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Biomedical subjects

D Summers

Publications and source records attributed to D Summers.

At least 19 recordsLinked to original sources

The heart-brain connection.

We have long known that patients with vascular disease in one system are at risk for vascular disease in other systems. Beyond this, we are recognizing the increased risk for cardiovascular patients to develop stroke not only as the result of arrhythmia, but also at the time of cardiovascular events or procedures. This presents clinical challenges to nurses with either neurological or cardiovascular expertise, requiring development of new awareness, clinical and critical thinking skills, and collaboration with their colleagues in other specialties. Three case studies illustrate patient presentations ranging from the subtle to the obvious. Pathophysiology of stroke is reviewed. Leading-edge management strategies and supporting literature highlight the benefits of prompt identification and management of the stroke patient. The Stroke Watch Action Team (SWAT) has proved to be an effective means of expediting patient identification and access to effective stroke treatment.

Adolescent↗

Development of clinical pathways for stroke management: an example from Saint Luke's Hospital, Kansas City.

Clinical pathways for stroke are important tools for improved case management and outcome assessment. The clinical path created at St. Luke's Hospital in Kansas City is described here. It evolved through the collaboration of a multidisciplinary team of clinical experts and is still evolving. Ideally, a clinical path should be used as a guide rather than a standard of care, which is to be individualized for each patient. This article describes the methods for writing the pathways and how they are used for documentation. It also summarizes how the pathway data support stroke outcome assessment.

Case Management↗

Transplanted neurons alter the course of neurodegenerative disease in Lurcher mutant mice.

Embryonic cerebellar, neocortical, and striatal tissues derived from NSE-LacZ transgenic mice were transplanted into the right cerebellar hemisphere of 8- to 10-day-old Lurcher or wild-type mice. Host mice survived for 30-90 days and the transplanted tissue was examined by light microscopy using Nissl staining, X-gal histochemistry, and immunohistochemistry for calcium binding protein and glutamic acid decarboxylase. Transplantation of cerebellar tissue, but not neocortical or striatal progenitors, resulted in robust infiltration of the lurcher mutant host cerebellar cortex by transgenic Purkinje neurons. Deep to the infiltrated molecular layer, the host granular layer was thicker and denser than the mutant granular layer, but transgenic cells did not contribute to the spared granular layer. The host inferior olivary complex consistently exhibited a noticeable bilateral asymmetry in Nissl-stained sections. A quantitative analysis of the olivary complex was performed in 10 90-day-old host mice. The results indicate that the left inferior olivary complex of 90-day-old host mice contained more neurons than the right inferior olive of the host mice and contained more neurons than was observed in 90-day-old Lurcher control mice. Analysis by olivary subdivision indicates that increased neuron numbers were present in all subdivisions of the host left inferior olive. These studies confirm the specific attractive effect of the mutant cerebellar cortex on transplanted Purkinje neuron progenitors and indicate that neural transplants may survive the neurodegenerative period to interact with developing host neural systems. The unilateral rescue of Lurcher inferior olivary neurons in cerebellar transplant hosts indicates that transplanted neurons may interact with diseased host neural circuits to reduce transneuronal degeneration in the course of a neurodegenerative disease.

Animals↗

Timing, self-control and a sense of direction are the secrets of multicopy plasmid stability.

Multicopy plasmids of Escherichia coli are distributed randomly at cell division and, as long as copy number remains high, plasmid-free cells arise only rarely. Copy number variation is minimized by plasmid-encoded control circuits, and the limited data available suggest that deviations are corrected efficiently under most circumstances. However, plasmid multimers confuse control circuits, leading to copy number depression. To make matters worse, multimers out-replicate monomers and accumulate clonally within the culture, creating a subpopulation of cells with a significantly increased rate of plasmid loss. Multimers of natural multicopy plasmids, such as ColE1, are resolved to monomers by a site-specific recombination system (Xer-cer) whose activity is limited to intramolecular recombination. Recombination requires the heterodimeric XerCD recombinase plus two accessory proteins (ArgR and PepA), which activate recombination and prevent intermolecular events. Evidence is accumulating that Xer-cer recombination is relatively slow, and there is a risk that cells might divide before multimer resolution is complete. The Rcd transcript encoded within cer may solve this problem by preventing the division of multimer-containing cells. Working in concert, the triumvirate of copy number control, multimer resolution and cell division control achieve an extremely high fidelity of plasmid maintenance.

