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Biomedical subjects

P A Janssen

Publications and source records attributed to P A Janssen.

At least 19 recordsLinked to original sources
PubMed2006

Effects of an intervention aimed at reducing night waking and signaling in 6- to 12-month-old infants.

This quasi-experimental one-group pre- and posttest pilot study evaluated an intervention aimed at reducing night waking and signaling for infants between 6 and 12 months of age. Thirty-nine healthy infants and their parents were recruited. Thirty-five infants completed the intervention and data collection. Both parents participated in a group teaching session with telephone follow-up for 2 weeks. Actigraphy and sleep diary data were collected at baseline and 6 and 16 weeks postintervention. We hypothesized a decrease in length and number of infant waking and crying periods and an increase in longest night sleep and nap time. Following the intervention, infants had significantly reduced length of night crying and number of wakes and longer night sleep periods. The intervention warrants evaluation with a randomized controlled design.

Adult↗
PubMed2004

Identifying women at-risk for postpartum depression in the immediate postpartum period.

OBJECTIVE: To develop a multifactorial predictive model of depressive symptomatology in the first week postpartum in order to assist in targeted screening procedures. METHOD: As part of a longitudinal study, a population-based sample of 594 mothers in a health region near Vancouver, British Columbia completed a mailed questionnaire at 1-week postpartum that included diverse risk factors from the following domains: sociodemographic, biological, pregnancy-related, life stressors, social support, obstetric and adjustment to motherhood. Following univariate analysis, sequential regression analysis was completed to develop a multifactorial predictive model. RESULTS: In the multivariate model, the factors predictive of depressive symptomatology at 1-week postpartum included immigration within the last 5 years, history of depression independent of childbirth, diagnosis of pregnancy-induced hypertension, vulnerable personality style, stressful life events, lack of perceived support, lack of readiness for hospital discharge and dissatisfaction with infant feeding method. CONCLUSION: The findings suggest that several risk factors for depressive symptomatology in the immediate postpartum period are consistent with previously identified factors but other factors such as recent immigrant status, feeling unready for hospital discharge, dissatisfaction with their infant feeding method, and pregnancy-induced hypertension should also be examined.

Adolescent↗
PubMed2001

Ibuprofen versus acetaminophen with codeine for the relief of perineal pain after childbirth: a randomized controlled trial.

BACKGROUND: Pain from episiotomy or tearing of perineal tissues during childbirth is often poorly treated and may be severe. This randomized double-blind controlled trial was performed to compare the effectiveness, side effects and cost of, and patient preference for, 2 analgesics for the management of postpartum perineal pain. METHODS: A total of 237 women who gave birth vaginally with episiotomy or a third- or fourth-degree tear between August 1995 and November 1996 at a tertiary-level teaching and referral centre for obstetric care in Vancouver were randomly assigned to receive either ibuprofen (400 mg) (n = 127) or acetaminophen (600 mg) with codeine (60 mg) and caffeine (15 mg) (Tylenol No. 3) (n = 110), both given orally every 4 hours as necessary. Pain ratings were recorded before the first dose and at 1, 2, 3, 4, 12 and 24 hours after the first dose on a 10-cm visual analogue scale. Side effects and overall opinion were assessed at 24 hours. RESULTS: Ibuprofen and acetaminophen with codeine had similar analgesic properties in the first 24 hours post partum (mean pain rating 3.4 and 3.3, mean number of doses in 24 hours 3.4 and 3.3, and proportion of treatment failures 13.8% [16/116] and 16.0% [16/100] respectively). Significantly fewer subjects in the ibuprofen group than in the acetaminophen with codeine group experienced side effects (52.4% v. 71.7%) (p = 0.006). There were no significant differences in overall patient satisfaction between the 2 groups. The major determinant of pain intensity was forceps-assisted delivery. Overall, 78% of the treatment failures were in women with forceps-assisted deliveries. INTERPRETATION: Since the 2 analgesics were rated similarly, ibuprofen may be the preferred choice because it is less expensive and requires less nursing time to dispense. Further studies need to address improved analgesia for women with forceps-assisted deliveries.

Acetaminophen↗
PubMed2001

Evolution of anti-HIV drug candidates. Part 1: From alpha-anilinophenylacetamide (alpha-APA) to imidoyl thiourea (ITU).

Stemming from work on a previous clinical candidate, loviride, and other alpha-APA derivatives, a new series of potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) has been synthesized. The ITU analogues, which contain a unique diarylated imidoyl thiourea, are very active in inhibiting both wild-type and clinically important mutant strains of HIV-1.

