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Biomedical subjects

S Brennan

Publications and source records attributed to S Brennan.

At least 37 records · Page 2Linked to original sources

Antenatal endotoxin and glucocorticoid effects on lung morphometry in preterm lambs.

In utero inflammation may accelerate fetal lung maturation but may also play a role in the pathogenesis of chronic lung disease. We examined the impact of endotoxin, a potent proinflammatory stimulus, on structural and functional maturation of preterm sheep lungs. Date bred ewes received 20 mg Escherichia coli endotoxin or saline by ultrasound guided intra-amniotic injection at 119 d gestation. A comparison group of animals received 0.5 mg/kg betamethasone, a known maturational agent, at 118 d gestation. Lambs were delivered by cesarean section at 125 d (term = 150 d) and ventilated for 40 min. Lung function data are reported elsewhere. Total and differential white cell counts were performed on amniotic fluid and fetal lung fluid samples. Morphometric analyses were performed on inflation fixed right upper lobes. Total cell count increased slightly but not significantly in both amniotic fluid and fetal lung fluid. Both endotoxin and betamethasone had similar effects on alveolarization: average alveolar volume increased by approximately 20% and total alveolar number decreased by almost 30%. Both treatments led to thinning of alveolar walls, although this was statistically significant in the betamethasone-treated group only. Although antenatal endotoxin leads to striking improvements in postnatal lung function, this may be at the expense of normal alveolar development.

Amniotic Fluid↗

[Effects of the statins in kidney transplantation].

A retrospective analysis was performed to assess the immunosuppressive activity of statins in kidney transplantation, determining their effects on serum cholesterol and triglyceride levels post-transplantation, on the incidence of acute rejection episodes and on renal function. A total of 97 patients who underwent a kidney transplant in a three-year period, had more than one-month graft survival, and a minimum of one year of follow-up, were included. Group A consisted of 38 patients who received statins; this group was subsequently divided into four subgroups, according to the time post-transplant when statins were prescribed. Group B consisted of 59 patients (control Group). Initial and final serum total cholesterol levels in Group A were not different (218 +/- 7.8 mg/dl vs 222 +/- 7.5 mg/dl); however, final levels were higher than initial values in Group B (216 +/- 6.0 mg/dl vs 189 +/- 6.4 mg/dl, P = 0.0021). Initial serum triglyceride levels were higher than final levels in Group A (305 +/- 25.5 mg/dl vs 188 +/- 10.6 mg/dl, P < 0.0001). Group A showed a better allograft survival (P = 0.0350), a reduction in the incidence of acute rejection episodes (1 vs 38 events, P < 0.0001) and a lower serum creatinine level (1.96 +/- 0.21 mg/dl vs 2.77 +/- 0.27 mg/dl, P = 0.0374). In Group A subgroups, kidney function was significantly better in patients who received statins early after transplantation. These data suggest that in kidney transplantation statins exert additional immunosuppressive effects, reduce the number of acute rejection episodes, improve allograft survival and kidney function and are effective in preventing serum cholesterol from rising; these effects correlate with a significant decrease in serum triglyceride but are independent of a hypocholesterolemic action.

Adult↗

FK506-associated thrombotic microangiopathy: report of two cases and review of the literature.

