Successful use of extracorporeal membrane oxygenation support in severe septic shock with associated acute cardiomyopathy.

A 24-year-old female presented with sepsis and cardiogenic shock 4 days after vaginal delivery. Veno-arterial extracorporeal membrane oxygenation (VA ECMO) therapy was used for cardiovascular support as a bridge for recovery. The use of VA ECMO in patients with cardiogenic shock secondary to sepsis is reviewed.

Mycoplasma genitalium symptoms, concordance and treatment in high-risk sexual dyads.

The objective of this study was to determine the prevalence and concordance of Mycoplasma genitalium (MG) among Mexican American and African American women and their male sexual partners. Secondary objectives were to determine symptoms of MG infection and persistence of MG after antibiotic therapy. Heterosexual couples were tested for MG and interviewed separately regarding symptoms and behavioural/epidemiologic variables at baseline, six and 12 months. The overall prevalence of MG among women and men was 9.5% and 10.6%, respectively. Subjects were five times more likely to be infected with MG if their sexual partner was MG positive. Among men and women, MG prevalence and mean bacterial loads were similar after receiving single-dose azithromycin, doxycycline or no antibiotics. MG was associated with current urethral discharge in men. No clinical symptoms were specifically diagnostic of MG infection in women.

Patients' perceptions and responses to procedural pain: results from Thunder Project II.

BACKGROUND: Little is known about the painfulness of procedures commonly performed in acute and critical care settings. OBJECTIVE: To describe pain associated with turning, wound drain removal, tracheal suctioning, femoral catheter removal, placement of a central venous catheter, and nonburn wound dressing change and frequency of use of analgesics during procedures. METHODS: A comparative, descriptive design was used. Numeric rating scales were used to measure pain intensity and procedural distress; word lists, to measure pain quality. RESULTS: Data were obtained from 6201 patients: 176 younger than 18 years and 5957 adults. Mean pain intensity scores for turning and tracheal suctioning were 2.80 and 3.00, respectively (scale, 0-5), for 4- to 7-year-olds and 52.0 and 28.1 (scale, 0-100) for 8- to 12-year-olds. For adolescents, mean pain intensity scores for wound dressing change, turning, tracheal suctioning, and wound drain removal were 5 to 7 (scale, 0-10); mean procedural distress scores were 4.83 to 6.00 (scale, 0-10). In adults, mean pain intensity scores for all procedures were 2.65 to 4.93 (scale, 0-10); mean procedural distress scores were 1.89 to 3.47 (scale, 0-10). The most painful and distressing procedures were turning for adults and wound care for adolescents. Procedural pain was often described as sharp, stinging, stabbing, shooting, and awful. Less than 20% of patients received opiates before procedures. CONCLUSIONS: Procedural pain varies considerably and is procedure specific. Because procedures are performed so often, more individualized attention to preparation for and control of procedural pain is warranted.

Sexual abuse and sexual risk behaviors of minority women with sexually transmitted diseases.

The relationship between sexual abuse and sexually transmitted disease (STD) represents an important and underinvestigated context of domestic violence. This study examined the association between sexual abuse, sexual risk behaviors, and risk for reinfection and HIV among minority women with STD. Mexican American and African American women (n = 617) with active STD entered a randomized study of behavioral intervention to reduce STD recurrence. Each underwent questioning at entry regarding sexual abuse and sexual risk behaviors. Comparisons of these behaviors using chi-square, t tests, and logistic regression were made by history of sexual abuse. Sexually abused women were more likely to have lower incomes, earlier coitus, STD history, currently abusive partners, new sex partners, anal sex, and bleeding with sex, placing them at increased risk for STD reinfection and HIV. Due to this association with sexual risk behavior, assessment for sexual abuse is essential in programs focusing on STD/HIV prevention.

Predictors of the vaginal microflora.

