Ultrasound-guided removal of Implanon devices.

Our study has shown that ultrasound-guided localisation and removal of Implanon rods is safe, practical and highly successful. Over a 4-year period, 119 patients had successful, uncomplicated removal of their subdermal devices.The technique is particularly useful for removal of the device when it is not palpable or when an attempt at removal of a palpable device has not been successful.

Posttranslationally modified tubulins and microtubule organization in hemocytes of the brine shrimp, Artemia franciscana.

Crustaceans possess blood cells (hemocytes) that mediate organismal defense and are analogous to vertebrate leukocytes. In order to more fully characterize these types of cells, hemocytes of the branchiopod crustacean, Artemia franciscana, were analyzed. The data indicate that Artemia have one type of hemocyte, ranging in morphology from compact and spherical to flat and spreading when examined in vitro. Electron microscopy revealed many cytoplasmic granules in the hemocytes and only a limited number of other membrane-bound organelles. Centrioles and microtubules were also visible in thin sections of chemically fixed samples. The cytoplasm of spherical hemocytes was completely labeled by general antitubulin antibodies, but in flattened hemocytes packing of cytoskeletal elements was less tight and individual microtubules were observed. Probing of Western blots disclosed acetylated, tyrosinated, and detyrosinated tubulin isoforms in hemocyte homogenates, the first characterization of posttranslationally modified tubulins in this cell type. Acetylated tubulin was restricted to a subset of microtubules, whereas tyrosinated microtubules were displayed more abundantly. Staining obtained with antibody to detyrosinated tubulin was unusual because it was limited to the perinuclear region of hemocytes. Incubation of blood cells with a monoclonal antibody to gamma-tubulin yielded fluorescent dots sometimes in pairs, a pattern characteristic of centrosomes. The findings support the conclusion that Artemia hemocytes undergo rapid morphogenesis in vitro accompanied by extensive rearrangement of their microtubules, the latter probably indicative of cytoskeletal changes that occur during cell movement and phagocytosis. Additionally, the hemocytes contain posttranslationally modified alpha-tubulins and centrosome-associated gamma-tubulin, both with the potential to influence microtubule organization and function.

Depo provera discussion paper on clinical care, effectiveness and side effects

Recent changes to the health services have led to an increased provision of clinical care in family planning clinics. While some women may only require contraceptive services, others may demand advice on a breadth of lifestyle issues, including diet and nutrition. Obesity affects 17% of women of childbearing age in Scotland and being overweight during pregnancy has significant health risks. A postal survey of 227 nurses identified as working in family planning clinics in Scotland was conducted in 1998. After a mail shot and one reminder, a net response rate of 64% (n = 145) was achieved. Overall, it was found that obesity was perceived as the most extensive problem in women of childbearing age. Seventy nurses (48%) reported that, in addition to offering family planning services, they gave dietary advice 'frequently' or 'always' to their clients without being asked. There were differences in nutrition-related activities in consultations between nurses offering family planning services only and those who routinely offered nutritional advice. Over half (61%) of the nurses reported that they would give advice regarding weight management even if the patients were not seeking help, although there was no significant difference between the two comparison groups. In some cases, the nutritional advice offered to clients highlighted a deficit in training. Most nutrition education came from diploma and/or training courses and scientific literature, followed by 'experience'. Those nurses already embracing a nutritional advice and guidance role were more interested in further nutrition training (p = 0.018) than the other nurses. However, overall, 67% of the nurses wished to train further in nutrition and weight management. The findings suggest that family planning nurses should be supported to develop nutritional advice and guidance skills, and that there is a pressing need for training in public health nutrition and weight management for nurses working in family planning services.

Depo Provera. Position paper on clinical use, effectiveness and side effects.