BACKGROUND: FK506 is a recently developed immunosuppressant that has been useful in improving the survival of transplanted organs. Among the numerous adverse side effects of FK506, thrombotic microangiopathy (TMA) stands out as an infrequent but severe complication. METHODS: We report two cases of FK506-associated TMA and review the 19 previous reported cases. RESULTS: From these 21 cases, the reported incidence of FK506-associated TMA is between 1% and 4.7%. It is more frequent in females, and the mean age at presentation is 47 years. Eighty-one percent of the cases occurred in patients with kidney allografts, and the remaining patients had liver, heart, or bone marrow transplants. Clinically, TMA was diagnosed at an average interval of 9.3 months from the time of transplantation. Patients may be asymptomatic or may present with the full-blown picture of hemolytic uremic syndrome. All patients had an elevated serum creatinine level but did not always show signs of hemolysis. Trough levels of FK506 were not predictive for the development of TMA, but generally a reduction of drug dose correlated with kidney function improvement and disappearance of the hemolytic picture. The renal allograft biopsy provided a conclusive diagnosis in all 17 cases in which this procedure was performed. Treatment, which mainly consisted of reduction or discontinuation of FK506, anticoagulation, and/or plasmapheresis with fresh-frozen plasma exchange, resolved TMA in most patients (57%). However, in one of these patients (5%), the graft was subsequently lost due to causes unrelated to TMA, such as acute or chronic rejection. Despite treatment, one patient (5%) lost the graft due to acute rejection and persistent TMA, and three other patients (14%) who had bone marrow, heart, and liver transplants, died of multiple organ failure, probably unrelated to TMA. In the remaining four patients (19%), response to treatment was not reported. CONCLUSIONS: TMA must be considered in organ transplant patients treated with FK506 whenever kidney function deteriorates, even in the absence of microangiopathic hemolytic anemia. Although TMA usually responds to treatment, it may, in rare cases, lead to loss of kidney function or even the patient's death.

Adult↗

The cognitive determinants of performance on the Austin Maze.

This study aimed to investigate which abilities are measured by the Austin Maze. One hundred and eight university students were administered a battery of eight neuropsychological tests including, the Austin Maze, the Tower of London, the Wisconsin Card Sort Test, Block Design, the Visual Spatial Learning Test, Digit Span Backwards, the Brown-Peterson Task and the Wide Range Achievement Test of Reading. Results indicated that visuospatial ability and memory both significantly contributed to performance on the Austin Maze, but differed in the degree to which they explained the performance depending on which measure of maze performance was employed. It appears that visuospatial ability is measured in early trials of the Austin Maze when individuals are orienting themselves to the path. In later trials individuals must call upon visuospatial memory to consolidate the details of the path. Executive function and working memory were not found to be significantly implicated in performance on the Austin Maze.

Adolescent↗

Dust mite proteolytic allergens induce cytokine release from cultured airway epithelium.

Endogenous proteolytic enzymes have been shown to be potential sources of airway inflammation inducing proinflammatory cytokine release from respiratory epithelial cells; however, whether any of the exogenous proteases from important allergen sources such as the house dust mite present in our environment behave in a similar fashion is unclear. To this end, we have investigated whether the mite cysteine and serine proteolytic allergens, Der p 1 and Der p 9, respectively, induced cytokine production from primary human bronchial epithelial cells and from the epithelial cell line BEAS-2B. Cells were exposed to mite proteases, and cells or supernatants were assayed for cytokine release, cytokine mRNA expression, and modulation of intracellular calcium ion concentration. Both proteases induced concentration- and time-dependent increases in the release of granulocyte-macrophage (GM)-CSF, IL-6, and IL-8 as well as an increase in the expression of IL-6 mRNA. Cytokine release and mRNA expression were first observed at 8 h and 2 h after protease exposure, respectively. The minimum concentration of each protease that was required to stimulate GM-CSF, IL-6, and IL-8 release was approximately 10 ng/ml. Cytokine release was initiated by 1 to 2 h of protease exposure, although maximum concentrations were detected only after a 24-h incubation. IL-6, but not IL-8 and GM-CSF, was shown to be degraded by both proteases at concentrations of > 2 microg/ml. The proteases also stimulated changes in the intracellular calcium ion concentration. All mite protease-induced phenomena were inhibited using appropriate protease inhibitors. These results suggest that the proteolytic activity of an allergen may stimulate the release of proinflammatory cytokines from human bronchial epithelium.

Allergens↗

The albumins of Chinook salmon (Oncorhynchus tshawytscha) and brown trout (Salmo trutta) appear to lack a propeptide.

