Biomedical subjects

Feng Lin

Publications and source records attributed to Feng Lin.

At least 73 records · Page 4Linked to original sources

PubMed2005

[Development of high speed UV-Vis spectrophotometer].

A high speed spectrophotometer based on a linear CCD was developed. The function and structure of the hardware and the software for the instrument were discussed. The elementary performance was tested as follows: wavelength range 200-820 nm, full spectrum scan time < 0.1 s, spectral bandwidth 0.7 nm, wavelength accuracy +/-1 nm, photometric accuracy +/- 0.005 AU, baseline flatness < 0.001 AU (rms), and stray light < 0.1%. Results showed that this instrument is easy to use, fast and with high analytical performance. In addition, it has internet function of remote control and remote access. With the powerful data processing and spectrum analyzing software, it will provide a strong tool for routine analysis and the research on dynamic reaction in chemistry and biology fields.

Equipment Design↗

PubMed2005

[Study on PBPs genes of penicillin-resistant Streptococcus pneumonia in Zhejiang province].

To elucidate alternations in gene/amino acid sequence of penicillin-binding proteins (PBPs) 1A, 2B, 2X from clinical isolates of penicillin-resistant Streptococcus pneumonia (PRSP) in Zhejiang Province, 26 strains of Streptococcus pneumonia were collected from November 2001 to January 2004. The antibiotics susceptibility of these strains was detected. PCR amplification and direct sequencing of PBP1A, 2B, 2X genes were performed. The sequence variations of PBP genes of the PRSPs in this region were studied by sequence BLAST analysis. It was shown that the main alternations of PBP1A were the four consecutive amino acid substitutions (Thr574Ala, Ser575Thr, Gln576Gly, Phe577Tyr) following the conservative motif KTG and the amino acid substitution Thr371Ser in the conservative motif STMK. The main alternation of PBP2B was Thr451Ala following the conservative motif SSN, and the main alternation of PBP2X was Thr338Ala in conservative motif STMK. The above mutation sites and drug resistant level were consistent to the data reported previously. Neither new gene mutation specific to these strains nor certain amino acid substitutions related to penicillin resistance reported was identified in the genes.

Amino Acid Sequence↗

PubMed2005

[Effects of pine wood nematode on propagation of its carrying bacteria].

In this paper, the aseptic eggs of Bursaphelenchus xylophilus were obtained after treated with 30% H202, and cultured with Pinus thunbergii callus. Ten B. xylophilus-carrying bacterial strains directly isolated from diseased P. thugbergii and P. massoniana in six epidemic provinces i.e., GcM6-2A Pseudomonas putida, GcM6-1A P. putida, ZpB1-2A P. putida, HeM2A Pseudomonas sp., HeM1A Pseudomonas sp., HeM142B Pseudomonas sp., GcM1-3A P. cepacia and HM3 Pantoeu sp., ZpB4-2B Staphylococcus sciuri and ZpB2-3A Enterobacter amnigenus, were collected, and the effects of axenic B. xylophilus (ABx) on their propagation were studied. The results showed that pine wood nematode (PWN) promoted the propagation of 7 bacterial strains in Pseudomonas and 1 bacterial strain in Pantoeu sp., including Pseudomonas putida, P. putida, P. putida , Pseudomonas sp., Pseudomonas sp., Pseudomonas sp., P. cepacia and Pantoeu sp., but inhibited Staphylococcus sciuri and Enterobacter amnigenus, which could explain the phenomenon that Pseudomonas was the prevailing genus of the bacteria carried by PWN, and might provide essential nutrition to the bacteria. The close relationship between PWN and bacterial strains in Pseudomonas might account for the pine wood nematode disease.

Animals↗

PubMed2004

MAN1, an integral protein of the inner nuclear membrane, binds Smad2 and Smad3 and antagonizes transforming growth factor-beta signaling.

