Subcapsular haematoma: a cause of post biopsy oliguria in renal allografts.
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Adult↗
Biomedical subjects
D Mitchell
Publications and source records attributed to D Mitchell.
Identification by 16S rRNA gene analyses of a potential novel mycobacterial species as an etiological agent of canine leproid granuloma syndrome.
PCR amplifications of the 16S rRNA gene were performed on 46 specimens obtained from 43 dogs with canine leproid granuloma syndrome to help determine its etiology. Sequence capture PCR was applied to 37 paraffin-embedded specimens from 37 dogs, and nested PCR was attempted on DNA from 9 fresh tissue specimens derived from 3 of the 37 aforementioned dogs and from an additional 6 dogs. Molecular analyses of the paraffin-embedded tissues and fresh tissue specimen analyses were performed at separate institutions. PCR products with identical sequences over a 350-bp region encompassing variable regions 2 and 3 of the 16S rRNA gene were obtained from 4 of 37 paraffin-embedded specimens and from all 9 specimens of fresh tissue originating from 12 of the 43 dogs. Identical sequences were determined from amplicons obtained from paraffin-embedded and fresh specimens from one dog. The consensus DNA sequence, amplified from paraffin-embedded tissue and represented by GenBank accession no. AF144747, shared highest nucleotide identity (99.4% over 519 bp) with mycobacterial strain IWGMT 90413 but did not correspond exactly to any EMBL or GenBank database sequence. With a probe derived from the V2 region of the novel canine sequence, reverse cross blot hybridization identified an additional four paraffin-embedded specimens containing the same novel sequence. In total, molecular methodologies identified the proposed novel mycobacterial sequence in 16 of 43 dogs with canine leproid granuloma syndrome, indicating that the species represented by this sequence may be the principal etiological agent of canine leproid granuloma syndrome.
Animals↗
Fever and motor activity in rats following day and night injections of Staphylococcus aureus cell walls.
Body temperature and physical activity are affected by both circadian cycles and pyrogens. We injected intraperitoneally 2.5 x 10(9) cell walls of the gram-positive organism Staphylococcus aureus or sterile saline at three different times in the circadian temperature and activity rhythm of Sprague-Dawley rats. Irrespective of whether pyrogen injections were made when the rats were inactive (injection at 0900), just before the nighttime rise in activity and body temperature (1630), or during high activity (2100), the peak body temperature attained and the time to reach peak temperature were indistinguishable. The fever response, as measured by the thermal-response index, was greatest, however, when body temperature and activity were in the lowest phase. Physical activity was inhibited by night but not day injection of S. aureus. Our results provide the first description of experimental fever resulting from a gram-positive pyrogen in rats and the first time an aspect of sickness behavior (suppressed motor activity) has been associated with fever resulting from simulated gram-positive bacterial infection.
Animals↗
EP(2) receptor mediates bronchodilation by PGE(2) in mice.
PGE(2) is an important cyclooxygenase product that modulates airway inflammatory and smooth muscle responses. Signal transduction is mediated by four EP receptor subtypes that cause distinct effects on cell metabolism. To determine the role of EP(2) receptor activation, we produced a mouse lacking the EP(2) receptor by targeted gene disruption. The effect of aerosolized PGE(2) and other agonists was measured using barometric plethysmography and by measurements of lung resistance in mechanically ventilated mice. Inhalation of PGE(2) inhibited methacholine responses in wild-type but not in mice lacking the EP(2) receptor [EP(2)(-/-)]. After airway constriction was induced by methacholine aerosol, PGE(2) reduced the airway constriction enhanced pause in wild-type mice (from 0.88 +/- 0.15 to 0.55 +/- 0.06) but increased it in EP(2)(-/-) mice (from 0.73 +/- 0. 08 to 1.27 +/- 0.19). Similar results were obtained in mechanically ventilated mice. These data indicate that the EP(2) receptor mediates the bronchodilation effect of PGE(2).
