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Biomedical subjects

D Mitchell

Publications and source records attributed to D Mitchell.

At least 37 records · Page 2Linked to original sources

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↗

Role conflict and confidentiality in multidisciplinary athlete support programmes.

As medical and scientific staff have increasingly been called upon to provide multidisciplinary support to elite performers the potential for ethical, professional, and legal conflicts has also increased. Although this has been recognised, little guidance has been provided to help resolve such conflicts. This paper identifies key issues in the provision of effective support and specifically addresses the roles of medical and scientific staff and their relations to coaches and performers. An athlete charter is presented that has successfully been used to resolve ethical conflicts and clarify the lines of communication, confidentiality, and responsibility within a national governing body.

Confidentiality↗

High nocturnal body temperatures and disturbed sleep in women with primary dysmenorrhea.

Primary dysmenorrhea is characterized by painful uterine cramps, near and during menstruation, that have an impact on personal life and productivity. The effect on sleep of this recurring pain has not been established. We compared sleep, nocturnal body temperatures, and hormone profiles during the menstrual cycle of 10 young women who suffered from primary dysmenorrhea, without any menstrual-associated mood disturbances, and 8 women who had normal menstrual cycles. Dysmenorrheic pain significantly decreased subjective sleep quality, sleep efficiency, and rapid eye movement (REM) sleep but not slow wave sleep (SWS), compared with pain-free phases of the menstrual cycle and compared with the controls. Even before menstruation, in the absence of pain, the women with dysmenorrhea had different sleep patterns, nocturnal body temperatures, and hormone levels compared with the controls. In the mid-follicular, mid-luteal, and menstrual phases, the dysmenorrheics had elevated morning estrogen concentrations, higher mean in-bed temperatures, and less REM sleep compared with the controls, as well as higher luteal phase prolactin levels. Both groups of women had less REM sleep when their body temperatures were high during the luteal and menstrual phases, implying that REM sleep is sensitive to elevated body temperatures. We have shown that dysmenorrhea is not only a disorder of menstruation but is manifest throughout the menstrual cycle. Furthermore, dysmenorrheic pain disturbs sleep, which may exacerbate the effect of the pain on daytime functioning.

Adult↗

Oral antibiotics reduce body temperature of healthy rabbits in a thermoneutral environment.

Nonabsorbable oral antibiotics, which reduce gut flora, decrease the daytime and night-time body temperatures of rats and mice. We investigated whether oral antibiotics would also lower the body temperature of healthy rabbits. Six rabbits received neomycin sulphate in their drinking water for ten days, and seven rabbits received a mixture of chloramphenicol and dihydroxystreptomycin for six days. Body temperatures, recorded using intra-abdominal radiotelemeters, decreased significantly, by 0.2-0.3 degree C, after three days of antibiotic treatment in both groups of rabbits. The drop in body temperature was transient; after six days body temperatures returned to pre-antibiotic levels. Antibiotic treatment had no effect on either the acrophase or the amplitude of the circadian rhythm in body temperature. Oral antibiotics therefore reduce body temperature of rabbits, without influencing the circadian rhythm in body temperature. Our results are consistent with the hypothesis that an agent arising from intestinal bacteria sustains an elevated body temperature in healthy animals.

Animals↗

A juxtacrine mechanism for neutrophil adhesion on platelets involves platelet-activating factor and a selectin-dependent activation process.