Bacteriocin Plasmids↗

Implementation and evaluation of stroke clinical pathways and the impact on cost of stroke care.

Saint Luke's Hospital is a 642-bed urban, tertiary, teaching hospital in metropolitan Kansas City, Missouri. In 1992, Saint Luke's developed a "Collaborative Care" program supported by tools such as clinical paths as a means to assure quality stroke care and to continually improve outcomes. This article describes the development of a comprehensive Collaborative Care Program for stroke patients, highlights the development of a dedicated stroke unit, and stroke clinical path, and describes the clinical and fiscal outcomes from these efforts.

Cerebrovascular Disorders↗

Clinical outcome of cryopreserved human pronuclear stage embryos resulting from intracytoplasmic sperm injection.

OBJECTIVE: To compare the survival rate and pregnancy rate (PR) of embryos from intracytoplasmic sperm injection (ICSI) or conventional IVF, which were cryopreserved at the pronuclear stage in cycles where fresh transfer was deferred. DESIGN: Comparative observational study. SETTING: University-associated IVF center. PATIENT(S): Ninety-nine patients who deferred ET and had all their embryos cryopreserved at the pronuclear stage after 153 oocyte retrievals. Thirty-nine patients had their oocytes inseminated by ICSI and 60 patients had conventional IVF insemination. INTERVENTION(S): All embryos were frozen-thawed at the two pronuclear stage and allowed to cleave for 2 days before transfer. MAIN OUTCOME MEASURE(S): Survival rate (morphologically intact after thaw), cleavage rate (cleaved by time of transfer), and the clinical PR after frozen ET. RESULT(S): In the ICSI group, 205 embryos were thawed for use in 57 frozen ETs; in the IVF group, there were 527 embryos thawed for use in 149 frozen ETs. There was no significant difference in any of the outcome measures by insemination method: survival rates (ICSI, 93.2%; IVF, 94.8%); cleavage rates (ICSI, 95.2%; IVF, 94.7%), and clinical PR (ICSI, 14.0%; IVF, 17.4%). CONCLUSION(S): Pronuclear embryos resulting from ICSI can be cryopreserved successfully, thawed, and the survival rate and PR are comparable to conventional IVF.

Adult↗

11 beta-Hydroxysteroid dehydrogenase enzyme activity in granulosa cells derived from ovarian follicles of in vitro fertilization patients.

11 beta-Hydroxysteroid dehydrogenase (HSD) activity was measured in freshly frozen granulosa cells isolated from follicles of twenty-one infertility patients undergoing in vitro fertilization-embryo transfer (IVF-ET). A total of 213 follicles were analyzed for 11 beta-HSD activity. Both nicotinamide-adenine dinucleotide (NAD) and nicotinamide-adenine dinucleotide phosphate (NADP) dependent 11 beta-dehydrogenase activities were measured in granulosa cells. The activity in reductive direction (11-oxoreductase activity) was not measurable either with NADH or NADPH as cofactors. NAD- and NADP-dependent dehydrogenase activities are in comparable levels at 100 nmol/l and 1 mumol/l corticosteroid concentrations. For comparing enzyme activities of individual follicles, significant enzyme activity was considered to be a level of > 2 nmol/l/min/mg. 41.3% of the follicles demonstrated enzyme activity, 58.7% did not. The mean 11 beta-dehydrogenase (11 beta-DH) activity was calculated for each patient. Those patients with levels > 2 nmol/l/min/mg were considered enzyme positive; those with mean levels < 2 nmol/l/min/mg were considered negative. No significant association was noted between follicle size, oocyte maturity or fertilization rates and 11 beta-DH activity. This study noted the presence of 11 beta-DH activity in granulosa cells, however, no association with oocyte maturity and fertilization was found.

11-beta-Hydroxysteroid Dehydrogenases↗

The effect of assisted hatching on pregnancy rates after frozen embryo transfer.