Administration, Inhalation↗
Absence of selective brain cooling in free-ranging zebras in their natural habitat.
We used implanted miniature data loggers to measure brain and arterial blood temperatures in three free-ranging zebras (Equus burchelli) in their natural habitat, every 5 min for 9 days. The animals experienced globe temperatures exceeding 40 C, and radiant heat load of about 1000 W m-2. Arterial blood exhibited a moderate amplitude (1.7 C) nychthemeral rhythm, with an acrophase at 19.00 h and a nadir late in the morning, at 10.00 h. Brain temperature consistently exceeded blood temperature, on average by 0.2-0.4 C, and changes in brain temperature closely tracked changes in blood temperature. There was no evidence of selective brain cooling, even during the hyperthermia which followed surgery or that associated with intense, short-duration exercise. The relationship between brain and arterial blood temperatures in free-ranging zebras was unlike that reported for horses in the laboratory. Our results do not support the view that mammals lacking a carotid rete can achieve selective brain cooling.
Animals↗
Effect on lipid, complete blood count and blood proteins of a standardized preparation for drawing blood: a randomized controlled trial.
OBJECTIVE: To compare a standardized recommended procedure for drawing blood to measure blood lipid and lipoprotein levels with the procedure commonly used in clinical practice. The aim was to see if hemoconcentration and spuriously elevated lipid levels could be avoided. DESIGN: An open randomized crossover clinical trial. SETTING: The University of Calgary. PATIENTS: Twenty-five patients with dyslipidemia. INTERVENTIONS: Blood drawing using a standardized procedure in which the patient remained seated for 5 minutes before blood collection and tourniquet use was minimized or avoided. MAIN OUTCOME MEASURES: Differences in lipid levels between the usual clinical procedure and the recommended procedure for drawing blood. RESULTS: Prior to drawing blood, laboratories have sat patients for an average of 1.4 minutes (95% CI, 0.9 to 1.9) and used a tourniquet in every patient. In the standardized procedure, patients rested for an average of 5.6 minutes (95% CI 5.0 to 6.2), and a tourniquet was used briefly in only 3 of 23 patients. There were no differences in lipid and lipoprotein values and no clinically significant difference in hemoglobin or albumin levels or in the calculation of hemoconcentration. CONCLUSIONS: Efforts to rest patients and avoid tourniquet use when drawing blood for assessment of lipid levels are unlikely to be useful.
Blood Cell Count↗
Time course for early adaptive responses to ultraviolet B light in the epidermis of SKH-1 mice.
Hairless SKH-1 mice were exposed once to UVB light (180 mJ/cm2), and mechanistically important early adaptive responses in the epidermis were evaluated by immunohistochemical and morphological methods. Interrelationships in the time course for these UVB-induced responses were examined. The number of epidermal cells with DNA strand breaks (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells) or with thymine dimers increased to maximal levels within 30 min after UVB. The number of cells with DNA strand breaks located specifically in the basal layer of the epidermis was increased substantially by 3-30 min after UVB and gradually increased further over the next 5.5 hours. DNA strand breaks specifically in the basal layer of the epidermis were increased maximally at 6 h after UVB. The number of epidermal cells with DNA strand breaks or thymine dimers decreased markedly between 12 and 36 h. Pyrimidine (6-4) pyrimidone photodimers (6-4 photoproducts) in isolated epidermal DNA were increased immediately after irradiation of the mice with UVB and decreased markedly during the next 6 h. Exposure to UVB caused a rapid 8-fold increase in the number of epidermal cells with the DNA mismatch repair protein, MSH2 (within 30-60 min), and the level of MSH2-positive cells remained elevated for at least 48 h. These observations suggest a possible role of MSH2 in the repair of UVB-induced DNA damage. The number of epidermal cells with wild-type p53 protein started