The aim of this study was to identify the molecular mechanisms involved in neutrophil adhesion to immobilized platelets with particular focus on the possible existence of a juxtacrine system for neutrophil-platelet interactions. Platelets were immobilized onto collagen (type I)-coated coverslips that were placed in a flow chamber and neutrophils were perfused across these confluent monolayers at a shear stress of 1 to 4 dynes/cm2. Neutrophils rolled, and a significant proportion (25% to 50%) adhered to platelet monolayers. P-selectin was expressed in very large quantities on the surface of platelets and mediated all of the rolling, whereas the beta2-integrin mediated firm adhesion. An activation mechanism for adhesion was necessary inasmuch as fixed neutrophils continued to roll on immobilized platelets, but did not adhere. Platelets adherent to collagen produced significant levels of platelet-activating factor (PAF). Accordingly, the firm adhesion of neutrophils to platelets was significantly inhibited by a PAF receptor antagonist (WEB 2086). Treatment of only the platelets with acetylhydrolase, which converts membrane-associated PAF to lyso-PAF, prevented 60% of the adhesion. These data suggest that PAF, on the surface of platelets, mediated a significant portion of the adhesive interaction. Addition of some selectin-binding carbohydrates (fucoidan or soluble SLEx analogs but not dextran sulfate) to the platelets caused rolling neutrophils to immediately adhere, an event that was not observed on histamine or thrombin-treated endothelium or P-selectin transfectants. These data support the view that a juxtacrine activation process exists on immobilized platelets for neutrophils. This process can be greatly enhanced on platelets and may involve a signaling mechanism through P-selectin.

Anticoagulants↗

Magnetic Field and Plasma Observations at Mars: Initial Results of the Mars Global Surveyor Mission

The magnetometer and electron reflectometer investigation (MAG/ER) on the Mars Global Surveyor spacecraft has obtained magnetic field and plasma observations throughout the near-Mars environment, from beyond the influence of Mars to just above the surface (at an altitude of approximately 100 kilometers). The solar wind interaction with Mars is in many ways similar to that at Venus and at an active comet, that is, primarily an ionospheric-atmospheric interaction. No significant planetary magnetic field of global scale has been detected to date (<2 x 10(21) Gauss-cubic centimeter), but here the discovery of multiple magnetic anomalies of small spatial scale in the crust of Mars is reported.

Journal Article↗

Mechanism of inhibition of electron transfer by amino acid replacement K362M in a proton channel of Rhodobacter sphaeroides cytochrome c oxidase.

The three-dimensional structure of cytochrome coxidase (COX) reveals two potential input proton channels connecting the redox core of the enzyme with the negatively charged (N-) aqueous phase. These are denoted as the K-channel (for the highly conserved lysine residue, K362 in Rhodobacter sphaeroides COX) and the D-channel (for the highly conserved aspartate gating the channel at the N-side, D132 in R. sphaeroides). In this paper, it is shown that the K362M mutant form of COX from R. sphaeroides, although unable to turnover with dioxygen as electron acceptor, can utilize hydrogen peroxide as an electron acceptor, with either cytochrome c or ferrocyanide as electron donors, with turnover that is close to that of the wild-type enzyme. The peroxidase activity is similar to that of the wild-type oxidase and is coupled to the generation of a membrane potential and to proton pumping. In contrast, no peroxidase activity is revealed in the D-channel mutants of COX, D132N, and E286Q. Reduction by dithionite of heme a3 in the fully oxidized oxidase is severely inhibited in the K362M mutant, but not in the D132N mutant. Apparently, mutations in the D-channel arrest COX turnover by inhibiting proton uptake associated with the proton-pumping peroxidase phase of the COX catalytic cycle. In contrast, the K-channel appears to be dispensable for the peroxidase phase of the catalytic cycle, but is required for the initial reduction of the heme-copper binuclear center in the first half of the catalytic cycle.

Amino Acid Substitution↗

Spontaneous movements during sleep in children: temporal organization and changes with age.

Developmental changes in the temporal organization of spontaneous movements during sleep was studied in children between 9 months and 11 years of age. Subjects were monitored in the home environment for the entire sleep period using actigraphy and videography. Rhythmicity in sleep-related spontaneous movements was examined using FFT and chi-square periodogram time series analyses. A dominant periodicity of 60-120 minutes was identified which was found to progressively lengthen with age. A microanalysis of the temporal structure of movements revealed a developmental decline in bout duration, but a paradoxical increase in bout frequency. These results show that motor activity becomes less robust and more fragmented as development progresses while retaining underlying rhythmic integrity, and argue for the dynamic influence of CNS maturation on the organization and expression of sleep-related spontaneous movements.

Age Factors↗