Impact of simplifications on numerical modelling of the shallow subsurface at city-scale and implications for shallow geothermal potential.

Anthropogenic infrastructures in the shallow subsurface, such as heated basements, tunnels or shallow geothermal systems, are known to increase ground temperatures, particularly in urban areas. Numerical modelling helps inform on the extent of thermal influence of such structures, and its potential uses. Realistic modelling of the subsurface is often computationally costly and requires large amounts of data which is often not readily available, necessitating the use of modelling simplifications. This work presents a case-study on the city centre of Cardiff, UK, for which high resolution data is available, and compares modelling results when three key modelling components (namely ground elevation, hydraulic gradient distribution and basement geometry) are implemented either 'realistically', i.e. with high resolution data, or 'simplified', utilising commonly accepted modelling assumptions. Results are presented at a point (local) scale and at a domain (aggregate) scale to investigate the impacts such simplifications have on model outputs for different purposes. Comparison to measured data at individual locations shows that the accuracy of temperature outputs from numerical models is largely insensitive to simplification of the hydraulic gradient distribution implemented, while changes in basement geometry affect accuracy of the mean temperature predicted at a point by as much as 3.5 °C. At the domain scale, ground temperatures within the first 20 m show a notable increase (approximately 1 °C volume-averaged and 0.5 °C surface-averaged), while the average heat flux over the domain is about 0.06 W/m2 at 20 m depth. These increased temperatures result in beneficial conditions for shallow geothermal utilisation, producing drilling cost savings of around £1700 per typical household system or about 9% increase in thermal energy potential. Simplifications of basement geometry and (to a lesser degree) the hydraulics can result in an overestimation of these temperatures and therefore over-predict geothermal potential, while the elevation simplification showed little impact.

Interaction among GSK-3, GBP, axin, and APC in Xenopus axis specification.

Glycogen synthase kinase 3 (GSK-3) is a constitutively active kinase that negatively regulates its substrates, one of which is beta-catenin, a downstream effector of the Wnt signaling pathway that is required for dorsal-ventral axis specification in the Xenopus embryo. GSK-3 activity is regulated through the opposing activities of multiple proteins. Axin, GSK-3, and beta-catenin form a complex that promotes the GSK-3-mediated phosphorylation and subsequent degradation of beta-catenin. Adenomatous polyposis coli (APC) joins the complex and downregulates beta-catenin in mammalian cells, but its role in Xenopus is less clear. In contrast, GBP, which is required for axis formation in Xenopus, binds and inhibits GSK-3. We show here that GSK-3 binding protein (GBP) inhibits GSK-3, in part, by preventing Axin from binding GSK-3. Similarly, we present evidence that a dominant-negative GSK-3 mutant, which causes the same effects as GBP, keeps endogenous GSK-3 from binding to Axin. We show that GBP also functions by preventing the GSK-3-mediated phosphorylation of a protein substrate without eliminating its catalytic activity. Finally, we show that the previously demonstrated axis-inducing property of overexpressed APC is attributable to its ability to stabilize cytoplasmic beta-catenin levels, demonstrating that APC is impinging upon the canonical Wnt pathway in this model system. These results contribute to our growing understanding of how GSK-3 regulation in the early embryo leads to regional differences in beta-catenin levels and establishment of the dorsal axis.

Maturation of human cyclin E requires the function of eukaryotic chaperonin CCT.

Cyclin E, a partner of the cyclin-dependent kinase Cdk2, has been implicated in positive control of the G1/S phase transition. Whereas degradation of cyclin E has been shown to be exquisitely regulated by ubiquitination and proteasomal action, little is known about posttranscriptional aspects of its biogenesis. In a yeast-based screen designed to identify human proteins that interact with human cyclin E, we identified components of the eukaryotic cytosolic chaperonin CCT. We found that the endogenous CCT complex in yeast was essential for the maturation of cyclin E in vivo. Under conditions of impaired CCT function, cyclin E failed to accumulate. Furthermore, newly translated cyclin E, both in vitro in reticulocyte lysate and in vivo in human cells in culture, is efficiently bound and processed by the CCT. In vitro, in the presence of ATP, the bound protein is folded and released in order to become associated with Cdk2. Thus, both the acquisition of the native state and turnover of cyclin E involve ATP-dependent processes mediated by large oligomeric assemblies.

