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PubMed1977

Stage I cervix cancer and pelvic node metastasis: special reference to the implications of the new and the recently replaced FIGO classifications on Stage Ia.

The current staging system for cervix cancer of the International Federation of Gynecology and Obstetrics (FIGO) has been in use for less than 2 years. It is criticized by many because of a lack of quantitative features. While quantative features are important, the over-all morphology of the histologic pattern--the qualitative features--are those utilized by most pathologists in interpretating the "invasiveness" of a lesion and therefore its biologic potential. The most recent, as well as the previous FIGO Staging System was applied to 108 personal cases with particular reference to lymih node metastasis. By comparing results of the new and older staging system, the validity of the new system is suggested, and the inordinately high rate of node metastasis when using the older system appears to be at least one reason for the relatively high rate of node metastasis reported in earlier series of Stage Ia lesions reported in the literature.

Cervix Uteri↗

PubMed1986

Effect of stage of lactation, stage of pregnancy, milk yield and herd management on seasonal variation in spontaneous lipolysis in bovine milk.

The free fatty acid (FFA) levels after milking (initial FFA) and after 22 h storage at 4 degrees C (FFA-22) were determined in milk from 57 cows every 2 weeks for one year. FFA levels which were higher in summer than in winter were explained by later stages of lactation occurring in summer. Initial FFA content increased regularly during lactation. FFA-22 content increased after 12 weeks, and further after 32 weeks of lactation. The first increase was due to stage of lactation. The second increase, which appeared in late lactation, was essentially due to the stage of pregnancy combined with the effect of milk yield. FFA-22 content increased in the second part of pregnancy, chiefly after 24 weeks. A low milk yield (less than or equal to 5 kg) further increased lipolysis, but only after 16 weeks of pregnancy. The effect of stage of pregnancy may have been enhanced by management factors such as feeding conditions. In this investigation, the seasonal FFA variation in bulk tank milk could be explained entirely by physiological factors.

Animals↗

PubMed2002

Differentiating stages of smoking intensity among adolescents: stage-specific psychological and social influences.

Researchers' understanding of the impact of sociocultural and psychological factors on the various stages of adolescent smoking uptake is limited. Using national data, the authors examined transitions across smoking stages among adolescents (N = 20,747) as a function of interpersonal, familial, and peer domains. Peer smoking was particularly influential on differentiating regular smoking, whereas alcohol use was most influential on earlier smoking. Although significant, depression and delinquency were attenuated in the context of other variables. Higher school grade was more likely to differentiate regular smoking from earlier smoking stages, whereas African American ethnicity and connectedness to school and family were protective of smoking initiation. Results lend support for an interactional approach to adolescent smoking, with implications for stage-matched prevention and intervention applications.

Adolescent↗

PubMed2005

Adjuvant sequential methotrexate --> 5-fluorouracil vs 5-fluorouracil plus leucovorin in radically resected stage III and high-risk stage II colon cancer.

The aim of the study was to determine whether modulation of 5-fluorouracil (FU) by methotrexate (MTX) improves survival compared to FU+6-s-leucovorin (LV) following potentially curative resection of stage II and III colon cancer. Within 8 weeks from surgery, 1945 patients with stage III (44%) or high-risk stage II (55%) colon cancer were randomly assigned to receive either 6 monthly cycles of FU 370 mg m(-2) i.v. bolus preceded by LV 100 mg m(-2) i.v. bolus on days 1-5, or 6 monthly cycles of sequential MTX 200 mg m(-2) i.v. days 1 and 15 and FU 600 mg m(-2) i.v. on days 2 and 16 followed by LV rescue (15 mg given p.o. q 6 h x 6 doses). Levamisole 50 mg p.o. t.i.d. on days 1-3, every 14 days for 6 months, was planned to be given in both arms. After a median follow-up of 4.2 years, 568 patients have relapsed and 403 have died. Survival was similar with MTX --> FU and FU+LV (77 vs 77% at 5 years; P = 0.90), as were 5-year disease-free survivals (67 vs 63%; P = 0.44). Efficacy results were similar for both stage III and II patients. There were two toxic deaths, two in the MTX --> FU arm (0.2%) and zero in the control arm. We conclude that biochemical modulation of FU with LV or with MTX produces similar results in the adjuvant setting of colon cancer.

Adult↗

PubMed1984

The modified Ombredanne repair for hypospadias--a comparison of single-stage and multi-stage procedures.

