Pharmaceutical care: improving practice for children in hospital.
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Child Health Services↗
Biomedical subjects
D Saunders
Publications and source records attributed to D Saunders.
Y chromosome analysis of infertile men and their sons conceived through intracytoplasmic sperm injection: vertical transmission of deletions and rarity of de novo deletions.
OBJECTIVE: To determine the prevalence and type of Yq microdeletions in 86 consecutive men that fathered 99 sons by intracytoplasmic sperm injection (ICSI) and to determine the incidence of vertical transmission and de novo deletions in these boys. DESIGN: Prospective clinical observational study. SETTING: Genetics laboratory associated with a university IVF unit. PATIENT(S): Eighty-six consecutive infertile men presenting to an IVF clinic and their 99 ICSI-conceived sons. Fifty of the 86 men (58%) had idiopathic seminiferous tubule failure (STF); the remainder had a variety of other clinical indications for ICSI. INTERVENTION(S): Collection of peripheral and cord blood samples. MAIN OUTCOME MEASURE(S): The Yq genetic status of fathers who underwent ICSI and of their sons by the presence or absence of 22 Y-specific markers covering the four azoospermia factor (AZF) subregions. RESULT(S): Yq deletions of the AZFd/c region were detected in two (6.9%) of 29 azoo- or severely oligospermic men with STF. Identical deletions were found in their respective sons. No de novo deletions were detected in the remaining 97 sons conceived by men without deletions. CONCLUSION(S): The detection of Yq deletions only in men with severe STF is consistent with previous studies, with the AZFd/c region being most commonly affected. This study demonstrates the vertical transmission of these Yq deletions through the use of ICSI and supports the notion that, in most cases, Yq deletions will be inherited by male offspring. The absence of de novo Yq deletions in the male offspring indicates that these events are rare following ICSI in men with both STF and other common male factor indications.
Fathers↗
Photoperiodic time measurement in insects: a review of clock models.
Based on analyses of responses of insects and mites to a wide range of diel and nondiel experimental light-dark schedules, a variety of models have been developed for the photoperiodic clocks in these species by nearly as many investigators. According to some of these models, the photoperiodic clock is based on a mechanism separate from the circadian system, that is, a so-called "hourglass." According to other models, the clock is based on one or more circadian oscillators that may be coupled to each other and that may or may not show a certain degree of damping. In this context, a rapidly damping oscillator could be regarded as an hourglass. The present article gives an overview of the many different clock models and their philosophies, and it makes comparisons among them to provide a better understanding about how these models are related, if at all, and why the double circadian oscillator model is the most favored model at present.
Animals↗
Practice management in dental schools--is there such a thing?
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Administrative Personnel↗
Plasminogen activator inhibitor type 2 in human corneal epithelium.
PURPOSE: To examine normal human corneal epithelium in vivo and in vitro for expression and status of plasniinogcn activ:ltor inhibitor type 2 (PAI-2). METHODS: Normal hiuman corneas were prepared for frozen sections and for culture of corneal keratinocytes. PAI-2 was analyzed by immunohistochemistry and western blot analysis uising antibodies that recognize all forms of PAI-2. RESULTS: In vivo and in vitro, PAI-2 was immunohistochemically localized to the superficial corneal keratinocytes. Immunostaining also revealed the presence of PAI-2 in its relaxed (i.e., cleaved) conformation. In vivo, the staining pattern of the relaxed form was identical with that of total PAI-2, but in vitro the relaxed form was detected in a smaller subpopulation of superficial cells. In vitro, the staining pattern indicated a cytoplasmic localization for PAI-2. Western blot analysis revealed that most of the PAI-2 was cell associated and functionally active. CONCLUSIONS: The present results are the first to show that PAI-2 is found in normal human corneal epithelium in vivo and in vitro, where it can be considered as a differentiation product. At least in vitro, all detectable PAI-2 is cell associated, with a cytoplasmic distribution. A subpopulation of keratinocytes also contains PAI-2 in its relaxed (i.e., cleaved) conformation. Cleavage by an as yet unidentified cytoplasmic proteinase may constitute a crucial aspect of the function of corneal epithelial PAI-2, which may be relevant to terminal differentiation and death of the corneal keratinocyte.
Blotting, Western↗
Fatal shoulder dystocia: a review of 56 cases reported to the Confidential Enquiry into Stillbirths and Deaths in Infancy.
