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Biomedical subjects

K Nanda

Publications and source records attributed to K Nanda.

At least 19 recordsLinked to original sources

Expectant care versus surgical treatment for miscarriage.

BACKGROUND: Miscarriage is a common complication of early pregnancy that can have both medical and psychological consequences like depression and anxiety. The need for routine surgical evacuation with miscarriage has been questioned because of potential complications such as cervical trauma, uterine perforation, hemorrhage, or infection. OBJECTIVES: To compare the safety and effectiveness of expectant management versus surgical treatment for early pregnancy loss. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (December 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2004, Issue 3), PubMed (1966 to March 2005), POPLINE (inception to March 2005), and LILACS (1982 to March 2005) and reference lists of reviews. SELECTION CRITERIA: Randomized trials comparing expectant care and surgical treatment (vacuum aspiration or dilation and curettage (D & C)) for miscarriage were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. MAIN RESULTS: Five trials were included in this review with 689 total participants. The expectant-care group was more likely to have an incomplete miscarriage (RR 5.37; 95% CI 2.57 to 11.22). However, the time frames for declaring the process incomplete varied across the studies. The need for unplanned surgical treatment (such as vacuum aspiration or D&C) was greater for the expectant-care group (RR 4.78; 95% CI 1.99 to 11.48). The expectant-care group had more days of bleeding (WMD 1.59; 95% CI 0.74 to 2.45) and a greater amount of bleeding (WMD 1.00; 95% CI 0.60 to 1.40). Post-procedure diagnosis of infection was lower in the expectant-care group (RR 0.29; 95% CI 0.09 to 0.87). Information on psychological outcomes and pregnancy was too limited to draw conclusions. AUTHORS' CONCLUSIONS: Expectant management led to a higher risk of incomplete miscarriage, need for surgical emptying of the uterus, and bleeding. None of these were serious. In contrast, surgical evacuation was associated with a significantly higher risk of infection. Given the lack of clear superiority of either approach, the woman's preference should play a dominant role in decision making. Medical management has added choices for women and their clinicians, but these were not reviewed here.

Abortion, Incomplete↗

Spermicide used alone for contraception.

BACKGROUND: Spermicides have been used as contraceptives for thousands of years. Despite this long use, only recently have studies examined the comparative efficacy and acceptability of these vaginal medications. Spermicides contain an active ingredient (most commonly nonoxynol-9) and a formulation used to disperse the product, such as foam or vaginal suppository. OBJECTIVES: This review examined all known randomized controlled trials of a spermicide used alone for contraception. SEARCH STRATEGY: We searched the following computerized databases from inception to July 2004 for randomized controlled trials of spermicides for contraception: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, POPLINE, LILACS, and EMBASE. We examined the reference list of each trial found as well as that of review articles and textbook chapters. SELECTION CRITERIA: We included any trial of a commercial product used alone for contraception. Each included trial must have provided sufficient information to determine pregnancy rates. We located reports from 14 trials. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted information from the trials identified. We did not conduct a meta-analysis, since most trials had large losses to follow-up. We entered the data into tables and presented the results descriptively. MAIN RESULTS: In the largest trial to date, the gel (Advantage S) containing the lowest dose of nonoxynol-9 (52.5 mg) was significantly less effective in preventing pregnancy than were gels with higher doses of the same agent (100 mg and 150 mg). Probabilities of pregnancy by six months were 22% for the 52.5 mg gel, 16% for the 100 mg dose, and 14% for the 150 mg dose. In the same trial, the three different vehicles with 100 mg of nonoxynol-9 had similar efficacy. Interpretation of these figures is limited, since 39% of participants discontinued the method or were lost from the trial. Few important differences in efficacy emerged in other trials. AUTHORS' CONCLUSIONS: The probability of pregnancy varied widely in reported trials. A gel containing nonoxynol-9 52.5 mg was inferior to two other products tested in the largest trial. Aside from this finding, personal characteristics and behavior of users may be more important than characteristics of the spermicide products in determining the probability of pregnancy. Gel was liked more than the film or vaginal suppository in the largest trial. Spermicide trials have the dual challenges of difficult recruitment and high discontinuation rates; the latter threatens trial validity.

Contraception↗

20 mcg versus >20 mcg estrogen combined oral contraceptives for contraception.