MAN1 (also known as LEMD3) is an integral protein of the inner nuclear membrane. Recently, mutations in MAN1 have been shown to result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. We show that the nucleoplasmic, C-terminal domain of human MAN1 binds to Smad2 and Smad3 and antagonizes signaling by transforming growth factor-beta (TGF-beta). In a yeast two-hybrid screen using the C-terminal domain of MAN1 as bait, eight positive clones were obtained that encoded Smad3. In direct two-hybrid assays, this portion of MAN1 bound to Smad2 and Smad3. In glutathione-S-transferase precipitation assays, the C-terminal domain of MAN1 bound to Smad2 and Smad3 under stringent conditions. Antibodies against MAN1 were able to co-immunoprecipiate Smad2 from cells, demonstrating that they reside in the same complex in vivo. TGF-beta treatment stimulated transcription from a reporter gene in control cells, but reporter gene stimulation was significantly inhibited in cells overexpressing MAN1 or its C-terminal domain but not its N-terminal domain. TGF-beta-induced cell proliferation arrest was also inhibited in stable cell lines overexpressing MAN1. These results show that the nuclear envelope regulates a signal transduction pathway and have implications for how mutations in nuclear envelope proteins cause different human diseases.

Cell Line↗

PubMed2004

Renal insufficiency as an independent predictor of mortality among women with heart failure.

OBJECTIVES: We sought to explore the association between renal insufficiency and mortality among women with heart failure (HF) and to evaluate this risk by the presence of preserved or depressed systolic function. BACKGROUND: Although HF is common in older women, little is known about their risk factors for mortality. METHODS: This prospective cohort study retrospectively analyzed data from the Heart and Estrogen/progestin Replacement Study (HERS). Of the 2,763 women in HERS, 702 had HF. Renal function was categorized as creatinine clearance (CrCl) >60 ml/min, 40 to 60 ml/min, and <40 ml/min. We used proportional hazards models to evaluate the association between renal insufficiency and mortality. RESULTS: Over a mean 5.8 years, 228 women with HF died (32%). Renal insufficiency was strongly associated with mortality, even after adjustment for co-morbid conditions, systolic function, and medications (adjusted hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.09 to 2.16 for CrCl 40 to 60 ml/min; adjusted HR 2.40, 95% CI 1.60 to 3.62 for CrCl <40 ml/min). Preserved or depressed systolic function did not modify the association between renal insufficiency and mortality risk, but the use of angiotensin-converting enzyme (ACE) inhibitors did modify this risk (ACE users: adjusted HR = 0.9, 95% CI 0.6 to 1.6; ACE nonusers: adjusted HR 2.1, 95% CI 1.3 to 3.2; p = 0.02 for interaction). Compared with other risk factors for mortality, renal insufficiency had the highest population attributable risk (27%). CONCLUSIONS: Renal insufficiency was a major predictor of mortality among women with HF and preserved or depressed systolic function. This risk was attenuated by the use of ACE inhibitors.

Aged↗

PubMed2004

Predictors of heart failure among women with coronary disease.