OBJECTIVE: Our purpose was to define influences on the patterns of the vaginal microflora. STUDY DESIGN: We enrolled 617 African American and Mexican American women in a 1-year longitudinal study of sexual behaviors and the vaginal microflora on the basis of the presence of gonorrhea, chlamydial infection, trichomoniasis, or syphilis at the initial visit. The patients were assigned randomly to a behavioral intervention or standard counseling regarding sexually transmitted disease. We reevaluated 508 (82%) and 549 (89%) women at 6 and 12 months, respectively. A comprehensive survey of lower genital tract organisms was conducted at baseline and at 6 and 12 months. Behavioral and microbiologic associations were screened by bivariate analysis. All variables associated with an organism at P < or = .15 were included in a multivariate analysis. Associations between behavior and the genital tract microflora were identified by logistic regression coefficients with P <.05. RESULTS: African American race had a consistent association with vaginal microflora, specifically, Mycoplasma hominis, Trichomonas vaginalis, bacterial vaginosis, group B streptococci, Neisseria gonorrhoeae, and Chlamydia trachomatis. Various behaviors had a less consistent effect, including multiple partners, douching, frequency of coitus >3 times a week, and cunnilingus, fellatio, and anal intercourse at the last sexual encounter. M hominis (but not Ureaplasma urealyticum ), Gardnerella vaginalis, and Lactobacillus species were associated with bacterial vaginosis. Lactobacillus species appeared to protect against bacterial vaginosis and infection with G vaginalis. Sexually transmitted diseases (caused by M hominis, N gonorrhoeae, C trachomatis, and T vaginalis ) were associated with each other. In contrast, hormonal status, vaginal blood, and foreign bodies had little effect. CONCLUSION: The presence of other microorganisms and race have a more consistent association with the presence or absence of a cervical-vaginal organism than sexual behavior, hormonal status, vaginal devices, or the presence of abnormal vaginal bleeding.

Minority women with sexually transmitted diseases: sexual abuse and risk for pelvic inflammatory disease.

Mexican American and African American women (N = 617) with a sexually transmitted disease (STD) underwent a targeted physical exam and questioning regarding sexual abuse, current genitourinary symptomatology, and pelvic inflammatory disease (PID) risk behaviors to determine the relationship between sexual abuse and risk for PID. Sexually abused women (n = 194) reported higher PID risk behaviors, including earlier coitus, more sex partners, higher STD recurrence, and a tendency toward delayed health-seeking behavior. They also reported more severe genitourinary symptomatology, confirmed by physical exam, and presumptive diagnoses of PID. These characteristics identify sexually abused women at high risk for PID. Because of its considerable impact on risk for PID, assessment for sexual abuse is essential in clinical management of women with STD and for diagnosis of PID.

Translating research into practice. Implications of the Thunder Project II.

The Thunder Project II study described procedural pain in a variety of acute and critical care settings. The procedures studied were turning, tracheal suctioning, wound drain removal, nonburn wound dressing change, femoral sheath removal, and central venous catheter insertion. Turning had the highest mean pain intensity, whereas femoral sheath removal and central venous catheter insertion had the least pain intensity in adults. Nonwound dressing change had the highest pain intensity for teenagers. Pain occurred in procedures that are often repeated several times a day as well as in those that may be single events. There is a wide range of pain responses to any of these procedures; as a result, standardized and thoughtful pain, and distress assessments are warranted. Planning of care, including the use of preemptive analgesic interventions, needs to be individualized. Future studies are needed to describe patient responses to other commonly performed nursing procedures and to identify effective interventions for reducing procedural pain and distress.

Fragilysin, the enterotoxin from Bacteroides fragilis, enhances the serum antibody response to antigen co-administered by the intranasal route.

Fragilysin, an extracellular zinc metalloprotease produced by enterotoxigenic strains of the anaerobic bacterium Bacteroides fragilis, disrupts the paracellular barrier by cleavage of the intercellular proteins between epithelial cells resulting in fluid secretion. Intranasal immunization of mice with fragilysin and co-administered ovalbumin (Ova) resulted in an Ova-specific serum IgG response that was over 18000-fold higher than Ova alone, as well as detectable levels of serum IgA. Serum IgG titers were comparable with those seen when whole cholera toxin was used as the adjuvant, although the responses obtained with fragilysin showed more variability between mice. Metalloproteases to which fragilysin is structurally related were ineffective as mucosal adjuvants. Our results and similar studies with enterotoxins that affect the paracellular barrier suggest that alteration of mucosal permeability may play an important role in the mechanisms of adjuvanticity.

Raf-1 kinase activity predicts for paclitaxel resistance in TP53mut, but not TP53wt human ovarian cancer cells.