Human Kaposi's sarcoma cell-mediated tumorigenesis in human immunodeficiency type 1 tat-expressing transgenic mice.

BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) transactivator (Tat) protein has been linked to the development and course of Kaposi's sarcoma (KS) associated with acquired immunodeficiency disease syndrome (AIDS-KS). Tat is an 86-101 amino-acid protein encoded by two exons. To evaluate the growth-promoting effects of Tat in AIDS-KS in vivo, we developed transgenic mice expressing the one-exon-encoded 72 amino-acid protein (Tat(72)) and the two-exon-encoded 86 amino-acid protein (Tat(86)). METHODS: Human KS SLK cells were injected subcutaneously into CD4(+) T-cell-depleted male mice, and the tumors that formed after 3-4 weeks were recovered and analyzed for the expression of Tat protein(s), different cytokine messenger RNAs (mRNAs), and matrix metalloproteinases (MMPs). All statistical tests were two-sided. RESULTS: The average tumor weight was maximum in Tat(86) mice ( approximately 600 mg) compared with Tat(72) ( approximately 200 mg) and nontransgenic ( approximately 100 mg) mice (P<.005). Histologic examination of tumors showed spindle-shaped SLK cells with prominent infiltrates of inflammatory cells. All of the tumors from Tat mice expressed abundant Tat mRNA, suggesting that the infiltrating mouse cells actively expressed Tat. A comparison of the growth-promoting cytokines in the tumors from Tat(86)-transgenic and nontransgenic mice showed that the expression of the following cytokines was substantially increased in the tumors of the Tat(86) mice: tumor necrosis factor-alpha, interleukin 6, interleukin 8, granulocyte-macrophage colony-stimulating factor, and basic fibroblast growth factor. Furthermore, these tumors showed abundant expression of a 105-kd MMP activity associated with infiltrates of host leukocytes in the lesions. CONCLUSION: Our in vivo data clearly suggest that extracellular Tat can contribute to the growth and tumorigenesis of human KS cells.

Microsatellite instability and 8p allelic imbalance in stage B2 and C colorectal cancers.

BACKGROUND: Microsatellite instability (MSI) and allelic imbalance involving chromosome arms 5q, 8p, 17p, and 18q are genetic alterations commonly found in colorectal cancer. We investigated whether the presence or absence of these genetic alterations would allow stratification of patients with Astler-Coller stage B2 or C colorectal cancer into favorable and unfavorable prognostic groups. METHODS: Tumors from 508 patients were evaluated for MSI and allelic imbalance by use of 11 microsatellite markers located on chromosome arms 5q, 8p, 15q, 17p, and 18q. Genetic alterations involving each of these markers were examined for associations with survival and disease recurrence. All P values are two-sided. RESULTS: In univariate analyses, high MSI (MSI-H), i.e., MSI at 30% or more of the loci examined, was associated with improved survival (P =.02) and time to recurrence (P =.01). The group of patients whose tumors exhibited allelic imbalance at chromosome 8p had decreased survival (P =.02) and time to recurrence (P =.004). No statistically significant associations with survival or time to recurrence were observed for markers on chromosome arms 5q, 15q, 17p, or 18q. In multivariate analyses, MSI-H was an independent predictor of improved survival (hazard ratio [HR] = 0.51; 95% confidence interval [CI] = 0.31-0.82; P =.006) and time to recurrence (HR = 0.42; 95% CI = 0.24-0.74; P =.003), and 8p allelic imbalance was an independent predictor of decreased survival (HR = 1.89; 95% CI = 1.25-2.83; P =. 002) and time to recurrence (HR = 2.07; 95% CI = 1.32-3.25; P =.002). CONCLUSIONS: Patients whose tumors exhibited MSI-H had a favorable prognosis, whereas those with 8p allelic imbalance had a poor prognosis; both alterations served as independent prognostic factors. To our knowledge, this is the first report of an association between 8p allelic imbalance and survival in patients with colorectal cancer.