Acetamides↗
PubMed2001

Evolution of anti-HIV drug candidates. Part 2: Diaryltriazine (DATA) analogues.

A synthesis program directed toward improving the stability of imidoyl thiourea based non-nucleoside reverse transcriptase inhibitors (NNRTIs) led to the discovery of diaryltriazines (DATAs), a new class of potent NNRTIs. The synthesis and anti-HIV structure-activity relationship (SAR) studies of a series of DATA derivatives are described.

Anti-HIV Agents↗
PubMed2001

Evolution of anti-HIV drug candidates. Part 3: Diarylpyrimidine (DAPY) analogues.

The synthesis and anti-HIV-1 activity of a series of diarylpyrimidines (DAPYs) are described. Several members of this novel class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) are extremely potent against both wild-type and a panel of clinically significant single- and double-mutant strains of HIV-1.

Anti-HIV Agents↗
PubMed2001

The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance.

Inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (RT) are widely used in the treatment of HIV infection. Loviride (an alpha-APA derivative) and HBY 097 (a quinoxaline derivative) are two potent non-nucleoside RT inhibitors (NNRTIs) that have been used in human clinical trials. A major problem for existing anti-retroviral therapy is the emergence of drug-resistant mutants with reduced susceptibility to the inhibitors. Amino acid residue 103 in the p66 subunit of HIV-1 RT is located near a putative entrance to a hydrophobic pocket that binds NNRTIs. Substitution of asparagine for lysine at position 103 of HIV-1 RT is associated with the development of resistance to NNRTIs; this mutation contributes to clinical failure of treatments employing NNRTIs. We have determined the structures of the unliganded form of the Lys103Asn mutant HIV-1 RT and in complexes with loviride and HBY 097. The structures of wild-type and Lys103Asn mutant HIV-1 RT in complexes with NNRTIs are quite similar overall as well as in the vicinity of the bound NNRTIs. Comparison of unliganded wild-type and Lys103Asn mutant HIV-1 RT structures reveals a network of hydrogen bonds in the Lys103Asn mutant that is not present in the wild-type enzyme. Hydrogen bonds in the unliganded Lys103Asn mutant but not in wild-type HIV-1 RT are observed between (1) the side-chains of Asn103 and Tyr188 and (2) well-ordered water molecules in the pocket and nearby pocket residues. The structural differences between unliganded wild-type and Lys103Asn mutant HIV-1 RT may correspond to stabilization of the closed-pocket form of the enzyme, which could interfere with the ability of inhibitors to bind to the enzyme. These results are consistent with kinetic data indicating that NNRTIs bind more slowly to Lys103Asn mutant than to wild-type HIV-1 RT. This novel drug-resistance mechanism explains the broad cross-resistance of Lys103Asn mutant HIV-1 RT to different classes of NNRTIs. Design of NNRTIs that make favorable interactions with the Asn103 side-chain should be relatively effective against the Lys103Asn drug-resistant mutant.

Acetamides↗
PubMed2001

Single room maternity care: the nursing response.

BACKGROUND: The introduction of single room maternity care in the 1990s necessitated a new approach to nursing education and practice. A focus on perinatal nursing requires competence across the spectrum of labor, delivery, postpartum and newborn care. We sought to evaluate the nursing response to this change by comparing satisfaction with the workplace environment among single room maternity care nurses before and after they worked in the setting and among nurses working in traditional birth settings. METHODS: Six months before the opening of a pilot seven-bed single room maternity care unit, nurses who planned to work in the new unit completed a survey about their satisfaction with aspects of their work environment. Three months after the new unit opened the survey was repeated with this study group and also by a sample of nurses working in the delivery and postpartum areas. RESULTS: Responses indicated that single room maternity care nurses before and after working in the unit were significantly more satisfied with the physical setting, their ability to respond to patients' needs, their opportunity for teaching families, the nursing practice environment, peer support, and their perceived level of competency. They rated their satisfaction significantly higher than that of their colleagues in the traditional delivery and postpartum settings. CONCLUSIONS: The positive transition to single room maternity care by obstetrical nurses was demonstrated by their improved overall satisfaction with the work environment. Evaluation of the nurses' responses to changes in health care delivery has important implications for justifying new clinical approaches and planning for future changes.

Adult↗
PubMed2001

Results of a 10 week community based strength and balance training programme to reduce fall risk factors: a randomised controlled trial in 65-75 year old women with osteoporosis.