We have recently reported that there is a significant Raf-1 kinase dependency of paclitaxel resistance in human cervical tumor cell lines. In light of the possibility that Raf-1 kinase inhibitors could be used to enhance paclitaxel responsiveness in ovarian cancer, we have characterized the Raf-1 kinase dependency of paclitaxel resistance in ovarian cancer cells. The relationship between Raf-1 kinase activity and the sensitivity to clinically relevant paclitaxel concentrations was determined in four ovarian cancer cell lines (CA-OV3, SK-OV3, 2780/WT and OAW42/WT). Furthermore, in recognition that such a drug combination would initially be used in patients whose tumors have recurred following cisplatin/paclitaxel treatment, we also determined the Raf-1 kinase dependency of paclitaxel cytotoxicity in cisplatin resistant variants of two of the ovarian cell lines (2780/CP and OAW42/CP). In the two cell lines (2780/WT and OAW42/WT) that possess a wild-type TP53 (TP53wt), the relationship between Raf-1 kinase activity and paclitaxel resistance was different from that observed in the cervical tumor cell lines. In these cell lines, paclitaxel-induced far more cell killing than would have been predicted from their Raf-1 kinase activity. However, in the ovarian cancer cell lines (CA-OV3, SK-OV3, 2780/CP and OAW42/CP) that have a mutant TP53 (TP53mut), the cytotoxicity induced by 60 nM paclitaxel exhibited the same relationship to Raf-1 kinase activity as previously observed in cervical tumor cell lines. These data suggest that the therapeutic efficacy of paclitaxel in ovarian cancer patient whose tumors have TP53mut might be increased if it is administered in combination with Raf-1 kinase inhibitors, e.g., ISIS 5132.

Modification of non-conservative double-strand break (DSB) rejoining activity after the induction of cisplatin resistance in human tumour cells.

The induction of collateral radioresistance after the development of cisplatin resistance is a well-documented phenomenon; however, the exact processes that are responsible for the cisplatin-induced radioresistance remain to be elucidated. There was no obvious difference in the level of radiation-induced DNA double strand breaks (DSBs), in DSB rejoining rates, or the level of the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) in the cisplatin- and radiation-sensitive 2780/WT and cisplatin-resistant 2780/CP cell lines. However, there was a significantly (P < 0.01) lower level of DSB misrejoining activity within nuclear protein extracts derived from the cisplatin- and radiation-sensitive 2780/WT and OAW42/WT tumour cell lines than in similar extracts from their cisplatin- (and radiation-) resistant 2780/CP and OAW42/CP counterparts. All of the DSB misrejoining events involved deletions of between 134 and 444 bp that arose through illegitimate recombination at short repetitive sequences, such as those that arise through non-homologous repair (NHR). These data further support the notion that the radiosensitivity of DSB repair proficient human tumour cell lines may be partly determined by the predisposition of these cell lines to activate non-conservative DSB rejoining pathways. Furthermore, our data suggest that the induction of acquired cisplatin resistance is associated with a two- to threefold decrease in the activity of a non-conservative DSB rejoining mechanism that appears to be a manifestation of NHR.

A randomized, controlled trial of a behavioral intervention to prevent sexually transmitted disease among minority women.

BACKGROUND: African-American and Hispanic women are disproportionately affected by sexually transmitted diseases, including the acquired immunodeficiency syndrome (AIDS). In the effort to reduce infection rates, it is important to create and evaluate behavioral interventions that are specific to the target populations. METHODS: We enrolled women with nonviral sexually transmitted diseases in a randomized trial of a sex- and culture-specific behavioral intervention. The intervention consisted of three small-group sessions of three to four hours each designed to help women recognize personal susceptibility, commit to changing their behavior, and acquire necessary skills. The control group received standard counseling about sexually transmitted diseases. The design of the intervention was based on the AIDS Risk Reduction Model and ethnographic data on the study populations. Participants in both groups underwent screening, counseling, and an interview before randomization and at the 6- and 12-month follow-up visits. The principal outcome variable was subsequent chlamydial or gonorrheal infection, which was evaluated on an intention-to-treat basis by logistic-regression analysis. RESULTS: A total of 424 Mexican-Americans and 193 African-American women were enrolled; 313 were assigned to the intervention group and 304 to the control group. The rate of participation in the intervention was 90 percent. The rates of retention in the sample were 82 and 89 percent at the 6- and 12-month visits, respectively. Rates of subsequent infection were significantly lower in the intervention group than in the control group during the first 6 months (11.3 vs. 17.2 percent, P=0.05), during the second 6 months (9.1 vs. 17.7 percent, P=0.008), and over the entire 12-month study period (16.8 vs. 26.9 percent, P=0.004). CONCLUSIONS: A risk-reduction intervention consisting of three small-group sessions significantly decreased the rates of chlamydial and gonorrheal infection among Mexican-American and African-American women at high risk for sexually transmitted disease.

High Raf-1 kinase activity protects human tumor cells against paclitaxel-induced cytotoxicity.