Microsatellite instability in colorectal cancer: different mutator phenotypes and the principal involvement of hMLH1.

Recent studies have demonstrated the presence of microsatellite instability (MSI) in tumors from patients with hereditary nonpolyposis colorectal cancer and in a large number of sporadic tumors. To further characterize the type of alterations at these loci and their frequency of involvement in colon cancer, we studied DNA extracted from paraffin-embedded tissue from 508 patients using 11 microsatellites localized to chromosomes 5, 8, 15, 17, and 18. Overall, MSI at each locus varied in character and frequency and was observed with at least one marker in 191 cases (37.6%). Based on the number of markers displaying instability per tumor, three groups of patients were defined: those with <30% of the markers showing instability (MSI-L,, n = 109, 21.5%); those with > or = 30% (MSI-H, n = 82, 16.1%); and those showing no instability (MSS, n = 317, 62.4%). These groups were tested for correlations with a number of clinical and pathological parameters, including age, sex, stage, ploidy status, and site of tumor. Comparing across the three groups and verified by pair-wise comparisons, the MSI-H group was associated with tumor site (proximal colon, P = 0.001), sex (females, P = 0.005), stage (Dukes' B, P = 0.01), and ploidy status (diploid, P = 0.03). No significant differences were noted between the MSI-L and MSS group for any of the parameters tested. An additional 188 consecutive surgical colorectal cancer cases were examined for the presence of MSI and for the immunohistochemical expression of hMLH1 and hMSH2 proteins. Of this group, 129 (68.6%) were classified as MSS, 17 (9.0%) as MSI-L, and 42 (22.3%) as MSI-H. None of the MSS and none of the MSI-L tumors had altered expression of either hMLH1 or hMSH2. However, the majority of MSI-H (40 of 42, 95%) cases demonstrated absence of staining for these proteins. The most frequently altered protein was hMLH1, occurring in 95% of the tumors with altered expression. Cumulatively, these data suggest that the tumor phenotype MSI-H is distinct from tumor phenotypes MSI-L and MSS, with no apparent differences between MSI-L and MSS. Furthermore, altered hMLH1 protein expression appears to be responsible for the mutator phenotype in the vast majority of MSI-H tumors.

Site-directed mutagenesis of the GTP-binding domain of beta-tubulin.

Tubulin binds guanine nucleotides with high affinity and specificity. GTP, an allosteric effector of microtubule assembly, requires Mg2+ for its interaction with beta-tubulin and binds as the MgGTP complex. In contrast, GDP binding does not require Mg2+. The structural basis for this difference is not understood but may be of fundamental importance for microtubule assembly. We investigated the interaction of beta-tubulin with guanine nucleotides using site-directed mutagenesis. Acidic amino acid residues have been shown to interact with nucleotide in numerous nucleotide-binding proteins. In this study, we mutated seven highly conserved aspartic acid residues and one highly conserved glutamic acid residue in the putative GTP-binding domain of beta-tubulin (N-terminal 300 amino acids) to asparagine and glutamine, respectively. The mutants were synthesized in vitro using rabbit reticulocyte lysates, and their affinities for nucleotide determined by an h.p.l.c.-based assay. Our results indicate that the mutations can be placed in six separate categories on the basis of their effects on nucleotide binding. These categories range from having no effect on nucleotide binding to a mutation that apparently abolishes nucleotide binding. One mutation at Asp224 reduced the affinity of beta-tubulin for GTP in the presence but not in the absence of Mg2+. The specific effect of this mutation on nucleotide binding is consistent with an interaction of this amino acid with the Mg2+ moiety of MgGTP. This residue is in a region sharing sequence homology with the putative Mg2+ site in myosin and other ATP-binding proteins. As a result, tubulin belongs to a distinct class of GTP-binding proteins which may be evolutionarily related to the ATP-binding proteins.