Depo Provera (medroxyprogesterone acetate, DMPA) when given as 150 mg by deep intramuscular injection every 12 calendar weeks (84 days+5 days), is a highly effective contraceptive with a very low failure rate comparable to modern copper IUDs and lower than many other methods. It should be available as a first line method to all who wish to make an informed choice about reversible methods of contraception. Pre-use counselling is essential to minimise the effect of menstrual change which occurs in most patients. However there is great patient variability. Use of DMPA is independent of intercourse and also independent of the user's memory (and thus of continuing motivation), other than remembering the 12 weekly appointments. For many women this is a great advantage. Oral contraceptive methods involve remembering to take a pill each day, in the case of the progestogen only pill within the same three hours each day. This places considerable strain on women who lead irregular lifestyles, who are very busy or travel frequently. Such women often describe a constant 'fear of forgetting', especially with the POP. The main potential disadvantage of DMPA in this country are likely to be menstrual disturbance and weight gain. The combined oral contraceptive pill gives the appearance of excellent cycle control because it removes the natural cycle altogether and replaces it with an artificial one. All progestogen-only methods, whether low or high dose, lead to menstrual disturbances, so in this respect DMPA is not unique. Although troublesome, the menstrual disturbances which occur in DMPA users very rarely require operative medical intervention, and can often be improved simply by short courses of oestrogen or shorter injection intervals. Again, women need to know what can be done so that they are aware that they should seek advice early, rather than miserably waiting.for their 12 week appointment. DMPA has no appreciable effects on blood pressure or thrombosis risk. In this it has an advantage over the combined oral contraceptive pill, and provides a simple, effective alternative for women who cannot use the pill for these reasons. Similarly, it has been suggested that women who suffer from focal migraine and are therefore advised against use of the combined oral contraceptive pill can still use progestogen-only contraceptives. Although the POP is medically safe in these circumstances, in young women it is less effective, and involves strict time keeping, which will be disadvantageous for some women. Side effects, long term use and schedules of administration are also discussed. The use of local protocols to allow nurse administration is to be supported both in general practice and the clinic situation. Perhaps the most important issue surrounding the use of DMPA is that of patient information. The method has had a particularly bad public image, which naturally makes potential users anxious and subject to misinformation from poorly informed or biased sources. Also, it is temporarily irreversible during its three months duration, so the duration of any problems or anxieties resulting from side effects may be longer than for other methods. It is of paramount importance that easily understood, accurate patient information leaflets are available, since biased and inaccurate information is readily available from women's magazines, perpetuating the myths surrounding the method.

PIP: This study presents a review of current clinical evidence on the usefulness of Depo Provera (medroxyprogesterone acetate, DMPA), a long-term method of reversible contraception. It is taken as an intramuscular long-acting agent (150 mg every 12 calendar weeks). The user failure rate approaches the method failure rate, which varies considerably with age. In terms of metabolic effects, it did not show changes in cholesterol or triglycerides and had no significant effect on hemostasis, which impairs the oral glucose tolerance test (OGTT) glucose response and increases insulin response. There were no significant adverse effects on long term growth and development in DMPA exposed children and no delays in return to fertility. For cancers, controlled surveillance of DMPA users found no overall increased risk of ovarian, liver or cervical cancer and even found a prolonged protective effect in reducing the risk of endometrial cancer. However, increased risk of breast cancer in recent users was observed; this could be due to enhanced detection of breast tumors of women using DMPA. The main DMPA disadvantages are menstrual disturbance and weight gain after 1 year. Bone mineral density (BMD) is found to be significantly lower. DMPA patients' sociodemographic characteristics and behavior placed then at higher risk for adverse pregnancy outcome in low infant birth weight and also possibly in polysyndactyl and chromosomal defects. Thus, for injectable progestogen, the data is again less conclusive. Risks may be similar to POP (progestogen-only contraceptive pill), but did not reach significance in the meta-analysis.

Characterization of gamma-tubulin in Artemia: isoform composition and spatial distribution in polarized cells of the larval epidermis.

Microtubule arrangement is influenced by gamma-tubulin, a soluble protein of the eukaryotic cell cytosol and a component of microtubule-organizing centers. In this study, affinity purified antibodies to gamma-tubulin were prepared and their specificity demonstrated by immunostaining of Western blots and in competitive ELISAs. When employed to label mouse fibroblasts, one or two brightly stained dots appeared in each cell, a pattern characteristic of centrosomes. Antibody 9, raised to a conserved amino-terminal peptide of gamma-tubulin, was used with TU-30 (from P. Dráber) to characterize gamma-tubulin in the crustacean, Artemia franciscana. Cell-free protein extracts from Artemia contained gamma-tubulin and it purified with alpha/beta-tubulin through several preparative steps. Probing of Western blots prepared from two-dimensional gels yielded a single isoform of gamma-tubulin in Artemia with a pI of about 5.6. Immunostaining with TAT, a general antibody to alpha-tubulin, demonstrated that Artemia possess two morphological types of immune blood cells (hemocytes) with distinctive microtubule arrays. Both the compact spherical hemocytes and the flatter, spreading cells exhibited fluorescent dots, often in pairs, when labelled with antibodies to gamma-tubulin. Microtubules in polarized cells of the epidermis were also brightly stained with antibody to alpha-tubulin, revealing interphase arrangements, anastral mitotic spindles and midbodies. Antibody 9 and TU-30 gave punctate staining patterns in interphase epidermal cell layers and they occasionally labelled midbodies. Unexpectedly, gamma-tubulin was seen only rarely at both poles of mitotic spindles in epidermal cells. The complete absence of asters and the apparent lack of gamma-tubulin at all but a small number of poles indicate that formation and structure of the mitotic spindle in epidermal cells of Artemia are unusual.

