Challenging behaviour and sleep cycle disorder following brain injury: a preliminary response to agomelatine treatment.

BACKGROUND: Sleep disturbances are common after acquired brain injury. Sedatives can exacerbate behavioural disorders. OBJECTIVES: This study reports the case of a severely brain damaged man (TM) who developed a non-24 hour sleep cycle disorder that was effectively managed by the administration of a melatonin receptor agonist, agomelatine. METHOD: TM suffered significant brain damage as a result of a large subarachnoid haemorrhage of his right anterior cerebral artery complicated by midline shift and subsequent infarction of his left middle cerebral artery. In addition to challenging behaviour and cognitive impairment, TM presented with a recurrent disturbed sleep-wake pattern that significantly worsened his quality-of-life. He was diagnosed as suffering of non-24 hour sleep-wake disorder. Challenge was recorded using the Overt Aggression Scale Modified for Neuro-Rehabilitation (OASMNR). RESULTS: Typical hypnotics had no or ill effects. Agomelatine prescription (25 mg) led to significant OASMNR and sleep efficiency change with effects apparent at 1.5 years later. CONCLUSIONS: Administration of the melatonin receptor (MT1 and MT2) agonist agomelatine each night resulted in an immediate and sustained improvement on sleep and on indices of challenging behaviour.

Use of computer-aided three-dimensional prototyping to surgically assist in tooth autotransplantation.

Autotransplantation is a surgical technique in which a donor tooth belonging to the same individual is repositioned into a surgically prepared socket or site of previous tooth extraction. It is beneficial in patients with teeth affected by agenesis, trauma, significant caries, and in teeth in a non-restorable condition or prognostically poor due to other pathology. It is particularly useful in paediatric patients, as properly transplanted teeth have a vital periodontium that allows for continuous growth and functional adaptation leading to preservation of the alveolar ridge. Technological advances in rapid prototyping combined with three-dimensional (3D) computed tomography (CT) have the ability to revolutionise autotransplantation. Preoperative planning for atraumatic extraction of the donor tooth and precise preparation of the recipient site with a rapid prototyped surgical template of the donor tooth considerably reduces the extra-alveolar time, and also reduces manipulation of the root sheath and periodontal ligament, and related trauma. This case series demonstrates the efficient and successful autotransplantation of various types of teeth with the use of a rapid prototyped surgical template produced from 3D CT. The use of this technology is expected to refine the surgical technique and improve treatment outcomes.

Institutionalizing health impact assessment in London as a public health tool for increasing synergy between policies in other areas.

OBJECTIVES: To describe the background to the inclusion of health impact assessment (HIA) in the development process for the London mayoral strategies, the HIA processes developed, how these evolved, and the role of HIA in identifying synergies between and conflicting priorities of different strategies. STUDY DESIGN: Case series. METHODS: Early HIAs had just a few weeks for the whole HIA process. A rapid appraisal approach was developed. Stages included: scoping, reviewing published evidence, a stakeholder workshop, drafting a report, review of the report by the London Health Commission, and submission of the final report to the Mayor. The process evolved as more assessments were conducted. More recently, an integrated impact assessment (IIA) method has been developed that fuses the key aspects of this HIA method with sustainability assessment, strategic environmental assessment and equalities assessment. RESULTS: Whilst some of the early strategy drafts encompassed some elements of health, health was not a priority. Conducting HIAs was important both to ensure that the strategies reflected health concerns and to raise awareness about health and its determinants within the Greater London Authority (GLA). HIA recommendations were useful for identifying synergies and conflicts between strategies. HIA can be successfully integrated into other impact assessment processes. CONCLUSIONS: The HIAs ensured that health became more integral to the strategies and increased understanding of determinants of health and how the GLA impacts on health and health inequalities. Inclusion of HIA within IIA ensures that health and health inequalities impacts are considered robustly within statutory impact assessments.

Anterior cervical discectomy: to graft or not to graft?