BACKGROUND: Although heart failure is common among women with coronary disease, the risk factors for developing heart failure have not been well studied. We determined the risk factors for developing heart failure among postmenopausal women with established coronary disease. METHODS AND RESULTS: This is a prospective cohort study using data from the Heart and Estrogen/progestin Replacement Study (HERS), a randomized, blinded, placebo-controlled trial of 4.1 years' duration, and subsequent open-label observational follow-up for 2.7 years (HERS II), performed at 20 US clinical centers between 1993 and 2000. Of the 2763 postmenopausal women with established coronary disease in the HERS trial, we studied the 2391 women with no heart failure at baseline by self-report and physical examination. The primary outcome of this analysis was incident heart failure defined by hospital admission or death from heart failure. During the 6.3+/-1.4-year follow-up, 237 women (10%) developed heart failure. Nine predictors were identified: diabetes (defined as a self-reported history of diabetes on treatment), atrial fibrillation, myocardial infarction, creatinine clearance <40 mL/min, systolic blood pressure >120 mm Hg, current smoking, body mass index >35 kg/m2, left bundle-branch block, and left ventricular hypertrophy. Randomization to estrogen/progestin was not associated with heart failure (hazard ratio=1.0; 95% CI, 0.7 to 1.3). Diabetes was the strongest risk factor (adjusted hazard ratio=3.1; 95% CI, 2.3 to 4.2). Diabetic women with elevated body mass index or depressed creatinine clearance were at highest risk, with annual incidence rates of 7% and 13%, respectively. Among diabetic women, hyperglycemia was associated with heart failure risk (adjusted hazard ratio=3.0; 95% CI, 1.2 to 7.5 for fasting glucose >300 mg/dL compared with fasting glucose 80 to 150 mg/dL). CONCLUSIONS: We identified 9 predictors of heart failure in postmenopausal women with coronary disease. Diabetes was the strongest risk factor, particularly when poorly controlled or with concomitant renal insufficiency or obesity.

Black or African American↗

PubMed2004

The incidence of end-stage renal disease is increasing faster than the prevalence of chronic renal insufficiency.

BACKGROUND: The steady increase in end-stage renal disease (ESRD) incidence is a worldwide public health crisis. OBJECTIVE: To determine whether the increasing incidence of ESRD in the United States is preceded by increased prevalence of chronic renal insufficiency. DESIGN: Birth cohort analysis. SETTING: Nationally representative Second and Third National Health and Nutrition Examination Surveys (NHANES II [1976-1980] and III [1988-1994]) and nationally comprehensive U.S. Renal Data System registry. PATIENTS: Adults, 20 to 74 years of age, surveyed in NHANES II (midpoint, 1978) and NHANES III (midpoint, 1991), and adults, 25 to 79 years of age, who developed ESRD in 1983 and 1996. MEASUREMENTS: Prevalent chronic renal insufficiency (estimated glomerular filtration rate, 15 to 59 mL/min per 1.73 m2) and new ESRD cases. RESULTS: From 1978 to 1991, the number of adults age 20 to 74 years with chronic renal insufficiency increased from 2.6 to 3.9 million, an increase in prevalence from 1970 to 2460 per 100 000 persons. However, the increased incidence of ESRD was even greater during this period. For every 1000 adults with chronic renal insufficiency in 1978, 9 new cases of ESRD developed in 1983, but every 1000 adults with chronic renal insufficiency in 1991 produced 16 new cases of ESRD in 1996 (relative risk, 1.7 [95% CI, 1.1 to 2.7]). LIMITATIONS: We could not follow individual patients with chronic renal insufficiency for the development of ESRD, and we used estimated rather than measured glomerular filtration rate. CONCLUSIONS: During the period examined, growth in incident ESRD outpaced growth in prevalent chronic renal insufficiency, demonstrating that the ESRD epidemic in the United States is not merely a function of more cases of kidney disease. Future research should examine other potential contributors to ESRD growth, such as improved survival from nonrenal diseases and more liberal entry into treatment programs.

Adult↗

PubMed2004

Synthesis of bidesmosidic dihydrodiosgenin saponins bearing a 3-O-beta-chacotriosyl moiety.

3-O-beta-Chacotriosyl-26-O-beta-D-glucopyranosyl-(25R)-furost-5-en (1), a mimic of the antitumor active proto-dioscin, was concisely synthesized from diosgenin in a linear nine steps and in 17% overall yield. Its congeners with a alpha-l-rhamnopyranosyl, beta-lactosyl, or without a substituent at the 26-OH (13-15) were also prepared. Compound 1, as well as 13-15, did not show any inhibition against tumor cells, implying that proto-dioscin might be also inactive, but readily converted into the antitumor active dioscin.

Antineoplastic Agents↗

PubMed2004

A facile preparation of uronates via selective oxidation with TEMPO/KBr/Ca(OCl)(2) under aqueous conditions.