BACKGROUND: Concern about estrogen-related adverse effects has led to progressive reductions in the estrogen dose in combination oral contraceptives (COCs). However, reducing the amount of estrogen to improve safety also could result in decreased contraceptive effectiveness and unacceptable changes in bleeding patterns. OBJECTIVES: To test the hypothesis that COCs containing </=20 mcg ethinyl estradiol (EE) perform similarly as those containing >20 mcg in terms of contraceptive effectiveness, bleeding patterns, discontinuation, and side effects. SEARCH STRATEGY: We searched computerized databases (CENTRAL, MEDLINE, EMBASE, and POPLINE) from their inception to November 2003, searched the references of eligible trials, and wrote to oral contraceptive manufacturers to identify eligible trials. SELECTION CRITERIA: English-language reports of randomized controlled trials that compare a COC containing </=20 mcg EE with a COC containing >20 mcg EE were eligible. We excluded studies where the interventions were designed to be administered for less than three consecutive cycles or to be used primarily as treatment for non-contraceptive conditions. Trials had to report on contraceptive effectiveness, bleeding patterns, trial discontinuation due to bleeding-related reasons or other side effects, or side effects to be included in the review. DATA COLLECTION AND ANALYSIS: The primary reviewer evaluated all titles and abstracts located in the literature searches to determine whether they met the inclusion criteria. Two reviewers independently extracted data from the studies identified for inclusion. We wrote to the authors when clarifications or additional data were needed. Data were entered and analyzed with RevMan 4.2. MAIN RESULTS: No differences were found in contraceptive effectiveness for the 11 COC pairs for which this outcome was reported. Several COCs containing 20 mcg EE resulted in higher rates of early trial discontinuation (overall and due to adverse events such as irregular bleeding) as well as increased risk of bleeding disturbances (both amenorrhea/infrequent bleeding and irregular, prolonged, frequent bleeding, or breakthrough bleeding or spotting) than their higher-estrogen comparison pills. AUTHORS' CONCLUSIONS: While COCs containing 20 mcg EE may be theoretically safer, this review did not focus on the rare events required to assess this hypothesis. Data from randomized controlled trials are inadequate to detect possible differences in contraceptive effectiveness. Low-dose estrogen COCs resulted in higher rates of bleeding pattern disruptions. However, most trials compared COCs containing different progestin types, and changes in bleeding patterns could be related to progestin type as well as estrogen dose.

Contraceptives, Oral, Combined↗

Fertility awareness-based methods for contraception.

BACKGROUND: "Fertility awareness-based methods" (FAB) of family planning "involve identification of the fertile days of the menstrual cycle, whether by observing fertility signs such as cervical secretions and basal body temperature, or by monitoring cycle days. FAB methods can be used in combination with abstinence or barrier methods during the fertile time" (WHO 2000). Several names have been used to describe this approach to contraception, including "rhythm," "natural family planning" and "periodic abstinence." Fertility awareness-based methods can be used with abstinence from sexual intercourse. Alternatively, they can be used with barrier contraceptives or withdrawal during presumed fertile times. OBJECTIVES: We retrieved and analyzed all randomized controlled trials that examined any fertility awareness-based methods used for contraception. SEARCH STRATEGY: We searched the computerized databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, POPLINE, EMBASE, and LILACS (each from its inception to January, 2004) for randomized controlled trials of fertility awareness-based methods. We examined the reference list of each trial as well as that of review articles. SELECTION CRITERIA: We included all randomized controlled trials in any language that compared any fertility awareness-based methods for contraception with a placebo; another method, including an alternative fertility awareness-based method; or fertility awareness-based methods used in conjunction with another contraceptive. DATA COLLECTION AND ANALYSIS: We assessed all titles and abstracts found for inclusion. We evaluated the methodological quality of the trials for potential biases by qualitatively assessing the study design; randomization method; allocation concealment; blinding; premature discontinuation rates; and loss to follow-up rates. Because of methodological weaknesses, we could not enter the trial results in RevMan, calculate measures of association, or aggregate data. MAIN RESULTS: Because of poor methods and reporting, pregnancy rates could not be determined. A trial in Colombia found similar numbers of pregnancies among women randomized to the ovulation and symptothermal methods. In contrast, a companion trial in Los Angeles observed more pregnancies in the group assigned to the ovulation method. In the two U.S. trials, recruitment of participants was unexpectedly difficult; this aspect was not mentioned in the report from Colombia. Continuation rates were poor. In the two larger trials, most participants discontinued their assigned method before entering the observation phase of the trial. REVIEWERS' CONCLUSIONS: The comparative efficacy of fertility awareness-based methods of contraception remains unknown. Despite intensive training and ongoing support, most participants in these trials discontinued prematurely. Contraceptive methods should be properly evaluated, preferably in randomized controlled trials, before adoption and dissemination.