Paclitaxel (Taxol) is becoming increasingly important in the treatment of many tumors, although a large proportion of tumors fail to respond to this drug. The identification of the processes that confer cellular paclitaxel resistance could provide potential targets for novel therapies that may help to eliminate paclitaxel-resistant tumors. Recent reports suggest that the Raf-1 protein kinase may have a profound influence on the level of paclitaxel-induced apoptosis. We have critically evaluated the relationship between Raf-1 kinase activity and de novo paclitaxel resistance in early-passage human cervical tumors. In the 12 cell lines studied, Raf-1 kinase activity was inversely correlated (P = 0.0016) with the level of cytotoxicity induced by 60 nM paclitaxel. The relationship between these two parameters seems to be more than an epiphenomenon, because genetic down-regulation of Raf-1 kinase activity led to an approximately 4-fold increase in paclitaxel-induced cytotoxicity. The data from both our transfection studies and those on the 12 unperturbed cell lines are consistent with Raf-1 kinase being a negative determinant of paclitaxel-induced cytotoxicity. Because the cytotoxicity of paclitaxel is primarily attributable to apoptosis, these data suggest that Raf-1 kinase acts to suppress paclitaxel-induced apoptosis. These data suggest that the clinical effectiveness of paclitaxel could be substantially improved by the use of Raf-1 kinase inhibitors, provided that a similar relationship between Raf-1 kinase activity and paclitaxel cytotoxicity exists in the clinic, especially in those tumor sites where paclitaxel is the current treatment of choice e.g., ovarian and breast cancer.

Paclitaxel is preferentially cytotoxic to human cervical tumor cells with low Raf-1 kinase activity: implications for paclitaxel-based chemoradiation regimens.

BACKGROUND AND PURPOSE: Low Raf- kinase activity has been reported to be associated with radioresistance in epithelial tumor cell lines and with paclitaxel sensitivity in cervical tumor cells. Paclitaxel might thus be effective in eliminating radioresistant clones from cervical tumors, even in the absence of synergistic interaction between these therapeutic modalities. We thus established the relationship between Raf-1 kinase activity and radiosensitivity in human cervical tumor cells and determined if paclitaxel is preferentially cytotoxic to radio-resistant tumor clones. MATERIALS AND METHODS: We established and contrasted the radiation and paclitaxel sensitivity of 12 human cervical tumor clones that exhibited a wide range of Raf-1 kinase activity. RESULTS: Raf-1 kinase activity was inversely correlated (P = 0.001) with SF2 values in the 12 cervical tumor clones studied. Paclitaxel was preferentially cytotoxic to radioresistant tumor clones, with the level of paclitaxel-induced cytotoxicity being significantly (P = 0.0016) influenced by Raf-1 kinase activity levels. CONCLUSIONS: Our in vitro data indicate that there are marked, but completely opposite, Raf-1 kinase dependencies of radiation and paclitaxel cytotoxicity in cervical tumor cells. The use of combined paclitaxel and radiotherapy treatment may thus lead to higher local control rates for squamous cell carcinoma of the cervix. Circumstantially, our data suggest that the greatest therapeutic gains might accrue if paclitaxel was administered when there is the greatest proportion of tumor clones with low Raf-1 kinase activity. It may thus be desirable to use paclitaxel towards the end of radiotherapy treatment or post-radiotherapy as consolidation therapy.

Positioning of chest tubes: effects on pressure and drainage.

BACKGROUND: Maintaining a chest drainage tube in a position that is free of dependent loops, as is commonly recommended, can be very difficult. Is there a beneficial effect on the patient's outcome when the drainage tubing is free of dependent loops? OBJECTIVE: The purpose of this study was to determine, under controlled laboratory conditions, (1) what are the differences in drainage with tubing in straight, coiled, or dependent-loop (with and without periodic lifting) positions and (2) what are the differences in pressure with each of the four tubing conditions? METHODS: In laboratory simulations, pressure and drainage were observed in a chest tube drainage system that was connected to a glass bottle simulating the lung. Pressure and drainage were measured for 1 hour with the drainage tubing placed in straight, coiled, and dependent-loop positions. For the periodic lifting condition, the dependent loop was lifted and drained every 15 minutes. RESULTS: We found no differences in pressure or drainage between straight and coiled positions of the drainage tubing. However, with the dependent-loop position, pressure at the "lung" side increased from about -18 cm H2O to as high as +8 cm H2O. Drainage dropped to zero without tube lifting. When the tube was lifted and drained every 15 minutes, there was no difference in drainage with the tubing in the straight or coiled positions. CONCLUSION: Findings support recommendations to maintain tubing free of dependent loops by placing tubing in straight or coiled positions. Frequently lifting and draining a dependent loop will provide the same total drainage amount as maintaining the tubing in a straight or coiled position, but pressures may be altered sufficiently within the tube to exceed recommended levels.

