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Biomedical subjects

K Henderson

Publications and source records attributed to K Henderson.

At least 19 recordsLinked to original sources
PubMed2006

Experimental study of the role of atomic interactions on quantum transport.

We report an experimental study of quantum transport for atoms confined in a periodic potential and compare between thermal and Bose-Einstein condensation (BEC) initial conditions. We observe ballistic transport for all values of well depth and initial conditions, and the measured expansion velocity for thermal atoms is in excellent agreement with a single-particle model. For weak wells, the expansion of the BEC is also in excellent agreement with single-particle theory, using an effective temperature. We observe a crossover to a new regime for the BEC case as the well depth is increased, indicating the importance of interactions on quantum transport.

Journal Article↗
PubMed2006

In situ split liver transplantation for adult and pediatric recipients: an answer to organ shortage.

BACKGROUND: We report our initial experience with in situ split liver transplantation (SLT) for adult and pediatric patients. PATIENTS AND METHODS: From June 2003 to August 2005, 177 liver transplantations in 165 patients, 133 adults (81%) and 32 children (19%), were performed at our institution. Over this period, 45 liver transplantations (25%) were performed with an in situ split liver technique in 44 patients: 17 (39%) were adults and 27 (61%) children. All of the adult split liver recipients were transplanted with an extended right graft (ERG; segments I + IV-VIII), while pediatric recipients received in 23 cases a left lateral segment (LLS; segments II-III) and in 4 cases an ERG from a pediatric donor. The 45 split liver grafts (21 ERGs and 24 LLSs) were generated from 35 donors. In 10 cases we used both grafts generated with an in situ split procedure to transplant our patients, while in 25 cases the procurement procedure was performed in collaboration with other transplant centers. RESULTS: After a median follow-up of 9 months (range, 1-27 months), the overall patient survival rate was 88% for adult patients and 82% for pediatric patients. Graft survivals were 88% and 79%, respectively. Two adult patients (12%) died from sepsis in the early postoperative period. Five children (18%) died after their transplantations. Only one pediatric recipient (2%) of primary SLT underwent retransplantation. Vascular complications were absent in adult recipients, whereas 4 arterial (14%) and 4 venous (14%) complications developed in the pediatric population. The incidence of biliary complications was 23% in adult and 18% in pediatric recipients. CONCLUSIONS: The use of in situ SLT for adult and pediatric populations allowed us to expand the cadaveric donor pool, significantly eliminating pediatric waiting list mortality without penalizing the adult population.

Adult↗
PubMed2006

Corticosteroid-free immunosuppression in pediatric liver transplantation: safety and efficacy after a short-term follow-up.

BACKGROUND: We report our results with the use of corticosteroid-free immunosuppression after pediatric liver transplantation, evaluating the efficiency and safety of this protocol in the early posttransplantation period. PATIENTS AND METHODS: From July 2003 to October 2005, 34 liver transplantations were performed in 32 pediatric patients (19 boys, 13 girls) at our institution. Recipient median age was 5 years (range, 0.2-14 years), and median body weight was 10 kg (range, 4-49 kg). Twenty-seven patients received a graft from in situ split liver transplantation, 5 a whole graft. Twenty-nine children (90%) received an immunosuppressive therapy based on methylprednisolone IV bolus at reperfusion (10 mg/kg) plus tacrolimus given at an initial dose of 0.08 mg/kg/d and then adjusted to obtain whole blood trough levels of 10 to 15 ng/mL during the first 3 months and 5 to 10 ng/mL after the 3rd month; basiliximab was given on postoperative days 0 and 4. Biopsy-proven acute rejection episodes were treated by methylprednisone IV boluses. RESULTS: After a median follow-up of 9 months (range, 1-27 months), the overall patient survival rate was 84% and graft survival rate was 79%. Three children (9%) died after their transplantations. Three (9%) experienced episodes of biopsy-proven acute rejection, always treated with IV steroid boluses. Mean RAI score was 4. One patient experienced PTLD that resolved with temporary reduction of immunosuppression. Cytomegalovirus infection rate was 14%. Sepsis occurred in 2 cases (6%). CONCLUSIONS: Initial results with a steroid-free immunosuppressive protocol are encouraging, with low rates of acute rejection and infectious complications as in steroid-based protocols.

Adolescent↗
PubMed2006

Prognostic factors for hyperdiploid-myeloma: effects of chromosome 13 deletions and IgH translocations.

