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Biomedical subjects

M Brown

Publications and source records attributed to M Brown.

At least 91 records · Page 5Linked to original sources
PubMed2001

Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia.

The gene that encodes nuclear factor kappaB (NF-kappaB) essential modulator (or NEMO, also known as IKKgamma) is required for activation of the transcription factor NF-kappaB. We describe mutations in the putative zinc-finger domain of NEMO that result in an X-linked primary immunodeficiency characterized by hyper-IgM syndrome and hypohydrotic ectodermal dysplasia (XHM-ED). These mutations prevent CD40 ligand (CD40L)-mediated degradation of inhibitor of NF-kappaB alpha (IkappaB-alpha) and account for the following observations: B cells from XHM-ED patients are unable to undergo immunoglobulin class-switch recombination and antigen-presenting cells (APCs) are unable to synthesize the NF-kappaB-regulated cytokines interleukin 12 (IL-12) or tumor necrosis factor alpha (TNF-alpha) when stimulated with CD40L. Nevertheless, innate immunity is preserved in XHM-ED patients because APCs retain the capacity to respond to stimulation by lipopolysaccharide or Staphylococcus aureus Cowan's antigen (SAC). Overall, the phenotype observed in XHM-ED patients shows that the putative zinc-finger domain of NEMO has a regulatory function and demonstrates the definite requirement of CD40-mediated NF-kappaB activation for B cell immunoglobulin class-switching.

Adolescent↗
PubMed2001

Dendritic cells signal T cells in the absence of exogenous antigen.

Interactions with self-major histocompatibility complex molecules on dendritic cells (DCs) are important for the survival of mature CD4+ T cells. We have followed the DC-mediated signal from the T cell surface to the nucleus and identified a pattern of activation that correlates with increased in vitro survival. This response is induced exclusively by DCs and is likely associated with a modulation of the T cell activation threshold. We have also found that DC-mediated activation results in antigen-independent cytokine gene expression, which points to a new role for DCs in shaping the cytokine milieu. Such antigen-independent activation of T cells may play a role in protective immunity, but may also induce and perpetuate autoimmune states such as multiple sclerosis.

Antigens↗
PubMed2001

Sibutramine reduces feeding, body fat and improves insulin resistance in dietary-obese male Wistar rats independently of hypothalamic neuropeptide Y.

We studied the effects of the novel noradrenaline and serotonin (5-HT) reuptake inhibitor sibutramine on feeding and body weight in a rat model of dietary obesity, and whether it interacts with hypothalamic neuropeptide Y (NPY) neurones. Chow-fed and dietary-obese (DIO) male Wistar rats were given sibutramine (3 mg kg(-1) day(-1) p.o.) or deionized water for 21 days. Sibutramine decreased food intake throughout the treatment period in both dietary-obese rats (P<0.0001) and lean rats (P<0.0001). Weight gain was reduced so that final body weight was 10% lower in dietary-obese (P<0.005) and 8% lower in lean (P<0.05) rats versus their untreated controls. Plasma leptin concentration was lower in sibutramine-treated dietary-obese rats (P<0.05), and in treated lean rats (P<0.05). Using the homeostasis model assessment (HOMA) as a measure of insulin resistance, untreated DIO rats were significantly more insulin resistant than controls (P<0.005), and this was corrected by sibutramine treatment (P<0.05). Neither hypothalamic NPY mRNA nor NPY peptide levels in a number of hypothalamic nuclei were significantly altered by sibutramine compared to untreated controls. The hypophagic and anti-obesity effects of sibutramine in dietary-obese Wistar rats appear not to be mediated by inhibition of ARC NPY neurones.

Adipose Tissue↗
PubMed2001

Women's experiences of 'being diagnosed' with a long-term illness.