Addition of solid Ca(OCl)(2) as the terminal oxidant in the TEMPO-mediated selective oxidation has the benefit of easier operation. A variety of partially protected saccharide derivatives (1a-l) have been successfully converted into the corresponding uronate derivatives, including disaccharide building blocks for GAG fragments and precursors to saponins. The beneficial effect of Aliquat 336 was also disclosed in the oxidation of certain substrates.

Bromides↗

PubMed2004

Effect of hysterectomy vs medical treatment on health-related quality of life and sexual functioning: the medicine or surgery (Ms) randomized trial.

CONTEXT: Although a quarter of US women undergo elective hysterectomy before menopause, controlled trials that evaluate the benefits and harms are lacking. OBJECTIVE: To compare the effect of hysterectomy vs expanded medical treatment on health-related quality of life. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized controlled trial (August 1997-December 2000) of 63 premenopausal women, aged 30 to 50 years, with abnormal uterine bleeding for a median of 4 years who were dissatisfied with medical treatments, including medroxyprogesterone acetate. The participants, who were patients at gynecology clinics and affiliated practices of 4 US academic medical centers, were followed up for 2 years. INTERVENTIONS: Participants were randomly assigned to undergo hysterectomy or expanded medical treatment with estrogen and/or progesterone and/or a prostaglandin synthetase inhibitor. The hysterectomy route and medical regimen were determined by the participating gynecologist. MAIN OUTCOME MEASURES: The primary outcome was mental health measured by the Mental Component Summary (MCS) of the 36-Item Short-Form Health Survey (SF-36). Secondary outcomes included physical health measured by the Physical Component Summary (PCS), symptom resolution and satisfaction, body image, and sexual functioning, as well as other aspects of mental health and general health perceptions. RESULTS: At 6 months, women in the hysterectomy group had greater improvement in MCS scores than women in the medicine group (8 vs 2, P =.04). They also had greater improvement in symptom resolution (75 vs 29, P<.001), symptom satisfaction (44 vs 7, P<.001), interference with sex (41 vs 22, P =.003), sexual desire (21 vs 3, P =.01), health distress (33 vs 13, P =.009), sleep problems (13 vs 1, P =.03), overall health (12 vs 2, P =.006), and satisfaction with health (31 vs 14, P =.01). By the end of the study, 17 (53%) of the women in the medicine group had requested and received hysterectomy, and these women reported improvements in quality-of-life outcomes during the 2 years that were similar to those reported by women randomized to the hysterectomy group. Women who continued medical treatment also reported some improvements (P<.001 for within-group change in many outcomes), with the result that most differences between randomized groups at the end of the study were no longer statistically significant in the intention-to-treat analysis. CONCLUSIONS: Among women with abnormal uterine bleeding and dissatisfaction with medroxyprogesterone, hysterectomy was superior to expanded medical treatment for improving health-related quality-of-life after 6 months. With longer follow-up, half the women randomized to medicine elected to undergo hysterectomy, with similar and lasting quality-of-life improvements; those who continued medical treatment also reported some improvements.

Adult↗

PubMed2004

Decay-accelerating factor deficiency increases susceptibility to dextran sulfate sodium-induced colitis: role for complement in inflammatory bowel disease.

