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Biomedical subjects

S Brooks

Publications and source records attributed to S Brooks.

At least 19 recordsLinked to original sources
PubMed2007

Acquired haemophilia masked by warfarin therapy.

Acquired haemophilia is a rare phenomenon and prompt diagnosis is essential for successful treatment. Early laboratory detection could minimize its potentially devastating consequences and reduce mortality but when a masking element such as anticoagulant therapy is present, delay in diagnosis is not uncommon. A prolonged activated partial thromboplastin time (APTT) may be falsely attributed to warfarin alone, particularly when it is associated with oral anticoagulant overdose. We describe two patients on treatment with warfarin who presented with a bleeding diathesis and disproportionately prolonged APTT, which led to the diagnosis of antibodies directed against factor VIII.

Aged↗
PubMed2006

Short course continuous, hyperfractionated, accelerated radiation therapy (CHART) as preoperative treatment for rectal cancer.

Determine feasibility and toxicity of preoperative short course pelvic CHART (25 Gy in 15 fractions over 5 days) for treatment of clinically resectable primary rectal tumours. Between 1998 and 2004, 20 patients with clinically staged T3 resectable rectal carcinoma were treated in this prospective pilot study with preoperative short course CHART to their pelvis. The aim was for total mesorectal excision within 7 days. Radiation toxicity, surgical morbidity, locoregional control (LRC), overall (OS), cause specific (CSS) and disease free survival (DFS) outcomes were documented. Nineteen of the 20 patients completed planned radiotherapy. One discontinued radiotherapy due to toxicity. All patients underwent potentially curative radical surgery. One patient developed grade 3, and three patients grade 2 gastrointestinal toxicity. With a median follow-up of 31 months (range 0.9-88), there is no grade 3, 4 or 5 late toxicity. Two patients experienced grade 2, and three patients grade 1 late bowel toxicity. Two patients died from postoperative complications, and two developed grade 2 abdominal wound infections. At 3 years LRC is 95% (95% CI 83-100), OS 72% (95% CI 51-94), CSS 86% (95% CI 68-100) and DFS 80% (95% CI 60-100). Two patients died from metastatic disease, one patient from a second primary and one patient is alive after successful resection of hepatic metastases. This small study suggests preoperative short course CHART for clinically resectable rectal carcinoma is feasible with acceptable compliance and tolerable side effects.

Adenocarcinoma↗
PubMed2005

The management of scaphoid fractures.

Appropriate management of scaphoid fractures is important because of the risk of long-term complications such as delayed or non-union, pain and disability. Up to 25% of scaphoid fractures are not visible on the initial radiographs. Consequently, all clinically suspected scaphoid fractures are treated as fractures with cast immobilisation until cause of the symptoms is clarified. The diagnosis often utilises a number of second line investigations that are generally performed 10-14 days after the injury. Bone scintigraphy is currently the most commonly used of these as it rarely misses a fracture. However, it does not visualise anatomical structure and therefore alternative diagnoses are difficult. Magnetic resonance imaging (MRI) is at least as sensitive and more specific than bone scanning and has the advantages of being able to identify other lesions and not expose the patient to any radiation. Furthermore, the scan may be performed as early as 2.8 days following an injury rather than 10 days later in the case of a bone scan. Although the cost of MRI is higher than other imaging modalities, it may be cost-effective in the overall management of patients with occult scaphoid fractures since it may prevent unnecessary cast immobilisation in active people. The most appropriate method of cast immobilisation is presently unclear but evidence exists for improved clinical outcomes in those that have both the thumb and elbow immobilised for the first six weeks.

Diagnostic Imaging↗
PubMed2005

Cost effectiveness of adding magnetic resonance imaging to the usual management of suspected scaphoid fractures.

