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Biomedical subjects

K Butler

Publications and source records attributed to K Butler.

At least 55 records · Page 3Linked to original sources

Xenopus eomesodermin is expressed in neural differentiation.

Our initial description of the Xenopus gene Eomesodermin (Eomes) indicated that it is expressed largely if not entirely in mesodermal cells of gastrula stage embryos. A more detailed examination, described here, shows that it continues to be expressed in the most anterior (future head) mesoderm during gastrula and neurula stages. However, during tail-bud stages, Eomes expression is re-born in the most anterior part of the brain, becoming strongly transcribed in the olfactory region of the telencephalon. This later Eomes expression marks a very localized region of the forebrain distinct from that of Otx-2, anterior to that of En-1 and overlapping that of Sox-3.

Animals↗

Multidisciplinary weight management in locoregional breast cancer: results of a phase II study.

Sixty-one women with newly diagnosed locoregional breast cancer (T1-3, N0-1, M0) having an initial Body Mass Index (BMI) between 20 and 35 kg/m2 who were receiving standard adjuvant treatment (chemotherapy, tamoxifen, and/or radiation) were asked to avoid weight gain (if initial BMI < or = 25 kg/m2) or to lose up to 10 kg (if initial BMI 25-35 kg/m2) over one year. Women participated in twenty group sessions (10 weekly, 10 monthly) which involved a psychological supportive-expressive group intervention supplemented by individual weight goals, and nutrition and exercise programs. Fifty-five non-censored women (5 developed recurrence, 1 died of a subarachnoid hemorrhage) lost a mean of 0.53 +/- 3.72 kg. Weight loss was greatest in initially overweight women (BMI > or = 25 kg/m2) who lost 1.63 +/- 4.11 kg (p = 0.01 compared to normal weight women) and in those not receiving chemotherapy who lost 2.15 +/- 2.83 kg (p = 0.0004 compared to those receiving chemotherapy). 70.9% met predefined criteria for success. Aerobic exercise increased significantly during the intervention (p = 0.00005) and was the strongest predictor of success (OR 1.73 for each additional 30 minutes of exercise weekly, p = 0.003). Changes in caloric intake were not significant, but fat intake decreased and carbohydrate and fibre intake increased significantly during the intervention. Eating behavior and psychological status improved significantly. Thus, this multidisciplinary weight management intervention successfully prevented weight gain in women with newly diagnosed locoregional breast cancer, and helped overweight women lose weight.

Adult↗

Coverage of bone marrow transplant patients: a survey of American and Canadian institutions.

Personnel involved in supportive care of bone marrow transplant (BMT) patients include fellows (F), medical house-staff (HS), nurse practitioners (NP), physician assistants (PA), and moonlighting physicians (MP). We have obtained surveys from 108 American and Canadian transplant centers on the composition of inpatient support teams. Eighty-seven percent of institutions responding to the survey were university-based programs. Eighty-eight percent of the centers performed both allogeneic and autologous transplants, and 60% performed unrelated donor grafts. The mean number of transplants performed annually at each center was 101 (range 4-515). For daytime coverage, the percent of programs involving F, HS, NP, PA, or MP was 57, 50, 35, 25, and 0%, respectively, and for nighttime coverage, the composition was 50, 56, 7, 6, and 13%, respectively. Medical HS were incorporated into the care of BMT patients at some level in 93% of the programs. Involvement by HS included full 24-hour coverage (44%), full nighttime coverage (8%), stat coverage (18%), and code blue only coverage (21%). HS involvement was similar in small and large transplant programs. HS were more involved in university-based programs. Programs on the East Coast had more HS involvement, with 54% of the programs reporting full 24-hour coverage by HS compared with 32% of the programs in the Pacific region. Coverage of transplant patients varies throughout the country, and nonphysician providers are often used. HS are more active in university-based programs, and their role is similar in both large and small programs.

Bone Marrow Transplantation↗

Speed and efficiency in the resuscitation of blunt trauma patients with multiple injuries: the advantage of diagnostic peritoneal lavage over abdominal computerized tomography.