Plasma samples from two members of the Salmonidae family, the chinook salmon (Oncorhynchus tshawytscha) and brown trout (Salmo trutta), were examined. Albumin, initially identified as the predominant anionic palmitate-binding band on agarose gel electrophoresis of plasma, was purified from both species by DEAE-ion exchange chromatography. Albumin has a plasma concentration of approximately 15 mg/ml in both species. Like other fish species, neither trout nor salmon albumin binds nickel; a characteristic of many mammalian albumins. Salmon and trout albumins have molecular masses of 65 and 67 kDa, respectively, indicating some sequence differences. However, N-terminal sequencing of the first 15 residues of both these proteins indicated identical sequences of 1QNQICTIFTEAKEDG15-. This showed that the mature N-terminal sequence (SQAQNQICTIFTEAKEDG-) predicted from the cDNA of Atlantic salmon albumin is in fact incorrect, with the actual N-terminus for salmonids starting three amino acids later than that predicted. Examination of the Atlantic salmon cDNA sequence suggested that salmonid albumin is unique, in lacking a propeptide. No proalbumin convertase site (RXYR/XYRR) is present and it appears that the salmonid albumin precursor is cleaved only by the signal peptidase, between -1 Ala and +1 Gln, to produce mature albumin. This site has a preferrred motif for the signal peptidase of -1 Ala and -3 Ser, as well as -2 Gln. Thus, salmonid albumin possesses a 21-residue prepeptide, but no propeptide.

Amino Acid Sequence↗

Nursing and motherhood constructions: implications for practice.

The present paper addresses the relationship between community based child health nursing services and social constructions of motherhood within Australia during the 1920s. Following the First World War, child health nursing services (then generally known as infant welfare or child welfare services) were established in all Australian states. The focus of the paper is mainly upon the development of the Tasmanian child health service, with some reference to similar services in other states. Within two decades of their establishment, most child-bearing women in Tasmania were in contact with child health services and this apparent success meant that, thereafter, women in Tasmania cared for their children under the 'expert' guidance of nurses. As the 1920s progressed, child health nurses increasingly promoted one particular, and ultimately extremely influential, construction of motherhood, 'scientific motherhood', based upon the philosophy of Dr Truby King. I argue that an understanding of how nursing services have historically reinforced and promoted ideological constructions of motherhood enhances the practice of present day nurses working with women. This argument is supported by reference to present day nursing practice in relation to postnatal depression.

Child↗

Suppressibility of plasma adrenocorticotropin by hydrocortisone: potential usefulness in the diagnosis of Cushing's disease.

Repeatedly normal cortisol suppressibility by dexamethasone in 2 patients with Cushing's disease led to the present study of the prevalence of this phenomenon in 58 patients with otherwise incontrovertible evidence of Cushing's disease. Because as many as 23% of these patients manifested this phenomenon, we investigated the suppressibility of plasma ACTH: 1) during i.v. infusion of hydrocortisone, after a priming dose (7 mg), at 3 mg/h in 8 patients and 8 normal controls; and 2) for 2 h, after oral hydrocortisone, 0.25 mg/kg, in 13 patients and 16 controls. The data showed invariable suppression of plasma ACTH to < or = 10 pg/mL (< or = 2.2 pmol/L) after 120 min of the infusion or at 90 min after oral hydrocortisone in 16 fasting normal subjects given oral hydrocortisone between 0800 and 0830 h. Plasma ACTH exceeded 10 pg/mL (2.2 pmol/L) at the same times in 14/14 patients with active Cushing's disease, including 3 patients whose cortisol suppressibility by dexamethasone had been misleadingly normal and in 4/7 patients with intermittent hypercortisolism. Occasional variations in plasma cortisol elevations after the oral dose require that plasma cortisol concentration be monitored at 60 min after the oral hydrocortisone dose, because the present evidence supports the validity of the conclusion that a plasma ACTH concentration below 10 pg/mL excludes Cushing's disease only when plasma cortisol concentration at 60 min lies between 16 and 38 microg/dL. Further evaluation of ACTH suppressibility by cortisol would be worthwhile, to confirm its potential value in facilitating positive diagnosis of Cushing's disease when dexamethasone suppressibility seems misleading.