OBJECTIVE: To use information collected by the Confidential Enquiry into Stillbirths and Deaths in Infancy to help obstetric, midwifery and paediatric practice in the management of shoulder dystocia. DESIGN: Review of casenotes by a multidisciplinary focus group. SAMPLE: All 56 cases reported to the Confidential Enquiry into Stillbirths and Deaths in Infancy from England, Wales and Northern Ireland in 1994 and 1995, where stillbirth or neonatal death was attributed to shoulder dystocia. MAIN OUTCOME MEASURES: Case notes were reviewed with respect to a range of perinatal variables. Comparisons were made with normative data from other studies when appropriate. RESULTS: Maternal obesity and big babies were over-represented in pregnancies complicated by fatal shoulder dystocia. Fetal compromise was recorded in 26% of labours. The median time interval between delivery of the head and the rest of the body was only five minutes. The lead professional at the time the head was delivered was a midwife in 65% of cases. Middle grade or senior obstetric staff were supervising 47% of cases by the time the body was delivered. CONCLUSIONS: Antenatal prediction of shoulder dystocia is imprecise, and the majority of deliveries are attended by midwives. A relatively brief delay in delivery of the shoulders may be associated with a fatal outcome.
Autopsy↗
Dendritic cells and T lymphocytes: developmental and functional interactions.
Dendritic cells (DCs) are specialized for presentation of antigen to T cells and are essential for primary T cell activation. Although DCs are generally considered to be myeloid derived, we now have evidence that a subgroup are of lymphoid origin. In particular, the DCs of the adult mouse thymus appear to be derived from the same early, lymphoid-restricted precursor cells that generate T lymphocytes. Purified early thymic T precursors have the capacity to produce T cells, B cells, NK cells and DCs, but not myeloid cells, on transfer to irradiated recipients. They also produce thymic DCs on culture with a mix of cytokines; this mix does not include GM-CSF, needed to generate myeloid-derived DCs. A subgroup of DCs in other lymphoid organs, which like thymic DCs express CD8 as an alpha alpha homodimer, may likewise be of lymphoid origin. These CD8+ DCs in mouse spleen differ functionally from the conventional CD8+ DCs. CD8+ DCs efficiently activate CD4+ T cells but then kill them via Fas ligand on the DC surface. CD8+ DCs efficiently recruit CD8+ T cells into the cell cycle, but their proliferation is then restricted by an inadequate production of interleukin 2. This subgroup of CD8+ DCs therefore appears to have a regulatory role.
Animals↗
Psychosocial adjustment and the quality of the mother-child relationship at four months postpartum after conception by in vitro fertilization.
OBJECTIVE: To examine psychological adjustment to early motherhood at 4 months postpartum in mothers who conceived by IVF-ET. DESIGN: Controlled clinical study. SETTING: Healthy human volunteers in an academic research environment. PATIENT(S): Sixty-five primiparous women undergoing IVF-ET and 62 age-matched primiparous women with no history of infertility. INTERVENTION(S): Completion of questionnaires, interviews, and videotaped interaction. MAIN OUTCOME MEASURE(S): Maternal self-reports of psychosocial adjustment and behavioral ratings of quality of mother-infant interaction based on a videotaped observation scored blind to IVF-ET status. RESULT(S): Mothers who conceived by IVF-ET did not differ from control mothers on measures of anxiety, postnatal depression, marital satisfaction, or use of support services. However, they reported lower self-esteem and lower maternal self-efficacy, and they rated their infants as more temperamentally difficult. (Ratings of temperament difficulty for the infants of mothers who conceived by IVF-ET are within the normal range when compared with Australian normative data for this age group.) The videotapes revealed no group differences in maternal behaviors, but the infants of mothers who conceived by IVF-ET displayed more negative behaviors in response to an interactive stress. Group differences were accounted for largely by those mothers who underwent more than one treatment cycle and by their infants. CONCLUSION(S): Overall, the results are reassuring for parents who conceive by IVF-ET. However, specific adjustment measures reveal some minor difficulties and suggest that mothers who conceive by IVF-ET may benefit from increased support in the early postpartum months.
Adaptation, Psychological↗
Anxiety during pregnancy and fetal attachment after in-vitro fertilization conception.