319 modified Ombredanne operations were carried out over a 17-year period, 149 were single-stage and 170 multi-stage procedures. 65 (20%) of the operations were carried out by registrars in training with no appreciable increase in the number of complications. The overall fistula rate was 5% with no significant difference between the types of repair. Preputial flap detachment or retraction occurred in 23 (7%) of patients. The most common complication was the minor one of an unsightly redundant prepuce which occurred in 30 (9%) of the patients and required a secondary plastic procedure. The length of hospital stay was halved in those patients undergoing the single-stage procedure when compared to the multi-stage group. Both techniques gave satisfactory cosmetic and functional results with a low incidence of serious complications.

Adolescent↗

PubMed1996

Early expression of Ig mu chain from a transgene significantly reduces the duration of the pro-B stage but does not affect the small pre-B stage.

During B cell development, V-J rearrangements at the Ig heavy mu chain (IgH mu chain) locus occur in early cycling precursors (pro-B stage). Subsequently, rearrangements at the Ig light (IgL) chain locus occur in late resting precursors (small pre-B stage). To study the effects of mu chain expression on the rate of B cell development, purified hematopoietic stem cells (HSC) bearing a mu chain transgene or wild-type HSC were transferred into immunodeficient RAG-2-/- mice and B cell development was followed over time. In addition, cycling B cell precursors were pulse-labeled by the injection of BrdU into transgenic and wild-type mice, and the production of BrdU-labeled kappa + and lambda + B cells was followed over time. These experiments suggested that early expression of the mu chain from the transgene significantly shortened the duration of the pro-B stage and immediately drove the precursors to differentiate into small pre-B cells. By contrast, the presence of the transgene did not affect the small pre-B stage, where IgL rearrangements occur. Thus, kappa and lambda rearrangements occurred only after the arrest of cell cycling as previously shown in wild-type mice, even when the mu chain is artificially expressed earlier in B cell development.

Animals↗

PubMed2005

Efficacy of entomopathogenic nematode Steinernema feltiae (Rhabditida: Steinernematidae) as influenced by Frankliniella occidentalis (Thysanoptera: Thripidae) developmental stage and host plant stage.

Entomopathogenic nematodes were investigated as an alternative biological control strategy for western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), in ornamental greenhouse crops, by using potted chrysanthemum as a model crop. The susceptibility of various life stages of F. occidentalis to different concentrations of the nematode Steinernema feltiae (Filipjev) (Rhabditida: Steinernematidae) was investigated in petri dish bioassays. This was followed with trials using potted chrysanthemums comparing the efficacy of nematode application to plants in vegetative (exposed habitat) versus flowering (cryptic habitat) stages. In both trials, the effect of the wetting agent Agral 90 (nonylphenoxy polyethoxyethanol), which is used in combination with the nematode spray, on F. occidentalis mortality was assessed. In petri dish trials, the prepupae and pupae were the most susceptible developmental stages of F. occidentalis to infection by S. feltiae. First and second instars were killed by very high rates of nematodes (> or =20,000 infective juveniles per milliliter), but corrected mortality was only approximately 28-37%. No significant mortality was observed for adult thrips. Results from the petri dish trials were confirmed on chrysanthemum plants. Foliar application of S. feltiae did not result in significant mortality in larvae or adults. No significant differences in efficacy were detected by application of nematodes on vegetative versus flowering chrysanthemum. Agral 90 had a significant impact on mortality on the first stage larvae and prepupae in the petri dish trials but not in the plant trials. Thrips control by S. feltiae in greenhouses may be partly or completely due to prepupal and pupal mortality.

Animals↗

PubMed1995

Reliability and accuracy of polymerase chain reaction amplification of two unique target sequences from biopsies of cleavage-stage and blastocyst-stage human embryos.

Human embryos have been biopsied at either the cleavage or the blastocyst stage of development. One to two blastomeres were removed from cleavage-stage embryos and 2-6 cells from blastocysts. The biopsy specimens were subjected to gene amplification by the polymerase chain reaction (PCR) and a comparison made of amplification efficiencies of two unique target sequences, one located within the beta-globin gene and containing the sickle-cell locus and the other a polymorphic dinucleotide repeat. When the cleavage-stage biopsy sample consisted of an intact blastomere with a clearly discernible nucleus, an amplification efficiency of 89% was achieved for each target locus. This was similar to that achieved with cleavage-stage biopsy samples consisting of two blastomeres or with blastocyst biopsy samples consisting of 2-3 trophectoderm cells. When biopsy samples consisted of four or more trophectoderm cells, both target loci were amplified in all samples tested. When the biopsy sample was heterozygous at the dinucleotide repeat locus and the biopsy consisted of one or more intact cells with a clearly discernible nucleus, both alleles were amplified in > 80% of biopsy samples. When four or more trophectoderm cells were used for the PCR, both alleles were amplified in all heterozygous samples. Target sequences were never amplified from biopsy samples which lysed prior to transfer into the reaction tube. Analysis of DNA fragments amplified from the dinucleotide repeat locus indicated that in most cases faithful amplification of biopsy DNA template had taken place.(ABSTRACT TRUNCATED AT 250 WORDS)

Beta-Globulins↗

PubMed2002

Stage-specific expression of the intermediate filament protein cytokeratin 13 in luminal epithelial cells of secretory phase human endometrium and peri-implantation stage rabbit endometrium.