OBJECTIVE: To compare clinical pregnancy and implantation rates after transfer of frozen-thawed embryos prepared according to an assisted hatching protocol or a nonassisted hatching protocol. DESIGN: A historical cohort study in which a cohort of patients who underwent an assisted hatching protocol was matched for clinical parameters to an external historical cohort treated before assisted hatching was available. SETTING: In vitro fertilization-ET facility of a university-based practice. PATIENTS: Seventy-nine matched pairs. INTERVENTIONS: Nonassisted hatching patients: embryos were thawed, cultured in human tubal fluid + 0.5% bovine serum albumin until 48 hours and transferred. Assisted hatching patients: embryos thawed, cultured in human tubal fluid + 10% synthetic serum substitute until 72 hours, had assisted hatching and transferred. MAIN OUTCOME MEASURES: Clinical pregnancy (gestational sac) and implantation rates. RESULTS: Twelve (15.2%) clinical pregnancies per transfer in nonhatched group versus 24 (30.4%) in hatched group. Nonhatched group: 284 embryos transferred; 15 (5.3%) implanted. Three pregnancies (25.0%) had two sacs. Hatched embryos: 269 were transferred; 37 (13.7%) implanted. Eleven pregnancies (45.8%) were multiple gestations (9 twins, 2 triplets). CONCLUSION: Clinical pregnancy and implantation rates were higher for group having assisted hatching protocol. It is not clear whether the improvement is due to the overall methodology change or to assisted hatching. Assisted hatching using the zona-drilling technique is not detrimental to frozen-thawed human embryos and may be beneficial.

Adult↗

Accessory proteins impose site selectivity during ColE1 dimer resolution.

The cer-Xer dimer resolution system of plasmid ColE1 is highly selective, acting only at sites on the same molecule and in direct repeat. Recombination requires the XerCD recombinase and accessory proteins ArgR and PepA. The Escherichia coli chromosome dimer resolution site dif and the type II hybrid site use the same recombinase but are independent of ArgR and PepA and show no site selectivity. This has led to the proposal that ArgR and PepA are responsible for the imposition of constraint. We describe here the characterization of a novel class of "conditionally constrained' multimer resolution sites whose properties support this hypothesis. In the presence of ArgR and PepA, plasmids containing conditionally constrained sites are monomeric, but in their absence, extensive multimerisation is seen. A mutant ArgR derivative (ArgR110), which is defective in cer-mediated dimer resolution, remains able to prevent plasmid multimerisation by a conditionally constrained site. This implies that the accessory factors block recombination in trans rather than ensuring rapid multimer resolution. When the distance between the ArgR and XerCD binding sites in a conditionally constrained site was altered by a non-integral number of helical turns, the site became unconstrained. Constraint was restored by the insertion of a full helical turn.

Aminopeptidases↗

Pregnancy after zona drilling of cryopreserved thawed embryos: case report.

OBJECTIVE: To confirm successful implantation of IVF, cryopreserved human embryos after assisted hatching with acidic Tyrode's solution. DESIGN: Case report. SETTING: In vitro fertilization-ET facility of a university-based practice. PATIENT: A 28-year-old female with nonoperable bilateral tubal occlusion and > 1 1/2 years of primary infertility. INTERVENTIONS: The patient was stimulated for egg retrieval after an hMG-controlled ovarian hyperstimulation regime. Luteal phase leuprolide acetate (1 mg) was administered SC for 10 days. The dose was then reduced to 0.5 mg, and she was given hMG and FSH IM twice daily until two lead follicles reached 20 mm average diameter. The patient was administered 10,000 IU hCG 36 hours before retrieval. MAIN OUTCOME MEASURES: Viable pregnancy documented by ultrasound (US). RESULTS: After the transfer of five cryopreserved-thawed human embryos that were subjected to assisted hatching using acidic Tyrode's solution, the patient established a triplet gestation as documented by US. CONCLUSION: This case report demonstrates that zona drilling can be successfully applied to frozen-thawed pronuclear stage embryos that were cultured to 72 hours without damaging them, as evidenced by continued cleavage and resulting implantation.

Adult↗

Saethre-Chotzen syndrome associated with balanced translocations involving 7p21: three further families.

We describe three families segregating different reciprocal chromosome translocations, t(7;18)(p21.2;q23), t(2;7)(q21.1;p21.2), and t(5;7)(p15.3;p21.2). A total of seven apparently balanced carriers have been identified and all manifest features of the Saethre-Chotzen syndrome, although only two have overt craniosynostosis. In one family the carriers are immediately recognisable by their unusual ears, and clefts of the hard or soft palate are present in all three families. These observations extend previous linkage and cytogenetic evidence that a locus for Saethre-Chotzen syndrome resides in band 7p21.2.

Acrocephalosyndactylia↗

Effects of intermittent mandatory ventilation on respiratory timing in preterm infants.