to increase at 1 h after UVB exposure and reached maximal levels by 8-12 h. The number of p53-positive cells fell markedly between 24 and 48 h. The time course for UVB-induced increases in the number of p53-positive cells was paralleled very closely by the time course for UVB-induced increases in the number of cells with p21(WAF1/CIP1), increases in morphologically distinct apoptotic sunburn cells, and decreases in the number of epidermal cells with bromodeoxyuridine (BrdUrd) incorporation into DNA. Although the start of UVB-induced increases in the number of p21(WAF1/CIP1)-positive cells was similar to that for the increase in p53-positive cells and very high levels of p21(WAF1/CIP1)-positive cells were observed at 8-12 h, maximal increases in p21(WAF1/CIP1)-positive cells were not achieved until 24 h after UVB irradiation (approximately 12 h after the peak value for p53). Myeloperoxidase-positive epidermal cells started to increase by 30 min after UVB exposure, and maximal numbers of myeloperoxidase-positive epidermal cells were observed at 2 h after UVB (18-fold higher than in nonirradiated control mice). An increased level of epidermal peroxidase enzyme activity in the epidermis was also observed from 1 to 24 h after exposure of the mice to UVB. Although neutrophil infiltration into the epidermis was not seen after exposure to UVB, neutrophil infiltration into the dermis (inflammatory response) was observed from 4 to 144 h after UVB exposure. In contrast to the marked inhibitory effect of UVB on BrdUrd incorporation into the DNA of epidermal cells observed at 8-12 h after UVB irradiation (>90% inhibition), BrdUrd incorporation into the DNA of epidermal cells was markedly increased (approximately 30-fold increase in the number of BrdUrd-positive cells) at 48 h after UVB exposure, and increases in epidermal cell layers and epidermal thickness (hyperplasia) were also observed. These later effects were associated with regeneration of the damaged epidermis.
Animals↗
Phase I study of (131)I-anti-CD45 antibody plus cyclophosphamide and total body irradiation for advanced acute leukemia and myelodysplastic syndrome.
Delivery of targeted hematopoietic irradiation using radiolabeled monoclonal antibody may improve the outcome of marrow transplantation for advanced acute leukemia by decreasing relapse without increasing toxicity. We conducted a phase I study that examined the biodistribution of (131)I-labeled anti-CD45 antibody and determined the toxicity of escalating doses of targeted radiation combined with 120 mg/kg cyclophosphamide (CY) and 12 Gy total body irradiation (TBI) followed by HLA-matched related allogeneic or autologous transplant. Forty-four patients with advanced acute leukemia or myelodysplasia received a biodistribution dose of 0.5 mg/kg (131)I-BC8 (murine anti-CD45) antibody. The mean +/- SEM estimated radiation absorbed dose (centigray per millicurie of (131)I) delivered to bone marrow and spleen was 6.5 +/- 0.5 and 13.5 +/- 1.3, respectively, with liver, lung, kidney, and total body receiving lower amounts of 2.8 +/- 0.2, 1.8 +/- 0.1, 0.6 +/- 0.04, and 0.4 +/- 0.02, respectively. Thirty-seven patients (84%) had favorable biodistribution of antibody, with a higher estimated radiation absorbed dose to marrow and spleen than to normal organs. Thirty-four patients received a therapeutic dose of (131)I-antibody labeled with 76 to 612 mCi (131)I to deliver estimated radiation absorbed doses to liver (normal organ receiving the highest dose) of 3.5 Gy (level 1) to 12.25 Gy (level 6) in addition to CY and TBI. The maximum tolerated dose was level 5 (delivering 10.5 Gy to liver), with grade III/IV mucositis in 2 of 2 patients treated at level 6. Of 25 treated patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS), 7 survive disease-free 15 to 89 months (median, 65 months) posttransplant. Of 9 treated patients with acute lymphoblastic leukemia (ALL), 3 survive disease-free 19, 54, and 66 months posttransplant. We conclude that (131)I-anti-CD45 antibody can safely deliver substantial supplemental doses of radiation to bone marrow (approximately 24 Gy) and spleen (approximately 50 Gy) when combined with conventional CY/TBI.