In preparation for blastocyst implantation, uterine luminal epithelial cells express new cell adhesion molecules on their apical plasma membrane. Since one mechanism epithelial cells employ to regulate membrane polarity is the establishment of specific membrane-cytoskeletal interactions, this study was undertaken to determine if new cytokeratin (CK) intermediate filament assemblies are expressed in endometrial epithelial cells during developmental stages related to blastocyst implantation. Type-specific CK antibodies were used for immunocytochemical and immunoblot analyses of 1) intermediate filament networks of the endometrial epithelium during embryo implantation in rabbits and 2) proliferative and secretory phases of the human menstrual cycle. CK18, a type I CK found in most simple epithelia, was expressed in all luminal and glandular epithelial cells of both the human and rabbit endometrium at all developmental stages analyzed; it was also strongly expressed in trophectoderm of the implanting rabbit blastocyst. In contrast, CK13, another type I cytokeratin, exhibited a regulated expression pattern in luminal, but not glandular, epithelial cells of secretory phase human and peri-implantation stage rabbit endometrium. Furthermore, in the rabbit implantation chambers, CK13 was predominantly localized at the cell apex of luminal epithelial cells, where it assembled into a dense filamentous network. These data suggest that the stage-specific expression of CK13 and a reorganization of the apical intermediate filament cytoskeleton of uterine luminal epithelial cells may play important functions in preparation for the implantation process.

Animals↗

PubMed2003

Doxazosin as combination therapy for patients with stage 1 and stage 2 hypertension.

The purpose of this paper is to review the role of doxazosin, a long-acting alpha(1)-blocker, as a component of combination therapy for patients with stage 1 and stage 2 hypertension and for patients with concomitant hypertension and hyperlipidemia or glucose intolerance. Recent studies that evaluated doxazosin as combination therapy in the treatment of patients with inadequately controlled hypertension and patients with concomitant hypertension and other disorders were reviewed. Data extraction was based on the tolerability and efficacy data of doxazosin in patients with hypertension. Compared with placebo, doxazosin combination therapy leads to significant improvements in sitting and standing blood pressure. Doxazosin is well tolerated, with only minor adverse effects (e.g., headache, dizziness) as the most commonly reported treatment-related complications. The studies described demonstrate that doxazosin is effective as combination therapy for patients with stage 1 and stage 2 hypertension. The positive effects of doxazosin on serum lipids make combination therapy with doxazosin an attractive treatment option for patients who have concomitant hyperlipidemia or glucose intolerance.

Antihypertensive Agents↗

PubMed1996

Comparison of soft tissue healing and osseointegration of IMZ implants placed in one-stage and two-stage techniques: a pilot study.

The osseointegration of endosseous dental implants is well documented. Implants have proven to be a viable treatment option for the replacement of missing teeth. The surgical phase of implant dentistry for most implant systems involves two stages--the placement of the implant and its subsequent uncovering. The IMZ (Interpore International) implant system is classically a two-stage system. No significant differences were demonstrated in osseointegration and soft tissue healing for IMZ implants placed in one-stage and two-stage procedures in this pilot study.

Bicuspid↗

PubMed2003

Effect of doxazosin GITS on 24-hour blood pressure profile in patients with stage 1 to stage 2 primary hypertension.