AIMS: In this paper we share women's storied accounts of 'being diagnosed' with a long-term illness. The purpose of the paper is to raise awareness of health professionals that receiving a medical diagnosis is a potentially calamitous event, challenging self-identity. BACKGROUND: The three authors were involved in three separate inquiries which explored women's experiences of living with illness. The authors realized that 'being diagnosed' was a common memorable event for the women across the inquiries. The literature around receiving a diagnosis was scarce. DESIGN: This paper is the result of secondary analysis of data from three different projects where we researched women living with long-term illness. In this paper, we focus on the experience of 'being diagnosed' as we share and show women's perceptions of receiving a medical diagnosis. FINDINGS: Receiving a medical diagnosis of a long-term illness was a memorable event in the women's lives. Many women felt alone with their illness, often without adequate information to find meaning in the relationship between their familiar self and their new identity as a woman living with illness. They felt vulnerable and lost as they tried to understand the meanings and consequences that the diagnosis held for their present and their future. Informational needs may be specific and individual. For many, receipt of a diagnostic label was momentous and should not be underestimated, despite the initial feeling of chaos, many women felt validated. CONCLUSION: Receiving a medical diagnosis is one event where health care professionals could be on standby. It is important to take the woman's articulation of the event seriously. Open, genuine communication, with willingness on behalf of the health professional to listen would be affirming for women who are coming to terms with the diagnosis of a chronic illness.

Adaptation, Psychological↗
PubMed2001

Towards the eradication of head lice: literature review and research agenda.

Head lice infestation is a public health issue. In the effort to compile an evidence-base about the physiology, detection, treatment, effects and management strategies of head lice infestations we reviewed current literature. This literature signalled significant evidence gaps and these gaps provide incentives for further research. Our conclusions from the literature are that parents of children are responsible for head lice detection and treatment but have varying access to advice about how best to treat this condition. Concern is exacerbated by misconceptions surrounding the circumstances of infestation. Head lice are a low priority for health professionals in Australia, whereas parents and teachers believe the problem necessitates greater attention. It is important to provide a unified evidence-based approach to good information. It is timely for health care professionals to re-examine and prioritize this public health issue. They should research and work collaboratively towards the eradication of head lice.

Animals↗
PubMed2001

Gonadectomy and reduced physical activity: effects on skeletal muscle.

OBJECTIVES: To examine the effects of testosterone (TST) loss on skeletal muscle contractile function and the potential interactive effects of TST loss and physical inactivity. DESIGN: Randomized control trial. ANIMALS: Forty-eight male rats (age, 6mo) were placed into control (Con) or gonadectomized (Orx) groups. INTERVENTION: Two weeks after Orx or sham surgery, half the Con and Orx rats were hind-limb unloaded (HLU) to reduce muscle activity for 2 weeks. Subsequently, in situ contractile function tests were performed on the soleus (SOL), plantaris (PLAN), peroneus longus (PER), and extensor digitorum longus (EDL). These 4 muscles and gastrocnemius (GAST) then were removed, weighed, sectioned, and stained with adenosine triphosphatase for fiber typing and fiber area measures. MAIN OUTCOME MEASURES: Peak tetanic tension (P(0)), time to peak twitch contraction (TPT), half relaxation time (RT(1/2)), muscle mass, fiber area, and specific tension (ratio of P(0)/muscle mass). RESULTS: Body weight and muscle mass were similar in the Con and Orx groups. The ratio of P(0) to muscle mass was significantly (p <.05) reduced with Orx in SOL (20%), PLAN (18%), PER (28%), and EDL (20%). TPT and RT(1/2) were significantly faster after Orx in PLAN, PER, and EDL. HLU significantly reduced muscle mass in SOL, PLAN, and GAST in Orx and intact groups. HLU also caused a significant decline in SOL and PLAN P(0). The loss in P(0) in the Orx-HLU rats was no greater than the decline in P(0) with HLU alone. CONCLUSIONS: Gonadectomy results in a loss of P(0) regardless of muscle fiber type or function, it is likely to speed up TPT and RT(1/2), and it does not exacerbate HLU-related atrophy and P(0) loss. Findings may have implications for men with reduced TST levels, as in aging, for instance.

