study. Diaphragms and cervical caps, in conjunction with spermicide, also provide pregnancy and STD prevention, but not as effectively as male condoms plus spermicide. Although most likely to use condoms in association with another birth control method, adolescents often find dual-method use cumbersome and difficult to comply with. Finally, although IUDs and periodic abstinence are safe methods of birth control for older women in monogamous relationships, they are unlikely to be appropriate for most adolescents. In many respects, we have come full circle back to our "nonhormonal contraceptive roots." As we enter the twenty-first century, we have found that no single "miracle" approach can be used to reduce adolescent pregnancy and STD rates. Rather, pediatricians are obliged to offer nonhormonal methods of contraception, often in conjunction with other birth control methods, as a means of preventing unwanted STDs and pregnancy. Through a comprehensive community approach that uses sex education, abstinence programs, condom-availability programs, and contraceptive-skills training, however, pediatricians can play a central role in the promotion of effective and consistent contraception by adolescents.
Production and release of proinflammatory mediators such as tumour necrosis factor-alpha and neopterin are common events following the activation of the cellular immune system. Concerning inflammatory disorders of the lung, e.g. sepsis or sarcoidosis, high serum neopterin levels have been reported to correlate well with the severity of the disease. These situations are often associated with an increased expression of ICAM-1 reported to be induced in type II alveolar epithelial cells. In our study we investigated the potential effects of neopterin on ICAM-1 synthesis in the type II-like pneumocyte cell line L2. Detection of ICAM-1 gene expression by reverse transcriptase-polymerase chain reaction revealed a dose-dependent effect of neopterin, with maximum impact following 12-h incubations. Comparable results were obtained when ICAM-1 protein synthesis was measured via a cell-based ELISA. In a second set of experiments we were able to show that coincubation of L2 cells with pyrrolidine dithiocarbamate (PDTC) significantly suppressed neopterin-induced ICAM-1 synthesis. Since PDTC is known to be a potent inhibitor of NF-kappaB, the stimulating effects of neopterin on ICAM-1 gene expression and protein generation may be mediated by activation of this transcription factor. From these data we conclude that neopterin stimulates ICAM-1 production in L2 cells. In vivo, these effects may contribute to the prolongation of the inflammatory response, including cytotoxic cell host defence mechanisms that impair the functions of the airway epithelium.
Stimulation of inducible nitric oxide synthase with subsequent release of nitric oxide in large amounts may play a critical part either in host defense reactions or in the pathophysiology of the inflammatory response syndrome leading to septic shock. The aim of the present study was to investigate whether human dermal microvascular endothelial cells exhibit the typical characteristics of an inducible nitric oxide synthase expressing cell. A strong effect on inducible nitric oxide synthase gene expression could be detected when the cells were coincubated with the proinflammatory cytokines interferon-gamma and tumor necrosis factor-alpha with inducible nitric oxide synthase cDNA concentrations averaging 11.7 +/- 0.6 amol per microg total RNA at 24 h, and 25.0 +/- 1.4 amol per microg total RNA at 48 h, respectively. Intracellular staining with an antibody recognizing inducible nitric oxide synthase protein and subsequent analysis by flow cytometry revealed a 4-fold increase of inducible nitric oxide synthase protein in human dermal microvascular endothelial cells treated with interferon-gamma/tumor necrosis factor-alpha. This was accompanied by a significant elevation in nitrite/nitrate concentrations in the cell-free culture supernatants. Our results indicate that human dermal microvascular endothelial cells are provided with an inducible nitric oxide synthase system and can be regarded as an appropriate cell model for investigating inducible nitric oxide synthase gene expression and nitric oxide properties in microvascular endothelial cells.
This review provides updated information relating to the timing of pubertal onset from a large study of girls seen in pediatric practices. In addition, new studies investigating the relationship of the hormone leptin to the onset of puberty are discussed, as well as new information on the neuroendocrine control of pubertal regulation. A provocative study documenting poor mental health, more behavior problems, and lower IQ in children with premature adrenarche when compared with controls raises the question of whether psychological stress triggers premature adrenarche or whether the early increase in adrenal hormone secretion causes psychosocial problems. Finally, significant advances in the management of central precocious puberty in girls have been made over the past year.
Numerous studies indicate that proinflammatory substances like tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) as well as macrophage-derived neopterin are increased in atherosclerotic tissue and thus are potentially involved in the process of atherogenesis. Since apoptotic death of vascular smooth muscle cells (VSMC) is reported to occur in atherosclerotic lesions, we investigated the effects of neopterin, TNF-alpha, and IFN-gamma on apoptosis in cultured VSMC. Morphological changes characteristic of apoptosis as well as DNA fragmentation were detected in cells treated with neopterin, TNF-alpha/IFN-gamma, and neopterin + TNF-alpha/IFN-gamma. Simultaneously, neopterin, TNF-alpha/IFN-gamma, and neopterin + TNF-alpha/IFN-gamma led to inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) synthesis. NO generation was significantly reduced when cells were cotreated with the competitive iNOS inhibitor aminoguanidine. This was accompanied by decreased percentual apoptosis as detected by FACS analysis using all kinds of stimuli. We conclude that neopterin as well as TNF-alpha/IFN-gamma are potent mediators of apoptotic death in VSMC which is at least in part triggered by NO synthesis induced by these proinflammatory mediators.
Synthesis and secretion of proinflammatory mediators like tumor necrosis factor-alpha and neopterin are common events in severe systemic inflammatory disorders, e.g. sepsis and septic shock. Recent data suggest that both substances show similarities with respect to their bioactivities. In the present study we investigated the potential interactions of neopterin and tumor necrosis factor-alpha on inducible nitric oxide synthase gene expression and nitric oxide generation in rat vascular smooth muscle cells. In addition, we studied the influence of neopterin on tumor necrosis factor-alpha synthesis in this cell type. Single stimulation of smooth muscle cells with either neopterin or tumor necrosis factor-alpha caused inducible nitric oxide synthase gene expression and nitric oxide production. Coincubation of cells with both compounds resulted in at least additive effects on nitric oxide synthesis. Quantification of tumor necrosis factor-alpha cDNA revealed a dose-dependent effect of neopterin on tumor necrosis factor-alpha gene expression. Similar results were obtained concerning the detection of tumor necrosis factor-alpha protein and the assessment of tumor necrosis factor-alpha bioactivity. These data suggest that neopterin and tumor necrosis factor-alpha are closely associated with regard to synthesis and effects, respectively. The interactions of both inflammatory mediators in vascular smooth muscle cells might contribute to the excessive release of nitric oxide observed during sepsis, thus triggering cellular destruction and multiple organ failure.
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Methods are proposed which, in combination with those described in an earlier publication by the author, enable the separate determination of the two main types of sulfonamide metabolites, the N4-acetyl derivative and the conjugates, besides the total and the active sulfonamide in body fluids.
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