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Biomedical subjects

Nadia Khan

Publications and source records attributed to Nadia Khan.

26 records · Page 2Linked to original sources

Metabolic changes after H(2) 15O-positron emission tomography with acetazolamide in a patient with moyamoya disease: case report and review of previous cases.

Perioperative ischemic complications not directly related to surgery require special attention in patients with moyamoya disease; positron emission tomography (H(2) 15O-PET) and single-photon emission computed tomography have been considered indispensable for evaluating pre- and postsurgical cerebral hemodynamics. The clinical records of 14 patients with moyamoya disease who underwent 26 extracranial-intracranial bypass operations were reviewed with special reference to perisurgical complications. One patient developed multiple postoperative ischemic infarctions and died of ischemic brain edema. The history of this patient with prolonged acidosis is analyzed, and the role of metabolic changes induced by H(2) 15O-PET with acetazolamide challenge is reviewed. Seven (77.8%) of nine patients operated on within 48 hours after H(2) 15O-PET with acetazolamide (group 1) developed metabolic acidosis, whereas only three (17.6%) of 17 patients operated on >48 hours (group 2) after the examination had intraoperative pH of <7.35. In group 1, the mean intraoperative pH was 7.328, which was significantly lower than the mean pH of 7.393 (P <.0001) in group 2. After H(2) 15O-PET with acetazolamide challenge, patients must be carefully observed concerning acidosis and volume state. We recommend at least 48 hours between examination and surgery for patients with moyamoya disease so that their conditions can stabilize. Furthermore, special care should be taken to avoid additional perioperative risk factors such as hypotension, hypocapnia, hypercapnia, and hypovolemia.

Acetazolamide↗

Long-term hypothermia in patients with severe brain edema after poor-grade subarachnoid hemorrhage: feasibility and intensive care complications.

The purpose was to evaluate the feasibility and intensive care complications of long-term hypothermia (>72 hours) in the treatment of severe brain edema after poor-grade subarachnoid hemorrhage (SAH) Hunt and Hess grade 4 to 5. Among 156 patients with SAH, 21 patients were treated with mild hypothermia (33.0 to 34.0 degrees C) combined with barbiturate coma because of severe brain edema and elevated intracranial pressure (>15 mm Hg) after early aneurysm clipping. Hypothermia was sustained for at least 24 hours after maintaining an intracranial pressure of <15 mm Hg. Nine patients were treated for <72 hours (group 1: mean 42.2 hours, range 8-66 hours) and 12 for >72 hours (group 2: mean 153.9 hours, range 78-400 hours). Three patients (14%) died during the hypothermia treatment. Good functional outcome after 3 months (Glasgow Outcome Score 4-5) was achieved in 10 patients (48%). The outcome did not differ between the two groups. All patients developed severe infections. In group 2 the mean value of minimal leukocyte counts during hypothermia was significantly lower (6.9 vs. 11.8 x 109/L; P = 0.001), and thrombocytopenia (<150 x 109/L) occurred significantly more often (48 vs. 33%; P = 0.032). In 48% of patients with poor-grade SAH, good functional outcome was achieved with combined mild hypothermia and barbiturate coma after early aneurysm surgery. This may be a feasible treatment even for longer than 72 hours. All patients developed severe infections as potentially hazardous side effects. To determine whether mild hypothermia alone is effective in the treatment of severe SAH patients, controlled studies to compare the effects of barbiturate coma alone, mild hypothermia alone, and combined barbiturate coma with hypothermia are needed.

Barbiturates↗

Emergency craniotomy for intraparenchymal massive hematoma after embolization of supratentorial arteriovenous malformations.