Analysis of Variance↗
PubMed2001

Role of angiotensin II type 1 receptor in the regulation of cellular adhesion molecules in atherosclerosis.

BACKGROUND: Inflammation is a central feature of coronary artery disease (CAD) that is characterized by increased expression of cellular adhesion molecules with the exception of L-selectin. L-selectin is a leukocyte adhesion molecule that is rapidly shed after leukocyte activation so that it appears to be decreased in CAD. The renin-angiotensin system (RAS) is implicated in atherogenesis and up-regulates these molecules. OBJECTIVES: The aim of this study was to investigate the effect of angiotensin type 1 (AT1) receptor antagonism on serum and leukocyte adhesion molecule expression in patients with CAD. Blood samples were collected from 31 patients before and after 8 weeks of treatment with losartan (44 +/- 2 mg/d, mean +/- SE), an AT1 receptor antagonist. We measured serum intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial-leukocyte adhesion molecule, and C-reactive protein (CRP). By flow cytometry, we also measured the expression of leukocyte CD11a, CD11b, CD11c, CD18, CD31, CD49d, and CD62L (L-selectin) in 13 patients. RESULTS: Treatment with losartan decreased systolic blood pressure (141 +/- 3 vs 135 +/- 4 mm Hg, P =.04) and increased plasma renin activity (1.2 +/- 0.4 vs 2.7 +/- 0.5 ng/mL/h, P =.001). There was a significant increase in L-selectin expression on monocytes (86 +/- 6 vs 118 +/- 10 MESF units, P =.007), lymphocytes (52 +/- 10 vs 79 +/- 8, P =.01), and granulocytes (124 +/- 7 vs 156 +/- 18, P =.056). However, there were no changes in the other leukocyte and serum adhesion molecules or CRP. CONCLUSIONS: These findings suggest that AT1 receptor antagonism selectively modulates L-selectin expression on leukocytes and that endogenous stimulation of AT1 receptors by the RAS contributes to the activation of leukocytes and decreased expression of L-selectin in CAD.

Angiotensin Receptor Antagonists↗
PubMed2001

Are very low birth weight infants born at high altitude at greater risk for adverse outcomes?

OBJECTIVE: To determine if neonatal intensive care at higher altitudes was associated with any variation in mortality or morbidity. METHODS: We reviewed demographic and outcome data on 5450 neonates with birth weights between 500 and 1500 g cared for in 76 different level II and III neonatal intensive care units (NICUs). The altitude break point of 4300 feet was prospectively chosen. Care was provided at 63 NICUs located below 4300 feet, "low-altitude," (n = 4534 neonates) and at 13 NICUs at or above 4300 feet, "high-altitude" (n = 916 neonates). RESULTS: Compared with neonates cared for at low altitude, neonates cared for at high altitude were more often non-Hispanic white and exposed to prenatal steroids. Neonates born at high altitude were more often treated with surfactant (60% vs 53%, P <.01). At 28 days of age, neonates cared for at high altitude were less often in room air (33% vs 50%, P <.01) compared with neonates cared for at low altitude. However, when corrected for barometric pressure, the calculated partial pressure of inspired oxygen at 28 days of age was lower for neonates cared for at high altitude compared with low altitude (165 +/- 80 vs 183 +/- 57, P <.01). There were no differences in the rates of mortality, severe intraventricular hemorrhage (grades 3 and 4), severe retinopathy of prematurity (stages 3 and 4), or necrotizing enterocolitis requiring surgical treatment. CONCLUSIONS: Being cared for at NICUs located above 4300 feet above sea level was not associated with any increase in adverse events compared with NICUs located below 4300 feet.

Altitude↗
PubMed2001

Correlations between the duration of pain and the success of shock wave therapy.

Patients who have had successful treatment for either chronic heel pain (plantar fasciitis) or humeral epicondylitis subsequently were evaluated for a comparable problem in the contralateral heel or elbow. Patients who had experienced symptoms in the contralateral heel or elbow for a shorter period were less likely to have a positive result from shock wave therapy than those patients who had received treatments for more chronic symptoms.