OBJECTIVE: To investigate the effect of the doxazosin gastrointestinal therapeutic system (GITS) on the 24 h blood pressure (BP) profile by ambulatory blood pressure measurements (ABPM) in patients with stage 1 to stage 2 primary hypertension. METHODS AND RESULTS: Seventeen hypertensive patients-either untreated or after a two-week run-in/washout period-underwent office and ABPM monitoring before and six weeks after an open-label once-daily morning dose of 4 mg of doxazosin GITS, an alpha(1)-adrenoceptor antagonist. Fourteen patients responded; three did not. Data analyses refers to the responders: linear analysis demonstrated statistically significant reductions from baseline in daytime, night-time, and total 24 h means for systolic BP (SBP) (7-10 mmHg) and diastolic BP (DBP) (5-10 mmHg) after treatment, with no statistically significant change in heart rate (HR). Rhythm analysis demonstrated statistically significant reductions from baseline in mean mesor (8 mmHg), maximum (6 mmHg) and minimum (10 mmHg) values in SBP, and in mean mesor (5 mmHg), maximum (7 mmHg) and minimum (5 mmHg) values in DBP. Circadian rhythm parameters in BP and HR were not significantly altered by treatment. Treatment with doxazosin GITS was well tolerated. CONCLUSIONS: A single morning dose of doxazosin GITS at 4 mg significantly reduced ambulatory SBP and DBP throughout a 24 h period while preserving a normal 24 h BP and HR rhythm profile in stage 1 to stage 2 hypertensives.

Adult↗

PubMed2002

The "long Snodgrass": applying the tubularized incised plate urethroplasty to penoscrotal hypospadias in 1-stage or 2-stage repairs.

PURPOSE: The technique of tubularized incised plate urethroplasty (Snodgrass modification) has gained wide acceptance for hypospadias repair. The reported experience with this surgical modification has been primarily in cases of distal hypospadias. We applied this technique to cases of penoscrotal hypospadias and incised the urethral plate for its entire distance. MATERIALS AND METHODS: In the last 24 months 21 boys 7 months to 8 years old with penoscrotal hypospadias were treated with a Thiersch-Duplay urethroplasty using the Snodgrass modification. The procedure was performed in 7 patients as a primary repair and in 14 at stage 2 of the 2-stage repair. The entire length of the urethral plate was incised along the midline in primary repairs, and the skin flaps and residual urethral plate were incised in the 2-stage repairs. The neourethra was tubularized over a 5 or 8Fr catheter. A layer of de-epithelialized tissue from the dorsal prepuce was used to cover the neourethra. No patient required skin flap to complete the urethroplasty. The urethral stent was removed in 7 to 10 days postoperatively. RESULTS: Of the 21 patients 19 (90%) required no other surgery as the repair provided a normal appearing penis (straight, terminal meatus, cosmetics) without complications such as meatal stenosis, fistula and diverticula, and voiding with a well directed full stream. One child had dehiscence of the glanular portion of the repair and 1 child had a pinpoint fistula, both of which were repaired successfully at a later date. Followup ranges from 5 to 12 months. CONCLUSIONS: The "long Snodgrass" modification to a Thiersch-Duplay repair is an effective technique for penoscrotal hypospadias as a single and 2-stage procedure. The success and complication rates are excellent in the short term. Longer term complications, such as strictures and diverticula, need to be assessed in the future.

Child↗

PubMedDate not supplied

Early-stage Alzheimer disease represents increased suicidal risk in relation to later stages.

The level of risk for suicide in individuals with Alzheimer disease (AD) generally is considered to be low. It is important to recognize, however, that suicide can occur in early-stage Alzheimer disease on the background of a distinct high-risk profile. The objective of this report is to describe the clinical profiles of individuals with very mild Alzheimer disease who either attempted or completed suicide. We describe two participants in a longitudinal study of early-stage Alzheimer disease who were in the ninth decade of life and had very mild Alzheimer disease. Consistent with earlier cases reported in the literature, both displayed the following high-risk phenotype predisposing to suicidal risk: male gender, highly educated professional, preserved insight, dysthymic symptoms that did not meet criteria for major depression and post-dated the onset of cognitive decline, and suicidal ideation. Neuropathological examination confirmed histologic Alzheimer disease in both cases. These cases, taken together, emphasize the need for awareness that early-stage Alzheimer disease may present a unique suicidal risk compared with later stages.

Aged↗

PubMed1978

Discrepancy between one-stage and two-stage assay of factor VIII:C.

Two methods (one-stage and two-stage) are commonly used for the assay of factor VIII clotting activity (VIII:C). We present collected data from seven separate studies of VIII:C assay which show that these methods do not give the same result when comparing concentrates and plasma. On average, two-stage assays detect 20% more VIII:C activity in concentrates as compared to plasmas than do one-stage assays.

Factor VIII↗

PubMed1988

Mature liver stages of cloned Plasmodium falciparum share epitopes with proteins from sporozoites and asexual blood stages.