Acute Disease↗
Global distribution of crustal magnetization discovered by the mars global surveyor MAG/ER experiment
Vector magnetic field observations of the martian crust were acquired by the Mars Global Surveyor (MGS) magnetic field experiment/electron reflectometer (MAG/ER) during the aerobraking and science phasing orbits, at altitudes between approximately 100 and 200 kilometers. Magnetic field sources of multiple scales, strength, and geometry were observed. There is a correlation between the location of the sources and the ancient cratered terrain of the martian highlands. The absence of crustal magnetism near large impact basins such as Hellas and Argyre implies cessation of internal dynamo action during the early Naochian epoch ( approximately 4 billion years ago). Sources with equivalent magnetic moments as large as 1.3 x 10(17) ampere-meter2 in the Terra Sirenum region contribute to the development of an asymmetrical, time-variable obstacle to solar wind flow around Mars.
Journal Article↗
Non-thermal signals govern selective brain cooling in pigs.
We used implanted miniature data loggers and fine thermistors to measure arterial blood and brain temperatures in four female pigs, to a resolution of 0.04 degree C, every 5 min, for 4 weeks. Within that period, pigs were exposed on different days, and in random order, to a cold (5 degrees C) or hot (38 degrees C) environment. In the thermoneutral environment of the pigs' home pens, brain temperature was usually lower than blood temperature. Such selective brain cooling was absent for 2 days after surgery, during handling and transport stress, and on waking. The magnitude of selective brain cooling was greatest when pigs were sleeping and body temperatures were low, and was smallest, or even absent, during hyperthermia and natural fever. Our results showed that selective brain cooling was present in pigs, but there was no clear relationship between blood temperature and the magnitude of selective brain cooling. Instead, the degree of selective brain cooling in pigs was governed by non-thermal factors, especially those associated with high sympathetic nervous system activity. Our results further support the concept that selective brain cooling does not serve to protect the brain from thermal damage during heat stress.
Animals↗
Evaluation of miniature data loggers for body temperature measurement during sporting activities.
We recorded body temperatures in four runners, two squash players and one swimmer at 1-min intervals using miniature data loggers. These single-channel loggers are small and light (25 g), and were easily carried by the athletes during their sporting activities. Wide-range loggers (-37 degrees C to +46 degrees C), which had a temperature resolution of 0.4 degrees C, were used to measure thigh skin temperature. Auditory canal temperature and rectal temperature were measured with narrow-range loggers (+34 degrees C to + 46 degrees C) which had a considerably higher resolution (0.04 degrees C). With the aid of visual analogue scales subjects reported that the thermometric equipment caused very little discomfort or impairment of exercise performance. Loggers connected to uncoated bead thermistors (used for skin and auditory canal temperatures) had a thermal time constant of 0.4 s, and that of the coated thermistors (rectal probes) was 6 s. We were able to waterproof the equipment and measure rectal temperature in a swimmer. Hot (35 degrees C) or cold (5 degrees C) ambient temperatures had an insignificant effect on the intrinsic accuracy of the data loggers, even when used without recalibration at those temperatures. We believe that miniature temperature loggers are convenient and accurate thermometers for use during sporting activities and may provide new insights into thermoregulation during exercise.
Adult↗
Brain, abdominal and arterial blood temperatures of free-ranging eland in their natural habitat.
