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Biomedical subjects

Michael J Higgins

Publications and source records attributed to Michael J Higgins.

11 recordsLinked to original sources
PubMed2006

Structured water layers adjacent to biological membranes.

Water amid the restricted space of crowded biological macromolecules and at membrane interfaces is essential for cell function, though the structure and function of this "biological water" itself remains poorly defined. The force required to remove strongly bound water is referred to as the hydration force and due to its widespread importance, it has been studied in numerous systems. Here, by using a highly sensitive dynamic atomic force microscope technique in conjunction with a carbon nanotube probe, we reveal a hydration force with an oscillatory profile that reflects the removal of up to five structured water layers from between the probe and biological membrane surface. Further, we find that the hydration force can be modified by changing the membrane fluidity. For 1,2-dipalmitoyl-sn-glycero-3-phosphocholine gel (Lbeta) phase bilayers, each oscillation in the force profile indicates the force required to displace a single layer of water molecules from between the probe and bilayer. In contrast, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine fluid (Lalpha) phase bilayers at 60 degrees C and 1,2-dioleoyl-sn-glycero-3-phosphocholine fluid (Lalpha) phase bilayers at 24 degrees C seriously disrupt the molecular ordering of the water and result predominantly in a monotonic force profile.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2006

Autologous blood transfusion for cardiopulmonary bypass: effects of storage conditions on platelet function.

OBJECTIVES: Cardiopulmonary bypass impairs formation of large stable platelet aggregates (macroaggregation), although formation of small aggregates (microaggregation) is preserved. A factor in the uncertain benefits of intraoperative autologous blood transfusion may be the effects of storage on platelet function. The effects of citrate preservative and heparinization before storage on platelet function was therefore assessed. METHODS: Twenty-seven patients undergoing elective coronary artery bypass grafting were randomly allocated to have 450 to 1,000 mL of blood taken into CPDA anticoagulant bags either before (n = 14) or after heparinization (n = 13). Samples from the patients and stored blood were anticoagulated with rhirudin, 200 U/mL. The macroaggregatory response to submaximal collagen was measured by impedance aggregometry and microaggregation by single platelet counting. RESULTS: During macroaggregation, before cardiopulmonary bypass, the ex vivo median (interquartile range) response was 16.3 (12.4-18.7) Omega. This decreased 10 minutes after heparin to 8.9 (3.3-11.0) Omega (p < 0.0001). In the blood bags (in vitro), the initial response for nonheparinized blood was 4.8 (0.1-7.5) Omega (p < 0.002 v ex vivo) and at end-cardiopulmonary bypass was 2.4 (1.6-8.2) Omega. During microaggregation, in vivo heparinization decreased microaggregation both ex vivo and in vitro in CPDA blood; the in vitro response of nonheparinized blood at end-cardiopulmonary bypass was greater than that seen after in vivo heparinization (p < 0.007). No difference in bleeding or transfusion requirements was seen. CONCLUSIONS: Collecting blood into CPDA anticoagulant caused a marked deterioration in platelet function. This was worse after in vivo heparinization and included depression of microaggregation.

Blood Preservation↗
PubMed2006

The role of psychiatry in U.S. Air Force primary care: research-based models for clinical consultation and education.

The integration of mental health treatment with primary care is a U.S. Air Force priority. Unfortunately, manning shortages limit the utility of psychiatry in existing Air Force health care models. In this study, we present efficient and data-driven models for psychiatric involvement with primary care. These models include the use of psychiatrists as clinical consultants and primary care educators. Certain factors are required to implement these models including command support for locating psychiatrists within primary care, data-driven educational approaches, collaborative clinical care, and administrative support.

Aerospace Medicine↗
PubMed2005

Frequency modulation atomic force microscopy reveals individual intermediates associated with each unfolded I27 titin domain.