Awareness↗

Steroid hormones for contraception in men.

BACKGROUND: Male hormonal contraception has been an elusive goal. Administration of sex steroids to men can shut off sperm production through effects on the pituitary and hypothalamus. However, this approach also decreases production of testosterone, so "add-back" therapy is needed. OBJECTIVES: To summarize all randomized controlled trials of male hormonal contraception. SEARCH STRATEGY: We searched the computerized databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Popline, and LILACS (each from inception to February, 2003) for randomized controlled trials of hormonal contraception in men. We wrote to authors of identified trials to seek unpublished or published trials that we might have missed. SELECTION CRITERIA: We included all randomized controlled trials in any language that compared a steroid hormone with another contraceptive. We excluded non-steroidal male contraceptives, such as gossypol. We included both placebo and active-regimen control groups. All trials identified included only healthy men with normal semen analyses. DATA COLLECTION AND ANALYSIS: Azoospermia (absence of spermatozoa on semen examination) was the primary outcome measure. Data were insufficient to examine pregnancy rates and side effects. MAIN RESULTS: The proportion of men who achieved azoospermia varied widely in reports to date. Few significant differences emerged from these trials. Levonorgestrel implants combined with injectable testosterone enanthate (100 mg IM) was significantly more effective than was levonorgestrel 125 mcg by mouth daily combined with testosterone patches (10 mg/d) (OR for azoospermia with the oral levonorgestrel regimen 0.03; 95%CI 0.00-0.29). The addition of levonorgestrel 500 mcg by mouth daily improved the effectiveness of testosterone enanthate 100 mg IM weekly by itself (OR for azoospermia with the combined regimen 4.0; 95%CI 1.00-15.99). Several regimens, including testosterone alone and GnRH agonists and antagonists, had disappointing results. REVIEWERS' CONCLUSIONS: No male hormonal contraceptive is ready for clinical use. All trials published to date have been small exploratory studies. As a result, their power to detect important differences has been limited and their results imprecise. In addition, the definition of oligospermia has been imprecise or inconsistent in many reports. To avoid bias, future trials need more attention to the methodological requirements for randomized controlled trials. Trials with adequate power would also be helpful.

Contraception↗

Extract of vinegar "Kurosu" from unpolished rice inhibits the proliferation of human cancer cells.

The effects of the ethyl acetate extract of "Kurosu" (EK), Japanese traditional vinegar from unpolished rice, on the proliferation of a variety of human cancer cell lines were investigated by using the alamar blue assay. Cancer cell lines included colon adenocarcinoma (Caco-2), lung carcinoma (A549), breast adenocarcinoma (MCF-7), bladder carcinoma (5637), and prostate carcinoma (LNCaP) cells. EK inhibited the proliferation of all tested cell lines in a dose-dependent manner, with inhibition mostly pronounced in Caco-2 cells (up to 62% inhibition at a dose level of 0.025%). Flow cytometry of EK-treated Caco-2 cells showed a decrease in cell number in the G2/M phase and an increase in the sub-G1 phase (apoptotic). In addition, DNA fragmentation was detected in Caco-2 cells cultured with EK by immunostaining. RT-PCR analysis revealed p21 mRNA expression was induced in EK-treated Caco-2 cells. Moreover, PARP cleavage was promoted in EK-treated Caco-2 cells. These results suggest that EK causes G0/G1 arrest through p21 induction and, thus, is a potential apoptosis inducer in Caco-2 cells.

Acetic Acid↗

Extract of vinegar "Kurosu" from unpolished rice inhibits the development of colonic aberrant crypt foci induced by azoxymethane.

The modifying effects of administrating an ethyl acetate extract of "Kurosu" (EK), a vinegar made from unpolished rice, on development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in male F344 rats. We also assessed the effects of EK on proliferating cell nuclear antigen (PCNA) index in ACF, prostaglandin (PG) E2 expression in the colonic mucosa and activities of detoxifying enzymes of glutathione S-transferase (GST) and quinone reductase (QR) in the liver. To induce ACF, rats were given two weekly subcutaneous injections of AOM (20 mg/kg body wt). They also received drinking water containing 0, 0.05, 0.1 or 0.2% EK for 4 weeks, starting 1 week before the first dosing of AOM. AOM exposure produced 140 +/- 23 ACF/rat at the end of the study (week 4). EK administration dose-dependently inhibited ACF formation and inhibition by 0.2% EK was statistically significant (P < 0.002). Treatment with EK significantly lowered PCNA index in ACF and reduced PGE2 content in the colonic mucosa, while EK elevated liver GST and QR activities. These findings suggest that EK may be effective for inhibiting colonic ACF, through induction of liver GST and QR and possibly alteration of PGE2 production.