Chromosomal hyperdiploidy is the defining genetic signature in 40-50% of myeloma (MM) patients. We characterize hyperdiploid-MM (H-MM) in terms of its clinical and prognostic features in a cohort of 220 H-MM patients entered into clinical trials. Hyperdiploid-myeloma is associated with male sex, kappa immunoglobulin subtype, symptomatic bone disease and better survival compared to nonhyperdiploid-MM (median overall survival 48 vs 35 months, log-rank P = 0.023), despite similar response to treatment. Among 108 H-MM cases with FISH studies for common genetic abnormalities, survival is negatively affected by the existence of immunoglobulin heavy chain (IgH) translocations, especially those involving unknown partners, while the presence of chromosome 13 deletion by FISH did not significantly affect survival (median overall survival 50 vs 47 months, log-rank P = 0.47). Hyperdiploid-myeloma is therefore a unique genetic subtype of MM associated with improved outcome with distinct clinical features. The existence of IgH translocations but not chromosome 13 deletion by FISH negatively impacts survival and may allow further risk stratification of this population of MM patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Ploidy status rarely changes in myeloma patients at disease progression.

Hyperdiploid and non-hyperdiploid multiple myeloma represents distinct biological entities characterized by different patterns of genetic changes. We sought to determine whether ploidy category (non-hyperdiploid versus hyperdiploid) remains stable over time from diagnosis to progression. Of the 43 patients studied (39 by flow cytometry DNA index and 4 by a FISH-based index), only five (12%) altered their ploidy status at progression. In three of these patients, the change may possibly be attributable to technical artifacts because of the low absolute change in DNA index. For those who retain their ploidy subtypes, the DNA index change minimally (3.75+/-4.87%). It would appear that the initiating genetic events underlying hyperdiploid and non-hyperdiploid MM that marks them out as distinct entities continue to dominate and persist during disease evolution and progression.

DNA, Neoplasm↗
PubMed2005

Cooperative partnerships or conflict-of-interest? A national survey of interaction between the pharmaceutical industry and medical organizations.

BACKGROUND: There is extensive and varied interaction between the pharmaceutical industry and the medical profession. Most empirical research concerns contact between individual physicians and industry, and reflects North American experience. We sought to clarify the extent and nature of relationships between the pharmaceutical industry and Australian medical organizations. METHODS: We administered questionnaires to 63 medical organizations concerned with clinical practice, continuing medical education or professional accreditation, or the political representation of medical professionals. RESULTS: Survey instruments were received from 29 organizations, giving a response rate of 46%. Seventeen of these organizations (59%) had received support from one or more pharmaceutical company in the past financial year. Support was predominantly for annual conferences, with some support for continuing medical education, research, travel and library purchases. The majority of organizations had an academic journal or newsletter, and 10 (34%) accepted revenue from pharmaceutical advertising. Twenty organizations (72%) had policies or guidelines covering their relationship with industry. Few organizations indicated that they would be unable to continue their activities without pharmaceutical industry support. CONCLUSION: These data indicate a high level of inter-action between the pharmaceutical industry and medical organizations in Australia. While most organizations have policies for guiding their relationship with industry, it is unclear whether these are effective in preventing conflicts of interest and maintaining public trust.

Australia↗
PubMed2003

Electromagnetic fields and breast cancer on Long Island: a case-control study.

The EMF and Breast Cancer on Long Island Study (EBCLIS) was a case-control study designed to evaluate the possible association between exposure to electromagnetic fields (EMFs) and breast cancer. Eligible women were participants in the population-based Long Island Breast Cancer Study Project, were under 75 years of age at enrollment, were residentially stable, and were identified between August 1, 1996, and June 20, 1997. Of those eligible, 576 cases and 585 controls participated in EBCLIS (87% and 83%, respectively). In-home data collection included various spot and 24-hour EMF measurements, ground-current magnetic field measurements, wire mapping of overhead power lines servicing the home, and an interview. Odds ratios and 95% confidence intervals were based on multivariate logistic regression analyses. All odds ratios were close to 1 and nonsignificant. For the highest quartile of 24-hour EMF measurements, the odds ratio was 0.97 (95% confidence interval (CI): 0.69, 1.37) in the bedroom and 1.09 (95% CI: 0.78, 1.51) in the most lived-in room. For the highest exposure category of ground-current measurements, the odds ratio was 1.13 (95% CI: 0.88, 1.44) in the bedroom and 1.08 (95% CI: 0.85, 1.38) in the most lived-in room. These and other EBCLIS results agree with other recent reports of no association between breast cancer and residential EMF exposures.