Adult↗
PubMed2001

Postextubation fiberoptic endoscopic evaluation of swallowing after prolonged endotracheal intubation: a randomized, prospective trial.

BACKGROUND: Critically ill trauma patients frequently require prolonged endotracheal intubation and ventilator support. After extubation, swallowing difficulties may exist in < or = 50% of patients. We sought to determine whether performing a swallowing evaluation would reduce the incidence of postextubation aspiration and subsequent pneumonia. DESIGN: Randomized, prospective clinical trial of fiberoptic endoscopic evaluation of swallowing (FEES) vs. routine clinical management in patients after prolonged intubation. METHODS: Seventy patients who were intubated for > 48 hrs were randomized. FEES examinations were performed within 24 +/- 2 hrs after extubation. Silent aspiration was defined as the appearance of liquid or puree bolus below the true vocal cords without coughing during a FEES examination. Clinical aspiration was defined as the removal of enteral content from below the vocal cords, usually during endotracheal tube placement. RESULTS: There were five episodes of aspiration and pneumonia in the FEES group (14%, two silent) and two in the clinical group (6%, not significant, Fisher exact test). Patients aged > 55 yrs and those with vallecular stasis on FEES examination were at significantly higher risk of postextubation aspiration. All patients with pneumonia had an associated aspiration episode. CONCLUSIONS: Patients with prolonged orotracheal intubation are at risk of aspiration after extubation. The addition of a FEES examination did not change the incidence of aspiration or postextubation pneumonia.

Adult↗
PubMed2001

Splanchnic perfusion evaluation during hemorrhage and resuscitation with gastric near-infrared spectroscopy.

OBJECTIVE: The purpose of this study was to use a prototype side-illuminating near-infrared spectroscopy (NIRS) nasogastric probe to continuously measure changes in gastric tissue oxygen saturation (Sto2) in a pig hemorrhage model. METHODS: Swine (n = 12; 6 per group) underwent laparotomy and placement of a gastric NIRS probe, jejunal tonometer, superior mesenteric artery (SMA) flow probe, and a portal vein catheter. Animals underwent hemorrhage (28 mL/kg) t = 0 to 20 minutes (where t = time). Pigs in group I were resuscitated (t = 20-40 minutes) with lactated Ringer's solution (84 mL/kg), whereas group II had no resuscitation. RESULTS: A significant decrease in mean arterial pressure and SMA flow was observed after hemorrhage. SMA flow significantly correlated in group I with both NIRS Sto2 (r = 0.58, p = 0.0001) and regional CO2 (r = -0.54, p = 0.0001). In group II, superior mesenteric flow correlated with NIRS Sto2 (r = 0.30, p = 0.03), but not regional CO2 (r = -0.23, p = 0.09). CONCLUSION: Direct measurement of tissue oxygen saturation with a prototype side-illuminating near-infrared spectroscopy gastric probe appeared to rapidly reflect changes in splanchnic perfusion.

Analysis of Variance↗
PubMed2001

Comparison of antral tap with endoscopically directed nasal culture.