OBJECTIVE: To determine the cost effectiveness of a magnetic resonance imaging scan (MRI) within 5 days of injury compared with the usual management of occult scaphoid fracture. METHODS: All patients with suspected scaphoid fractures in five hospitals were invited to participate in a randomised controlled trial of usual treatment with or without an MRI scan. Healthcare costs were compared, and a cost effectiveness analysis of the use of MRI in this scenario was performed. RESULTS: Twenty eight of the 37 patients identified were randomised: 17 in the control group, 11 in the MRI group. The groups were similar at baseline and follow up in terms of number of scaphoid fractures, other injuries, pain, and function. Of the patients without fracture, the MRI group had significantly fewer days immobilised: a median of 3.0 (interquartile range 3.0-3.0) v 10.0 (7-12) in the control group (p = 0.006). The MRI group used fewer healthcare units (median 3.0, interquartile range 2.0-4.25) than the control group (5.0, 3.0-6.5) (p = 0.03 for the difference). However, the median cost of health care in the MRI group (594.35 dollars AUD, 551.35-667.23 dollars) was slightly higher than in the control group (428.15 dollars, 124.40-702.65 dollars) (p = 0.19 for the difference). The mean incremental cost effectiveness ratio derived from this simulation was that MRI costs 44.37 dollars per day saved from unnecessary immobilisation (95% confidence interval 4.29 dollars to 101.02 dollars). An illustrative willingness to pay was calculated using a combination of the trials measure of the subjects' individual productivity losses and the average daily earnings. CONCLUSIONS: Use of MRI in the management of occult scaphoid fracture reduces the number of days of unnecessary immobilisation and use of healthcare units. Healthcare costs increased non-significantly in relation to the use of MRI in this setting. However, when productivity losses are considered, MRI may be considered cost effective, depending on the individual case.

Adult↗
PubMed2004

Effects of hyperthermia on the metabolic responses to repeated high-intensity exercise.

In this study, we investigated the metabolic and performance responses to hyperthermia during high-intensity exercise. Seven males completed two 30-s cycle sprints (SpI and SpII) at an environmental temperature of 20.6 (0.3) degrees C [mean (SD)] with 4 min recovery between sprints. A hot or control treatment preceded the sprint exercise. For the hot trial, subjects were immersed up to the neck in hot water [43 degrees C for 16.0 (3.2) min] prior to entering an environmental chamber [44.2 (0.8) degrees C for 30.7 (7.1) min]. For the control trial, subjects were seated in an empty bath (15 min) and thereafter in a normal environment [20.2 (0.6) degrees C for 29.0 (1.9) min]. Subjects' core temperature prior to exercise was 38.1 (0.3) degrees C in the hot trial and 37.1 (0.3) degrees C in the control trial. Mean power output (MPO) was significantly higher in the hot condition for SpI [683 (130) W hot vs 646 (119) W control ( P<0.025)]. Peak power output (PPO) tended to be higher in the hot trial compared with the control trial for SpI [1057 (260) W hot vs 990 (245) W control ( P=0.03, NS)]. These differences in power output were a consequence of a faster pedal cadence in the hot trial ( P<0.025). There were no differences in sprint performance in SpII in the hot trial compared to the control trial; however, MPO was significantly reduced from SpI to SpII in the hot condition but not in the control condition ( P<0.025). Plasma ammonia was higher in the hot trial at 2 min post-SpI [169 (65) micromol l(-1 )hot vs 70 (26) micromol l(-1) control ( P<0.01)], immediately and at 2 min post-SpII [231 (76) micromol l(-1) hot vs 147 (72) micromol l(-1) control ( P<0.01)]. Blood lactate was higher in the hot trial compared with the control trial at 5 min post-SpII ( P<0.025). The results of this study suggest that an elevation in core body temperature by 1 degrees C can improve performance during an initial bout of high-intensity cycle exercise but has no further beneficial effect on subsequent power production following a 4-min recovery period.

Adult↗
PubMed2004

Assignment of the appaloosa coat colour gene (LP) to equine chromosome 1.

A single autosomal dominant locus, leopard complex (LP) controls the presence of appaloosa pigmentation patterns in the horse. The causative gene for LP is unknown. This study was undertaken to map LP in the horse. Two paternal half sib families segregating for the LP locus and including a total of 47 offspring were used to perform a genome scan which localized LP to horse chromosome 1 (ECA1). LP was linked to ASB08 (LOD = 9.99 at Theta = 0.02) and AHT21 (LOD = 5.03 at Theta = 0.14). To refine the map position of LP, eight microsatellite markers on ECA1 (UM041, LEX77, 1CA41, TKY374, COR046, 1CA32, 1CA43, and TKY002) were analysed in the two half sib families. Results from this linkage analysis showed LP was located in the interval between ASB08 and 1CA43. Tight junction protein (TJP1), which lies within the LP interval on ECA1, was used to determine the homologous chromosomes in humans (HSA15) and mice (mouse chromosome 7). We propose that the pink eyed dilution (p) gene and transient receptor potential cation channel subfamily M, member 1 (TRPM1) are positional candidate genes for LP.