Medicare-certified home health services: national and regional supply in the 1980s.

The number of Medicare-certified home health agencies nearly doubled from 1980 to 1990. Using Health Care Financing Administration data, this study documented national and regional patterns of entry and exist by Medicare home health providers from 1980 to 1990. Nationally, agency origination rates accelerated during the early 1980s and then dropped abruptly in the second half of the decade. The proprietary sector, accounting for approximately 42% of agencies in existence during the period of the study, exhibited the greatest volatility. Regional differences are also evident. Both expansion and contraction in Medicare home health services appear to be a response to the incentives of legislation implemented during this period.

Growth and decline in the supply of providers of Medicare-covered home health services in the 80's: national and regional experience.

Using Health Care Financing Administration (HCFA) data, this study documents national and regional patterns of market entry and exit in the home health industry from 1980 to 1990. Nationally, agency origination rates accelerated during the early 1980's, then dropped abruptly in the second half of the decade. The for-profit sector exhibited the greatest volatility. Of the 3,620 proprietary agencies in existence during the decade, 3,284 (90.7%) were new entrants, and 1,551 exited the market by 1990. Regional differences in growth rates and the timing of market entry are also evident. Both growth and decline in the home health industry appear to be a response to the incentives of legislation implemented during this period.

Infants at risk for schizophrenia: sequelae of a genetic neurointegrative defect. A review and replication analysis of pandysmaturation in the Jerusalem Infant Development Study.

A 1975 report stated that a schizophrenic genotype may be manifested in infants by a neurointegrative defect called pandysmaturation. Recent evidence supports this: (1) 12 studies found delayed development in schizophrenics' infants and in preschizophrenics; (2) "blind" psychometric evaluations favored an adult schizotypal disorder in four to six of seven high-risk subjects with pandysmaturation in the New York study; and (3) finally, in a partial replication of this method using the Jerusalem data, blind diagnoses of "probable" and "possible" pandysmaturation were significantly related to a parental diagnosis of schizophrenia and to cognitive and motor neurointegrative deficits at 10 years. Obstetrical complications were unrelated to diagnosis, pandysmaturation, or outcome in the overall sample. However, we found a small subgroup of schizophrenic offspring in whom the most severe motor deficits at follow-up were related to obstetrical complications, pandysmaturation, and low birth weight.

Formal thought disorder in childhood onset schizophrenia and schizotypal personality disorder.

The Kiddie Formal Thought Disorder Rating Scale (K-FTDS) was examined in a sample of 29 schizophrenic, 10 schizotypal, and 54 normal children, aged 5-12.5 yrs. The schizophrenic and schizotypal children had significantly more illogical thinking and loose associations than the normal children. There were no significant differences between the illogical thinking and loose associations ratings of the schizophrenic and schizotypal children. Young schizophrenic, schizotypal, and normal children had more illogical thinking and loose associations than older children in their respective groups. The diagnostic, developmental, and cognitive implications of the study's results are discussed.

A quantitative study of dendrite complexity in selected areas of the human cerebral cortex.

This study seeks relationships between the degree of dendrite complexity of four areas of the human cerebral cortex and the type of function subserved by those areas. Quantitative studies of basilar dendrite patterns in the trunk and hand-finger receptive zones of areas 3 and 1, superior gyrus of the prefrontal cortex (area 9), and supramarginal gyrus (area 39) of the parietal lobe, in the left hemisphere of 10 subjects are reported. Measurements of dendrite complexity were based on the Sholl method of counting dendrite intersections with a series of superimposed concentric rings centered on the middle of the neuron soma. The data were analyzed graphically to show (1) characteristic dendrite profiles generated by cells in each of these areas, (2) comparisons between dendrite systems of two paired areas, i.e., trunk vs. hand-finger, and hand-finger vs. supramarginal, and (3) cumulative dendrite-ring intersection patterns for all areas studied. The data provided only partial support for our working hypothesis suggesting a relationship between complexity of the dendrite arbor and the nature of the computational tasks performed by the area. However, complexity of dendrite systems in the trunk area was found to be generally less than that of any other. In addition, there were suggestive associations between the complexity of dendrite systems of the hand-finger zone of the primary sensory receptive area and the nature of the work with which the individual had been associated during his/her working life. It proved more difficult to discern relationships between structure and function in the cortical associative areas. The study underlines the large degree of interindividual variation in dendrite structure and the need for much more extensive information about the life history of individuals who serve as subjects for this type of study.