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Biomedical subjects

D J Cooper

Publications and source records attributed to D J Cooper.

At least 19 recordsLinked to original sources

Salines, osmoles and albumin.

In 2004, two large randomised multi-centre Australian clinical trials provided new information concerning optimal resuscitation for patients with traumatic brain injury (TBI). One examined hypertonic saline (HTS) and the other, albumin versus saline.( )For the first time in a randomised trial, hypertonic saline was tested for pre-hospital resuscitation of hypotensive patients with traumatic brain injury, and for the first time a resuscitation fluid trial measured long term neurological function as the primary outcome. Despite many potential advantages which may have much greater relevance in the hospital setting, in the paramedic based VICn trauma system, HTS did not improve neurological outcome compared to conventional pre-hospital fluid protocols. Nevertheless, HTS resuscitation was confirmed to be safe in TBI patients and may find application in future pre-hospital military settings where fluid weight is of primary importance. The very large randomised SAFE trial found that there was no difference in 28 day survival between albumin and saline resuscitation for intensive care patients, and by providing very high quality data, this study has largely settled a generation old controversy. Intriguingly however, the SAFE study also reported that within a subgroup of 492 patients with TBI, 28 day survival was superior in patients receiving saline. This subgroup result was not considered definitive, but a post hoc examination of the TBI patients currently in progress by the SAFE investigators, is expected to provide further guidance for clinicians. In the meanwhile, and until more high quality data is available, many clinicians are likely to prefer crystalloid resuscitation for trauma patients, and especially for trauma patients with brain injury.

Journal Article↗

Clearing the cervical spine in unconscious head injured patients - the evidence.

Cervical spine injury occurs in 5-10% of patients with traumatic brain injury (TBI) and the consequences of missing significant cervical injuries in unconscious blunt trauma patients are potentially devastating. An adequate cervical spine clearance protocol for unconscious patients must avoid missed injuries, but must also avoid unnecessary cervical immobilisation and the associated morbidity. Existing protocols include various combinations of plain X-rays, helical CT, dynamic flexion-extension X-rays and MRI. Some clinicians also maintain immobilisation until clinical clearance is eventually enabled by the return of an adequate conscious state. Plain X-rays alone are inadequate and miss 12-16% of cervical injuries. Swimmer's views and/or oblique views identify more injuries, but are frequently inadequate. Helical CT is sensitive to fractures and subluxation/dislocation injuries but may be insufficient to exclude unstable ligamentous injuries. Dynamic flexion-extension fluoroscopy may better identify unstable ligamentous injuries, but at The Alfred Hospital Trauma Centre in Melbourne, this modality was insensitive in the routine protocol and repeatedly missed significant cervical instability. Furthermore at The Alfred Hospital, when routine dynamic flexion/ extension fluoroscopy and helical CT reconstructions were directly compared, flexion/extension identified no new injuries that had not already been diagnosed by early helical CT reconstructions. Cervical MRI is intuitively appealing as it detects ligament, disc interspace, and cord injury more efficiently than other imaging modalities, but MRI also increases cervical clearance times, increases the risks associated with complex transports and is not an ideal acute screening tool. Nevertheless, recently at The Alfred Hospital, extremely high-risk TBI patients have had unstable cervical injuries detected solely by MRI. Current generation multi-slice CT with reconstructions may obviate the need for MRI even in these patients. The current Alfred Hospital cervical clearance protocol for unconscious patients, and the evolutionary steps in its development, will be discussed.

Journal Article↗

Prevalence of oral mucosal lesions in alcohol misusers in south London.