BACKGROUND: The difference in speed, efficiency, and safety between diagnostic peritoneal lavage (DPL) and abdominal computerized tomography in the evaluation of adult blunt trauma patients with multiple injuries was investigated. METHODS: A prospective protocol was analyzed. Adult blunt trauma patients admitted to a Level I trauma center in 1994 were examined. Registry and chart data were used. Patients admitted before the institution of the protocol (January 1-June 30, 1994) were compared with those admitted afterward (July 1-December 31, 1994). Time spent in the emergency department before definitive placement or surgical intervention was studied. RESULTS: Patients in the second period, when DPL was used more frequently, spent significantly less time in the emergency department and radiology. No missed injuries were identified in either group. The percentages of nontherapeutic laparotomies were similar between the two groups. Cost was significantly lower in the group that underwent DPL. CONCLUSION: Patients with severe head injury, open fractures, or any evidence of hemodynamic instability are better served by DPL as the primary diagnostic modality. Its sensitivity and specificity are equivalent to those of computerized tomography; this facilitates evaluation and allows for simultaneous procedures and quicker initiation of definitive treatment.

Abdominal Injuries↗

A group therapy approach to facilitate integration of risk information for women at risk for breast cancer.

OBJECTIVE: To describe and illustrate elements of a group counselling approach designed to enhance the communication of risk information on breast cancer (BC) to women with a family history of this disease. Breast cancer is a leading cause of female cancer death. The most important risk factor for BC is a positive family history in at least 1 first-degree relative, and approximately one-third of women with BC have a family history of the disease. Recent evidence suggests that there is a significant psychological impact associated with having a family history of BC, and this may influence the psychological adjustment and response to being counselled for personal risk. New counselling approaches are required. METHOD: This paper describes a group therapy approach that incorporates principles of supportive-expressive therapy designed to address the emotional impact of being at risk for BC and to promote accuracy of perceived risk. The key elements of the intervention are described along with clinical illustrations from groups that are part of an ongoing study to develop and standardize the group therapy. CONCLUSION: Qualitative data from the groups suggest that this model of therapy is both feasible and effective.

Adaptation, Psychological↗

Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a Dublin paediatric hospital.

Klebsiella pneumoniae resistant to third-generation cephalosporins and gentamicin was isolated from two patients in a paediatric intensive care unit within a two-week period. The double-disc diffusion test indicated the presence of an extended-spectrum beta-lactamase (ESBL). The unit was closed to admissions, and stringent infection control procedures were implemented. Environmental screening and screening of staff and patients on the unit were commenced. Two weeks later, K. pneumoniae with an identical antibiogram was isolated from the urine of a patient in a different ward. Blood-culture isolates possessed the K16 antigen, while the urine isolate was non-typeable. The isolates were shown to be similar when banding patterns of XbaI chromosomal DNA digests were compared. The resistance to the extended-spectrum cephalosporins was shown to be transferable in association with a large plasmid > 98 mDa. Resistance to gentamicin always co-transferred with beta-lactamase resistance and appeared to be encoded by the same plasmid.

Child, Preschool↗

Interhospital versus direct scene transfer of major trauma patients in a rural trauma system.

The purpose of organized trauma systems is to ensure the expeditious transfer of seriously injured patients to the facility best equipped to care for their injuries. Patients are referred to our trauma center, either by ambulance or helicopter, directly from the scene or through interhospital transfer. We examined the difference in outcome between those patients sent directly to the trauma center versus those seen at other hospitals and subsequently referred to the trauma center. Our hypothesis was that a delay at the referring hospital is detrimental to patient outcome. Adult trauma patients with Injury Severity Scores > 15, treated over 16 months from July 1, 1994, to October 31, 1995, were studied. Patients who survived 24 hours experienced significantly shorter intensive care unit (14 vs 10 days; P < 0.05) and hospital (21 vs 16 days; P < 0.05) lengths of stay when taken directly to the trauma center. In addition, there were significantly fewer deaths in patients with a probability of survival > 0.5 and a slightly lower overall mortality in those patients who survived at least 1 day. This study demonstrates that patients with major trauma taken directly to the trauma center had shorter hospital and intensive care unit stays and lower mortality. The study supports the paradigm that, when possible, major trauma patients should be sent to trauma centers directly from the injury scene.

Adult↗

Blunt splenic trauma: characteristics of patients requiring urgent laparotomy.