A model of the nucleotide-binding site in tubulin.

Tubulin uses GTP to regulate microtubule assembly and is thought to be a member of a class of GDP/GTP-binding proteins (G-proteins) as defined by Hughes [(1983) Febs Lett. 164, 1-8]. How tubulin is structurally related to G-proteins is not known. We use a synthesis of sequence comparisons between tubulin, other G-proteins, and ADP/ATP-binding proteins and topological arguments to identify potential regions involved in nucleotide binding. We propose that the nucleotide-binding domain in the beta-subunit of tubulin is an alpha/beta structure derived from amino acid residues approximately 60-300. Five peptide sequences are identified which we suggest exist as 'loops' that extend from beta-strands and connect alpha-helices in this structure. We argue that GDP binds to four of the five loops in an Mg2+-independent manner while GTP binds in an Mg2+-dependent manner to a different combination of four loops. We propose that this switch between loops upon GTP binding induces a conformational change essential for microtubule assembly.

Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial.

BACKGROUND: Insulin sensitizing agents may be useful in treatment of non-alcoholic fatty liver disease. AIM: A pilot study to evaluate the efficacy and safety of metformin in non-alcoholic fatty liver disease. METHODS: In an open labelled study, patients with histologically confirmed non-alcoholic fatty liver disease were given metformin (20 mg/kg) for 1 year. Insulin resistance (by log homeostasis assessment model analysis for insulin resistance and Quantitative Insulin Sensitivity Check Index) and post-treatment hepatic histology were compared with pre-treatment histology. RESULTS: Fifteen patients completed 1 year of treatment. During the initial 3 months, there was improvement in alanine aminotransferase and aspartate aminotransferase (P-value 0.01 and 0.02, respectively) along with improvement in insulin sensitivity. However, after 3 months, there was no further improvement in insulin sensitivity and there was gradual rise in aspartate aminotransferase and alanine aminotransferase back to pre-treatment levels. Among the 10 patients with post-treatment biopsy, three (33%), showed improvement in steatosis, two (20%) showed improvement in inflammation score and one (10%) showed improvement in fibrosis. CONCLUSION: Metformin treatment was associated with only a transient improvement in liver chemistries. A progressive, sustainable reduction in insulin sensitivity was not noted during treatment.

Epidemiology of breast carcinoma: Age, menstrual status, and exogenous hormone usage in patients with lobular carcinoma in situ.

Lobular carcinoma in situ (LCIS) of the breast is a neoplastic condition associated with premenopausal women and it is largely for this reason that LCIS has been considered to be an estrogen-dependent lesion. In this report we present the results of a study of age at diagnosis, menstrual status, and exogenous hormone usage in 59 women with LCIS and in 190 patients with duct carcinoma. When LCIS was associated with duct carcinoma, 46% of patients were postmenopausal and in the group that also had infiltrating lobular carcinoma 71% were postmenopausal. Nine of 39 (23%) patients whose only carcinoma was LCIS were postmenopausal, 56% were premenopausal and 21% were menopausal. Seven of the nine postmenopausal women had never used a hormone-containing medication. In a comparison group with only duct carcinoma, 59.4% were postmenopausal and 35.2% had taken a hormone preparation. The high proportion of postmenopausal patients with LCIS leaves considerable doubt as to whether all lesions termed LCIS are equally dependent on estrogens at all stages in their evolution. We found no evidence to link LCIS with exogenous hormone usage in postmenopausal women. Prospective studies of hormone levels in patients with LCIS and in their relatives may provide an explanation for persistence of the lesion in postmenopausal women and could aid in identifying women at risk of developing invasive carcinoma.