Animals↗
PubMed2003

Is bilateral knee arthroscopy suitable as a day-case procedure?

A retrospective analysis of 100 out of 108 cases has been audited for suitability of bilateral knee arthroscopy as a day-case procedure. Fifty-three female and 47 male patients with age range of 15-78 years underwent bilateral knee arthroscopy. All patients had general anaesthetic and were ASA grade 1 or 2. Eight patients had more than one diagnosis and procedures. Post-operatively 68% could walk without walking aids, 1% had 1 stick and 31% needed 2 sticks and were given elbow crutches. One patient stayed overnight due to poor pain control and 1 attended A&E due to effusion. There were 5 (2.5%) major and 62 (31%) minor complications in 200 knees. Mild post-operative pain was the commonest minor complication in 52 (26%) out of 62 knees and was attributed to high number of bilateral arthritis cases in this study. Complication rate of bilateral arthroscopy is similar to unilateral arthroscopy. It is concluded that bilateral arthroscopy is safe as a day-case procedure.

Adolescent↗
PubMed2002

The role of desaturases in cold-induced lipid restructuring.

All organisms respond to environmental challenge by adaptive responses, although, in many cases, the underlying molecular mechanisms are not understood. In the case of membranes, the physical structure of membrane phospholipids is conserved in the face of cold, rigidifying conditions by the elevated proportions of unsaturated fatty acids. We have observed a clear positional specificity in this substitution and head group preferences in carp liver membranes. We have also demonstrated changes in the activity of lipid desaturases that mediate the unsaturation response, caused by both transcriptional and post-translational mechanisms. Another hepatic isoform has recently been discovered with sensitivity, not to cooling, but to dietary variations. Finally, we are testing the importance of desaturase inductions in the inducible cold tolerance of the whole animal.

Animals↗
PubMed2002

Electrospray ionisation mass spectrometric analysis of lipid restructuring in the carp (Cyprinus carpio L.) during cold acclimation.

Cold acclimation of carp from 30 degrees C to 10 degrees C causes a restructuring of liver microsomal phospholipids characterised by increased proportions of monounsaturated fatty acid in phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Here, we have used electrospray ionisation mass spectrometry (ESI-MS) to determine the patterns of alteration to individual molecular species compositions of PC, PE and phosphatidylinositol (PI) in response to gradually decreasing temperature. The results demonstrate that cold induces precise changes to a limited number of phospholipid species, and that these changes are distinct and different for each phospholipid class. The major change for PC was increased 16:1/22:6, but for PE the species that increased was 18:1/22:6. By contrast, the PI species that increased during cold acclimation were characterised by an sn-1 monounsaturated fatty acid in combination with arachidonoyl or eicosapentaenoyl fatty acid at the sn-2 position. Analysis of acyl distribution indicates that cold only caused the accumulation of monounsaturated fatty acids at the sn-1 and not at the sn-2 position of phospholipids. These results highlight the tight and restricted range of modifications that membranes make to their phospholipid composition in response to thermal stress.

Animals↗
PubMed2001

A frameshift mutation in exon 28 of the OPA1 gene explains the high prevalence of dominant optic atrophy in the Danish population: evidence for a founder effect.