BACKGROUND: Information on alcohol-associated oral mucosal lesions (OMLs) and conditions is meagre. A prevalence survey among alcohol misusers in south London was therefore undertaken. METHODS: Six hundred and ninety-three subjects (388 alcohol misusers and 305 alcohol + substance abuse) attending several clinical care facilities in south London between 1994 and 1999 were interviewed on their alcohol and drug habits. A comprehensive oral mucosal examination was performed, and soft tissue lesions found were classified by the clinical criteria of Axéll. RESULTS: Mean age of the sample was 40.5 years. The majority was white (92.6%); of the whites, 29.9% were Celts (i.e. Irish, Scots resident in London). Many subjects reported misusing more than one type of beverage. Two hundred and twenty-seven OMLs were found in 195 subjects (28.1%). The highest prevalences were found for frictional keratosis (8.8%), scar tissue of the lips (4.8%) and candidiasis (3.8%). Angular cheilitis was present in 21 subjects (3.0%). The alcohol-related OMLs detected were three white patches compatible with a diagnosis of leukoplakia and one treated oral carcinoma. No erythroplakias were detected. The differences in prevalence of mucosal lesions in the two groups were not significant (chi(2) = 2.18; P = 0.14). The prevalence of tobacco smoking was high in both study groups. OMLs were found with all four types of beverages consumed, and there was little variation by the units per week consumed. Concurrent use of substances and alcohol did not make a significant difference to the prevalence of OML. In the logistic regression analysis, minority ethnic groups (Black or Asian), smokers, those with a body mass index (BMI) under 20 and beer drinkers had an increased risk of an OML in this group of alcohol misusers. CONCLUSIONS: In comparison with previous oral mucosal screening programmes undertaken in several settings in the UK, the present study has yielded a higher prevalence of oral mucosal diseases and conditions in this risk population. There are several ways in which alcohol could contribute to these detected oral lesions, either directly or indirectly.

Adult↗

Role of beer lipid-binding proteins in preventing lipid destabilization of foam.

The negative effect of fatty acids on the foam stability of beer has been assessed. Long-chain fatty acids are far more damaging than short-chain fatty acids on the foam stability of beer at the concentrations employed. Polypeptides have been isolated from an all malt beer by hydrophobic interaction chromatography. Using this technique five groups of polypeptides were isolated, group 1 being the least hydrophobic and group 5 the most hydrophobic, all of which exhibited similar polypeptide compositions by SDS-PAGE. All five hydrophobic polypeptide groups bound [(14)C]linoleic acid; however, group 5, the most hydrophobic group, bound the most linoleic acid. Groups 1 and 5 were titrated with cis-parinaric acid (CPA) to produce binding curves, which were compared with a binding curve obtained for bovine serum albumin (BSA). Groups 1 and 5 both produced binding curves that saturated at approximately 5.5 microM and 4 microM CPA and had association constants (K(a)) of 6.27 x 10(7) and 1.62 x 10(7) M(-1), respectively. In comparison, BSA produced a binding curve that saturated at 6 microM CPA and had a K(a) of 3.95 x 10(7) M(-1). Further investigation has shown that group 1 is pH sensitive and group 5 pH insensitive with respect to lipid binding. The lipid-binding activity of group 5 was also shown to be unaffected by ethanol concentration. Linoleic acid (5 microM) when added to beer resulted in unstable foam. Group 5 was added to the lipid-damaged beer and was shown to restore the foam stability to values that were obtained for the control beer. It has therefore been demonstrated that proteins isolated from beer have a lipid-binding capacity and that they can convey a degree of protection against lipid-induced foam destabilization.

Beer↗

Oral manifestations of an HIV positive cohort in the era of highly active anti-retroviral therapy (HAART) in South London.

BACKGROUND: Human Immunodeficiency Virus (HIV) infection is associated with oral manifestations of diagnostic and prognostic importance. With the advent of Highly Active Anti-retroviral Therapy (HAART) there is anecdotal evidence to suggest that the prevalence of oral lesions has declined. The number of prevalence studies, carried out in the era of HAART is, however, meagre. Our aim was to study the prevalence of the oral manifestations of HIV in a population, predominantly on HAART, attending a Genito-Urinary Medicine Centre in South London. METHODS: This cross sectional study included 203 adult volunteers, comprising 76% males and 24% females. One third of the subjects were from the predominantly African or Afro- Caribbean ethnic minority groups resident in London. The relationship between the prevalence of oral lesions and demographic variables, therapeutic regimes, viral load and CD4 counts were evaluated. RESULTS: One hundred (49%) of the patients had no detectable oral lesions. Oral lesions detected most frequently included oral hairy leukoplakia (9.9%), HIV associated periodontal diseases (9.9%) and oral candidiasis (4.9%). Three subjects had multiple papillomatous growths. Most cases (n = 17/20) of oral hairy leukoplakia were in individuals with a detectable (> 400 copies/ml) plasma RNA viral load. The majority (n = 8/10) of our patients with oral candidiasis had a plasma RNA viral load > 10,000 copies/ml and half (n = 5/10) had a CD4 count < 200 cells/mm3. Logistic regression analysis suggested that the presence of an oral lesion was not associated with any demographic features except for periodontal diseases which were associated with tobacco smoking (P = 0.023). CONCLUSIONS: The prevalence of so called 'strongly associated' oral lesions of HIV is low in this South London HIV-infected population on HAART, and the relative frequency is different from that cited in the literature from the pre-HAART era. The oral lesions detected were found mostly in people with low CD4 counts and high HIV-1 RNA viral loads, suggesting they were very immunocompromised, not on, or declining therapy, or that their therapy was failing.