OBJECTIVE: We sought to evaluate the efficacy of emergency craniotomy for patients with massive hematoma secondary to endovascular embolization of supratentorial arteriovenous malformations (AVMs) and to investigate relevant factors affecting outcome. METHODS: Within the past 15 years, 605 patients with intracranial AVMs have undergone 1066 endovascular embolizations at our institution. Of these, 24 patients experienced intracranial hemorrhage during or after the procedure. Fourteen patients were demonstrated to have massive intraparenchymal hematomas and deteriorated to a comatose state (Glasgow Come Scale score < or =6). Twelve patients underwent craniotomy within 170 minutes of being diagnosed with intraparenchymal hemorrhage. The surgical procedures performed were hematoma evacuation with total (6 patients) or partial (2 patients) resection of the AVM or hematoma evacuation only (4 patients). The clinical records of these 12 patients were analyzed retrospectively. RESULTS: Nine patients recovered to a favorable condition (good recovery, four patients; moderately disabled, five patients), one patient remained in a persistent vegetative state, and two patients died. The interval between hemorrhage and emergency craniotomy was significantly shorter in patients with favorable outcomes than in those with poor clinical outcomes. Advanced age and a larger volume of intraoperative blood loss were the factors relevant to poor outcome. Temporal lobe location of the AVM and incomplete embolization tended to correlate to poor clinical outcome, but this correlation was not statistically significant. The sizes of the AVM and the hematoma did not correlate to patient outcome. There was no difference in outcomes with regard to the surgical procedure performed. CONCLUSION: In patients with massive postembolization hematomas, emergency craniotomy should be performed as soon as possible to achieve a favorable outcome. Cooperation among interventional neuroradiologists, intensive care physicians, and neurosurgeons is essential to manage AVM patients with critical postembolization hemorrhage. There is no need to persist in performing simultaneous total resection of the AVM at the emergency craniotomy.

Adult↗

Detection and localization of Cripto-1 binding in mouse mammary epithelial cells and in the mouse mammary gland using an immunoglobulin-cripto-1 fusion protein.

Human Cripto-1 (CR-1), a member of the epidermal growth factor-CFC (EGF-CFC) family of peptides, is expressed in the developing mouse mammary gland and can modulate mammary epithelial cell migration, branching morphogenesis and milk protein expression in vitro. In order to screen for a CR-1 receptor and to identify potential CR-1 target tissues, we constructed a fusion protein comprising the EGF-like domain of CR-1 and the Fc domain of a human IgG1. The recombinant CR-1 fusion protein (CR-1-Fc) was biologically active as it was able to activate the ras/raf/mitogen activated protein kinase (MAPK) pathway and to inhibit transcription of the milk protein beta-casein in NMuMG and HC-11 mouse mammary epithelial cells. By using immunocytochemistry and by an in situ enzyme-linked immunosorbent assay (ELISA), CR-1-Fc was found to specifically bind to NMuMG and HC-11 cells. Finally, immunohistochemical analysis using CR-1-Fc showed a specific localization of CR-1 binding to tissue sections from mouse mammary gland. In particular, more than 60% of the epithelial cells were intensely stained with the CR-1-Fc fusion protein in the lactating mouse mammary gland, whereas approximately 25% of the mammary epithelial cells were stained in the gland from pregnant mouse. Since expression of mouse cripto-1 (Cr-1) in the pregnant and lactating mouse mammary gland as well as its presence in milk has been previously demonstrated, these data strongly suggest that an autocrine pathway involving Cr-1 and its putative receptor is operating in the mouse mammary gland during pregnancy and lactation.

Animals↗

Cripto-1 activates nodal- and ALK4-dependent and -independent signaling pathways in mammary epithelial Cells.

Cripto-1 (CR-1), an epidermal growth factor-CFC (EGF-CFC) family member, has a demonstrated role in embryogenesis and mammary gland development and is overexpressed in several human tumors. Recently, EGF-CFC proteins were implicated as essential signaling cofactors for Nodal, a transforming growth factor beta family member whose expression has previously been defined as embryo specific. To identify a receptor for CR-1, a human brain cDNA phage display library was screened using CR-1 protein as bait. Phage inserts with identity to ALK4, a type I serine/threonine kinase receptor for Activin, were identified. CR-1 binds to cell surface ALK4 expressed on mammalian epithelial cells in fluorescence-activated cell sorter analysis, as well as by coimmunoprecipitation. Nodal is coexpressed with mouse Cr-1 in the mammary gland, and CR-1 can phosphorylate the transcription factor Smad-2 in EpH-4 mammary epithelial cells only in the presence of Nodal and ALK4. In contrast, CR-1 stimulation of mitogen-activated protein kinase and AKT in these cells is independent of Nodal and ALK4, suggesting that CR-1 may modulate different signaling pathways to mediate its different functional roles.