In victims of blunt abdominal trauma, the spleen is the most common organ damaged, it is the most likely source of serious injury, and is associated with significant morbidity and mortality. The participants in this study were emergency department (ED) patients with splenic trauma determined via imaging study, surgical exploration, or autopsy. Patients were located using both the institution's trauma registry and discharge diagnoses (ICD-9 codes) involving splenic injury resulting from blunt trauma. Medical records including pre-hospital, ED, and hospital information were reviewed. Chi Square and Fisher's exact test were used for statistical analysis where appropriate, with a P value of less than 0.05 considered significant. Fifty-five patients (60% male) were analyzed with a mean age of 31 years (range, 1 to 78 years). Sixteen (30%) patients (mean age 44 years) were managed operatively, with 14 patients receiving only a diagnostic peritoneal lavage. All 38 patients (70%, mean age 26 years) who received nonoperative management were diagnosed by computed tomography. The motor vehicle crash represented the most frequent mechanism of injury in both groups; the nonoperative group, however, experienced other injury mechanisms more frequently. Clinical variables suggestive of the need for urgent surgical intervention (from ED to the surgical suite) include hypotension (systolic blood pressure less than 90 mm/Hg) in the pre-hospital setting or ED; tachycardia (heart rate greater than 100 beats/min) in the ED; abnormal hematocrit (less than 30) or coagulopathy (prothrombin time greater than 14 seconds) in the ED; multiple injuries; or blood transfusion in the ED. Complaints of pain resulting from traumatic injury and abdominal examination findings did not identify patients requiring urgent operative management. Hemodynamic instability, evidence of multiple injuries, abnormal laboratory parameters, and the requirement for blood transfusion in the ED identifies a patient population likely to require operative therapy of their splenic injury. Emergency physicians should consider early surgical consultation or urgent transfer to the regional trauma center in patients with these characteristics.

Adolescent↗

Development of the Nimbus/Pittsburgh axial flow left ventricular assist system.

Nimbus, Inc. and the University of Pittsburgh's School of Medicine have been collaborators developing rotary blood pump technology since 1992. Currently, a major focus is on an implantable left ventricular assist system (LVAS) that utilizes an electric powered axial flow blood pump. In addition to the blood pump, a major development item is the electronic controller and the control algorithm for modulating the pump speed in response to varying physiologic demands. Methods being used in developing the axial flow LVAS include the use of computational fluid dynamic modeling of the interior flow field of the pump, flow visualization of the flow field using laser based imaging, and computer simulation of blood pump-physiological interactions as well as an extensive in vivo test program. Results to date include successful in vivo tests of blood pumps with nonlubricated bearings and demonstrations of auto speed control using electrical current as the observable parameter.

Algorithms↗

Activation of the human histamine H2 receptor is linked to cell proliferation and c-fos gene transcription.

We examined whether histamine could regulate cell proliferation and expression of the early response gene c-fos in HEK-293 cells stably transfected with the human H2 receptor (HEK-H2). Histamine stimulated [3H]thymidine incorporation [50% effective concentration (EC50) = 3.6 x 10(-6) M] in HEK-H2 cells in a cimetidine-sensitive manner and increased c-fos mRNA in a time-dependent fashion, reaching maximal induction after 30 min. Histamine induced luciferase activity in HEK-H2 cells transiently transfected with a construct containing the luciferase reporter gene (Luc) coupled to the serum response element (SRE) of the c-fos gene promoter (EC50 = 1.5 x 10(-6) M) or a plasmid containing the SRE core fragment (bases -320 to -298). The protein kinase C (PKC) inhibitor staurosporine and long-term pretreatment of HEK cells with phorbol ester inhibited the effect of histamine on PKC activation, SRE-Luc activity, and [3H]thymidine incorporation. We have demonstrated that activation of the human H2 receptor can lead to induction of c-fos gene transcription and cell proliferation through a PKC-dependent mechanism.

Cell Division↗

Coagulopathy in severe closed head injury: is empiric therapy warranted?

Closed head injuries account for a significant portion of the morbidity and mortality following blunt trauma. Severe closed head injuries can be complicated by the development of a coagulopathy that may worsen blood loss and delay invasive neurosurgical procedures. Awaiting the results of coagulation studies prior to initiating treatment of such a coagulopathy introduces an inherent delay that may allow worsening of the coagulation disturbance and negatively influence outcome. This study was undertaken to see if a subgroup of patients with severe closed head injuries had a high probability of developing a coagulopathy and would warrant empiric treatment with fresh frozen plasma. The records of adult patients admitted to our trauma center with a Glasgow coma score (GCS) of < or = 8 and an extracranial abbreviated injury score of < or = 2 during a 9-month period were reviewed. Patients with penetrating trauma or whose altered level of consciousness was due to sedation or shock were excluded. The presence of coagulation abnormalities was determined according to prothrombin time and partial thromboplastin time obtained on admission. The time to invasive neurosurgical procedures for both coagulopathic and noncoagulopathic patients was determined as well as the mean number of hospital days, intensive care unit days, and the mortality for each group. Eighty-one per cent of the patients with a GCS < or = 6 were coagulopathic on admission, and all patients with a GCS of 3 or 4 were coagulopathic. In contrast, no patient with a score of 7 or 8 was coagulopathic. The coagulopathic patients tended to have a higher mortality than the noncoagulopathic patients (53 versus 22%) as well as longer intensive care unit and hospital stays. The mean time to neurosurgical intervention for the coagulopathic group was 226.0 +/- 190.9 minutes versus 84.8 +/- 38.4 minutes for the noncoagulopathic patients. We conclude that patients with closed head injuries who present with a GCS of 6 or less are candidates for empiric treatment for coagulopathy. Such treatment will negate the delay of awaiting coagulation studies. Whether or not such therapy shortens the interval between admission and neurosurgical procedures or alters outcome will require prospective study.