Acetic Acid↗

Terbutaline pump maintenance therapy after threatened preterm labor for preventing preterm birth.

BACKGROUND: Women with preterm labor that is arrested with tocolytic therapy are at increased risk of recurrent preterm labor. Terbutaline pump maintenance therapy has been given to such women to decrease the risk of recurrent preterm labor, preterm birth, and its consequences. OBJECTIVES: To determine the effectiveness and safety of terbutaline pump maintenance therapy after threatened preterm labor in preventing preterm birth and its complications. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (searched May 2002) and the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2002). SELECTION CRITERIA: Randomized trials comparing terbutaline pump maintenance therapy with alternative therapy, placebo, or no therapy after threatened preterm labor. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the studies for inclusion and then extracted data from eligible studies. MAIN RESULTS: We included two studies. Terbutaline pump maintenance therapy did not appear to offer any advantages over the saline placebo pump or oral terbutaline maintenance therapy in preventing preterm births by prolonging pregnancy or its complications among women with arrested preterm labor. The weighted mean difference (WMD) for gestational age at birth was -0.1 weeks (95% confidence interval (CI) -1.7 to 1.4) for terbutaline pump therapy compared with saline placebo pump for both trials combined and 1.4 weeks (95% CI -1.1 to 3.9) for terbutaline pump versus oral terbutaline therapy for the first trial. The second trial reported a relative risk (RR) of 1.17 (95% CI 0.79 to 1.73) of preterm birth (less than 37 completed weeks) and a RR of 0.97 (95% CI 0.51 to 1.84) of very preterm birth (less than 34 completed weeks) for terbutaline pump compared with saline placebo pump. Terbutaline pump therapy also did not result in a higher rate of therapy continuation or a lower rate of infant complications. No data were reported on long-term infant outcomes, costs, or maternal assessment of therapy. REVIEWER'S CONCLUSIONS: Terbutaline pump maintenance therapy has not been shown to decrease the risk of preterm birth by prolonging pregnancy. Furthermore, the lack of information on the safety of the therapy, as well as its substantial expense, argues against its role in the management of arrested preterm labor. Future use should only be in the context of well-conducted, adequately powered randomized controlled trials.

Drug Administration Schedule↗

The diaphragm with and without spermicide for contraception: a Cochrane review.

BACKGROUND: The diaphragm is usually used with a spermicide. However, some practitioners have suggested that spermicides offer no additional contraceptive protection and have advocated alternative guidelines for the use of diaphragms. The objective of this review was to compare the effectiveness, safety and acceptability of the diaphragm with and without spermicide. METHODS AND RESULTS: We searched Medline, Embase, Popline, CINAHL, the Cochrane Controlled Trials Register and reference lists of relevant articles. In addition, we contacted experts in the field to identify unpublished studies. Randomized controlled trials comparing women of reproductive age using the diaphragm with and without spermicide as the sole contraceptive method that reported clinical outcomes were selected. Two reviewers independently extracted data on outcomes and trial characteristics and any discrepancies were resolved by consensus or by consultation with the third reviewer. The results of the one identified study are presented descriptively. We identified only one study. No significant difference was found in the pregnancy rates (with typical use or consistent use) or discontinuation rates between the diaphragm-with-spermicide and diaphragm-without-spermicide groups. There was a trend towards higher pregnancy rates in the diaphragm-without-spermicide group. However, this study failed to recruit the planned number of participants and was consequently underpowered. CONCLUSIONS: As only one underpowered study was identified, we cannot distinguish between the contraceptive effectiveness of the diaphragm with and without spermicide. We cannot draw any conclusion at this point; further research is needed.

Contraception↗

Diaphragm versus diaphragm with spermicides for contraception.