Decay-accelerating factor (DAF or CD55) is expressed on colonic epithelial cells but its function in the mucosa is unknown. In humans, a proportion of DAF-deficient (Cromer INAB) patients develop inflammatory bowel disease (IBD). To evaluate how DAF deficiency may contribute to gut inflammation and thus could play a role in IBD pathogenesis, we compared the severity of dextran sulfate sodium-induced colitis in Daf1 gene-targeted and control mice. Seven days after consuming 3% dextran sulfate sodium in their drinking water, Daf1(-/-) mice suffered markedly greater weight loss (-24.7 +/- 7.5% vs -14.2% +/- 4.9%), exhibited uniformly bloody diarrhea as compared with soft stool in control mice, developed shortened colons, and had larger spleens. Histological examination of distal colons showed massively increased neutrophilic and mononuclear cell infiltration, greater epithelial cell destruction, and increased ulcerations. Cytokine production in organ cultures of colonic explants showed increased levels of IL-12 and IL-6. Fourteen days after switching back to regular water, in contrast to the Daf1(+/+) controls which showed little stool abnormality, all Daf1(-/-) mice continued to have diarrhea. Organ culture cytokine measurements at this time point, i.e., the end of the recovery phase, showed markedly increased levels of IL-10 (6-fold), IL-12 (4-fold), and IL-6 (2-fold), as well as TNF-alpha (>10-fold) compared with the controls. Our findings argue that, as shown for IL-10 in IL-10(-/-) mice and IL-2 in IL-2(-/-) mice, DAF control of complement additionally is important in regulating gut homeostasis and consequently its activity may participate in protecting against IBD.

Administration, Oral↗

PubMed2004

Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3.

The Bcl-2 family proteins are key regulators of apoptosis in human diseases and cancers. Though known to block apoptosis, Bcl-2 promotes cell death through an undefined mechanism. Here, we show that Bcl-2 interacts with orphan nuclear receptor Nur77 (also known as TR3), which is required for cancer cell apoptosis induced by many antineoplastic agents. The interaction is mediated by the N-terminal loop region of Bcl-2 and is required for Nur77 mitochondrial localization and apoptosis. Nur77 binding induces a Bcl-2 conformational change that exposes its BH3 domain, resulting in conversion of Bcl-2 from a protector to a killer. These findings establish the coupling of Nur77 nuclear receptor with the Bcl-2 apoptotic machinery and demonstrate that Bcl-2 can manifest opposing phenotypes, induced by interactions with proteins such as Nur77, suggesting novel strategies for regulating apoptosis in cancer and other diseases.

Apoptosis↗

PubMed2004

Respective roles of decay-accelerating factor and CD59 in circumventing glomerular injury in acute nephrotoxic serum nephritis.

Decay-accelerating factor (DAF or CD55) and CD59 are regulators that protect self cells from C3b deposition and C5b-9 assembly on their surfaces. Their relative roles in protecting glomeruli in immune-mediated renal diseases in vivo are unknown. We induced nephrotoxic serum (NTS) nephritis in Daf1(-/-), CD59a(-/-), Daf1(-/-)CD59a(-/-), and wild-type (WT) mice by administering NTS IgG. After 18 h, we assessed proteinuria, and performed histological, immunohistochemical, and electron microscopic analyses of kidneys. Twenty-four mice in each group were studied. Baseline albuminuria in the Daf1(-/-), CD59a(-/-), and Daf1(-/-)CD59a(-/-) mice was 82, 83, and 139 as compared with 92 microg/mg creatinine in the WT controls (p > 0.1). After NTS, albuminuria in CD59a(-/-) and WT mice (186 +/- 154 and 183 +/- 137 microg/mg creatinine, p > 0.1) was similar. In contrast, Daf1(-/-) mice developed severe albuminuria (378 +/- 520, p < 0.05) that was further exacerbated in Daf1(-/-)CD59a(-/-) mice (577 +/- 785 micro g/mg creatinine, p < 0.05). Glomerular histology showed essentially no infiltrating leukocytes in any group. In contrast, electron microscopy revealed prominent podocyte foot process effacement in Daf1(-/-) mice with more widespread and severe damage in the double knockouts compared with only mild focal changes in CD59a(-/-) or WT mice. In all animals, deposition of administered (sheep) NTS Ig was equivalent. This contrasted with marked deposition of both C3 and C9 in Daf1(-/-)CD59a(-/-) and Daf1(-/-) mice, which was evident as early as 2 h post-NTS injection. The results support the proposition that in autoantibody-mediated nephritis, DAF serves as the primary barrier to classical pathway-mediated injury, while CD59 limits consequent C5b-9-mediated cell damage.

