Hyperemesis gravidarum and long-term mortality: a population-based cohort study.

OBJECTIVE: To investigate whether exposure to hyperemesis gravidarum (HG) is associated with increased maternal long-term mortality. DESIGN: Population-based cohort study. SETTING: Medical Birth Registry of Norway (1967-2002) linked to the Cause of Death Registry. POPULATION: Women in Norway with singleton births in the period 1967-2002, with and without HG. Women were followed until 2009 or death. METHODS: Cox proportional hazard regression model was applied to estimate hazard ratios (HRs) with 95% confidence interval (CI). MAIN OUTCOME MEASURES: The primary outcome was all-cause mortality during follow up. Secondary outcomes were cause-specific mortality (cardiovascular mortality, deaths due to cancer, external causes or mental and behavioural disorders). RESULTS: Of 999 161 women with singleton births, 13 397 (1.3%) experienced HG. During a median follow up of 26 years (25 902 036 person-years), 43 470 women died (4.4%). Women exposed to HG had a lower risk of long-term all-cause mortality compared with women without HG (crude HR 0.82; 95% CI 0.75-0.90). When adjusting for confounders, this reduction was no longer significant (adjusted HR 0.92; 95% CI 0.84-1.01). Women exposed to HG had a similar risk of cardiovascular death as women not exposed (adjusted HR 1.04; 95% CI 0.83-1.29), but a lower long-term risk of death from cancer (adjusted HR 0.86; 95% CI 0.75-0.98). CONCLUSION: In this large population-based cohort study, HG was not associated with an increased risk of long-term all-cause mortality. Women exposed to HG had no increase in mortality due to cardiovascular disease, but had a reduced risk of death from cancer. TWEETABLE ABSTRACT: Population-based cohort study: Hyperemesis was not associated with an increased risk of long-term mortality.

A comparison study on the effects of prewarming patients in the outpatient surgery setting.

Maintenance of core body temperature in surgical patients presents a challenge to perioperative nurses. Core temperatures less than 36 degrees C are associated with multiple adverse outcomes postoperatively. Internal redistribution of heat from the body core to the colder periphery results in core temperature decreases of 0.5 degrees C to 1.5 degrees C in the first 30 minutes after induction of anesthesia. The purpose of this study was to determine if there was a difference in arrival temperatures to the PACU between surgical patients who had been warmed preoperatively with a forced warm air blanket and those patients warmed with cotton blankets. One hundred patients were randomly assigned to receive prewarming by using a forced-air warm blanket (n = 50) or a cotton blanket (n = 50). Temperatures were monitored every 15 minutes throughout the preoperative and postoperative periods. Patients in the forced warm air group had significantly higher temperatures on arrival to the PACU from the OR than did patients in the warm blanket group (P =.000). Patients in the forced warm air group exhibited a change in temperature of 0.0067 degrees C (+/-.52) compared with a decrease of 0.22 degrees C (+/-.48) for patients in the control group.

The Escherichia coli SeqA protein binds specifically to two sites in fully and hemimethylated oriC and has the capacity to inhibit DNA replication and affect chromosome topology.

The SeqA protein was identified as a factor that prevents reinitiation of newly replicated, hemimethylated origins. SeqA also seems to inhibit initiation of fully methylated origins, thus contributing to the regulation of chromosomal replication. The SeqA protein was found to bind to two sites in the left part of the origin, near the AT-rich region where strand separation takes place during initiation of replication. The same binding sites seemed to be preferred irrespective of whether the origin was in the newly replicated (hemimethylated) state or not. In addition to binding specifically to groups of GATC sites, the SeqA protein was capable of interacting non-specifically with negatively supercoiled DNA, restraining the supercoils in a fashion similar to that seen with histone-like protein HU. The restraint of supercoils by SeqA was, in contrast to that of HU, cooperative.

NILR-1, a novel immunoglobulin-like receptor expressed by neutrophilic granulocytes, is encoded by a leukocyte receptor gene complex on rat chromosome 1.