Is limb-sparing surgery applicable to neurogenic sarcomas of the extremities?

The presentation, treatment, and outcome of 12 patients with high-grade neurogenic sarcoma (NS) of the extremity were compared with those of 21 patients with high-grade extremity soft-tissue sarcoma of nonneural origin in a retrospective study from January 1976 to January 1988. Pain and neurologic deficit were more common in the NS group. Limb-sparing surgery was carried out with equal frequency in both groups. Local recurrence was six times more frequent in the NS group at three-year follow-up (59% vs 10%). Width of resection margin was the dominant prognostic variable bearing on local control after limb-sparing surgery. Anatomic and functional constraints tended to limit resection margin in patients with NS arising from mixed motor-sensory or predominantly motor nerves.

Discontinuous appendiceal involvement in ulcerative colitis: pathology and clinical correlation.

Continuous mucosal involvement from the rectum proximally is one of the hallmarks of ulcerative colitis. However, recent pathologic series report appendiceal ulcerative colitis in the presence of a histologically normal cecum, representing a "skip" lesion. The clinical significance of this finding has not been established. Eighty patients, 54 males and 26 females, average age 37.9 years (range 14 to 82 years) who underwent proctocolectomy for ulcerative colitis from January 1990 to September 1995 were examined to determine the rate of discontinuous appendiceal involvement. Excluded were 12 patients with prior appendectomy and 11 with fibrotic obliteration of the appendiceal lumen. Of the remaining 57 patients, seven (12.3%) had clear appendiceal involvement in the presence of a histologically normal cecum. These seven patients clinically were indistinguishable from the 50 patients without skip involvement of the appendix in terms of age at surgery, pretreatment medications, type of surgery, interval from diagnosis to definitive procedure, complications, functional results, and clinical course. Discontinuous appendiceal involvement was found in 12.3% of patients undergoing proctocolectomy for ulcerative colitis, and clinically these patients behave as those without this feature.

Clinical outcome of gliosarcoma compared with glioblastoma multiforme: North Central Cancer Treatment Group results.

OBJECT: Gliosarcoma, a rare malignancy of the central nervous system, consists of gliomatous and sarcomatous elements. There are conflicting reports regarding its aggressiveness and cell line of origin compared with those of glioblastoma multiforme (GBM). The goal of this study was to compare clinicopathological features such as disease-free survival time and actual survival time in patients with gliosarcoma with a matched group of patients with GBM as well as with the entire group of patients with GBM. METHODS: The authors report on 18 cases of gliosarcoma derived from a series of 748 Grade 4 astrocytoma cases that were part of four consecutive randomized Phase III trials conducted between 1979 and 1996. In this series the gliosarcoma group represented only 2.4% of all GBMs and included 11 men and seven women with a median age of 61.5 years (range 31-81 years). The median tumor size was 5 cm (range 2-8 cm). The locations, all supratentorial, included temporal in 44%, parietal in 28%, frontal in 17%, and occipital in 11%. The 18 patients with gliosarcomas, all Grade 4 (World Health Organization classification), were compared with the entire group of 730 patients with GBM and a control group of 18 patients with GBM matched for known prognostic factors including patient age, randomization date, performance status, extent of resection, and protocol number. Patients in all treatment groups received radiation and nitrosourea-based chemotherapy. The median time to progression and the median survival times for the patients with gliosarcoma were 28.0 and 35.1 weeks as compared with 24.7 and 41.6 weeks for the entire group of patients with GBM (log rank test, p = 0.94 and 0.27, respectively) and 16.7 and 34.4 weeks in the control group (p = 0.20 and 0.84, respectively). In previous molecular cytogenetic analyses of gliosarcoma these authors have shown similar genetic changes in the gliomatous and sarcomatous components. CONCLUSIONS: The data obtained in this study support the conclusion that gliosarcoma shares significant clinical and genetic similarities with GBM and that the same principles should be applied for patient enrollment in research protocols and treatment for these two kinds of tumor.