Acute Disease↗

PubMed2004

Synthetic human insulin 4 does not activate the G-protein-coupled receptors LGR7 or LGR8.

In contrast to the cellular receptors for insulin and insulin-like growth factors that are known to be protein tyrosine kinases, those of both insulin 3 and relaxin have recently been identified as being members of the leucine-rich repeat-containing G-protein coupled receptor (LGR) family, LGR8 and LGR7, respectively. This has prompted an examination into the possibility that they might also be specific for another member of the insulin superfamily, namely, insulin 4. Towards this aim, a two-chain peptide corresponding to the predicted primary structure of insulin 4 was prepared by solid phase synthesis. As conventional aeration and combination of the two S-reduced chains in solution at high pH failed to produce target product, selectively S-protected A- and B-chains were prepared followed by stepwise, individual formation of each of the three disulfides, one intramolecular within the A-chain and two intermolecular. Chemical characterization confirmed the purity and identity of the synthetic insulin 4 analogue. However, secondary structural analysis indicated that the peptide was devoid of tertiary conformation suggesting that the native peptide may well be either significantly longer in length or is similar to insulin-like growth factor I or II in that it is a single chain product. Screening of the synthetic analogue for activation of transfected cells bearing LGR7, and LGR7 splice variant or LGR8 failed to identify a specific interaction. Thus, the in vivo structural identity of insulin 4 and its receptor (if any) as well as its potential function remains unknown.

Alternative Splicing↗

PubMed2004

A hierarchical clustering algorithm for MIMD architecture.

Hierarchical clustering is the most often used method for grouping similar patterns of gene expression data. A fundamental problem with existing implementations of this clustering method is the inability to handle large data sets within a reasonable time and memory resources. We propose a parallelized algorithm of hierarchical clustering to solve this problem. Our implementation on a multiple instruction multiple data (MIMD) architecture shows considerable reduction in computational time and inter-node communication overhead, especially for large data sets. We use the standard message passing library, message passing interface (MPI) for any MIMD systems.

Algorithms↗

PubMed2004

Complement regulators in extraocular muscle and experimental autoimmune myasthenia gravis.

Complement activation at motor endplates is the primary effector mechanism in myasthenia gravis (MG). In this study, we evaluated whether differences in gene transcript levels and protein expression of cell-surface complement regulators could be a factor in the increased susceptibility of extraocular muscle (EOM) compared to other skeletal muscles to MG. Experimental autoimmune MG (EAMG) was induced in mice by administration of a monoclonal antibody (mAb) directed toward the acetylcholine receptor (AChR). Standard RT-PCR and real-time PCR (qPCR) were used to assess mRNA levels of decay-accelerating factor (DAF), CD59, and complement receptor 1-related gene/protein y (Crry). Gene transcript levels of the alpha- and gamma-subunits of the AChR were also evaluated by qPCR. Protein expression of the three intrinsic complement regulators at the neuromuscular junction was assessed by immunohistochemistry. Under constitutive conditions by RT-PCR, no significant differences were detected, but qPCR, EOM showed lower mRNA levels of all three complement regulators, but higher levels of alpha- and gamma-subunit gene transcripts. With EAMG, significant decreases in mRNA levels of all three complement regulators as well as AChR subunits occurred in EOM, but not in the diaphragm. Immunoreactivity for all three complement regulators was highly concentrated at diaphragm junctions, whereas it was less intense or absent at EOM junctions. With EAMG, immunoreactivity for Crry and DAF increased at diaphragm junctions and for DAF at EOM junctions. Diminished intrinsic complement regulatory activity may contribute to the susceptibility of EOM to MG. Our findings suggest that complement inhibitor-based therapies could be useful in treating ocular manifestations of MG.

Animals↗

PubMed2004

Creatinine levels and cardiovascular events in women with heart disease: do small changes matter?

