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Biomedical subjects

S Grewal

Publications and source records attributed to S Grewal.

At least 19 recordsLinked to original sources

Engraftment and survival following hematopoietic stem cell transplantation for osteopetrosis using a reduced intensity conditioning regimen.

Autosomal recessive osteopetrosis (OP) is a disease characterized by osteoclast dysfunction, leading to multisystem morbidity and death of most affected children. Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for OP, but this patient population is particularly prone to post-transplant complications and death after myeloablative conditioning. To determine the potential of achieving improved overall outcomes in these patients by decreasing pre-transplant mortality, we investigated engraftment and survival following a reduced intensity regimen including busulfan, fludarabine and total lymphoid irradiation. We report outcomes in 11 patients. All six patients who received a bone marrow or peripheral stem cell graft engrafted with >75% donor chimerism. In contrast, all five recipients of unrelated cord blood as a stem cell source for a first graft failed to demonstrate donor hematopoietic chimerism. The day 100 and 6-month mortality was low at 9%. One year after HSCT, six of 11 patients (55%) were surviving. Our data suggest that this regimen results in low peri-transplant mortality without compromising engraftment when a marrow or peripheral stem cell graft is used. An umbilical cord blood graft, however, should be used with caution for patients with OP when this or a similar reduced intensity regimen is used.

Child, Preschool↗

Epidural abscesses.

Until recently epidural abscess was considered a rare, almost theoretical, complication of central nerve block, but anecdotal reports suggest that this is no longer the case. Thus a review of the risk factors, pathogenesis, clinical features and outcome of this condition is appropriate, the primary aim being to make recommendations on best anaesthetic practice to minimize the risk of this serious complication. A search of EMBASE(c), PUBMED(c) and MEDLINE(c) databases from 1966 to September 2004 was performed using several strategies, supplemented by reference list screening. Spontaneous epidural abscess is rare, accounting for 0.2-1.2 cases per 10,000 hospital admissions per year. Estimates of the incidence after central nerve block vary from 1:1,000 to 1:100,000. Risk factors (compromised immunity, spinal column disruption, source of infection) are present in the majority of patients, whether the condition is spontaneous or associated with central nerve block. Presentation is vague, fever and back pain usually preceding neurological deficit. Diagnosis requires a high index of suspicion and modern imaging techniques. Treatment involves early surgical drainage to prevent permanent deficit and high dose parenteral antibiotics chosen with bacteriological advice. Primary prevention depends on proper use of full aseptic precautions. Epidural abscess can be a catastrophic consequence of central nerve block. Early diagnosis will minimize permanent damage, but primary prevention should be the aim. There is a need for a large survey to indicate the true incidence to better inform the risk-benefit ratio for central nerve block.

Anesthesia, Epidural↗

Mitogen-activated protein kinase (MAPK)-docking sites in MAPK kinases function as tethers that are crucial for MAPK regulation in vivo.

Docking sites on targets of mitogen-activated protein kinases (MAPKs) facilitate accurate and efficient substrate phosphorylation. MAPK/ERK kinases (MEKs, or MKKs), the upstream regulators of MAPKs, also contain N-terminal MAPK-docking sites, or 'D-sites'; however, the in vivo functions of MEK D-sites are incompletely understood. Here we found that the ability of constitutively-active human MEK1 and MEK2 to stimulate ERK phosphorylation and to induce the neoplastic transformation of NIH 3T3 cells required the integrity of the D-site. In addition, D-site mutants of otherwise wild-type MEK1/2 were unable to anchor unphosphorylated ERK2 in the cytoplasm. ERK activation, cytoplasmic anchoring and release were completely retained in 'swap' mutants in which MEK2's D-site was replaced with the D-site of MEK1 or yeast Ste7. Furthermore, these abilities were significantly retained when MEK2's D-site was moved to its C-terminus, or replaced by an unrelated MAPK-binding domain taken from the Ets-1 transcription factor. We conclude that the D-sites in MEKs are crucial for the activation of their cognate MAPKs in vivo, and that their primary function is to tether their cognate MAPKs near the MEK's kinase domain. This proximity effect is sufficient to explain the contribution that the D-site interaction makes to several biologically important signaling events.

Animals↗

Self-phlebotomy in eating disorders.