In this study, we apply a dynamic atomic force microscopy (AFM) technique, frequency modulation (FM) detection, to the mechanical unfolding of single titin I27 domains and make comparisons with measurements made using the AFM contact or static mode method. Static mode measurements revealed the well-known force transition occurring at 100-120 pN in the first unfolding peak, which was less clear, or more often absent, in the subsequent unfolding peaks. In contrast, some FM-AFM curves clearly resolved a force transition associated with each of the unfolding peaks irrespective of the number of observed unfolded domains. As expected for FM-AFM, the frequency shift response of the main unfolding peaks and their intermediates could only be detected when the oscillation amplitudes used were smaller than the interaction lengths being measured. It was also shown that the forces measured for the dynamical interaction of the FM-AFM technique were significantly lower than those measured using the static mode. This study highlights the potential for using dynamic AFM for investigating biological interactions, including protein unfolding and the detection of novel unfolding intermediates.

Aluminum Silicates↗
PubMed2005

Intrauterine penetrating direct fetal head trauma following gunshot injury: a case report and review of the literature.

CASE REPORT: An unusual case of an intrauterine penetrating head injury due to a pellet from an airgun is described. A 28-year-old pregnant woman, at term, shot herself intravaginally with a toy BB gun. Following a spontaneous precipitous vaginal delivery, the neonate presented with persistent seizure disorder, meningitis, cerebritis, and a right parietal region scalp swelling. Imaging studies revealed intracranial hemorrhage, and the metallic pellet was adjacent to the right lateral ventricle, which was removed through a parietal craniotomy. Computed tomography of the brain after 1 week demonstrated early abscess formation in the left frontal operculum and a subdural empyema in the posterior fossa. The abscesses were evacuated, and the meningitis was treated vigorously with broad-spectrum antibiotics. Although well for the past 6 years, the child demonstrates significant mental handicap and developmental delay. DISCUSSION: The pathogenesis, management, and medicolegal issues pertaining to the above case are discussed, and the relevant literature is briefly reviewed.

Adult↗
PubMed2005

Normobaric hyperoxia reduces cardiac index in patients after coronary artery bypass surgery.

OBJECTIVE: The purpose of this study was to assess the hemodynamic changes in response to normobaric hyperoxia in patients immediately after coronary artery bypass surgery. DESIGN: Observational study. SETTING: Single-center university hospital. PARTICIPANTS: Patients immediately after coronary artery bypass surgery. INTERVENTION: Change of fractional inspired oxygen concentration from baseline (< or =0.60) to 1.0 and return to baseline. MEASUREMENTS AND MAIN RESULTS: Cardiovascular changes were assessed with a lithium dilution technique. Cardiac index decreased from 2.82 to 2.52 L/min/m2 (10.6%). Heart rate decreased from 85.9 to 82.5 beats/min (4.0%), and the systemic vascular resistance index increased from 1,858 to 2,304 dyne/s/cm5/m2 (24.1%). Stroke index or mean arterial pressure did not change significantly. On reducing the FIO2 from 1.0 to the baseline FIO2 , there was significant reversal of the previous changes in heart rate and systemic vascular resistance. Heart rate increased from 82.5 to 84.0 beats/min (1.8%), and the systemic vascular index decreased from 2304 to 1932 dyne/s/cm5/m2 (16.1%). The cardiac output did not return to baseline, and the mean arterial pressure decreased from 69.6 to 64.4 mmHg (7.6%). CONCLUSIONS: Exposing patients after coronary artery surgery to hyperoxia induces significant hemodynamic changes.

Aged↗
PubMed2005

Integrated medical-psychiatric care of a dying borderline patient: a case of dynamically informed "practical psychotherapy".

Combined training in family practice and psychiatry is relatively new and consists of equal proportions of each specialty intermixed throughout a 5-year period. This blending of two distinct skill sets and patient populations creates opportunities to provide unique patient care. An understanding of psychodynamic principles is vital to treating patients with comorbid medical and psychiatric illnesses in a primary care setting. The patient presented in this article had several medical and psychiatric problems and was treated by a combined family practice-psychiatry resident who cared for her medically and psychiatrically until the time of her death from cancer. Complex patients such as this defy the use of purely applied school-specific psychotherapies. Rather, they require the creative application of integrated psychotherapeutic strategies. Integrated approaches to psychotherapy have been increasingly advocated in recent years. In keeping with terminology used by Carl Jung, this approach may be thought of simply as practical psychotherapy.