Impact of patient counseling on acceptance of the levonorgestrel implant contraceptive in the United Kingdom.

Patient counseling is an important aspect of family planning. Patient choice, compliance, and satisfaction with a contraceptive method depend heavily on the counseling experience. This is especially true in the United Kingdom where contraceptives are provided to patients at no direct cost to them. Women are therefore more likely to choose a contraceptive option based on perceived desirability as opposed to cost. We surveyed physicians from six family planning centers in the United Kingdom who have extensive experience with levonorgestrel contraceptive implants with respect to counseling issues and patient acceptability of levonorgestrel implants. The physicians reported on their experience with 521 women. They acknowledged the need for and importance of counseling, and these centers provided preinsertion counseling 100% of the time. Primary responsibility for counseling was handled by the physician who spent, on average, 19 minutes per patient discussing the advantages and risks of levonorgestrel implants. Physicians felt that the majority of women (82%) accepting levonorgestrel implants had a positive experience. The incidence of bleeding irregularities was consistent with that reported in clinical trials, and this did not substantially affect the postinsertion acceptability of the product. Effective counseling is no doubt responsible for the high level of patient acceptance of these side effects. In a review of the literature, we found counseling to be a significant factor in a woman's tolerance of contraceptive-induced bleeding irregularities, which are frequently experienced with levonorgestrel implants. The results of our survey support the literature findings.

Abuse history and chronic pain in women: I. Prevalences of sexual abuse and physical abuse.

OBJECTIVE: To compare the prevalences of childhood and adult physical and sexual abuse in women with chronic pelvic pain to those in women with chronic nonpelvic pain (headache) and pain-free women. METHODS: Using a structured interview, we assessed the prevalence rates of both sexual abuse and physical abuse in 64 women with chronic pelvic pain, 42 women with chronic headache, and 46 pain-free women. Abuse histories were stratified by age at occurrence and severity. Demographic characteristics of the three groups were also assessed. RESULTS: Women with chronic pelvic pain were found to have a higher lifetime prevalence of sexual abuse, involving penetration or other contact with the unclothed genitals or anus (ie, major sexual abuse), than either comparison group. Further, more women in the chronic pelvic pain group had experienced major sexual abuse in both childhood and adulthood than women in the headache group, but there was no difference with the pain-free group. With respect to physical abuse, women in the chronic pelvic pain group had a higher lifetime prevalence than pain-free women, but not compared to those with chronic headache. In addition, more women with chronic pelvic pain reported physical abuse in both childhood and adulthood and both major sexual abuse and physical abuse at some time in their lives than did either comparison group. CONCLUSIONS: These results support a specific association between major sexual abuse and chronic pelvic pain and a more general association between physical abuse and chronic pain. Moreover, the global nature of the abuse histories of the women in the chronic pelvic pain group suggests that more rigorous studies of the relation between abuse history and chronic pelvic pain are needed.

Abuse history and chronic pain in women: II. A multivariate analysis of abuse and psychological morbidity.

OBJECTIVE: To assess the potential role of childhood and adulthood physical and sexual abuse and complaints of chronic pain in accounting for psychiatric symptomatology in adult women. METHODS: We assessed sexual abuse, physical abuse, depression, anxiety, and somatization in 64 women with chronic pelvic pain, 42 women with chronic headache, and 46 women without chronic pain complaints. Using multiple regression analyses, we tested a model comprising sociodemographic, chronic pain, childhood sexual abuse and physical abuse, and adulthood sexual abuse and physical abuse variables in the prediction of depression, anxiety and somatization. RESULTS: This model significantly predicted all three outcomes. However, childhood sexual abuse was not significant in the prediction of any of the outcome variables, whereas childhood physical abuse was significant in the prediction of all three. Further, the adulthood abuse variable set contributed significantly to the prediction of somatization, and the individual variable of adulthood sexual abuse was predictive of anxiety. CONCLUSIONS: The relation observed between childhood sexual abuse and the outcomes of depression, anxiety, and somatization in women may be a function of its association with other forms of abuse, particularly childhood physical abuse. Further investigation is clearly needed of the nature of the relations between the various categories of abuse and psychological morbidity.

A multicenter efficacy and safety study of an oral contraceptive containing 150 micrograms desogestrel and 30 micrograms ethinyl estradiol.