Using implanted miniature data loggers we measured brain, arterial blood and abdominal temperatures at 5-min intervals in two free-ranging eland (Tragelaphus oryx) in their natural habitat. The animals were subjected to a nychthemeral range of globe temperature which exceeded 40 degrees C. Arterial blood exhibited a moderate amplitude (2.3 degrees C) nychthemeral rhythm, with a temperature peak at 1600-1800 hours, and a trough in the early morning at 0600-0800 hours. Mean abdominal temperature was 0.2-0.3 degrees C lower than the corresponding blood temperature, and had a peak-to-trough amplitude of 2.6 degrees C. Brain temperature closely paralleled changes in blood temperature but usually exceeded blood temperature by about 0.5 degrees C. Sporadic episodes of selective brain cooling occurred in one animal, but the duration and magnitude of such cooling was small (less than 0.4 degrees C), and took place only well above the mode of blood temperature. Our results do not support the concept that eland routinely employ adaptive heterothermy and selective brain cooling to survive in their natural environment.
Abdomen↗
Inhaled corticosteroids for asthma: are ED visits a missed opportunity for prevention?
Inhaled corticosteroids are effective but underused. This study evaluated the outpatient management of emergency department (ED) patients presenting with acute asthma and the relation of inhaled corticosteroid use to the patient's primary care provider (PCP) status. ED patients were interviewed by the hospital's asthma education program staff about their asthma. Overall, 85% (101 of 119) of asthmatics reported having a PCP. Although patients with a PCP and patients without a PCP both were using inhaled beta-agonists (93% v 89%, respectively; P = .54), patients without a PCP were less likely to be using inhaled corticosteroids (49% v 11%, P = .003). Controlling for age, acute asthma severity, and asthma hospitalizations during the past year, PCP status remained a significant predictor of inhaled corticosteroid use (odds ratio = 5.6; 95% confidence interval 1.1 to 27). Even among ED patients with a PCP, inhaled corticosteroids appear to be underused. ED asthma visits present an opportunity to initiate preventive measures such as inhaled corticosteroid use.
Acute Disease↗
Positive predictive value of the Breast Imaging Reporting and Data System.
BACKGROUND: The American College of Radiology has established guidelines for outcomes monitoring known as the Breast Imaging Reporting and Data System (BIRADS). These recommendations include calculation of positive predictive values (PPV) and tracking of both benign and malignant histology. We collected this data for 688 radiographically guided biopsies and organized it according to the BIRADS assessment categories. The objective was to evaluate the contribution of the BIRAD System when used to stratify PPV, histology, and biopsy modality data according to the overall assessment rating. STUDY DESIGN: This study included data from 688 image-guided biopsies. Mammographic studies were either assigned a BIRADS rating at the time of examination or, if the image was taken before our use of BIRADS, examined retrospectively and rated. In these retrospective cases, the histologic outcomes of the biopsy remained unknown to the radiologist until ratings were assigned. Positive predictive value was calculated for each BIRADS category. RESULTS: The overall PPV for the sample was 0.23. The PPVs increased with increasing level of suspicion as follows: category 1 (0.0), category 2 (0.04), category 3 (0.03), category 4 (0.23), category 5 (0.92). Category 1 lesions represented 0.1% of the biopsies; category 2, 3.6%; category 3, 46.8%; category 4, 34.0%; and category 5, 15.4%. The most common histologic diagnoses of benign lesions biopsied were fibroadenoma and fibrocystic changes-proliferative and nonproliferative. The most common histologic diagnoses of malignant lesions biopsied were infiltrating ductal carcinoma and ductal carcinoma in situ. Utilization rates of the biopsy techniques varied by BIRADS category. CONCLUSIONS: Our study revealed that BIRADS does improve the quality of the risk assessment information by making the PPV more specific to a patient's mammogram rather than simply related to an overall PPV. Our histology analysis showed category 3 and category 4 benign biopsies were predominantly because of fibrocystic changes. Category 5 lesions were predominantly invasive ductal carcinoma. Analysis of biopsy modalities indicated the preferred method for management of radiographically detected lesions evolved from stereotactic core biopsy to directional, vacuum-assisted biopsy over the course of the study.
Biopsy, Needle↗
Pharyngeal pouch endoscopic stapling--are post-operative barium swallow radiographs of any value?