A core breast biopsy diagnosis of invasive carcinoma allows for definitive surgical treatment planning.

BACKGROUND: We reviewed our image-guided core needle breast biopsy (IGCNBB) experience with patients diagnosed with invasive carcinoma (IC) to determine the accuracy of a core biopsy diagnosis of invasion and our ability to perform a single definitive cancer operation. METHODS: All IGCNBBs between July 1993 and July 1997 were reviewed to identify patients diagnosed with IC. Data included initial surgical treatment, surgical pathology, and subsequent surgical treatment. RESULTS: Of the 1,676 biopsies, invasive carcinoma was diagnosed in 208 with follow-up in 204 cases. Invasive carcinoma diagnosis was confirmed in 202 of 204 cases (99%). One hundred ninety-two patients had surgical treatment. Of these 192 patients, 173 (90%) could have achieved definitive surgical treatment with a single operation. CONCLUSIONS: An IGCNBB diagnosis of IC is accurate and allows for definitive breast cancer therapy. The potential impact on patient management is that a single operation can usually accomplish what traditionally has required at least two surgical procedures.

Contraceptive efficacy of the Copper T 380A and Copper T 200 intrauterine devices: results from a comparative clinical trial in six developing countries.

The clinical performance of the Copper T 380A (TCu 380A) and the Copper T 200 (TCu 200) intrauterine devices (IUDs) was evaluated for 12 months in a group of women who had one of the two IUDs inserted. Results are from a multicenter randomized clinical trial at one site in each of six developing countries. The pregnancy rate with the TCu 380A IUD was significantly lower than the pregnancy rate with the TCu 200 IUD at 12 months (0.5 and 2.6 per 100 women, respectively, p < 0.01). No statistically significant differences between the two study IUDs were found with regards to expulsion or removals due to bleeding/pain, personal, medical, or planned pregnancy. The TCu 380A IUD did not have a disproportionately higher incidence of side effects such as intermenstrual bleeding or pain, inflammations or infections, or insertion-related events compared to the TCu 200 IUD. TCu 380A IUD users, however, were significantly more likely to report increased dysmenorrhea than were TCu 200 IUD users. The performance of the TCu 380A IUD in preventing pregnancy during this trial indicates that this IUD may be a better option than the TCu 200 IUD for women wishing to practice effective, long-term, reversible birth control without having to resort to hormonal methods.

The effect of adding copper onto Lippes Loop IUDs: results from a ten-year study in Yugoslavia.

The present study is the first randomized ten-year comparison of the standard, non-medicated Lippes Loop D and the same device with the addition of 200 mm2 of copper in the form of copper sleeves. The devices were randomly inserted immediately after first trimester medical termination of pregnancy. Out of 400 postabortal IUD insertions, 371 were followed for up to ten years. Gross cumulative life-table accidental pregnancy rates after one year of use were 0.56 for the copper-bearing Lippes Loop and 4.63 for the standard Lippes Loop. After two, four and ten years, these rates were 1.24, 2.70 and 3.62 and 6.03, 7.58 and 14.94, respectively (in all comparisons, rates were significantly different at the 0.05 level or lower). At each time interval, expulsion/displacement rates were 4.49, 4.49, 5.23 and 6.32 for the copper-bearing Lippes Loop and 12.61, 13.29, 15.46 and 19.79 for the standard Lippes Loop (rates were significantly different at the 0.01 level or lower). Differences in removal rates for bleeding and/or pain were not significantly different at any of the follow-up intervals. The lower event rates for copper-bearing Lippes Loop D users indicates that the addition of copper to the Lippes Loop IUD may result in better long-term efficacy profiles for this device among postabortal women. The results also suggest that large, medicated IUDs may be more efficacious for women with larger uteri who often experience higher failure rates due to expulsion or displacement of smaller IUDs into the lower uterine segment.