Adult↗

Reed bed dewatering of agricultural sludges and slurries.

In trials at Rugeley, UK, reed beds were used for dewatering agricultural sludges and slurries. Three beds, each of 3.5 m2, were employed, two planted with Phragmites australis, the third left unplanted as control. The sludge contained partly oxidised solids from a Biological Aerated Filter (BAF) treating weak pig slurry. It was supplemented with untreated settled pig slurry. Following reed establishment planted Bed A was fed at a constant similar rate to the unplanted Control Bed C. The second planted Bed B was fed at higher rates alternating with rest periods. On this bed the aeration pipes were blocked off. The trials were run for 16 months, which included two summer periods. The results showed that the planted Bed A had definitely better dewatering ability than the unplanted one fed at a similar rate. During the summer months Bed B could be fed at over twice the rate used for the constant input beds. The percolate from the control bed was more highly oxidised than from the planted beds, probably due to a longer holdup time in the absence of reeds. On Bed B the reed quality deteriorated during the second year, after use of untreated slurry as feed.

Agriculture↗

Factors contributing to fatal outcome of traumatic brain injury: a pilot case control study.

OBJECTIVE: Patients with traumatic brain injury (TBI) have a high mortality and morbidity. This pilot study was undertaken to identify contributors to outcome in the early management of patients with TBI and to investigate the feasibility of a larger study. METHODS: Road trauma patients who died between January 1 and April 30, 2000 were selected from the Alfred Hospital's Intensive Care Traumatic Brain Injury database. These patients were matched with 2 survivors from the data base during the same period for age, injury severity score (ISS) and severity of brain injury using the head abbreviated injury score (head AIS). Patient injury scoring (using the revised trauma score, trauma and injury severity score and Glasgow coma score), arterial blood gas analysis, lactate concentration, inspired oxygen concentration, systolic and mean arterial blood pressure, intracranial pressure, intravenous fluid and blood transfusion volumes, body temperature, haemoglobin, white cell count, INR, APTT, temperature and plasma glucose, urea and creatinine concentrations were recorded for 48 hours from the time of injury. Time periods from the accident to key events (e.g. arrival of ambulance at accident scene, intubation, arrival at the emergency department, insertion of intracranial pressure monitor and primary surgery) were also recorded. RESULTS: Eighteen patients (6 deceased, 12 survivors) were identified. Despite matching, deceased patients had lower initial Glasgow Coma Scores (GCS) (3.6 vs. 7.4, P = 0.01) and lower revised trauma scores (4.41 vs. 5.75; P = 0.044) compared with survivors. There were no significant differences in other parameters. However, deceased patients tended to have longer times to treatment (P = NS) and experienced trauma at night more frequently, and survivors received almost double the volume of fluid resuscitation during the first 12 hours (19.7 +/- 19.1 vs. 11.8 +/- 2.7 mL/kg/hr, P = 0.513). CONCLUSIONS: Both initial GCS and severity of brain injury should be used to match TBI patients for injury severity in future studies. Lower initial GCS in deceased patients was likely due to greater severity of brain injury, although it is also possible that the lower GCS was due to decreased brain perfusion (perhaps reflecting inadequate resuscitation) in these patients. Volume of early fluid resuscitation, time to definitive therapy, and time of presentation to hospital may also be important determinants of patient outcome. A large case control outcome study is required to extend these observations.

Journal Article↗

Novel octaketide macrolides related to 6-deoxyerythronolide B provide evidence for iterative operation of the erythromycin polyketide synthase.