The liver merozoites of malaria parasites are of paramount importance, as they initiate the parasite invasion of red blood cells and start the cycle associated with the clinical features of malaria. Investigating liver merozoite antigen is difficult because of the lack of a rodent model of human malaria. In addition, only a low proportion of cells are obtained in vivo, the parasites from Cebus and Aotus monkeys are immature, and in-vitro experiments with liver cells are often confounded by contamination with the natural mosquito flora copurified with the sporozoites used for seeding the liver cultures. In our study, mature liver schizonts were shown to possess many of the antigenic determinants recognized by MoAbs and sera specific for defined sporozoite and blood-stage antigens. We employed an immunofluorescence procedure based on evaluating parasites in cryosections prepared from infected chimpanzee liver. Sufficient numbers of sectioned parasites were evaluated with each antibody to assure the reproducibility of the results, and the fixation procedure used was sufficiently non-destructive to parasite antigens so that clear differences between reactions of specific antibodies and negative controls were observed. Our evidence for sharing of epitopes by liver merozoites and sporozoites or by liver merozoites and asexual blood-stage parasites raises the possibility that immune responses elicited against sporozoites or asexual stage antigens being considered as vaccine candidates may also act against this important, little-studied stage of the parasite.

Animals↗

PubMed1999

Misoprostol dose-related shivering and pyrexia in the third stage of labour. WHO Collaborative Trial of Misoprostol in the Management of the Third Stage of Labour.

OBJECTIVE: To select the misoprostol dose to be used in a large multicentre randomised trial comparing misoprostol with oxytocin in the routine management of the third stage of labour. DESIGN: Randomised pilot trial, double-blinded with the use of double placebos. SETTING: Two of the nine hospitals that will participate in the main multicentre trial. The hospitals were located in Johannesburg, South Africa and Khon Kaen, Thailand. POPULATION: Women during second stage of labour about to be delivered vaginally. METHODS: The trial had three arms: misoprostol 400 microg versus misoprostol 600 microg versus intramuscular oxytocin 10 IU. Each group received an injection and three tablets immediately after the birth of the baby. MAIN OUTCOME MEASURES: Shivering and pyrexia rates were the main outcome measures. Data on other side effects and characteristics of the third stage of labour were also collected. Side effects were noted as none, mild, moderate or severe. RESULTS: Both shivering and pyrexia (temperature > 38 degrees C) were most common in the 600 microg misoprostol group (28% and 7.5% for shivering and pyrexia, respectively) compared with 400 microg misoprostol (19% and 2%), and the oxytocin group (12.5% and 3%). The increase in shivering in the misoprostol 600 microg group was due primarily to a higher rate of moderate shivering. None of the women had a temperature > 40 degrees C. There were no increases in severe side effects and other adverse events in the misoprostol 600 microg group. CONCLUSIONS: When used in the management of the third stage of labour oral misoprostol is associated with an increase in the rate of moderate shivering and pyrexia which seems to be dose-related. Based on the results of this pilot trial, the Steering Committee has decided to use 600 microg misoprostol in the main trial, comparing it with oxytocin, in order to achieve higher effectiveness.

Adult↗

PubMed2005

Process development and analysis of liver-stage antigen 1, a preerythrocyte-stage protein-based vaccine for Plasmodium falciparum.

Plasmodium falciparum liver-stage antigen 1 (LSA-1) is expressed solely in infected hepatocytes and is thought to have a role in liver schizogony and merozoite release. Specific humoral, cellular, and cytokine immune responses to LSA-1 are well documented, with epitopes identified that correlate with antibody production, proliferative T-cell responses, or cytokine induction. With the goal of developing a vaccine against this preerythrocyte-stage protein, we undertook the good manufacturing practices (GMP) manufacture of a recombinant LSA-1 construct, LSA-NRC, incorporating the N- and C-terminal regions of the protein and two of the centrally placed 17-amino-acid repeats. To improve the protein yield, a method of codon harmonization was employed to reengineer the gene sequence for expression in Escherichia coli. A 300-liter GMP fermentation produced 8 kg of bacterial cell paste, and a three-step column chromatographic method yielded 8 mg of purified antigen per g of paste. The final bulk protein was >98% pure, demonstrated long-term stability, and contained <0.005 endotoxin units per 50 microg of protein. To accomplish the initial stages of evaluation of this protein as a human-use vaccine against malaria, we immunized rabbits and mice with LSA-NRC in Montanide ISA 720. New Zealand White rabbits and A/J (H-2K) mice produced high-titer antibodies that recognized liver-stage parasites in infected cultured human hepatocytes. Gamma interferon-producing cells, which have been associated with LSA-1-mediated protection, were detected in splenocytes harvested from immunized mice. Finally, sera taken from people living in a region where malaria is holoendemic recognized LSA-NRC by Western blotting.

Amino Acid Sequence↗