Attitude to Death↗
PubMed2004

Placental growth retardation due to loss of imprinting of Phlda2.

The maternally expressed/paternally silenced genes Phlda2 (a.k.a. Ipl/Tssc3), Slc22a1l, Cdkn1c, Kcnq1, and Ascl2 are clustered in an imprinted domain on mouse chromosome 7. Paternal deletion of a cis-acting differentially methylated DNA element, Kvdmr1, causes coordinate loss of imprinting and over-expression of all of these genes and the resulting conceptuses show intrauterine growth restriction (IUGR). To test the specific contribution of Phlda2 to IUGR in the Kvdmr1-knockout, we crossed Kvdmr1(+/-) males with Phlda2(+/-) females. Conceptuses with the (Phlda2(+/+); Kvdmr1(+/-)) genotype showed fetal and placental growth retardation. Restoration of Phlda2 dosage to normal, as occurred in the conceptuses with the (Phlda2(-/+); Kvdmr1(+/-)) genotype, had a marginally positive effect on fetal weights and no effect on post-natal weights, but significantly rescued the placental weights. As we previously reported, loss of Phlda2 expression in the wild-type background (Phlda2(-/+); Kvdmr1(+/+) genotype) caused placentomegaly. Thus Phlda2 acts as a true rheostat for placental growth, with overgrowth after gene deletion and growth retardation after loss of imprinting. Consistent with this conclusion, we observed significant placental stunting in BAC-transgenic mice that over-expressed Phlda2 and one flanking gene, Slc22a1l, but did not over-express Cdkn1c.

Animals↗
PubMed2002

Regional loss of imprinting and growth deficiency in mice with a targeted deletion of KvDMR1.

Genomic imprinting is an epigenetic modification that results in expression from only one of the two parental copies of a gene. Differences in methylation between the two parental chromosomes are often observed at or near imprinted genes. Beckwith-Wiedemann syndrome (BWS), which predisposes to cancer and excessive growth, results from a disruption of imprinted gene expression in chromosome band 11p15.5. One third of individuals with BWS lose maternal-specific methylation at KvDMR1, a putative imprinting control region within intron 10 of the KCNQ1 gene, and it has been proposed that this epimutation results in aberrant imprinting and, consequently, BWS1, 2. Here we show that paternal inheritance of a deletion of KvDMR1 results in the de-repression in cis of six genes, including Cdkn1c, which encodes cyclin-dependent kinase inhibitor 1C. Furthermore, fetuses and adult mice that inherited the deletion from their fathers were 20-25% smaller than their wildtype littermates. By contrast, maternal inheritance of this deletion had no effect on imprinted gene expression or growth. Thus, the unmethylated paternal KvDMR1 allele regulates imprinted expression by silencing genes on the paternal chromosome. These findings support the hypothesis that loss of methylation in BWS patients activates the repressive function of KvDMR1 on the maternal chromosome, resulting in abnormal silencing of CDKN1C and the development of BWS.

Alleles↗
PubMed2002

Characterization of the adhesive mucilages secreted by live diatom cells using atomic force microscopy.

Atomic Force Microscopy (AFM) resolved the topography and mechanical properties of two distinct adhesive mucilages secreted by the marine, fouling diatom Craspedostauros australis. Tapping mode images of live cells revealed a soft and cohesive outer mucilage layer that encased most of the diatom's siliceous wall, and force curves revealed an adhesive force of 3.58 nN. High loading force, contact mode imaging resulted in cantilever 'cleaned' cell walls, which enabled the first direct observation of the active secretion of soft mucilage via pore openings. A second adhesive mucilage consisted of strands secreted at the raphe, a distinct slit in the silica wall involved in cell-substratum attachment and motility. Force measurements revealed a raphe adhesive strand(s) resistant to breaking forces up to 60 nN, and these strands could only be detached from the AFM cantilever probe using the manual stepper motor.

Adhesiveness↗