BACKGROUND: The macrolide antibiotic erythromycin A, like other complex aliphatic polyketides, is synthesised by a bacterial modular polyketide synthase (PKS). Such PKSs, in contrast to other fatty acid and polyketide synthases which work iteratively, contain a separate set or module of enzyme activities for each successive cycle of polyketide chain extension, and the number and type of modules together determine the structure of the polyketide product. Thus, the six extension modules of the erythromycin PKS (DEBS) together catalyse the production of the specific heptaketide 6-deoxyerythronolide B. RESULTS: A mutant strain of the erythromycin producer Saccharopolyspora erythraea, which accumulates the aglycone intermediate erythronolide B, was found unexpectedly to produce two novel octaketides, both 16-membered macrolides. These compounds were detectable in fermentation broths of wild-type S. erythraea, but not in a strain from which the DEBS genes had been specifically deleted. From their structures, both of these octaketides appear to be aberrant products of DEBS in which module 4 has 'stuttered', that is, has catalysed two successive cycles of chain extension. CONCLUSIONS: The isolation of novel DEBS-derived octaketides provides the first evidence that an extension module in a modular PKS has the potential to catalyse iterative rounds of chain elongation like other type I FAS and PKS systems. The factors governing the extent of such 'stuttering' remain to be determined.

Anti-Bacterial Agents↗

Percutaneous tracheostomy in critically ill patients: a prospective, randomized comparison of two techniques.

OBJECTIVE: To prospectively compare two commonly used methods for percutaneous dilational tracheostomy (PDT) in critically ill patients. DESIGN: Prospective, randomized, clinical trial. SETTING: Trauma and general intensive care units of a university tertiary teaching hospital, which is also a level 1 trauma center. PATIENTS: One hundred critically ill patients with an indication for PDT. INTERVENTIONS: PDT with the Ciaglia technique using the Ciaglia PDT introducer set and the Griggs technique using a Griggs PDT kit and guidewire dilating forceps. MEASUREMENTS AND MAIN RESULTS: Surgical time, difficulties, and surgical and anesthesia complications were measured at 0-2 hrs, 24 hrs, and 7 days postprocedure. Groups were well matched, and there were no differences between the two methods in surgical time or in anesthesia complications. Major bleeding complications were 4.4 times more frequent with the Griggs PDT kit. With the Ciaglia PDT kit, both intraoperative and at 2 and 24 hrs, surgical complications were less common (p = .023) and the procedure was more often completed without expert assistance (p = .013). Tracheostomy bleeding was not associated with either anticoagulant therapy or an abnormal clotting profile. Multivariate analysis identified the predictors of PDT complications as the Griggs PDT kit (p = .027) and the Acute Physiology and Chronic Health Evaluation (APACHE) II score (p = .041). The significant predictors of time required to complete PDT were the APACHE II score (p = .041), a less experienced operator (p = .0001), and a female patient (p = .013). CONCLUSIONS: Patients experiencing PDT with the Ciaglia PDT kit had a lower surgical complication rate (2% vs. 25%), less operative and postoperative bleeding, and less overall technical difficulties than did patients undergoing PDT with the Griggs PDT kit. Ciaglia PDT is, therefore, the preferred technique for percutaneous tracheostomy in critically ill patients.

APACHE↗

Early diagnosis of traumatic aortic valve rupture in ICU patients using transoesophageal echocardiography.

A case is presented of a 60-year-old man who sustained spinal and chest wall injuries following a collision between his glider and an aeroplane. The severity of his injuries required him to be managed with bilateral underwater seal drains, cervical spine stabilisation and sedation with mechanical ventilation. Due to the severity of his chest trauma, a transoesophageal echocardiograph was performed which revealed a partial dehiscence and prolapse of the left coronary cusp of the aortic valve with mild to moderate aortic regurgitation. Despite conservative treatment, severe cardiac failure developed six days later requiring aortic valve replacement. After a prolonged stay in the Intensive Care Unit during which the patient developed acute respiratory distress syndrome, methicillin resistant Staphylococcus aureus pneumonia and Enterobacter septicaemia, the patient was discharged, returning to his pre-admission lifestyle. In patients with complex and severe chest trauma, transoesophageal echocardiography is of great benefit, not only in allowing good image quality, compared with transthoracic echocardiography, but having a greater reliability and accuracy in diagnosing cardiac and mediastinal trauma in complex monitoring environments.

Journal Article↗

Massive baclofen overdose.

A case is presented of a massive baclofen overdose with the highest blood baclofen concentrations currently reported. Interesting clinical features included profound hypotension, distributive shock and absent brainstem reflexes. Cerebral recovery was surprisingly slow but complete, and was then unexpectedly terminated by a sudden major splenic arterial haemorrhage followed by a severe haemorrhage of the aorta which proved to be due to cystic medial necrosis. This arterial anatomic abnormality and cause of death may have been coincidental, or may instead be a previously unreported complication of massive baclofen toxicity.

Journal Article↗