The study reported herein is the primary efficacy and safety study conducted to support U.S. registration of an oral contraceptive containing 150 micrograms desogestrel and 30 micrograms ethinyl estradiol. A large multicenter study enrolled 1,221 women at 50 centers in the United Kingdom. A total of 11,656 cycles of exposure was accumulated, corresponding to approximately 879 women-years of use. Contraceptive efficacy was high; no subject conceived as a result of method failure. The product was generally well tolerated with excellent cycle control, causing fewer than 2% of the subjects to discontinue because of bleeding irregularities. The study medication demonstrated no adverse effects on cervical cytology, blood pressure, body weight or laboratory variables, while pre-existing benign breast disease generally improved. The study did not identify any medication-related adverse experiences. This study confirmed that the monophasic oral contraceptive with 150 micrograms desogestrel and 30 micrograms ethinylestradiol is a safe and effective oral contraceptive with excellent cycle control and patient acceptability.

PIP: This multicenter efficacy and safety study was conducted to support US registration of an oral contraceptive (OC) containing 150 mcg desogestrel and 30 mcg ethinyl estradiol. A total of 11,656 cycles of exposure were accumulated, corresponding to about 879 women-years of use. The absence of any method failure confirms its high contraceptive efficacy. The product was generally well tolerated with excellent cycle control, causing fewer than 2% of the subjects to discontinue because of bleeding irregularities. The study medication demonstrated no adverse effects on cervical cytology, blood pressure, body weight or laboratory variables, while pre-existing benign breast disease generally improved. Furthermore, the study did not identify any medication-related adverse experiences. In conclusion, a monophasic OC with 150 mcg desogestrel and 30 mcg ethinyl estradiol is a safe and effective OC with excellent cycle control and patient acceptability.

Hormonal replacement therapy for postmenopausal women: a review of sexual outcomes and related gynecologic effects.

The impact of hormonal replacement therapy on sexual behavior and functioning in postmenopausal women was examined. A methodological overview discusses issues of subject characteristics, research design, and the assessment of sexual functioning and related outcomes. Current therapy regimens include estrogen, progestogen, androgen, and combination therapy (e.g., cyclic estrogen and progestogen). With estrogen, significant gynecologic improvement (i.e., reduction in atrophic vaginitis) occurs, and this may in turn provide the context for sexual activity/functioning to proceed unimpaired. Although there are medical indications for the addition of progestogen to an estrogen regimen, there appear to be no improvements in sexual functioning beyond those that occur with estrogen alone. Finally, androgen may affect sexual functioning for specific subgroups of postmenopausal women (i.e., surgically postmenopausal rather than naturally postmenopausal women).

Function and regulation of yeast copperthionein.

A functional copperthionein (CUP1) gene in Saccharomyces cerevisiae is essential to prevent copper-mediated cytotoxicity, but is dispensable for cell growth in the absence of exogenous copper. The CUP1 gene is negatively autoregulated, as observed by the necessity for a functional CUP1 gene in order to repress basal level transcription from the CUP1 promoter. Both the copper protection and transcriptional autoregulatory functions can be complemented by expression in yeast of either of two monkey metallothionein isoform cDNAs. The expression of the CUP1 gene is induced at the level of transcription by copper via cis-dominant upstream control sequences which are tandemly repeated. Synthetic CUP1 upstream control sequences confer copper inducibility on a heterologous yeast promoter in a manner similar to that observed for the authentic upstream control region.

Phosphate transport across rat jejunum: influence of sodium, pH, and 1,25-dihydroxyvitamin D3.

Inorganic phosphate (Pi) transport in intact, rat jejunal epithelium was measured in vitro under short-circuited conditions. Transepithelial net absorptive Pi flux increased linearly with increases in extracellular sodium concentration ([Na]) up to 144 mM. Transmucosal border Pi influx, in contrast, displayed a biphasic Na dependency. Pi influx increased as [Na] was raised from 0 to 100 mM. A further increase in [Na] to 144 mM caused unanticipated reduction in Pi influx. The reason for this dissociation between transmucosal border influx and transepithelial absorptive flux is not clear. We then examined the effect of changes in extracellular pH on Pi influx. Reduction in pH from 7.4 to 6.0 was associated with 150% increase in Pi influx, an observation consistent with the reported reciprocal relation between intestinal brush-border membrane vesicles (BBMV) Pi uptake and extravesicular pH. In contrast to BBMV data, however, a smaller increase (50%) in mucosal Pi influx was noted in intact epithelium when pH was increased from 7.4 to 8.5. Under optimized conditions for Pi influx, i.e., [Na] = 90 mM and pH 6.0, the effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on Pi influx was measured. The total influx could be resolved into a saturable, Na-dependent and a nonsaturable, Na-independent component. 1,25(OH)2D3 stimulated the saturable component of Pi influx.