We present the case of a health-care professional with anorexia nervosa who used self-phlebotomy as a form of purge. Self-phlebotomy is most prevalent in young females employed in medical or paramedical professions. The occurrence in eating disorders of severe, unexplained, or rapidly appearing anemia; unexplained needle tracks, or past or present employment as a health-care worker should raise suspicion of self-phlebotomy.

Adult↗

Continued neurocognitive development and prevention of cardiopulmonary complications after successful BMT for I-cell disease: a long-term follow-up report.

I-cell disease or mucolipidosis type II, a rare inherited storage disorder of lysosomal enzyme localization, is characterized by dysostosis multiplex, progressive severe psychomotor retardation and death by 5-8 years from congestive heart failure and recurrent pulmonary infections. A 19-month old girl with I-cell disease received a bone marrow transplant (BMT) from an HLA-identical carrier brother. At the age of 7 years, 5 years after BMT, she has no history of respiratory infections. Her cardiac function remains normal with a shortening fraction of 47%, and she continues to gain neurodevelopmental milestones, albeit at a very slow rate. Musculoskeletal deformities have worsened despite BMT. This is the first report describing neurodevelopmental gains and prevention of cardiopulmonary complications in I-cell disease after BMT.

Bone Marrow Transplantation↗

Monocyte activation markers during cardiopulmonary bypass.

Extracorporeal support during cardiac surgery initiates an inflammatory response, causing damage to cardiac, pulmonary and renal tissue [Post Pump Syndrome (PPS)]. This is accompanied by a neutrophil leucocytosis and lymphopenia, but less is known about the role of monocytes and markers of monocyte activity. We studied 19 patients undergoing cardiac surgery, obtaining blood samples from the aortic root (AR) and from the coronary sinus ( < s) before the cardiopulmonary bypass (CPB), 1 min after release of the aortic crossclamp and 10 min after weaning from CPB (periods 1, 2 and 3). Leucocyte count, monocyte count and HLA-DR, CD15, CD11b and CD62L activation markers were measured. In samples obtained from the coronary sinus (CS), HLA-DR, expressed as a percentage of the monocyte count, decreased between periods 1, 2 and 3 by 78%, 66% and 43%, respectively. A similar change was observed in samples from the AR. Conversely, CD62L increased in the CS samples (55%, 68% and 73%), but revealed a lesser increase in the AR samples (51%, 68% and 63%). The other markers showed little change throughout the procedure. Reduced immunological competence could result from the decrease in HLA-DR counts. Increases in CD62L sensitizes monocytes to the tethering effects of endothelial integrins and might contribute to the atherosclerotic process.

Adult↗

STAT-3 activation is required for normal G-CSF-dependent proliferation and granulocytic differentiation.

To investigate the role of signal transducer and activator of transcription (STAT) proteins in granulocyte colony-stimulating factor (G-CSF)-regulated biological responses, we generated transgenic mice with a targeted mutation of their G-CSF receptor (termed d715F) that abolishes G-CSF-dependent STAT-3 activation and attenuates STAT-5 activation. Homozygous mutant mice are severely neutropenic with an accumulation of immature myeloid precursors in their bone marrow. G-CSF-induced proliferation and granulocytic differentiation of hematopoietic progenitors is severely impaired. Expression of a constitutively active form of STAT-3 in d715F progenitors nearly completely rescued these defects. Conversely, expression of a dominant-negative form of STAT-3 in wild-type progenitors results in impaired G-CSF-induced proliferation and differentiation. These data suggest that STAT-3 activation by the G-CSFR is critical for the transduction of normal proliferative signals and contributes to differentiative signals.

Animals↗

The desi ways: traditional health practices of South Asian women in Canada.

Although many South Asian immigrants have made their homes in Canada, little research has examined health behaviors in this population and fewer studies have examined the use of traditional health practices. As part of a larger study on health-seeking patterns of South Asian women living in Western Canada, an analysis was done on the use of traditional health practices. Using critical ethnographic methods, data were collected through face-to-face individual interviews (n = 50), focus group discussions (n = 12), and community meetings with a cross section of women in the South Asian community. Interviews were conducted in the language of each participant's choice. Thematic analysis was done on the transcribed interviews. Women's descriptions of traditional health practices varied and consisted of home remedies, dietary regimens, prayers, rituals, and consultation with hakims, veds, babajis, pundits, homeopaths, and jyotshis. Choosing to use traditional health practices was influenced by family members, the nature and severity of problems, beliefs and prior experiences, and the feasibility of using these practices. Traditional health practices were used on a daily or episodic basis. Women rarely used traditional health practices exclusively. Traditional health practices were used for small problems or when conventional medicines did not work. For women to meet their health needs, health care providers must be culturally sensitive and respect women's choices to use traditional health practices.