Clinical evaluation of the TCu 380A IUD at six Latin American centers.

Compared with other contraceptive methods such as sterilization and oral contraceptives, the prevalence of IUD use in Latin American countries is relatively low. This study evaluated the clinical performance of the TCu 380A IUD in six Latin American clinics to determine whether its performance was a determining factor in its low prevalence, and to provide efficacy and safety data based on local data sets to Latin American service providers. The 12-month unintended pregnancy rate ranged from 0.0 to 1.7 per 100 women and the 12-month discontinuation rates for all reasons, from 3.3 to 21.0 per 100 women. Statistically significant differences in discontinuation rates were observed among clinics, and could be explained, in part, by the different sociodemographic and clinical characteristics of women attending the clinics. The overall performance and acceptability of the TCu 380A IUD was considered satisfactory and comparable to those reported from other countries. Thus, the low prevalence of IUD use in Latin America is probably related to barriers to its use rather than its clinical performance.

PIP: Although the IUD is one of the most widely used contraceptive methods in the world, only 4.1% of reproductive aged married women in Latin America currently use it. Chile, Colombia, and Ecuador are among the few countries in the region where more than 10% of such women report its use. The authors report their findings from a clinical evaluation of the performance of the TCu 380A IUD at six clinic sites in Chile, Mexico, El Salvador, Peru, and Venezuela. Data were analyzed for two sites in Mexico. The study investigated whether the performance of the IUD was a determining factor in its low prevalence and provided efficacy and safety data based upon local data sets to Latin American service providers. The twelve-month unintended pregnancy rate among the 854 subjects ranged from 0.0-1.7 per 100 women, while the twelve-month discontinuation rates for all reasons ranged 3.3-21.0 per 100 women. The statistically significant differences in discontinuation rates observed among clinics may be partly explained by the different sociodemographic and clinical characteristics of women attending the clinics. Overall, the performance and acceptability of the TCu 380A IUD were found to be satisfactory and comparable to those reported from other countries. The low prevalence of IUD use in Latin America is therefore probably related to barriers to its use instead of to its clinical performance.

Twelve-month comparative multicenter study of the TCu 380A and ML 250 intrauterine devices in Bangkok, Thailand.

The long-term effectiveness of the copper-bearing intrauterine device (IUD) has been documented. This paper reports 12-month results from a multiyear comparative study of the Copper T (TCu) 380A and Multiload (ML) 250 IUD in Bangkok, Thailand, among 1396 women. Continuation of the assigned IUD was relatively high after 12 months of use, with continuation rates of 90.17 and 87.54 per 100 women, respectively. Whereas the accidental pregnancy rate was higher for the ML 250 IUD than for the TCu 380A IUD (1.0 and 0.2 per 100 women, respectively), this difference was not considered statistically significant (p < 0.69). The rate of IUD expulsion was significantly higher among women using the ML 250 IUD than for women using the TCu 380A IUD (4.61 and 2.40 per 100 women, respectively, p = 0.05).

PIP: The performance of the Copper T 380A and Multiload 250 IUDs over a 4-year period were compared in a prospective study of 1396 women from Bangkok, Thailand, who were randomly assigned to be fitted with 1 of the 2 devices. This paper presents the findings from the first 12 months (1995-96) of the study. At insertion, 8-10% of women in both groups reported mild pelvic pain. After 12 months of use, the continuation rate was 90.2% for the Copper T 380A and 87.5% for the Multiload 250 device. Menstrual problems were the most common complaint during the follow-up period; such disturbances--primarily spotting and dysmenorrhea--were reported by 59.1% of Copper T 380A users and 44.4% of women in the Multiload 250 group. The accidental pregnancy rate after 12 months was higher, but nonsignificantly, among Multiload 250 users (1.0/100 women) than Copper T 380A acceptors (0.2/100 women). The IUD expulsion rate was significantly higher among Multiload 250 acceptors (4.61%) than users of the Copper T 380A (2.4%). The higher efficacy, lower risk of expulsion, and longer life span (10 years) of the Copper T 380A compared to the Multiload 250 IUD suggest this is an ideal method for women who desire long-term protection against pregnancy but do not wish to be sterilized.