BACKGROUND: The diaphragm is usually used with a spermicide. However, some practitioners have suggested that spermicides offer no additional contraceptive protection and have advocated alternative guidelines for the use of diaphragms. OBJECTIVES: The objective of this review was to compare the effectiveness, safety and acceptability of the diaphragm with and without spermicide. SEARCH STRATEGY: We searched MEDLINE, EMBASE, POPLINE, CINAHL, the Cochrane Controlled Trials Register, and reference lists of relevant articles. In addition, we contacted experts in the field to identify unpublished studies. SELECTION CRITERIA: Randomized controlled trials comparing women of reproductive age using the diaphragm with and without spermicide as the sole contraceptive method that reported clinical outcomes. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data on outcomes and trial characteristics and any discrepancies were resolved by consensus or by consultation with the third reviewer. The results of the one identified study are presented descriptively. MAIN RESULTS: We identified only one study. No significant difference was found in the pregnancy rates (with typical use or consistent use) or discontinuation rates between the diaphragm-with-spermicide and diaphragm-without-spermicide groups. There was a trend towards higher pregnancy rates in the diaphragm-without-spermicide group. However, this study failed to recruit the planned number of participants and was consequently underpowered. REVIEWER'S CONCLUSIONS: As only one underpowered study was identified, we cannot distinguish between the contraceptive effectiveness of the diaphragm with and without spermicide. We cannot draw any conclusion at this point, further research is needed.

Contraception↗

Randomized crossover trial comparing the eZ.on plastic condom and a latex condom.

This randomized crossover trial compared the breakage and slippage rates, safety, and acceptability of the recently developed polyurethane bi-directional eZ.on condom with a marketed latex condom. Three hundred sixty couples were asked to use 4 eZ.on condoms and 4 latex condoms. Like several other non-latex condoms tested to date, the eZ.on condom had a higher clinical breakage rate than its latex comparator, while the slippage rates were similar. The clinical breakage rate for the eZ.on condom was 5.6%, compared with 0.9% for the latex condom (difference = 4.76%, with upper 95% confidence bound on the difference = 6.26%). Thus, based on an a priori definition of a 2% clinically acceptable difference, the study failed to conclude equivalence relative to clinical breakage. The complete slippage rate for eZ.on was 1.6%; compared to 0.7% for latex (difference = 0.87%, with upper 95% confidence bound = 1.55%). Thus, based on an a priori definition of a 2% difference we concluded equivalence relative to complete slippage. The safety profile of the eZ.on condom was good and similar to the latex condom. The eZ.on was also found to be easier to don and remove than the latex condom. Although no overall preference existed for either condom, nearly 30%women and men strongly preferred the eZ.on condom to the latex condom. The eZ.on condom may be an acceptable alternative for couples unable or unwilling to use latex condoms.

Adult↗

Technologic advances for evaluation of cervical cytology: is newer better?

Among those women who have cervical cancer and have been screened, 14% to 33% of the cases represent failure to detect abnormalities that existed at the time of screening. New technologies intended to improve detection of cytologic abnormalities include liquid-based, thin-layer cytology (ThinPrep, AutoCyte), computerized rescreening (PAPNET), and algorithm-based computer rescreening (AutoPap). This report combines evidence reviews conducted for the U.S. Preventive Services Task Force and the Agency for Healthcare Research and Quality, in which we systematically identified articles on cervical neoplasia, cervical dysplasia, and screening published between January 1966 and March 2001. We note the challenges for improving screening methods, providing an overview of methods for collecting and evaluating cytologic samples, and examining the evidence about the diagnostic performance of new technologies for detecting cervical lesions. Using standard criteria for evaluation of the diagnostic tests, we determined that knowledge about the sensitivity, specificity, and predictive values of new technologies is meager. Only one study of liquid-based cytology used a reference standard of colposcopy, with histology as indicated, to assess participants with normal screening results. Lack of an adequate reference standard is the overwhelming reason that test characteristics cannot be properly assessed or compared. Most publications compare results of screening using the new technology with expert panel review of the cytologic specimen. In that case, the tests are not independent measures and do nothing to relate the screening test findings to the true status of the cervix, making determination of false-negatives, and thus sensitivity, specificity, and negative predictive value, impossible. We did not identify any literature about health outcomes or cost effectiveness of using these tools in a system of screening. For the purposes of guiding decision making about choice of screening tools, the current evidence is inadequate to gauge whether new technologies are "better" than conventional cytology..

Colposcopy↗

Characterization of acetic acid bacteria in traditional acetic acid fermentation of rice vinegar (komesu) and unpolished rice vinegar (kurosu) produced in Japan.