The aim of this study was to compare 70 couples who had conceived by in-vitro fertilization (IVF) with 63 matched controls for the prevalence of anxiety and quality of attachment to the baby during pregnancy. Results for mothers showed no group differences using a global measure of anxiety, the Spielberger State-Trait Anxiety Inventory. However, pregnancy-specific measures revealed significantly higher levels of anxiety in IVF mothers about the survival and normality of their unborn babies, about damage to their babies during childbirth and about separating from their babies after birth. When IVF mothers were differentiated according to the number of treatment cycles, more differences in anxiety level were revealed, with most increases occurring in mothers who had experienced two or more treatment cycles. IVF fathers did not differ from controls on the global anxiety measure. No data on pregnancy-specific anxiety were available for fathers. Neither IVF mothers nor IVF fathers differed from controls on measures of attachment to the baby during pregnancy. Results are discussed in the context of the need for researchers to employ differentiated and issue-specific measures to identify concerns that may be unique to IVF couples. Clinical implications regarding the need for psychological support during pregnancy are also discussed.
Adult↗
Social class, spoken language and pattern of care as determinants of continuity of carer in maternity services in east London.
BACKGROUND: The Government's policy of Changing childbirth gives priority to user-oriented outcomes, such as continuity of carer. It has been assumed that the organization (or pattern) of maternity care is the main determinant of continuity, with relatively little attention paid to sociodemographic factors. The aim of this study was to assess the relative contribution of social class, spoken language and pattern of care in determining continuity of carer. METHOD: Postal questionnaires were sent 14 days after delivery to East London and the City Health Authority residents delivering within a three-week period in May 1994. Bilingual interviews were carried out for non-English-speaking women. Pattern of care was assigned by the midwife as either hospital or community (including team based care, 'domino' and home births). The main outcome measure was self-reported continuity of carer in antenatal, delivery and postnatal care. RESULTS: The response rate was 69 per cent (370/533). The community pattern of care affected only antenatal continuity (62 per cent community vs 50 per cent hospital, p < 0.05). Women whose main spoken language was English or whose social class was I-IIIn reported higher levels of continuity at each phase of care, although this effect was largely confined to the community pattern of care. The odds ratios (95 per cent confidence intervals) for the effect of social class (I-IIIn vs other) on antenatal, labour and postnatal continuity within the community pattern of care were 3.64 (1.09-12.18), 3.08 (1.09-8.74) and 4.93 (1.48-16.46), respectively. CONCLUSION: Spoken English and high social class were associated with continuity of carer, although this effect was mainly confined to women with a community pattern of care. Achievement of national targets for continuity of carer may not be possible in east London without explicit consideration of sociodemographic factors.
Adolescent↗
Glycosaminoglycans regulate elastase inhibition by oxidized secretory leukoprotease inhibitor.
Secretory leukoprotease inhibitor (SLPI) is one of the major physiological inhibitors protecting respiratory epithelium from attack by excess human leukocyte elastase (HLE), a serine protease released by neutrophils upon activation in response to inflammatory stimuli. Reaction with N-chlorotaurine, a major long-lived oxidant generated by activated neutrophils, oxidized all four methionine residues, but no other amino acids, in SLPI, resulting in substantial diminution of its elastase inhibitory activity. Oxidation of the P1' residue, Met73, accounted for most of the diminution in activity since a site-directed mutant of SLPI with leucine at the P1' position retained much higher residual activity after reaction with N-chlorotaurine. The diminished activity of oxidized SLPI could be almost completely restored when an iduronate-containing glycosaminoglycan, such as heparin, heparan sulfate, or dermatan sulfate, was added to the reaction medium. Addition of a sulfated glucuronate-containing glycosaminoglycan, chondroitin 4- or 6-sulfate, to the medium resulted in smaller but significant restoration of the lost activity, whereas the effects of hyaluronic acid and keratan sulfate were negligible. Kinetic analysis revealed that glycosaminoglycans greatly accelerated the association of oxidized SLPI and HLE, whereas iduronate-containing glycosaminoglycans also stabilized the enzyme-inhibitor complex formed. Based on these findings, we suggest that oxidized SLPI is a functionally active form of the inhibitor but that expression of its elastase inhibitory activity is regulated by sulfated uronate-containing glycosaminoglycans. Because its methionine residues have already been oxidized, this form of SLPI is resistant to the oxidant species that selectively attacks methionine residues in proteins. These findings indicate that SLPI may play a previously unexpected role in elastase inhibitory function in the lungs when significant inflammation is present.
Glycosaminoglycans↗
CESDI: a review.
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Annual Reports as Topic↗
Dendritic cell development in culture from thymic precursor cells in the absence of granulocyte/macrophage colony-stimulating factor.