Adult↗
PubMed2002

Persistence of pregnant mare serum gonadotrophin in plasma of Japanese quail (Coturnix coturnix japonica).

Pregnant mare serum gonadotrophin (PMSG) is currently being used to develop a hormone regime that will stimulate reproductive development in Japanese quail (Coturnix coturnix japonica). In this study, the persistence of PMSG in quail plasma was examined after a single injection of the hormone (500 IU). Plasma concentrations of PMSG increased to a peak 12 h after injection and declined to approximately 50% of peak concentrations 24 h after injection. Pregnant mare serum gonadotrophin concentrations declined gradually thereafter and had not returned to basal levels by 96 h after injection. Cloacal diameter, and ovarian and oviducal mass, had increased significantly by 96 h after injection. The persistence of PMSG in quail plasma has implications for the use of the hormone in future regimes stimulating reproductive activity in birds.

Animals↗
PubMed2001

A crystallographic map of the transition from B-DNA to A-DNA.

The transition between B- and A-DNA was first observed nearly 50 years ago. We have now mapped this transformation through a set of single-crystal structures of the sequence d(GGCGCC)2, with various intermediates being trapped by methylating or brominating the cytosine bases. The resulting pathway progresses through 13 conformational steps, with a composite structure that pairs A-nucleotides with complementary B-nucleotides serving as a distinct transition intermediate. The details of each step in the conversion of B- to A-DNA are thus revealed at the atomic level, placing intermediates for this and other sequences in the context of a common pathway.

Base Sequence↗
PubMed2001

Identification of a chromosome 11q23.2-q24 locus for familial aortic aneurysm disease, a genetically heterogeneous disorder.

BACKGROUND: Aortic aneurysms cause significant mortality, and >20% relate to hereditary disorders. Familial aortic aneurysm (FAA) has been described in such conditions as the Marfan and Ehlers-Danlos type IV syndromes, due to defects in the fibrillin-1 and type III procollagen genes, respectively. Other gene defects that cause isolated aneurysms, however, have not thus far been described. METHODS AND RESULTS: We studied 3 families affected by FAA. No family met the diagnostic criteria for either Marfan or Ehlers-Danlos syndrome. Echocardiography defined involvement of both the thoracic and abdominal aorta. In family ANA, candidate gene analysis excluded linkage to loci associated with aneurysm formation, including fibrillin-1, fibrillin-2, and type III procollagen, and chromosome 3p24.2-p25. Genome-wide linkage analysis identified a 2.3-cM FAA locus (FAA1) on chromosome 11q23.3-q24 with a maximum multipoint logarithm of the odds score of 4.4. In family ANB, FAA was linked to fibrillin-1. In family ANF, however, FAA was not linked to any locus previously associated with aneurysm formation, including fibrillin-1 and FAA1. CONCLUSIONS: FAA disease is genetically heterogeneous. We have identified a novel FAA locus at chromosome 11q23.3-q24, a critical step toward elucidating 1 gene defect responsible for aortic dilatation. Future characterization of the FAA1 gene will enhance our ability to achieve presymptomatic diagnosis of aortic aneurysms and will define molecular mechanisms to target therapeutics.

Adolescent↗
PubMed2001

Collagen IV synthesis is restricted to the enteroendocrine pathway during multilineage differentiation of human colorectal epithelial stem cells.