OBJECTIVES/HYPOTHESIS: The diagnosis of acute bacterial rhinosinusitis continues to generate controversy in critically ill patients. The efficacy of endoscopically directed cultures in these patients is unknown. We compared antral tap (AT) with endoscopic tissue culture (ETC) of the osteomeatal complex in an intensive care unit (ICU) setting. METHODS: Twenty patients admitted to a surgical/trauma ICU were evaluated by AT and ENB for the presence of rhinosinusitis. All patients had 1) a fever of unknown origin without resolution on empiric antibiotic therapy for > or =48 hrs; 2) other sources of fever ruled out; 3) computed tomography scan evidence of mucoperiosteal thickening +/- sinus air/fluid levels; and 4) attempt at conservative treatment with topical decongestants and removal of all nasal intubation. Microbiologic data were collected and analyzed for any statistical difference between groups. RESULTS: A total of 29 sides underwent simultaneous tap and endoscopically directed tissue culture. The mean age was 40 years (range, 23-77 y) with 85% being males. Fifteen of 20 (75%) patients in the AT group were culture-positive. Of the 49 isolates from the AT, 55% yielded Gram-negative bacilli (Acinetobacter sp. 37%) and 45% yielded Gram-positive cocci. The ETC group was culture-positive in 18 of 20 (90%) patients. Of the 52 isolates from the ETC, Gram-negative bacilli were found in 58% (Acinetobacter sp. 33%) and 42% yielded Gram-positive cocci. The ETCs were culture-positive in all but 1 patient with positive taps. There appeared to be a concordance between AT and ETC in 60% of the patients. In five instances (25%), results of the AT or ETC changed ICU management. Two patients ultimately required sinus surgery. CONCLUSIONS: Sinus taps and/or endoscopically directed tissue cultures led to a change in ICU care in 25% of ICU patients studied. In patients with fever of unknown origin and computed tomography evidence of sinusitis, an antral tap continues to provide important information concerning maxillary sinusitis. However, ETC may give as good a representation of the microbiology and secondary inflammatory changes responsible for bacterial ICU rhinosinusitis causing fever of unknown origin. Further study on a larger group of patients is needed.

Adult↗
PubMed2001

Endocervical Gram stain smears and their usefulness in the diagnosis of Chlamydia trachomatis.

OBJECTIVE: To evaluate the usefulness of endocervical Gram stain smears in the diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae in a female population attending a STD clinic. METHODS: 494 females attending a STD clinic and undergoing a speculum examination had endocervical specimens submitted for C trachomatis culture, direct fluorescent antibody testing (DFA), and N gonorrhoeae culture. Endocervical smears were also collected for Gram stain. The number of polymorphonuclear leucocytes (PMN) per high power field (HPF), presence of bacteria, yeast, red blood cells, and clue cells were recorded. Clinical signs of cervicitis were also documented. RESULTS: N gonorrhoeae was isolated from one subject who was co-infected with C trachomatis and no further analysis was done regarding N gonorrhoeae. Analysis was performed on 220 participants. The prevalence of C trachomatis infection was 13%. Of the Gram smears collected, 55% were inadequate owing to the presence of vaginal contamination. There were an equal number of C trachomatis isolates in patients with < or = 10 PMN/HPF (48%) and > 10 PMN/HPF (52%). Endocervical mucopus and erythema were statistically significant for the presence of C trachomatis (p < 0.001 and 0.02 respectively). The presence of any signs of cervicitis-that is, mucopus, friability, erythema, and ectropion together with > 10 PMN/HPF was statistically significant for the presence of C trachomatis. CONCLUSION: The use of endocervical Gram smear results together with clinical information can be used to identify high risk women for C trachomatis infection.

Adolescent↗
PubMed2001

Varicella zoster virus-associated neurological disease in HIV-infected patients.

Varicella zoster virus (VZV) is an uncommon but well recognized cause of neurological disease in HIV-infected patients. Analysis of cerebrospinal fluid (CSF) using the polymerase chain reaction (PCR) in HIV-infected patients presenting with neurological disease has increasingly allowed diagnosis of VZV-associated pathology. We report clinical, radiological and virological data from 15 consecutive patients with VZV-associated neurological disease. Clinical presentation was varied, including meningo-encephalitis in 9 and isolated cranial nerve palsies in 6. VZV deoxyribonucleic acid (DNA) was detected by PCR in CSF of 11/15; pleocytosis was present in only 6/15, raised protein in 11/15. Magnetic resonance imaging (MRI) appearances were focal signal abnormalities in 8, meningeal enhancement in 2 and normal in 2. With specific anti-VZV therapy 10 patients recovered fully. The predictive value of PCR on CSF for diagnosis of VZV-associated neurological disease should take into account the patient's clinical presentation, concurrent infections and response to anti-VZV therapy.

Adult↗