The earliest lymphoid precursor population in the adult mouse thymus had previously been shown to produce not only T cells, but also dendritic cell (DC) progeny on transfer to irradiated recipients. In this study, culture of these isolated thymic precursors with a mixture of cytokines induced them to proliferate and to differentiate to DC, but not to T lineage cells. At least 70% of the individual precursors had the capacity to form DC. The resultant DC were as effective as normal thymic DC in the functional test of T cell stimulation in mixed leukocyte cultures. The cultured DC also expressed high levels of class I and class II major histocompatibility complex, together with CD11c, DEC-205, CD80, and CD86, markers characteristic of mature DC in general. However, they did not express CD8 alpha or BP-1, markers characteristic of normal thymic DC. The optimized mixture of five to seven cytokines required for DC development from these thymic precursors did not include granulocyte/macrophage colony stimulating factor (GM-CSF), usually required for DC development in culture. The addition of anti-GM-CSF antibody or the use of precursors from GM-CSF-deficient mice did not prevent DC development. Addition of GM-CSF was without effect on DC yield when interleukin (IL) 3 and IL-7 were present, although some stimulation by GM-CSF was noted in their absence. In contrast, DC development was enhanced by addition of the Flt3/Flk2 ligand, in line with the effects of the administration of this cytokine in vivo. The results indicate that the development of a particular lineage of DC, probably those of lymphoid precursor origin, may be independent of the myeloid hormone GM-CSF.
Animals↗
Thrombin inhibitory and clot-specific fibrinolytic activities of the urokinase variant, M23 (rscu-PA-40 kDa/Hir).
The recombinant bifunctional urokinase variant, M23 (rscu-PA-40 kDA/Hir), comprising the kringle and protease domain of single-chain urokinase-type plasminogen activator and a C-terminal fragment of hirudin in one single-chain molecule, was evaluated for its thrombin-inhibitory and fibrinolytic properties in vitro and in vivo. M23 inhibited thrombin-activated coagulation of human blood and thrombin-induced aggregation of human platelet rich plasma in a concentration-dependent manner. The ADP-induced aggregation of human platelet rich plasma was not influenced by M23. In contrast, recombinant single-chain urokinase-type plasminogen activator (saruplase) inhibited neither blood coagulation nor platelet rich plasma aggregation. M23 and saruplase both lysed radiolabelled human thrombi immersed in human plasma (Chandler Loop system) with equal potency. However, there was a significantly lower systemic generation of plasmin (measured as consumption of alpha 2-antiplasmin) by M23 compared to saruplase. In anaesthetized non-heparinized rabbits, experimental femoral artery thrombosis was treated with intravenous bolus injections of M23 or saruplase (6 mg/kg, each). Thrombolytic restoration of arterial blood perfusion was significantly higher in M23- than in saruplase-treated rabbits. Plasma fibrinogen concentrations were decreased markedly in saruplase-treated animals, but remained at significantly higher levels in M23-treated rabbits. In conclusion, the bifunctional molecule, M23, showed thrombin inhibitory and fibrinolytic properties in human in vitro systems and exerted superior thrombolytic effects to saruplase in rabbit femoral artery thrombosis. In vitro and in vivo data indicate that the fibrinolytic activity of M23 is highly clot-specific.
Animals↗
Update on adolescent health care in pediatric practice.
PURPOSE: To determine current adolescent health care practices of pediatricians and evaluate whether changes have taken place during the past decade. METHODS: A questionnaire completed by 101 pediatricians in 1985 was abbreviated and adapted by Committee on Youth of Chapter 2, District II of the American Academy of Pediatrics and sent to 1,633 members of the Chapter in June 1993. RESULTS: Forty-three percent of the 436 respondents in 1993 were female, 43% < or = 40 years of age and 53% were in private practice. Most accept new patients > or = 16 years of age (76%), continue to see patients > or = 19 years of age (63%), and interview adolescents without their parents (86%). Although between one-third and two-thirds of respondents report having equipment for gynecologic examinations, most indicate they are "not entirely comfortable" treating adolescent issues and therefore refer to others for management. Between one-quarter and one-half indicate they are "very interested" in learning more about adolescent issues and an additional 40-50% are "somewhat interested." Obstacles to providing adolescent care include: "image as a baby doctor" (65%), fear that parents would object (61%), no separate hours (57%), difficulty in providing confidential care (56%), and difficulty in charging appropriate fees (47%). Females and younger pediatricians are more comfortable with some aspects of gynecologic care and more likely to be satisfied with the adolescent care they are providing. There were few differences between responses in 1993 and 1995. CONCLUSIONS: Few of the pediatricians surveyed provide comprehensive care to adolescent patients. Future policy decisions and medical education must respond to these realities in pediatric practice.