Dominant optic atrophy (DOA) is a hereditary optic neuropathy characterised by decreased visual acuity, colour vision deficits, centro-coecal scotoma and optic nerve pallor. The gene OPA1, encoding a dynamin-related GTPase, has recently been identified within the genetic linkage interval for the major locus for DOA on chromosome 3q28 and shown to harbour genetic aberrations segregating with disease in DOA families. The prevalence of the disorder in Denmark is reported to be the highest of any geographical location, suggestive of a founder effect. In order to establish the genetic basis of disease in a sample of 33 apparently unrelated Danish families, we screened DNA from affected members for OPA1 gene mutations by heteroduplex analysis and direct sequencing. A novel identical mutation in exon 28 (2826delT) was associated with DOA in 14 pedigrees and led to a frameshift and abnormal OPA1 protein -COOH terminus. Haplotype analysis of a region of approximately 1 Mb flanking the OPA1 gene using eight polymorphic markers revealed a common haplotype shared by all 14 patients; this haplotype was markedly over-represented compared with ethnically matched controls. Statistical analysis confirmed significant linkage disequilibrium with DOA over approximately 600 kb encompassing the disease mutation. We have therefore demonstrated that the relatively high frequency of DOA in Denmark is attributable to a founder mutation responsible for approximately 42% of the examined families and suggest that presymptomatic screening for the (2826delT) mutation may facilitate diagnosis and genetic counselling in a significant proportion of DOA patients of Danish ancestry.

Alleles↗
PubMed2001

Low cerebrospinal fluid hypocretin (Orexin) and altered energy homeostasis in human narcolepsy.

Hypocretins (orexins) are hypothalamic neuropeptides involved in sleep and energy homeostasis. Hypocretin mutations produce narcolepsy in animal models. In humans, narcolepsy is rarely due to hypocretin mutations, but this system is deficient in the cerebrospinal fluid (CSF) and brain of a small number of patients. A recent study also indicates increased body mass index (BMI) in narcolepsy. The sensitivity of low CSF hypocretin was examined in 38 successive narcolepsy-cataplexy cases [36 human leukocyte antigen (HLA)-DQB1*0602-positive] and 34 matched controls (15 controls and 19 neurological patients). BMI and CSF leptin levels were also measured. Hypocretin-1 was measurable (169 to 376 pg/ml) in all controls. Levels were unaffected by freezing/thawing or prolonged storage and did not display any concentration gradient. Hypocretin-1 was dramatically decreased (<100 pg/ml) in 32 of 38 patients (all HLA-positive). Four patients had normal levels (2 HLA-negative). Two HLA-positive patients had high levels (609 and 637 pg/ml). CSF leptin and adjusted BMI were significantly higher in patients versus controls. We conclude that the hypocretin ligand is deficient in most cases of human narcolepsy, providing possible diagnostic applications. Increased BMI and leptin indicate altered energy homeostasis. Sleep and energy metabolism are likely to be functionally connected through the hypocretin system.

Adolescent↗
PubMed2001

Chromium transport, oxidation, and adsorption in manganese-coated sand.

We examine how the processes of advection, dispersion, oxidation-reduction, and adsorption combine to affect the transport of chromium through columns packed with pyrolusite (beta-MnO2)-coated sand. We find that beta-MnO2 effectively oxidizes Cr(III) to Cr(VI) and that the extent of oxidation is sensitive to changes in pH, pore water velocity, and influent concentrations of Cr(III). Cr(III) oxidation rates, although initially high, decline well before the supply of beta-MnO2 is depleted, suggesting that a reaction product inhibits the conversion of Cr(III) to Cr(VI). Rate-limited reactions govern the weak adsorption of each chromium species, with Cr(III) adsorption varying directly with pH and Cr(VI) adsorption varying inversely with pH. The breakthrough data on chromium transport can be matched closely by calculations of a simple model that accounts for (1) advective-dispersive transport of Cr(III), Cr(VI), and dissolved oxygen, (2) first-order kinetics adsorption of the reduced and oxidized chromium species, and (3) nonlinear rate-limited oxidation of Cr(III) to Cr(VI). Our work supplements the limited database on the transport of redox-sensitive metals in porous media and provides a means for quantifying the coupled processes that contribute to this transport.

Adsorption↗
PubMed2000

The premature infant and painful procedures.