Twenty preterm infants (25-36 weeks' gestation) were studied during intermittent mandatory ventilation (IMV) at rates of 10-34 inflations/min. Airway pressure and abdominal capsule signals were recorded at varying postnatal ages. Spontaneous interbreath interval (IBI), inspiratory (Ti) and expiratory (Te) duration were measured over 100-1000 ventilator cycles. Baseline Te was 0.48 s (+/- 0.129) and increased to 0.65 s (+/- 0.182) when associated with a mechanical inflation. Baseline Ti was 0.34 s (+/- 0.062) and increased to 0.38 s (+/- 0.081) with inflation. IBI increased from 0.82 s (+/- 0.161) to 1.03 s (+/- 0.201) with inflation. 1:1 entrainment (phase-locking) was observed at rates of ventilation below the spontaneous respiratory rate but spontaneous inspiration and mechanical inflation were always out of phase. A linear relationship was noted between the prolongation of IBI and the timing of inflation within the spontaneous respiratory cycle during IMV. This relationship could be used to estimate the range of rates of mechanical inflation capable of inducing 1:1 entrainment.

Birth Weight↗

Localization of the genetic locus for Saethre-Chotzen syndrome to a 6 cM region of chromosome 7 using four cases with apparently balanced translocations at 7p21.2.

Saethre-Chotzen syndrome is a common autosomal dominant form of craniosynostosis, which results in the premature fusion of cranial sutures. Craniosynostosis is commonly associated with abnormalities of 7p; Vortkamp et al. (Nature 352, 539-540) demonstrated that the GLI3 gene in 7p13 was disrupted in, patients with Greig syndrome and, more recently, the linkage of genetic markers from 7p with the Saethre-Chotzen syndrome locus has been reported (2,3). Here we report the analysis by fluorescence in situ hybridization of four patients with Saethre-Chotzen syndrome associated with apparently balanced translocations involving band 7p21.2 and different reciprocal chromosomes. We show that in all four patients the breakpoints in 7p are situated within a 6 cM region flanked by the genetic markers D7S488 and D7S493. These results provide further evidence that the genetic locus for Saethre-Chotzen syndrome is located in distal 7p.

Acrocephalosyndactylia↗

Close linkage of a gene for X linked deafness to three microsatellite repeats at Xq21 in radiologically normal and abnormal families.

We have used three highly polymorphic microsatellite repeats from Xq21 to type families in whom a gene for X linked deafness with perilymphatic gusher (DFN 3) was segregating. All three markers were tightly linked to the disease in its radiologically normal and abnormal forms, with a maximum lod score of 10.37 with DXS995 and 8.44 with DXS986 at zero recombination, and 14.03 with DXS1002 at theta = 0.01. In an isolated case of deafness of this type, DXS995 indicated either the first recombination observed between the marker and the disease gene or a new mutation in the proband. Southern blotting using a cosmid fragment from the candidate region has confirmed a de novo mutation by showing a deletion in the proband which is not present in his mother as judged by dosage analysis. We also describe a family with a paracentric inversion associated with a microdeletion and discuss how deletion mapping using these and other markers in the region has helped to define a candidate region for the gene.

Base Sequence↗

Cytogenetic evidence that the Saethre-Chotzen gene maps to 7p21.2.

Evidence for the location of the Saethre-Chotzen acrocephalosyndactyly mutation on 7p21-22 is based on genetic linkage studies in families segregating for this autosomal dominant disorder. Linkage studies were guided by several reports of chromosome deletions in this region giving rise to craniosynostosis and some other manifestations of Saethre-Chotzen syndrome. We report on a family where a father and daughter carry an apparently balanced t(7;10)(p21.2;q21.2) translocation (de novo in the father) and have the Saethre-Chotzen syndrome. These observations support the localization of the Saethre-Chotzen gene to 7p21.2.

Acrocephalosyndactylia↗

Chaos in a periodically forced predator-prey ecosystem model.

We subject to periodic forcing the classical Volterra predator-prey ecosystem model, which in its unforced state has a globally stable focus as its equilibrium. The periodic forcing is effected by assuming a periodic variation in the intrinsic growth rate of the prey. In nondimensional form the forced system contains four control parameters, including the forcing amplitude and forcing frequency. Numerical experiments carried out over sections of the parameter space reveal an abundance of steady-state chaotic solutions. We graph Poincaré maps and calculate Lyapunov exponents and fractal dimensions for a representative selection of strange attractors. The transitions to chaos were found to be either via a Feigenbaum cascade of period-doubling bifurcations or via frequency locking.

Animals↗