Adult↗

A comparison of fibrous tissue formation surrounding intraperitoneal and subcutaneous implantation of ALCAP, HA, and TCP ceramic devices.

It is well demonstrated in the literature that ceramic drug delivery systems are highly compatible and non-immunogenic. Recent studies in our laboratory have documented the need of an experiment comparing foreign body reactions of several different types of ceramics used for implantation and/or drug delivery. The specific objective of this study was to compare the subcutaneous (s.c.) and intraperitoneal (i.p.) foreign body reactions and biocompatibility of the following implantable materials presently used in orthopedics: ALCAP (aluminum calcium phosphate), HA (hydroxyapatite), and TCP (tricalcium phosphate). The rats were divided into four groups: Group I consisted of 10 rats implanted with ALCAP i.p. and s.c., Group II (n = 10) animals were implanted i.p. and s.c. with HA, Group III consisted of 10 rats implanted i.p. and s.c. with TCP, and Group IV consisted of 10 control animals that were housed under the same environmental conditions as the three experimental groups. At 90 days post-implantation, rats in all four groups were euthanized. The microscopic evaluation of the fibrous tissue surrounding i.p. and s.c. implants revealed the following: 1) all of the ceramic devices had varying degrees of fibrous capsule formation at the time of sacrifice, 2) the thickness of the fibrous tissue capsule was dependent on the type of ceramic used, and 3) the thickness of the fibrous tissue capsules around the subcutaneous devices differed remarkably from implants placed intraperitoneally. The data from this study indicates that capsule formation is dependent upon factors such as ceramic composition and surgical implantation site.

Aluminum Compounds↗

One year histopathological evaluation of fibrous tissue surrounding TCPL implants using adult rats as a model.

Fibrous tissue formation is often used as a screening method to determine the biocompatibility of orthopaedic and dental implanted material. In this investigation, porous implants of tricalcium phosphate-lysine delivery devices were implanted intraperitoneally (IP) using adult male rats as a model. The fibrous tissue surrounding the implant was studied histologically to determine the infiltration of inflammatory cells and other healing components. Fibrous capsular tissues were carefully dissected away from the capsule noting the tissue closest to the implanted material. Evaluation of the sections (5um, H&E) collected from various areas of the implants (n = 5 per group) revealed that: (1) The use of TCPL implants resulted in the formation of three distinct cell layers of fibrous tissue. (2) The fibrous tissue thickness was found to be directly proportional to the duration of the implant. (3) The infiltration of macrophages, polymorphonuclear leukocytes, and fibroblasts were present in all phases studied. (4) Ordered collagen was observed only at the end of the 6, 9, and 12 month phases. (5) Remarkable progression of vascularity was present in the second and third layers of the fibrous tissue. In conclusion, these observations confirm our previous finding using different bioceramic material.

Animals↗

Stress-induced cardioadaptation reveals a code linking hormone receptors and spatial redistribution of PKC isoforms.

Extracellular agents, including growth factors, cytokines and hormones, transmit their information into cells utilizing a balanced mosaic of intracellular phosphatases and kinases. How do these agonists select the correct substrates and modify them in order to produce defined physiological responses? Our studies have centered on the mechanisms of stress-induced cardioprotection (preconditioning) against postischemic dysfunction. In several species, the ischemia-reperfusion resistant phenotype appears to be induced by metabotropic-receptor pathways linked to PKC. Our results on the isolated rat heart show that each protective stimulus involves a characteristic mosaic of PKC isoforms, translocating into distinct cellular compartments. The distinct receptor-stimulated PKC isoform profile engaged by each extracellular metabotropic agent could allow the heart several overlapping modes of phenotypic adaptation to ischemia.

Animals↗