Attitude↗

Binocular vision recovery in bilateral keratoplasty.

PURPOSE: To determine the benefit of bilateral penetrating keratoplasty with regard to binocular vision. METHODS: We compared patients who underwent corneal transplantation bilaterally with patients who had successful corneal transplantation in one eye and corneal disease in the other eye. Specifically, changes in fusion, stereopsis, and binocular vision function were analyzed. A questionnaire regarding performance of daily tasks was given. RESULTS: Patients with bilateral keratoplasty performed better in all the analyzed functions. Fusion was achieved by 81.25% in the unilateral group versus 100% in the bilateral group (p = 0.15). Stereopsis was present more in the bilateral group (100% vs. 62.5%, p = 0.008) and the quantity of stereopsis was significantly better in the bilateral group (121 seconds of arc vs. 1,284 seconds of arc, p = 0.014). 88.8% of the patients subjectively improved in daily activities after second eye surgery. CONCLUSION: There are objective and subjective improvements after bilateral penetrating keratoplasty.

Activities of Daily Living↗

Cervical cancer screening in ethnocultural groups: case studies in women-centered care.

INTRODUCTION: The purpose of this study was to identify and describe critical elements of women-centered care within the context of providing cervical screening to three ethnocultural groups in Canada: Asian, South Asian and First Nations. METHODS: Data for this collective case study included open-ended interviews with purposive samples of women and key informants from each target group. Following thematic analysis, cross-case analysis was completed by comparing and contrasting issues and contextual factors influencing women's and providers' experiences. RESULTS: Cervical screening services for each group were shaped by attention to ethnocultural values, women's desire for thorough explanations, and the importance of a comfortable setting. While participation rates varied across clinics, women were positive about their experiences in obtaining cervical screening. Some women's expectations that they could address a range of health concerns with female health providers at the clinics were stymied by structural barriers that prevented staff from addressing issues beyond those directly related to cervical screening. Cross-case analysis revealed three key elements of women-centered care: respectful and culturally appropriate interactions between women and health providers, the importance of providing acceptable alternatives for women, and the need for comprehensive health services. CONCLUSION: While the establishment of Pap test clinics for ethnocultural groups has the potential to enhance participation in cervical screening, changes in health policy and the structure of health services are required for existing programs to fully implement the elements of women-centered health care identified in this study. Other models of providing health care to women in ethnocultural groups, including the use of clinics staffed by nurse practitioners, should be evaluated.

Adult↗

Genistein induces apoptosis and topoisomerase II-mediated DNA breakage in colon cancer cells.

The present study was undertaken to determine if (a) genistein induces topo II-mediated DNA damage in HT-29 colon cancer cells; and (b) if this damage is required to induce apoptosis. DNA damage was evaluated using the comet assay. Apoptosis was determined by the ethidium bromide/acridine orange staining technique. DNA breakage was noted within 1 h of treatment. Apoptosis was only induced with high concentrations (>/=60 microM) of genistein. Marked inhibition of HT-29 cell growth was evident at concentrations ranging from 60 to 150 microM. This was associated with a cell cycle arrest at G(2)/M. Similar findings were obtained in SW-620 and SW-1116 colon cancer cell lines. Aclarubicin, a topo II antagonist, reduced genistein-induced DNA breaks but did not reduce apoptosis. These data suggest that, in colon cancer cells, topo II serves as the enzymatic target of genistein. Furthermore, topo II-mediated DNA cleavage is not required for the induction of apoptosis.

Aclarubicin↗

Penetrating keratoplasty for varicella-zoster virus keratopathy.