Several receptors expressed by subsets of leukocytes and with sequence homology to the killer cell inhibitory receptors have recently been identified both in man and mouse. Here we describe a rat cDNA that encodes a novel receptor of this group, designated neutrophil immunoglobulin-like receptor-1 (NILR-1). The predicted 58.7-kDa mature NILR-1 protein is a type I integral membrane protein, with three C2-type immunoglobulin superfamily domains, a transmembrane region devoid of charged amino acids, and a cytoplasmic tail containing four immunoreceptor tyrosine-based inhibition motif-like regions. NILR-1 shows greatest sequence homology to the mouse paired immunoglobulin-like receptor-B and members of the human leukocyte immunoglobulin-like receptor/immunoglobulin-like transcript group of receptors. As shown by Northern blot analysis, NILR-1 was transcribed by neutrophilic granulocytes. Although weaker transcription was found with a macrophage cell line, no signal was detected with peritoneal macrophage or spleen RNA. Linkage analysis localized Nilr1 to chromosome 1, closely linked to a locus encoding a rat NKp46 orthologue. The two loci define a rat leukocyte receptor gene complex, in a region syntenic to human chromosome 19q13.4 and the proximal part of mouse chromosome 7, that harbors the human and mouse leukocyte receptor gene complexes.

Contact activation factors in plasma from women on estrogen replacement therapy after ovariohysterectomy.

The plasma levels of factor XII, prekallikrein, factor XI, and high molecular weight kininogen were studied in women with bilateral oophorectomy and hysterectomy who received hormone replacement therapy with a 2 mg daily dose of estradiol valerate. Also plasminogen activator activity was investigated. The observations made provide support for the assumption that the low doses of estrogen used in hormone replacement therapy do not significantly affect the levels of contact activation or fibrinolytic factors in plasma. Plasma obtained from young, healthy women was used as a standard reference material. Significantly higher levels of factor XII and prekallikrein were registered in functional tests in the ectomized women than in the reference material, an increase not observed in the immunological assays. These observations are discussed in light of recently published data from our laboratory on an increase in the measured level of factor XII obtained upon the removal of IgG before assay. Also a marked increase in urokinase activity was registered in the ectomized women. The high levels of factor XII, prekallikrein, and urokinase, as compared with the reference material, seemed to be age dependent, being also observed in a group of naturally postmenopausal women.

Identification of a human member of the Ly-49 multigene family.

Three classes of multigene family-encoded receptors enable NK cells to discriminate between polymorphic MHC class I molecules: Ly-49 homodimers, CD94/NKG2 heterodimers and the killer cell inhibitory receptors (KIR). Of these, CD94/NKG2 has been characterized in both rodents and humans. In contrast, Ly-49 family members have hitherto been found only in rodents, and KIR molecules only in the human. In this report, we describe a human cDNA, termed Ly-49L, that constitutes the first human member of the Ly-49 multi-gene family. Compared with rodent Ly-49 molecules, the Ly-49L sequence contains a premature stop codon and predicts a truncated protein that lacks the distal part of a C-terminal lectin domain. Evidence is presented that the premature stop codon results from incomplete excision of the intron between the first two lectin domain exons. Splice variants predicting a full-size Ly-49L protein were not detected. As demonstrated by Northern blot analysis, Ly-49L was transcribed by IL-2-activated NK cells, but not by freshly isolated B or T cells. PCR screening of a 22-clone yeast artificial chromosome contig localized the LY49L locus to the human NK gene complex on chromosome 12p12-p13. Southern blot analysis of genomic DNA showed a simple pattern with a full-length Ly-49L probe at low stringency hybridization conditions, suggesting that Ly-49L may be the only human member of the Ly-49 multigene family.

Molecular characterization of rat NKR-P2, a lectin-like receptor expressed by NK cells and resting T cells.