Activin Receptors, Type I↗

Prescription medication use among an aboriginal population accessing addiction treatment.

OBJECTIVES: Inappropriate prescription medication use can have significant consequences. Although it is suspected that Aboriginal populations within Canada have high rates of inappropriate use, published information is lacking. To better understand this issue, we studied an Aboriginal population seeking addiction treatment. METHODS: We surveyed Aboriginal clients who accessed addiction treatment in Calgary, Alberta, for prescription medication use in the previous year, frequency of medication use, and medication source(s), if inappropriately used. RESULTS: Sixty-nine percent of the clients completed the survey (n = 144). Most respondents were aged 31 to 50 years (56%), and 52% were male. Of the respondents, 48% reported that they used prescription medication inappropriately, 8% indicated appropriate use, and the rest indicated no medication use. Sedatives or relaxants were most frequently used inappropriately. Among those who inappropriately used medication, 47% used medication more than 10 times in the previous year. Common sources for those who used medication inappropriately included medication given by a friend or a stranger (52%), medication bought on the street (45%), and medication prescribed by a physician (41%). Age greater than or equal to 30 years was associated with inappropriate use. Sex, residence, and Aboriginal status were not found to be associated with inappropriate use. CONCLUSION: Inappropriate prescription medication use was a significant problem among an Aboriginal population that sought addiction treatment, and many of these individuals accessed medication from a prescribing physician.

Adolescent↗

Histological yield, complications, and technological considerations in 114 consecutive frameless stereotactic biopsy procedures aided by open intraoperative magnetic resonance imaging.

OBJECT: The authors undertook a prospective study of frameless, magnetic resonance (MR)-guided stereotactic brain biopsy procedures performed with the aid of an open MR system. Morbidity and mortality rates, frequency of postoperative hemorrhage, and histological yield were evaluated, as well as the size and location of the lesions under investigation. METHODS: During a period of 51 months (July 1996-November 2000), 114 consecutive frameless stereotactic biopsy procedures were performed with the aid of an open intraoperative MR system to investigate supratentorial lesions in 113 patients. The median volume of the lesions was 33.5 cm3, and 31.9% were deep seated. All biopsy samples comprised pathological tissue and in 111 (97.4%) of 114 a specific neuropathological diagnosis was made. A follow-up computerized tomography (CT) scan was obtained on the 1st postoperative day in all patients to evaluate postoperative complications. In two cases (1.8%), a hemorrhage was found on postoperative CT scans, with no neurological worsening of the patients. Morbidity with neurological worsening was seen in three patients; it was transient in two of them (1.8%), and in one (0.9%) subsequent emergency craniotomy was necessary because of increased edema. There were no infections, but there was one death (0.9%) CONCLUSIONS: Open intraoperative MR imaging transforms a blind conventional stereotactic procedure into a visually controlled procedure that is adaptable to dynamic anatomical changes. Routine postprocedural MR imaging makes follow-up CT scanning obsolete. This largest reported series of intraoperative MR-guided biopsy procedures shows results that are at least comparable with those in reports of larger series of conventional stereotactic biopsy sampling. The mean procedure time was 60 minutes including planning, and this method produced low morbidity and complication rates and a high histological yield.

Adolescent↗

Cancer associated retinopathy (CAR): An autoimmune-mediated paraneoplastic syndrome.

Cancer associated retinopathy (CAR) is an uncommon paraneoplastic retinopathy in which antibodies are directed against retinal antigens. Vision loss is associated with abnormal ERG findings. Few case reports and lack of controlled clinical trials make management of this syndrome especially challenging for the clinician. Herein, we describe the clinical, histopathologic and electrophysiologic features of CAR, along with a summary of previously employed management options. Cancer associated retinopathy syndrome has been recognized as a paraneoplastic disorder, most commonly associated with small cell lung cancer, in which cross-reacting autoantibodies against retinal antigen cause retinal dysfunction. Bilateral vision loss as a result of both rod and cone dysfunction in CAR may occur over a period of months, and visual symptoms may precede diagnosis of the systemic malignancy. The heterogeneity in antigens that have been identified as targets of antibody-mediated retinal damage perhaps help to explain the complexity of symptoms and the treatment challenges posed by patients with CAR.

Autoantibodies↗