Adolescent↗
Cultural aspects of African American eating patterns.
The high mortality from diet-related diseases among African Americans strongly suggests a need to adopt diets lower in total fat, saturated fat and salt and higher in fiber. However, such changes would be contrary to some traditional African American cultural practices. Focus group interviews were used to explore cultural aspects of eating patterns among low- and middle-income African Americans recruited from an urban community in Pennsylvania. In total, 21 males and 32 females, aged 13-65+ years were recruited using a networking technique. Participants identified eating practices commonly attributed to African Americans and felt that these were largely independent of socioeconomic status. They were uncertain about links between African American eating patterns and African origins but clear about influences of slavery and economic disadvantage. The perception that African American food patterns were characteristically adaptive to external conditions, suggest that, for effective dietary change in African American communities, changes in the food availability will need to precede or take place in parallel with changes recommended to individuals. Cultural attitudes about where and with whom food is eaten emerged as being equivalent in importance to attitudes about specific foods. These findings emphasize the importance of continued efforts to identify ways to increase the relevance of cultural context and meanings in dietary counseling so that health and nutrition interventions are anchored in values as perceived, in this case, by African Americans.
Adolescent↗
Nonpeptide endothelin receptor antagonists. VII: Binding characteristics of [3H]SB 209670, a novel nonpeptide antagonist of endothelin receptors.
The data presented in this manuscript describes the binding characteristics of [3H]SB 209670, a potent nonpeptide tritium-labeled endothelin (ET) receptor antagonist. The binding of this antagonist to cloned human ETA and ETB receptors was specific, saturable and of high affinity. The apparent dissociation constants were 0.20 and 1.0 nM for ETA and ETB receptors, respectively. The maximum binding was 4.7 and 22.5 pmol/mg protein for ETA and ETB receptors, respectively. Unlike [125]ET-1, the binding of [3H]SB 209670 was reversible. The half-times (T1/2) for dissociation of this ligand from ETA and ETB receptors were approximately 60 and 10 min, respectively. Competition binding studies using [3H]SB 209670 and unlabeled agonists ET-1, ET-3 and S6c indicated that these agonists displayed similar affinities for human ETB receptors, whereas with ETA receptors, ET-1 was approximately 50-fold and 1500-fold more potent than ET-3 and S6c, respectively. Of the peptide antagonists tested, BQ123 (ETA-selective peptide antagonist), displayed Ki values of 40 and > 2300 nM for ETA and ETB, whereas RES701 (ETB-selective antagonist) displayed Ki values of > 1600 and 81 nM for ETA and ETB receptors, respectively. The nonselective peptide antagonist, PD 142893, was approximately 2-fold more potent for ETA compared with ETB receptors. Similar observations were made with nonselective nonpeptide antagonists, Bosentan, (+/-) SB 209670, SB 209670, and (-) SB 209670. All these compounds were 2 to 10 times more potent for ETA than ETB receptors.
Animals↗
Synthesis of classical pathway complement components by chondrocytes.
Using immunohistochemical studies, C1q, C1s, C4 and C2 were detected in chondrocytes in normal human articular cartilage and macroscopically normal articular cartilage from the inferior surfaces of hip joints of patients with osteoarthritis. Using reverse-transcribed polymerase chain reaction (RT-PCR), mRNA for C1q, C1s, C4 and C2 was also detected in RNA extracted from articular cartilage. C1r, C3, C1-inhibitor, C4-binding protein and factor I were not detected by either technique. Articular chondrocytes cultured in vitro synthesized C1r, C1s, C4, C2, C3 and C1-inhibitor but not C1q, C4-binding protein or factor I, as assessed by enzyme-linked immunosorbent assay (ELISA) and Northern blot analysis. Thus cultured articular chondrocytes have a complement profile that is similar to that of cultured human fibroblasts rather than that of articular chondrocytes in vivo. Complement synthesis in cultured chondrocytes was modulated by the cytokines interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), showing that cytokines can probably regulate complement synthesis in intact cartilage. The possible roles of local synthesis of complement components by chondrocytes in matrix turnover and the regulation chondrocyte function are discussed.
Base Sequence↗