The gene for a rat NK lectin-like receptor (NKLLR), named NKR-P2, has been cloned and characterized. Sequence analysis shows that it represents the orthologue of human NKG2D and that the two molecules form a distinct NKLLR family, no more related to NKG2A/B, -C or -E than to other NKLLR families. Nkrp2 is a single-copy gene containing seven introns, mapping to the rat NK gene complex. Rat NKR-P2 differs from the human orthologue in that its cytoplasmic tail contains 13 additional amino acids, encoded by a separate exon. Splice variants lacking this exon were not detected in T cells or NK cells. NKR-P2 is strongly expressed by NK cells. In contrast to other NKLLR, it is also strongly expressed by resting thoracic duct CD4+ and CD8+ T cells, but not by thymocytes or other hemopoietic cells.

Two genes in the rat homologous to human NKG2.

Two different lectin-like receptors for MHC class I molecules have so far been identified on natural killer (NK) cells, the Ly-49 homodimeric receptors in mice and the NKG2/CD94 heterodimeric receptors in humans. The recent identification of a rat CD94 orthologue implied that NK cell receptors equivalent to NKG2/CD94 also exist in rodents. Here we describe the cDNA cloning of two rat genes homologous to members of the human NKG2 multigene family. The deduced rat NKG2A protein contains a cytoplasmic immunoreceptor tyrosine-based inhibition motif (ITIM), whereas the cytoplasmic tail of rat NKG2C lacks ITIM. The genes map to the rat NK gene complex and are selectively expressed by NK cells. The expression is strain dependent, with high expression in DA and low in PVG NK cells, correlating with the expression of rat CD94. Ly-49 genes have previously been identified in the rat, and the existence of rat NKG2 genes in addition to a CD94 orthologue suggests that NK cell populations utilize different C-type lectin receptors for MHC class I molecules in parallel.

Constant temperature monitoring: a study of temperature patterns in the postanesthesia care unit.

Patients admitted to the PACU from the operating room exhibit fluctuations in core body temperature during the course of their stay in the PACU. Some patients present with normothermia and experience temperature decreases later in their stay. PACU policy does not dictate that temperatures be measured at a predetermined frequency in the absence of hypothermia; thus, it is possible that hypothermia may not be detected at its onset. The major purpose of this study was to describe the core body temperature patterns of postsurgical patients during the PACU stay. Secondary objectives were to (1) identify at which point in time patients become hypothermic and (2) describe length of stay in patients who develop hypothermia. Hypothermia was defined as a core tympanic temperature of less than 35.5 degrees C. A descriptive design was used using a convenience sample of 150 elective surgical patients over the age of 1 month who were normothermic on admission to the PACU. Data were analyzed using descriptive statistics. Concurrent tympanic and continuous axillary temperatures were monitored for comparison and trend monitoring. Temperatures showed clinically significant decreases into the hypothermic range (< 35.5 degrees C). Fifty-seven percent of the sample (n = 86) had temperatures that dropped after PACU admission and another 13% fell below 35.5 degrees C. Hypothermia occurred within the first 15 minutes of the PACU stay. The average length of stay for those that developed hypothermia was 1.83 hours. Monitoring temperatures more frequently will result in detecting hypothermia at its onset. Nurses may use the axillary device as a trend for continuous monitoring. Length of stay may be shortened if temperature management is embraced by the PACU nurse.

Molecular characterization of a gene in the rat homologous to human CD94.

Three classes of major histocompatibility (MHC) class I binding receptors on natural killer (NK) cells have so far been described: CD94/NKG2 heterodimeric receptors and killer cell inhibitory receptors in the human, and Ly-49 homodimers in rodents. CD94, NKG2 and Ly-49 belong to the C-type lectin superfamily. As yet, CD94 and NKG2 molecules have not been detected in rodents or Ly-49 in humans. It has therefore been proposed that the two receptors represent functional equivalents in these species. The present study describes the cDNA cloning of a novel rat gene encoding a protein of 179 amino acids, 54.2% identical to human CD94. The single-copy Cd94 gene is localized to the rat NK gene complex (NKC), within 50 kb from Nkrp2, between the Nkrp1 and Ly49 gene clusters. By Northern blot analysis, we showed that rat CD94 is selectively expressed by NK cells and a small subset of T cells, similar to the human orthologue. This expression is strain dependent, with high expression in DA NK cells and low in PVG NK cells. Evidence is presented that this difference is not due to receptor repertoire shaping by MHC-encoded ligands, but is controlled by genetic elements residing within the NKC. The identification of a rat CD94 orthologue suggests that NK cell populations utilize two different C-type lectin receptors for MHC class I molecules in parallel.