OBJECTIVE: To test the efficacy of a community based 10 week exercise intervention to reduce fall risk factors in women with osteoporosis. METHODS: Static balance was measured by computerised dynamic posturography (Equitest), dynamic balance by timed figure of eight run, and knee extension strength by dynamometry. Subjects were randomised to exercise intervention (twice weekly Osteofit classes for 10 weeks) or control groups. RESULTS: The outcome in 79 participants (39 exercise, 40 control) who were available for measurement 10 weeks after baseline measurement is reported. After confounding factors had been controlled for, the exercise group did not make significant gains compared with their control counterparts, although there were consistent trends toward greater improvement in all three primary outcome measures. Relative to the change in control subjects, the exercise group improved by 2.3% in static balance, 1.9% in dynamic balance, and 13.9% in knee extension strength. CONCLUSIONS: A 10 week community based physical activity intervention did not significantly reduce fall risk factors in women with osteoporosis. However, trends toward improvement in key independent risk factors for falling suggest that a study with greater power may show that these variables can be improved to a level that reaches statistical significance.

Accidental Falls↗
PubMed2001

Differences in institutional cesarean delivery rates-the role of pain management.

BACKGROUND: The objective of our study was to compare cesarean delivery rates for low-risk nulliparous women in a community hospital and a tertiary-level maternity hospital and to determine factors influencing those rates. METHODS: We performed a retrospective cohort study of 857 women who did not have obstetric risk factors. The association between hospital and cesarean delivery rate was examined in a multivariate analysis using logistic regression. In a follow-up cohort study, we observed labor management for 24 couples in the community and 26 in the tertiary hospital. RESULTS: The odds of having a cesarean birth (age-adjusted) at the tertiary center were 3.4 (95% confidence interval, 2.1-5.4) compared with the community hospital. Maternal age, cervical dilatation on first examination, and use of epidural analgesia were the primary factors associated with the difference in cesarean delivery rates, with epidural analgesia having the largest effect. Labor support between the 2 hospitals appeared to be similar with the exception of increased use of ambulation in the community hospital and fewer numbers of caregivers for each woman in labor. Women in the tertiary center were more often offered epidural analgesia. CONCLUSIONS: Differences in use of epidural analgesia may contribute to differences in institutional rates of cesarean delivery. Use of epidural analgesia may be related to use of ambulation, consistency of caregiver during labor, availability of epidural, and suggestion for its use by caregivers.

Anesthesia, Epidural↗
PubMed2000

Single room maternity care and client satisfaction.

BACKGROUND: Single room maternity care is the provision of intrapartum and postpartum care in a single room. It promotes a philosophy of family centered care in which one nurse cares for the family consistently throughout the intrapartum and postpartum periods. At B.C. Women's Hospital, a tertiary level obstetric teaching hospital in Vancouver, British Columbia, a seven-bed, single room maternity care unit was developed and opened as a demonstration project. As part of the evaluation of this unit, client satisfaction was compared between women enrolled in single room maternity care and those in a traditional setting. METHOD: The study group included 205 women who were admitted to the single room maternity care unit after meeting the low-risk criteria. Their responses on a satisfaction survey were compared with those of a historical comparison group of 221 women meeting the same eligibility criteria who were identified through chart audits 3 months before the single room maternity care unit was opened. A second, concurrent comparison group comprised 104 women who also met eligibility criteria. RESULTS: Study group women were more satisfied than comparison groups in all areas evaluated, including provision of information and support, physical environment, nursing care, patient education, assistance with infant feeding, respect for privacy, and preparation for discharge. CONCLUSIONS: Single room maternity care was associated with a significant improvement in client satisfaction because of many factors, including the physical setting itself, avoidance of transfers, and improved continuity of nursing care.

Adult↗
PubMed1999

Synthesis and anti-HIV activity of 1,3,4,5-tetrahydro-2H-1,4-benzodiazepin-2-one (TBO) derivatives. Truncated 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2( 1H)-on es (TIBO) analogues.

4,5,6,7-Tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1 H)-ones (TIBO), 1, have been shown to significantly inhibit HIV-1 replication, as reported in detail in our prior publications. Since our earlier reports, we have modified the TIBO structures 1 by removing the 5-membered ring of 1, generating 1,3,4,5-tetrahydro-2H-1,4-benzodiazepin-2-ones (TBO), 4, a bicyclic series of compounds. Although compounds 4 possess modest activity when compared to TIBO analogues 1, they clearly demonstrated significant anti-HIV-1 activity.

Anti-HIV Agents↗
PubMed1998

Prediction of binding affinities for TIBO inhibitors of HIV-1 reverse transcriptase using Monte Carlo simulations in a linear response method.