The human large intestine is lined by a rapidly renewing epithelial monolayer where cell loss is precisely balanced with cell production. The continuous supply of new cells is produced by undifferentiated multipotent stem cells via a coordinated program of proliferation and differentiation yielding three epithelial lineages: absorptive, goblet and enteroendocrine. Cell-matrix interactions have been suggested to be regulators of the multilineage differentiation program of the colorectal crypt but the expression of matrix proteins or their receptors does not appear to have the subtlety expected for this task. We have developed an in vitro model system of intestinal epithelial stem cells to facilitate the direct analysis of stem cells undergoing lineage commitment and differentiation. Using this culture system, we can now directly investigate the role of cell-matrix signalling in stem-cell decisions. In this study, collagen-IV synthesis has been followed in monolayers of multipotent cells that have been induced to differentiate into absorptive, goblet and enteroendocrine cells. Our experiments demonstrate that commitment to the enteroendocrine lineage is specifically accompanied by the expression of type-IV collagen that remains enteroendocrine-cell associated. Undifferentiated cells, absorptive cells and goblet cells do not express collagen IV. To confirm that the differential lineage-specific expression of collagen IV observed in the model system was representative of the in vivo situation, collagen-IV synthesis was analysed in isolated human colorectal crypts and tissue sections using immunocytochemistry and in situ hybridisation. These studies confirmed the in vitro findings, in that implementation of the enteroendocrine differentiation program involves synthesis and accumulation of a collagen-IV matrix. Thus, human colorectal enteroendocrine cells are unique in the colorectal crypt in that they assemble a cell-associated collagen-IV-rich matrix not observed on other colorectal epithelial cells. This study provides the first evidence for differential matrix synthesis between colorectal epithelial lineages in human colorectal epithelium. The specialised pericellular environment of the enteroendocrine cells might explain some of the unique phenotypic characteristics of this cell lineage. Furthermore, these findings suggest a potential mechanism whereby individual epithelial cells could modulate their cell-matrix signalling even while rapidly migrating in heterogeneous sheets over a shared basement membrane.

Cell Differentiation↗
PubMed2001

Protective effect of short-tem calcitriol or cyclical etidronate on bone loss after cardiac or lung transplantation.

Bone loss is most rapid in the immediate period after cardiac or lung transplantation. This randomized study compared the efficacy of 6 months of treatment with either calcitriol (1,25-dihydroxyvitamin D3; 0.5 microg/day) or two cycles of etidronate plus calcium in preventing bone loss in 41 patients undergoing cardiac or lung transplantation. Patients were followed for 18 months after cessation of treatment. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). There were no significant differences between groups with respect to age or cumulative dose of prednis(ol)one or cyclosporin over the 2 years. Bone loss did not differ between groups after 6 months and, despite 6 months prophylaxis with either agent, bone loss was significant in both groups at 6 months and 12 months. However, compared with an untreated reference group, both therapies offered significant protection at 6 months and etidronate provided significant protective carryover after therapy had been discontinued. These data suggest short-term prophylaxis with calcitriol or cyclical etidronate is partially effective in reducing bone loss after cardiac or lung transplantation but treatment needs to be continued for a longer term.

Adrenal Cortex Hormones↗
PubMed2000

Pulmonary arteriovenous malformations: cerebral ischemia and neurologic manifestations.

BACKGROUND: There is an increasingly recognized association between pulmonary arteriovenous malformations (PAVM) and cerebral ischemia, frequently attributed to paradoxical embolization. PAVM occur in 20 to 30% of the hereditary hemorrhagic telangiectasia (HHT) population. OBJECTIVE: To evaluate the risk determinants for cerebral ischemia and neurologic manifestations in patients with PAVM. METHODS: A retrospective cross-sectional study was performed on consecutive patients admitted between 1988 and 1992 for treatment of PAVM. The number of PAVM, feeding artery (FA) diameters, and aneurysmal sizes were determined by pulmonary angiography. Patients were categorized as having single or multiple PAVM with an FA diameter of > or = 3 mm. History, examination, and cerebral imaging studies were used to determine the prevalence of neurologic manifestations. Patients were defined as having cerebral paradoxical embolization if there was radiologic evidence of cortical infarction. RESULTS: There were 75 cases: 26 single PAVM and 49 multiple PAVM. Cortical infarction was present in 14% of patients with single PAVM. Patients with multiple PAVM had a greater prevalence of any infarction (OR 3.2; 95% CI, 1.2 to 9.44, p = 0.030), cortical infarctions (OR 2.3; 95% CI, 0.58 to 9.2, p = 0.230), subcortical infarctions (OR 2.1; 95% CI, 0.58 to 7.95, p = 0.249), abscesses (OR 2.3; 95% CI, 0.46 to 11.94; p = 0.295), and seizures (OR 6.4, 95% CI 0.77 to 53.2, p = 0.054). Patients with multiple PAVM had markedly greater odds of having any clinical or radiologic evidence of cerebral ischemic involvement (OR 4.5; 95% CI, 1.47 to 14; p = 0.008). CONCLUSION: There is a strong association between single PAVM and various neurologic manifestations. The prevalence is greater for patients with multiple PAVM, suggesting increased predisposition for paradoxical embolization with a greater number of malformations.

Adolescent↗