Urokinase and non-urokinase fibrinolytic activity in protease-inhibitor-deprived plasma, assayed by a fibrin micro-plate method.

In the classical fibrin-plate assay, fibrinolytic activity is determined by measuring the area of the lysis zone formed when sample is applied on a planar fibrin gel. However, this method is characterized by low capacity and uncertainty in the determination of the lysis zones. To overcome these limitations an assay modified for microtiter plates was developed. Fibrin clots, with a suitable dye incorporated, were formed in wells of standard high adsorbtion microtiter plates. Each plate contained a serial dilution of urokinase as standard. Citrated test plasmas were treated with acetone to remove inhibitors before applied to the wells. The lyzate formed after appropriate incubation was removed, and the remaining volume of fibrin photometrically determined after being completely dissolved by plasmin. The fibrinolytic activity was determined as the difference in absorption before and after lysis. This is an accurate and relatively simple method for the assessment of urokinase and non-urokinase fibrinolytic activity in plasma. It is further a sensitive and quantitative fibrinolytic micro-technique with a high capacity.

An autosomal dominant locus, Nka, mapping to the Ly-49 region of a rat natural killer (NK) gene complex, controls NK cell lysis of allogeneic lymphocytes.

Natural Killer (NK) cells can recognize and kill MHC-incompatible normal bone marrow-derived cells. Presently characterized MHC-binding receptors on NK cells, including the Ly-49 family in the mouse, transmit inhibitory signals upon binding to cognate class I MHC ligands. Here we study in vivo NK-mediated lysis of normal allogeneic lymphocytes in crosses between alloreactivity-competent PVG rats and alloreactivity-deficient DA rats. NK cells from both strains are able to lyse standard tumor targets. We identify an autosomal dominant locus, Nka, that controls NK-mediated alloreactivity. Individuals carrying the dominant PVG allele in single dose were fully competent in eliminating allogeneic target cells, suggesting that Nka encodes or regulates a gene product inducing or activating alloreactivity. By linkage analysis and pulsed field gel electrophoresis, a natural killer gene complex (NKC) on rat chromosome 4 is described that contains the rat NKR-P1 and Ly-49 multigene families plus a rat NKG2D homologue. Nka maps within the NKC, together with the most telomeric Ly-49 family members, but separate from NKG2D and the NKR-P1 family. The Nka-encoded response, moreover, correlates with the expression of transcripts for Ly-49 receptors in NK cell populations, as Northern blot analysis demonstrated low expression of Ly-49 genes in DA NK cells, in contrast to high expression in alloreactivity-competent PVG, (DA X PVG)F1, and PVG.1AVI NK cells. The low Ly-49 expression in DA is not induced by MHC haplotype, as demonstrated by high expression of Ly-49 in the DA MHC-congenic PVG.1AVI strain. Finally, we have cloned and characterized the first four members of the rat Ly-49 gene family. Their cytoplasmic domains demonstrate substantial heterogeneity, consistent with the hypothesis that different Ly-49 family members may subserve different signaling functions.

Perioperative oxygen saturation levels of pediatric patients.