Monte Carlo (MC) simulations in combination with a linear response approach were used to estimate the free energies of binding for a series of 12 TIBO nonnucleoside inhibitors of HIV-1 reverse transcriptase. Separate correlations were made for the R6 and S6 absolute conformations of the inhibitors, as well as for the analogous N6-monoprotonated species. Models based upon the neutral unbound inhibitors produced overall better fits to experimental values than did those using the protonated unbound inhibitors, with only slight differences between the neutral R6 and S6 cases. The best results were obtained with a three-parameter linear response equation containing van der Waals (alpha), electrostatic (beta), and solvent accessible surface area (SASA, gamma) terms. The averaged (R6 and S6) rms error was approximately 0.88 kcal/mol for the observed range of 4.06 kcal/mol in inhibitor activities. The averaged values of alpha, beta, and gamma were -0.150, 0.114, and 0. 0286, respectively. Omission of the alpha term gave beta 0.152 and gamma 0.022 with a rms of 0.92. The unweighted van der Waals components were found to be highly attractive but failed to correlate well across the series of inhibitors. Contrastingly, while the electrostatic components are all repulsive, they show a direct correlation with inhibitor activity as measured by DeltaGbinding. The role of gamma is primarily to produce an overall negative binding energy, and it can effectively be replaced with a negative constant. During the MC simulations of the unbound solvated inhibitors, the R6 and S6 absolute conformations do not interconvert due to the formation of a favorable hydrogen bond to solvent. In the complex, however, interconversion of these conformations of the inhibitor is observed during the course of the simulations, a phenomenon which is apparently not observed in the crystalline state of the complex. Hydrogen bonding of the inhibitor to the backbone NH of K101 and the lack of such an interaction with the C=O of K101 or with solvent correlate with enhanced activity, as does the ability to assume a number of different orientations of the inhibitor dimethylallyl moiety with respect to residues Y181 and Y188 while retaining contact with W229. Overall, the use of a combination of MC simulation with a linear response method shows promise as a relatively rapid means of estimating inhibitor activities. This approach should be useful in the preliminary evaluation of potential modifications to known inhibitors to enhance activity.

Anti-HIV Agents↗
PubMed1997

Determinants of vaginal-perineal integrity and pelvic floor functioning in childbirth.

OBJECTIVES: Our purpose was to evaluate risk factors for severe vaginal-perineal trauma and to ascertain determinants of pelvic floor strength. STUDY DESIGN: Secondary analysis of 459 nulliparous women enrolled in a randomized controlled trial of episiotomy was carried out. In a multivariate analysis we examined the association between (1) sulcus tears, (2) third- or fourth-degree tears, and (3) pelvic floor strength and selected demographic, physiologic, pregnancy-related, and intrapartum factors. RESULTS: Unemployment and shorter second stage of labor were significant predictors of sulcus tears. Episiotomy, forceps use, and birth weight were important predictors of third- and fourth-degree tears. Whereas perineal intactness (use of episiotomy and spontaneous tears) was not influenced by exercise, a strong exercise profile was associated with fewer third- and fourth-degree tears in the presence of episiotomy. Exercise did not influence the rate of sulcus tears. A total of 35% of the variability in postpartum pelvic floor strength was explained by antepartum strength; however, we were only able to identify 5% of the factors contributing to antepartum pelvic floor strength. CONCLUSIONS: Determinants of sulcus tears appear to be present before pregnancy; third- and fourth-degree tears are related to physician management. Exercise mitigates the potential for severe trauma induced by episiotomy.

Adolescent↗
PubMed1997

Molecular modeling of HIV-1 reverse transcriptase drug-resistant mutant strains: implications for the mechanism of polymerase action.

A computer model of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) either alone, or complexed with a non-nucleoside inhibitor (NNI), was constructed using crystal coordinate data from a subset of the protein surrounding the binding pocket region. Molecular mechanics calculations were carried out on solvated wild-type RT and RT that contained modifications corresponding to resistance-engendering mutations. Results from the calculations revealed that the r.m.s. difference between 12 modified proteins and that of wild-type RT could be qualitatively correlated with the measured polymerase activity of the enzyme in the presence of these mutations. In addition, the level of activity was related to the measured distance between the primer grip and dNTP binding regions of the protein. These data suggest a direct correlation between RT structure and function. Complexes of RT-8-C1 TIBO and RT-alpha-APA were also minimized in models containing modifications corresponding to key drug-resistant mutants. The variant complexes all showed weaker binding than wild-type RT, while giving rise to similar, but critical changes in the protein. Therefore, the design of new inhibitors should center on obtaining stronger binding drugs to key drug-resistant RT variants.

Anti-HIV Agents↗