Intestinal phosphate absorption: influence of vitamin D and non-vitamin D factors.

The transport of inorganic phosphate (P) was measured in the absence of electrochemical gradients across rat jejunum in vitro. Active P absorption was demonstrated in young, vitamin D-deficient (-D) rats, whereas active P secretion was found in normal, non-vitamin D-deficient adult rats, suggesting regulation of intestinal P transport by age-dependent but vitamin D-independent mechanisms. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] stimulated mucosal-to-serosal P flux (Jm----s) without affecting serosal-to-mucosal P flux (Js----m), causing further increases in net P absorption (Jnet) in -D rats and reduction in net P secretion in normal adult rats, confirming a previously described role of this hormone on P absorption. We then examined the effect of increasing extracellular (buffer) P concentration [P] on this 1,25(OH)2D3-stimulated active P absorption in jejunum from -D rats. At [P] of 0.024, 0.24, and 2.4 mM, 1,25(OH)2D3 consistently stimulated Jm----s without affecting Js----m, causing an increment in Jnet. At 7.5 mM [P], however, this Jm----s stimulatory effect of 1,25(OH)2D3 was no longer observed. Moreover, at this [P] the Js----m exceeded Jm----s in both -D and 1,25(OH)2D3-repleted rats, converting the active P absorption into active P secretion in both treatment groups. These observations suggest the participation of local mechanisms, such as the ambient [P] of the transporting enterocytes, in the regulation of intestinal P absorption. Finally, the influence of dietary P deprivation on P absorption was studied in -D rats, with or without either vitamin D3 or 1,25(OH)2D3 repletion.(ABSTRACT TRUNCATED AT 250 WORDS)

Mammalian metallothionein is functional in yeast.

Expression of two monkey metallothioneins in yeast leads to complementation of both known functions of the endogenous yeast copperthionein gene, namely copper detoxification and autoregulation of transcription. The metallothionein-like proteins of higher and lower eukaryotes are therefore functionally analogous despite their dissimilar primary sequences.

Jejunal phosphate transport is not regulated by the PTH-adenylate cyclase system. Further studies on the contrasting features between intestinal and renal phosphate transport mechanisms.

Direct application of parathyroid hormone (PTH) to renal proximal tubule in vitro stimulates the adenylate cyclase system which in turn causes reduction in phosphate (P) reabsorption. Similar application of parathyroid extract to rat jejunum fails to induce changes in P transport. In the present study we examined the basis for this PTH-unresponsiveness in rat jejunum. The effect of PTH, and another peptide hormone, salmon calcitonin (SCT) and sodium fluoride (NaF) on jejunal adenylate cyclase activity was first examined in both vitamin D-deficient (-D) rats and similar rats after 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] repletion. Jejunal cyclic 3',5'-AMP (cAMP, pmol/mg protein/min) increased from 11.0 +/- 1.1 in -D rats to 23.0 +/- 2.2 in 1,25(OH)2D3-repleted rats (p less than 0.001). Neither PTH nor SCT had any effect on adenylate cyclase activity in jejunum from either -D or 1,25(OH)2D3-repleted rats. NaF caused the anticipated stimulation in cAMP generation, a response independent of the vitamin D nutritional status of the animal [-D: 76.8 +/- 1,25(OH)2D3: 86.9 +/- 8.5]. We then examined the question if exogenous cAMP, which reduces renal P reabsorption, also causes decrease in intestinal P absorption. The effect of dibutyryl cAMP (DbcAMP) on transepithelial, net P absorption was examined in short-circuited jejunal epithelia from rats maximally stimulated by 1,25(OH)2D3. DbcAMP caused the anticipated increase in short-circuit current (+212%) without affecting the net, active P absorption. We conclude that, unlike the renal proximal tubule, the adenylate cyclase system in jejunum is insensitive to PTH, and the P absorptive mechanism is resistant to cAMP.

Duplicated heavy metal control sequences of the mouse metallothionein-I gene.

We present evidence that two distinct regions of the DNA upstream from the mouse metallothionein-I gene contain metal-responsive regulatory sites. This result was obtained by analyzing a systematic series of deletion, insertion, duplication, and clustered point mutations introduced into cultured cells on a simian virus 40 plasmid vector. The two upstream regions contain a duplicated evolutionarily conserved DNA sequence. While either upstream region is sufficient to confer heavy metal responsiveness, both are required to give maximal levels of induced transcription.