PURPOSE: To examine and report the results of penetrating keratoplasty performed in patients with varicella-zoster virus keratopathy. METHODS: The authors retrospectively reviewed the records of 15 patients who had penetrating keratoplasty for varicella-zoster virus keratopathy from January 1989 through December 1998 on the Cornea Service at Wills Eye Hospital. RESULTS: Twelve patients had a preoperative diagnosis of herpes zoster ophthalmicus, and three, of varicella. Four eyes had lateral tarsorrhaphies performed in conjunction with penetrating keratoplasty. Three eyes had endothelial rejection episodes that responded well to treatment with topical steroids. One eye had a regraft 1 month after primary failure, and this second graft also failed because of recurrent neurotrophic keratopathy. Three eyes that had repeated penetrating keratoplasty for graft failure had clear grafts at the last examination. At an average follow-up time of 50 months, 13 (86.7%) grafts remained clear, and the best corrected visual acuity was 20/100 or better in eight (53.3%) eyes. Five patients had decreased visual acuity because of retinal diseases. CONCLUSION: Although varicella-zoster virus keratopathy is an uncommon indication for penetrating keratoplasty, effective visual rehabilitation can be achieved in these patients. Careful postoperative management, frequent lubrication, and lateral tarsorrhaphies to protect the corneal surface are major factors in the successful outcome of these cases.

Adolescent↗

Phototherapeutic keratectomy for Schnyder's crystalline corneal dystrophy.

PURPOSE: To describe the treatment of Schnyder's crystalline dystrophy (SCD) with excimer laser phototherapeutic keratectomy (PTK). METHODS: Chart review of three patients (four eyes) with SCD treated with PTK between March 1992 and December 1998. Pre- and posttreatment visual acuity, subjective glare, photophobia, manifest refraction, ultrasound pachymetry, hyperopic shift, and biomicroscopic findings were studied. Brightness acuity testing (BAT) was evaluated in two eyes. RESULTS: Four eyes were treated during the study period. The average best corrected visual acuity (BCVA) improved from 20/175 to 20/40 under bright conditions. All patients reported subjective improvement in glare and photophobia. No visually significant recurrence was observed during the follow-up period which ranged from seven months to three years. The mean spherical equivalent refractive shift was +3.28 diopter (D). One patient developed irregular astigmatism from an eccentric ablation. No vision threatening complications were observed. CONCLUSION: PTK can be effective at improving visual symptoms in patients with SCD. It can be a useful therapeutic alternative to lamellar or penetrating keratoplasty in these patients.

Cornea↗

Effect of pipecuronium and pancuronium on intracranial pressure and cardiovascular parameters in patients with supratentorial tumours.

A prospective, randomised, single blind study was conducted to evaluate and compare the intracranial pressure (ICP) and cardiovascular effects of pipecuronium (PPC) and pancuronium (PNC) in 20 patients undergoing supratentorial surgery. Patients were randomly divided into two groups. Patients in Group I (n = 10) received pancuronium (0.1 mg kg(-1)) and in Group II (n = 10) pipecuronium (0.07 mg kg(-1)) for intubation. Intracranial pressure (ICP), heart rate (HR), systolic, diastolic and mean arterial pressures (SAP, DAP, MAP), central venous pressure (CVP), nasopharyngeal temperature and arterial blood gases (ABG) were monitored at the following time periods: before induction (0 minutes); 3 minutes after thiopentone and muscle relaxant; immediately after intubation; and 4, 6, 8, 10, 20 and 30 minutes following intubation. The rise in intracranial pressure at intubation was significantly greater in group I (21.10+/-3.97 torr, 122.59%) when compared to group II patients (1.80+/-0.70 torr, 10.04%) (p<0.0 1). Cardiovascular parameters also showed a significantly greater degree of rise in group I when compared to group II patients. Heart rate increased by 29+/-6.32 beats min(-1) (33.52%) and systolic arterial pressure by 11.60+/-7.37 torr (9.47%) in group I. These parameters did not change significantly in group II. No significant alterations were observed in the other measured parameters in either of the two groups.

Adolescent↗

South Asian womens' views on the causes of breast cancer: images and explanations.

Using ethnoscience methods, interviews with 50 South Asian women living in Western Canada were conducted and analyzed to explore explanations and images of breast cancer. Embedded in the women's stories of breast cancer were distinctive, often vivid and fear-provoking images of abnormal growth. Explanations about the causes of breast cancer involved five domains of belief. The first domain was of a physical nature and centred on damage to the breast. A second domain of explanations, 'can catch it,' focused on the way this disease could be spread to others. Other women attributed breast cancer to the ways women could 'bring it upon yourself,' often linking a negative lifestyle with the development of cancer. Many women attributed cancer to being 'in the hands of others,' explaining the cancer was caused by careless words, curses or divine power. Finally, breast cancer was seen as something that could be passed down in the family. The taxonomy developed in this study provides a useful framework for understanding the explanations that might underlie women's health-seeking behaviours and for developing culturally suitable counseling strategies.

Adult↗