BACKGROUND: Small changes in creatinine levels have been incrementally associated with increased risk for heart failure morbidity, but their association with cardiovascular events has not been evaluated in persons with established coronary heart disease (CHD). METHODS: This was an observational study from the Heart and Estrogen/Progestin Replacement Study (HERS) and the HERS-II follow-up study. Participants were 2,763 postmenopausal women with CHD who were followed up for a mean of 4.1 years during HERS and an additional 2.7 years during HERS-II. We evaluated the association of worsened renal function (creatinine level increase > or = 0.3 mg/dL [> or =26.5 micromol/L]) during HERS with CHD outcomes (nonfatal myocardial infarction and CHD death) that occurred during HERS-II. RESULTS: Only 194 participants (9%) had worsened renal function during HERS, and they were characterized by a greater prevalence of diabetes, lower high-density lipoprotein cholesterol and higher triglyceride levels, and increased rate of cardiovascular events during HERS (all P < 0.01). After adjustment for only baseline creatinine levels, worsened renal function was associated with HERS-II CHD events (relative hazard [RH], 1.54; 95% confidence interval [CI], 1.04 to 2.29). After adjustment for baseline characteristics, HERS cardiovascular events, and medication use, worsened renal function was no longer associated with CHD events (RH, 1.08; 95% CI, 0.70 to 1.67). However, baseline creatinine levels from HERS were remarkably strong predictors of HERS-II events. CONCLUSION: Although baseline renal function was among the strongest predictors of CHD events during 7 years of HERS follow-up, we found no significant association of worsened renal function with cardiovascular outcomes after adjustment for cardiovascular risk factors and interim events.

Aged↗

PubMed2004

Hysterectomy versus expanded medical treatment for abnormal uterine bleeding: clinical outcomes in the medicine or surgery trial.

OBJECTIVE: To compare clinical outcomes after randomization to hysterectomy versus medical treatment in patients with chronic abnormal uterine bleeding refractory to medroxyprogesterone acetate. METHODS: We randomly assigned 63 premenopausal women with abnormal uterine bleeding refractory to cyclic medroxyprogesterone acetate treatment to receive either a hysterectomy or expanded medical treatment. Within each randomized group, the specific treatment approach was determined by patient and provider preference. The primary analysis compared changes in clinical outcomes at 6 and 24 months by using an intention-to-treat approach. Secondary as-treated analyses after adjustment for baseline covariates compared participants randomly assigned to medical treatment who continued the medical approach with those who crossed over to hysterectomy. RESULTS: The intention-to-treat analyses at 6 months revealed greater symptom improvement in the hysterectomy group than in the medicine group for pelvic pain (P <.01), urinary urgency (P =.03), incomplete bladder emptying (P =.03), breast pain (P =.02), and cessation of vaginal bleeding (87% versus 11%, P <.001). Seventeen of 32 women assigned to medicine (53%) eventually crossed over and received a hysterectomy, and by 24 months the statistically significant differences by intention-to-treat were limited to greater improvement in hot flushes (P <.01) and cessation of vaginal bleeding (P <.01). Within-group analyses at year 2 showed statistically significant improvements from baseline on most symptoms for women who had a hysterectomy, whether through randomization or crossover. Women remaining on medical treatments had statistically significant improvements in pelvic pain, pelvic/bladder pressure, and stress incontinence. In a nonrandomized comparison with women who remained on medical treatments through year 2, those crossing over to hysterectomy experienced greater improvements in bleeding (P <.01), pelvic pain (P <.01), low back pain (P =.02), breast pain (P =.01), urinary frequency (P =.01), and urgency (P =.02). However, they also experienced more days off from work or usual activities (P <.01) and more days spent in bed (P <.01) than those who remained on medicine. CONCLUSION: For patients with abnormal uterine bleeding refractory to medroxyprogesterone acetate, hysterectomy is superior to expanded efforts with oral medications for alleviating clinical symptoms but may lead to more days of restricted activity.

Adult↗