Effectiveness of the non-spermicidal fit-free diaphragm.

Standard instructions for diaphragm use call for an individually sized latex diaphragm, used in conjunction with spermicide jelly. However, some investigators have reported that the diaphragm can be effective without a spermicide. A non-randomized trial designed to measure the contraceptive effectiveness of the diaphragm used without spermicide was conducted. A total of 110 self-selected women were enrolled to use a non-spermicide fit-free (60mm) diaphragm for a period of one year. They were advised to wear the diaphragm continuously, removing it once each day for washing but not within six hours after intercourse. Product-related problems related to insertion, retention and removal were few at both the 6- and 12-month follow-up visits, most commonly odor. The 12-month life table accidental pregnancy rate during typical use was 24.1 per 100 women (29.5 per 100 women without female barrier experience and 17.9 per 100 women with barrier experience). Over 85% of the women who returned for follow-up visits reported using the diaphragm during every act of intercourse. Until better data refute the traditional recommendations, users should be advised to add spermicide to fitted latex diaphragms.

PIP: In a 12-month prospective, non-randomized trial designed as a pilot study, the contraceptive effectiveness of the diaphragm used without spermicide was assessed. A total of 200 self-selected 18-35 year old women were to be enrolled to use a nonspermicide fit-free (60 mm) diaphragm for a period of one year, but recruitment was halted after 110 women had been enrolled because of the high pregnancy rate observed. Volunteers had to be in a current sexual relationship, with no history of infertility or serious gynecologic problems, and highly motivated to prevent pregnancy. Participants were advised to wear the diaphragm continuously, removing it once each day but not within 6 hours after intercourse. Pelvic exams were done at 6-month intervals, and participants were interviewed about any complaints related to the method. Enrollment began in 1981, and follow-up ended in 1983. About 1/3 were married. Approximately 90% had been using a contraceptive immediately prior to admission, and about 2/3 had experience using a diaphragm. Product-related problems associated with insertion, retention, and removal were few at both the 6- and 12-month follow up visits. The most common complaint was odor. Although about 10% of the women discontinued use because of lack of confidence in the method, many indicated that they would continue irrespective of the pregnancy risk. The 12-month life table accidental pregnancy rate for all participants during typical use was 24.1/100 women. The pregnancy rate was 29.5/100 women without female barrier experience and 17.9 among women with barrier experience. Over 85% of the women at both follow-up visits reported using the diaphragm during every act of intercourse, yet there was an almost 3-fold increase in the pregnancy rate from 6 months (8.4) to 12 months (24.1). Until better data refute the traditional recommendations, users should be advised to add spermicide to fitted latex diaphragms.

Do retroverted uteri adversely affect insertions and performance of IUDs?

A large international multi-center IUD data set (N = 5520) coordinated by Family Health International was analysed to determine if the uterine position of a woman (anteverted, mid-positioned or retroverted) affects the ease of IUD insertion and if knowledge of uterine position would diminish insertion-related problems and improve IUD performance. Findings showed that insertion-related events were rare irrespective of uterine position. Women with retroverted uteri were not associated with higher termination rates for accidental pregnancy, expulsion or removal for bleeding and/or pain after 12 months of IUD use, as compared to the other two uterine position groups. All insertions in this data set were performed by experienced obstetricians/gynecologists, and our findings suggest that women with retroverted uteri should be equally good candidates for IUD contraception.