Posterior pharyngeal pouch endoscopic stapling has gained increasing popularity among otolaryngologists especially in elderly patients. Post-operative barium swallow appearances can create confusion with the appearance of persistent pouches. We describe our experience in 10 patients, three of whom had external excision with cricopharyngeal myotomy and the remaining seven had endoscopic stapling approach. All three patients who had external excision showed no residual pouch whereas all seven patients who had endoscopic techniques performed showed some residual pouch. We were unsuccessful in our attempt to correlate post-operative symptoms with radiological appearance. Attempts by other radiologists at identifying pre- and post-operative barium swallow radiographs in patients who had endoscopic stapling of pharyngeal pouch were unsuccessful. We conclude that post-operative barium swallow radiography plays no role in determining the success of endoscopic stapling of pharyngeal pouch.
Aged↗
Early allogeneic transplantation for refractory or relapsed acute leukaemia following remission induction with FLAG.
The prognosis for patients with secondary AML, primary resistant AML or ALL and early (<12 months) relapse of acute leukaemia remains extremely poor with conventional chemotherapy. As part of a strategy to improve the outcome for these patients we have treated 22 consecutive patients (18 AML, four ALL, median age 35 years) with either primary resistant disease (n=3), early relapsed leukaemia (n= 12) or secondary AML (n= 7, four RAEBt, two antecedant ALL and one antecedant Hodgkin's disease) with 'FLAG' induction chemotherapy with the aim of proceeding to early allogeneic transplantation either from sibling or unrelated donors. Eighteen patients achieved CR after one course of FLAG, including five patients who had documented p-glycoprotein-induced multidrug resistance and 10 patients with adverse cytogenetic abnormalities. Eight patients were consolidated with a second course of FLAG prior to transplantation and so far 16 patients have undergone allogeneic transplantation, 10 from unrelated donors and six from sibling donors (one mismatched). By the time of transplant three patients had progressed and were in early relapse and all have relapsed post BMT. Of the remaining 13 patients transplanted in remission, nine remain in CCR at a range of 4-26 months, three have died of transplant-related complications (18%) and one patient has relapsed. We conclude that the use of FLAG induction therapy followed by early allogeneic transplantation from either a sibling or unrelated donor can be an effective strategy for the treatment of this difficult group of young patients with poor risk acute leukaemia and appears to be associated with a low procedure-related risk.
Adolescent↗
Central nervous system sarcoidosis--diagnosis and management.
A series of 68 patients with neurosarcoidosis is reported, with particular emphasis on clinical aspects, diagnosis and treatment. A classification system based on clinical diagnostic probability is proposed, consisting of probable and definite disease, the latter being dependent on finding sarcoid granulomas on nervous system histology, which was obtained in 12 patients (18%). The role of investigations, including magnetic resonance imaging (MRI), chest radiography, Kveim skin test, Gallium 67 isotope scanning and cerebrospinal fluid (CSF) studies, is considered. Sixty-two percent of patients presented with nervous system disease, most commonly affecting the optic nerve and chiasm. Other common presentations included cranial nerve palsies, spinal cord and brainstem manifestations. Investigations yielding most diagnostic information included the Kveim test (41/48, 85% positive), raised CSF protein and/or cells (50/62, 81%) and gallium 67 scan (14/31, 45%). Eleven out of 29 patients (38%) patients showed meningeal enhancement on MRI scanning and 43% of scans demonstrated multiple white-matter lesions. Mean follow-up for the group was 4.6 years. Forty-seven patients were seen for > 18 months, and over half of these patients progressed despite corticosteroid and other immunosuppressive therapies. The benefit of a large patient database prospectively studied, with extended follow-up is discussed in order to learn more about prognosis and advance therapy in neurosarcoidosis.
Adrenal Cortex Hormones↗
Blastic natural killer cell.
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Acute Disease↗