Adolescent↗

Regional cancer cytogenetics: a report on 1,143 diagnostic cases.

The results of studies from a regional cancer cytogenetics diagnostic service are reported. In a 10-year period, 1,143 marrow samples from patients with newly diagnosed leukemia and myelodysplastic syndrome were referred. Successful studies were completed on 992 cases (87%). Among all referred cases, the rates of detection of cytogenetically abnormal clones were 95% for chronic myelogenous leukemia (CML), 54% for acute lymphoblastic leukemia (ALL), 51% for acute myeloid leukemia (ANLL), and 43% for myelodysplastic syndrome (MDS). Of 169 cases of CML studied, 90.5% bore the standard Philadelphia chromosome (Ph), 3.55% had an unusual Ph, and 5.33% were Ph-negative. Among the 59 cases of cytogenetically abnormal MDS, common abnormalities observed were trisomy 8 and changes resulting in loss of material from the long arm of chromosomes 5 and 7, and 20q-. Of the 168 abnormal ANLL, there was a strikingly non-random pattern of aneuploidy, with monosomy 7 and trisomy 8 predominating. Common structural changes observed were changes resulting in loss of material from the long arm of chromosomes 5 and 7, trisomy 8, rearrangements of 11q23, t(15;17), t(8;21), rearrangements of 12q13 and 3q, inversion 16, trisomy 11, Ph, trisomy 21, t(6;9) and t(1;22). The differences between adult and pediatric findings were minor, with the exception of chromosome 5 abnormalities, which were common among adults with ANLL but rare in the pediatric cases. There were 273 ALLs with abnormal cytogenetic findings. There was preferential gain of chromosomes 21, X, 14, 6, 4, 18, 17, and 10 (in decreasing order of frequency) in leukemic clones. Of the 193 ALLs with structural changes, many fell into-well-defined categories with established correlations to FAB subtypes. Common changes in ALL were rearrangements of 9p, 12p, 6q, TCR loci, 11q23, Ig loci, and 8q24, and duplication of 1q, Ph, i(17q), t(1;19), i(9q) and dic(9;12). The detailed documentation of the cytogenetic findings in this relatively large, single-institution study will likely facilitate the further characterization of rare, primary cytogenetic changes associated with leukemias and MDS. From a managed health care perspective, regional cancer cytogenetic services may be cost-effective alternatives to single-institution laboratories.

Adult↗

MRI abnormalities in major psychiatric disorders: an exploratory comparative study.

MRI scan reports from 536 psychiatric inpatients in 10 DSM-III-R diagnostic categories and 51 normal control subjects were reviewed for incidence and severity of four types of abnormality: deep white matter hyperintensities, periventricular hyperintensities, ventricular enlargement, and cortical atrophy. Multivariate analysis revealed significant effects for both diagnosis and age and a significant interaction. After age covariance, the most discriminant type of abnormality was ventricular enlargement, with normal control subjects having significantly less enlargement than 6 of 10 patient groups, including the personality disorder and the depressed nonpsychotic groups. The data also suggested important diagnosis by age by type-of-abnormality interactions deserving of further study.

Adult↗

Unusual presentation of glomerulocystic kidney disease in an adult patient.

A 38-year-old Latin-American man developed uremic syndrome without any evidence of previous kidney diseases or any other health problems. Ultrasound and CT scan confirmed normal size of the kidneys without evidence of urinary tract obstruction or renal parenchymal cysts. Kidney biopsy showed cystic dilatation of Bowman's space (glomerulocystic kidney disease). The patient was started on hemodialysis. Severe renal dysfunction and uremic symptoms are a rare initial manifestation of glomerulocystic kidney disease. This pathology should be considered in the differential diagnosis of patients with normal size kidney and chronic renal failure.

Adult↗