Airway compromise is of immediate concern for any patient after surgery but more so for pediatric patients because they are subject to more acute airway changes than adults. The purpose of this study was to identify those pediatric post-surgical patients in an acute care setting at risk for oxygen saturation less than 90% during transport from the OR to the PACU. A descriptive, correlational design was employed using a convenience sample of 45 male and female pediatric patients between the ages of 0 months and 16 years who underwent elective surgery with general anesthesia lasting longer than 1 hour. Data were collected on each pediatric subject at four points in time (1) in the preoperative holding area (2) in the OR, (3) during transport to the PACU, and (4) on arrival to and during the stay in the PACU. Results showed that more than 50% of the sample (N = 45) desaturated to oxygen levels below 95%. Specifically, 48% desaturated between 90% to 95% and 8% desaturated below 90%. Pediatric patients age 2 years and younger showed the greatest risk for desaturation below 90%. In addition, as transport time increased, the number of subjects with oxygen saturation levels below 95% increased.

Dendritic leucocytes pulsed with monoclonal antibody-hapten conjugates elicit vigorous primary humoral responses in vivo.

Purified dendritic leucocytes (DL) were pulsed briefly in vitro with haptenated monoclonal antibodies (MoAb) to MHC class II and immediately injected i.v. into syngeneic recipients. Strong anti-hapten humoral responses were observed even though only a few picomoles of specific MoAb-hapten conjugates were injected with the DL. In contrast, DL pulsed with control conjugates, i.e. haptenated non-binding MoAbs, gave only weak responses. DL thus, can take up, process and present protein antigens even after brief exposure in vitro, and their immunogenicity is enhanced by pulsing with antigen conjugated to specific MoAbs. Furthermore, in the presence of fetal calf serum (FCS), but not normal rat serum, the control MoAb W6/32 (against human MHC class I) bound to DL. The vigorous primary humoral response achieved following this pulsing indicates that it is the binding and the corresponding increased uptake that enhances the immunogenicity of the DL.

Expression of CD43 epitopes on NK and T cells.

CD43 epitope expression was studied with a panel of monoclonal antibodies (MoAbs) by immunohistochemistry on freeze sections of lymphoid tissues. The MoAb WEN3 stained most cells weakly in the T areas and scattered splenic red pulp cells strongly, whereas the other MoAbs strongly stained the majority of the cells in the T areas but gave variable staining patterns of cells in the non-T areas. Flow cytometry on CD4+ and CD8+ T cells (T4 and T8 cells), freshly isolated NK cells and LAK cells showed distinct staining profiles for each cell type, with epitope expression patterns of T8 cells lying between those of T4 cells and NK/LAK cells. T8 cells were split by one of the MoAbs, the NK cells, but not LAK cells, were split by two other MoAbs.

Contact factors in plasma from women on oral contraception--significance of factor XI for the measured activity of factor XII.

The plasma levels of contact activation factors were measured in women using a low estrogen dose oral contraceptive (OC). Basic values for factor XII (FXII), factor XI (FXI), prekallikrein (PK), and high molecular weight kininogen (HK) were obtained in immunoassays by comparing with control plasma. The plasma levels of FXII and PK were significantly increased in OC plasma, to 147% and 146% respectively, whereas no significant increase could be registered for FXI (106%) or for HK (107%). Functional assays carried out with different peptide substrates (S-2222 for FXIIa, and S-2222, S-2302 and Bz-Pro-Phe-Arg-pNA for kallikrein) showed increases in OC plasma to about 150% for both proteases, in accordance with results obtained in radial immunodiffusion (RID). However, when FXIIa was measured with the high molecular weight substrate PK, no significant increase could be registered. Further experiments suggested this result to be due to the low level of FXI present in OC plasma, as compared to the levels of FXII and PK. Assays were carried out in mixtures of test plasma (OC or control plasma) and plasma deficient in FXI or FXII. The results obtained suggested that FXIa was present in some kind of association with part of FXIIa and part of kallikrein present. At low concentrations of FXI the functional activity of FXIIa was reduced, and the assay data indicated that an appropriate level of FXI was required to obtain maximum rate of hydrolysis of prekallikrein by FXIIa.(ABSTRACT TRUNCATED AT 250 WORDS)