Pain management for premature infants raises challenging questions for nurses. This group of infants is often physiologically fragile and they may undergo frequent painful procedures on a daily basis. Contrary to ideas from the past, premature infants are able to feel pain, and nervous system elements required for the transmission of painful stimuli are functional by 24 weeks gestation. Painful procedures are harmful to the infant's physiological stability and the ability to self-regulate, which includes maintenance of motor control and stable sleep/wake cycles. Assessment of pain in the premature infant is complex. Major indicators of pain include facial grimaces and physiological parameters such as heart rate and oxygen saturation. The Premature Infant Pain Profile (PIPP) is one tool designed specifically for preterm infants. Nonpharmacological nursing measures such as swaddling or nesting and offering a pacifier are useful strategies to help infants cope with painful procedures. The nurse may also maintain a therapeutic environment to assist the infant in self-regulation. Pharmacological agents such as morphine, fentanyl, and acetaminophen are effective in relieving procedural pain. The use of oral sucrose before and during painful procedures offers new possibilities for pain relief. Recent research shows that oral sucrose is a safe and effective analgesic for short-term procedures. Research studies to determine the most effective doses and modes of oral sucrose administration are ongoing. It is thought that the relief of pain is owing to the sweet taste of the sucrose that activates endogenous pain-modulating systems.

Analgesics, Opioid↗
PubMed1999

Molecular cloning and expression of ovarian cathepsin D in seabream, Sparus aurata.

In marine fish producing pelagic eggs, the acquirement of buoyancy by the eggs through the hydration process is a key event of reproduction; moreover, the yolk proteolysis, which leads to buoyancy, seems to affect the fertility and survival of the spawned eggs. Recently we demonstrated that cathepsin D is the aspartic protease responsible for this intraoocytic processing of vitellogenin into yolk proteins. In the present study, we isolated, cloned, and sequenced the cDNA encoding cathepsin D and studied expression of the message by Northern blotting and whole-mount in situ hybridization. The full-length seabream cathepsin D cDNA is 1837 base pairs long, encoding a protein of 400 amino acids (aa) consisting of a signal peptide of 19 aa, a prosequence of 44 aa, and a mature peptide of 336 aa. An absolute sequence conservation at the aspartyl residues (+33 and +221) was found, and there are three potential N-glycosylation sites at +70, aa +189, and aa +274. The aa sequence of seabream cathepsin D reveals a high degree of sequence similarity with cathepsin D mRNAs from other organisms (73% sequence homology to mouse and rat, 72% to human and trout, 69% to chicken, 66% to pig, and 65% to Xenopus). The cathepsin D mRNA in floating eggs was present as a single band that was approximately 1.9 kilobases (kb) in size, while in the sinking eggs there were several fast-migrating bands (size range 1.3-0.2 kb). Whole-mount hybridization was used to investigate transcription of cathepsin D in the developing embryo; during the hatching period, cathepsin D mRNA-positive cells were distributed in a wide region between the trunk and the tail, and in the ventral region over the yolk ball. The highest levels of cathepsin D enzymatic activity were found in the sinking eggs and during the hatching period of embryonic development. These data suggest that cathepsin D can be considered a possible marker for egg quality.

Amino Acid Sequence↗
PubMed1998

Reduction in vancomycin-resistant Enterococcus and Clostridium difficile infections following change to tympanic thermometers.

OBJECTIVE: To contain a nosocomial outbreak of vancomycin-resistant Enterococcus (VRE). DESIGN: Intervention study, with comparison of incidence rates before and after intervention to assess whether changes in incidence followed the intervention and were greater than expected based on trends observed before the intervention. SETTING: A 343-bed acute-care hospital serving a predominantly elderly population referred from nursing homes, as well as patients admitted from the community. METHODS: Interventions strategies were tested on three high-risk nursing stations. These included enhanced environmental sanitation; intensive staff retraining in Universal Precautions, body substance isolation, and proper use of gloves; and the use of tympanic thermometers to avoid possible rectal or oral VRE transmission during temperature taking. RESULTS: Nosocomial VRE infections were reduced by 48% 9 months after switching to tympanic thermometers; incidence of Clostridium difficile infections also was reduced. As a result, tympanic thermometers were introduced facilitywide; additional observation for 20 months showed a risk reduction of 60% for VRE and 40% for C difficile. CONCLUSION: Cross-transmission of VRE and C difficile during temperature taking may result in bowel colonization, placing the patient at increased risk for infection. This risk may be reduced by the use of tympanic thermometers.

Anti-Bacterial Agents↗