Bacterial strains were isolated from samples of Japanese rice vinegar (komesu) and unpolished rice vinegar (kurosu) fermented by the traditional static method. Fermentations have never been inoculated with a pure culture since they were started in 1907. A total of 178 isolates were divided into groups A and B on the basis of enterobacterial repetitive intergenic consensus-PCR and random amplified polymorphic DNA fingerprinting analyses. The 16S ribosomal DNA sequences of strains belonging to each group showed similarities of more than 99% with Acetobacter pasteurianus. Group A strains overwhelmingly dominated all stages of fermentation of both types of vinegar. Our results indicate that appropriate strains of acetic acid bacteria have spontaneously established almost pure cultures during nearly a century of komesu and kurosu fermentation.

Acetic Acid↗

Mathematical model for the natural history of human papillomavirus infection and cervical carcinogenesis.

The authors constructed a Markov model as part of a systematic review of cervical cytology conducted at the Duke University Evidence-based Practice Center (Durham, North Carolina) between October 1997 and September 1998. The model incorporated states for human papillomavirus infection (HPV), low- and high-grade squamous intraepithelial lesions, and cervical cancer stages I-IV to simulate the natural history of HPV infection in a cohort of women from ages 15 to 85 years. The age-specific incidence rate of HPV, and regression and progression rates of HPV and squamous intraepithelial lesions, were obtained from the literature. The effects of varying natural history parameters on cervical cancer incidence were evaluated by using sensitivity analysis. The base-case model resulted in a lifetime cervical cancer risk of 3.67% and a lifetime cervical cancer mortality risk of 1.26%, with a peak incidence of 81/100,000 at age 50 years. Age-specific distributions of precursors were similar to reported data. Lifetime risk of cancer was most sensitive to the incidence of HPV and the probability of rapid HPV progression to high-grade lesions (two- to threefold variations in risk). The model approximates the age-specific incidence of cervical cancer and provides a tool for evaluating the natural history of HPV infection and cervical cancer carcinogenesis as well as the effectiveness and cost-effectiveness of primary and secondary prevention strategies.

Adolescent↗

Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review.

PURPOSE: To evaluate the accuracy of conventional and new methods of Papanicolaou (Pap) testing when used to detect cervical cancer and its precursors. DATA SOURCES: Systematic search of English-language literature through October 1999 using MEDLINE, EMBASE, other computerized databases, and hand searching. STUDY SELECTION: All studies that compared Pap testing (conventional methods, computer screening or rescreening, or monolayer cytology) with a concurrent reference standard (histologic examination, colposcopy, or cytology). DATA EXTRACTION: Two reviewers independently reviewed selection criteria and completed 2 x 2 tables for each study. DATA SYNTHESIS: 94 studies of the conventional Pap test and three studies of monolayer cytology met inclusion criteria. No studies of computerized screening were included. Data were organized by cytologic and histologic thresholds used to define disease. For conventional Pap tests, estimates of sensitivity and specificity varied greatly in individual studies. Methodologic quality and frequency of histologic abnormalities also varied greatly between studies. In the 12 studies with the least biased estimates, sensitivity ranged from 30% to 87% and specificity ranged from 86% to 100%. CONCLUSIONS: Insufficient high-quality data exist to estimate test operating characteristics of new cytologic methods for cervical screening. Future studies of these technologies should apply adequate reference standards. Most studies of the conventional Pap test are severely biased: The best estimates suggest that it is only moderately accurate and does not achieve concurrently high sensitivity and specificity. Cost-effectiveness models of cervical cancer screening should use more conservative estimates of Pap test sensitivity.

Cervix Uteri↗

Amino acid residues of S-modulin responsible for interaction with rhodopsin kinase.

S-modulin in frog or its bovine homologue, recoverin, is a 23-kDa EF-hand Ca(2+)-binding protein found in rod photoreceptors. The Ca(2+)-bound form of S-modulin binds to rhodopsin kinase (Rk) and inhibits its activity. Through this regulation, S-modulin is thought to modulate the light sensitivity of a rod. In the present study, we tried to identify the interaction site of the Ca(2+)-bound form of S-modulin to Rk. First, we mapped roughly the interaction regions by using partial peptides of S-modulin. The result suggested that a specific region near the amino terminus is the interaction site of S-modulin. We then identified the essential amino acid residues in this region by using S-modulin mutant proteins: four amino acid residues (Phe(22), Glu(26), Phe(55), and Thr(92)) were suggested to interact with Rk. These residues are located in a small closed pocket in the Ca(2+)-free, inactive form of S-modulin, but exposed to the surface of the molecule in the Ca(2+)-bound, active form of S-modulin. Two additional amino acid residues (Tyr(108) and Arg(150)) were found to be crucial for the Ca(2+)-dependent conformational changes of S-modulin.

Amino Acid Sequence↗