The debate regarding whether to perform an interbody fusion after anterior cervical discectomy (ACD) has been going on for the last 50 years. Several prospective randomized clinical trials have been performed to evaluate the clinical outcome following anterior cervical discectomy with and without interbody fusion. None of these studies show a significant difference between the two techniques in terms of relief of arm pain or neck pain. The operative time, in-hospital stay and time for return to work seem to be slightly longer following anterior cervical discectomy with interbody grafting (ACDF) compared to ACD alone. However a temporary increase in postoperative axial pain seems to be a common complication following ACD. There is also no difference in the clinical outcomes between ACD and ACDF with plating and ACDF with interbody spacers. However, if a fusion procedure is undertaken, the use of interbody spacers does have the advantage of avoiding donor site complications. There is also some evidence to suggest that plate fixation can lead to increased fusion rates. There is a significant risk of a degree of segmental kyphosis following ACD. These radiological features, however, do not correlate with the clinical outcome. Radiological and clinical studies fail to show a significant difference in recurrence of foraminal narrowing or the rates of reoperation following ACD or ACDF. The available body of evidence suggests that the addition of a fusion procedure following anterior cervical decompression may give improved radiological results but does not necessarily result in improved clinical outcomes.

Multiple schwannomas: report of two cases.

In this paper authors present two cases of multiple schwannomas without the features of neurofibromatosis (NF). The authors retrospectively reviewed the hospital charts, radiology films, operative notes and pathology slides of these two patients. There was no family history of neurofibromatosis. The two patients had contrast enhanced MRI, which was negative for vestibular schwannomas. Both underwent surgical excision of symptomatic lesions. Histopathology confirmed these lesions as schwannomas. Molecular genetic analysis in case 1 demonstrated two distinct mutations of the NF2 gene in two different schwannomas, with concomitant loss of heterozygosity in both tumours. In contrast peripheral blood lymphocytes did not reveal mutations of NF2. The authors recommend surgery for symptomatic lesions. Asymptomatic tumours can be monitored. Regular follow up is essential as they may develop fresh lesions at any time. The relevant literature is discussed.

Electrolytic treatment of an industrial wastewater from a hosiery plant.

Textile plant wastewater being treated in a facultative pond system had too high of a solids concentration to be reused in the dying and rinsing processes. Electrocoagulation was evaluated to further treat the pond effluent to remove turbidity, which was caused by dyes and microorganisms. A range of amperages were tested for removal of turbidity and chemical oxygen demand (COD). Electrocoagulation lowered the turbidity from 1400 NTU to below 50 NTU; and COD was lowered from 550 mg/L to approximately 250 mg/L, which was acceptable for reuse. In addition, a laboratory-scale sedimentation study was conducted on the electrocoagulated pond effluent, which indicated that a settling time of 35 minutes would provide for 80% removal of suspended solids, which was acceptable for reuse of the water in plant processes.

Removal versus retention of asymptomatic third molars in mandibular angle fractures: a randomized controlled trial.

The treatment dilemma provided by asymptomatic third molars in mandibular angle fractures remains controversial. This prospective randomized controlled trial was undertaken to determine whether there is an advantage to extraction or retention of the third molar whilst repairing a mandibular angle fracture. Sixty-four patients were allocated randomly to the two treatment groups. All underwent open reduction and internal fixation (ORIF) with standard postoperative care. The primary outcome measure was uncomplicated fracture healing. Secondary measures were surgical duration, malocclusion, wound healing, nerve injury, and return to theatre. All patients had uncomplicated fracture healing. The incidence of nerve injury was 16% for the retention group compared with 39% for the removal group (P=0.038). The average operating time for ORIF and third molar retention cases was 58.5min and for ORIF and third molar removal cases was 66.3min (P=0.26). There was no statistically significant difference between groups for wound healing, occlusion outcomes, or return to theatre. Given the additional risk of nerve injury and the additional operating time required for removal of a third molar, in the absence of an absolute indicator for removal of the third molar, it appears justifiable to advise retaining the tooth in the line of a mandibular angle fracture.

Male transgenic glycine receptor alpha1 (S267Q) mutant mice display a hyperekplexia-like increase in acoustic startle responses.

Glycine receptors (GlyR) are ligand-gated ion channels that inhibit neurotransmission in the spinal cord and brainstem, and mutations in GlyR can cause the human disease hyperekplexia, which is characterized by elevated startle responses. Recently, the GlyR alpha1S267Q mutation was shown to disrupt normal GlyR function, and knock-in mice harboring this mutation displayed profoundly increased acoustic startle responses and reduced glycine-stimulated the chloride flux [Findlay, G.S., Phelan, R., Roberts, M.T., Homanics, G.E., Bergeson, S.E., Lopreato, G.F., Mihic, S.J., Blednov, Y.A., Harris, R.A. 2003. Glycine receptor knock-in mice and hyperekplexia: comparisons with the null mutant. J Neurosci 23, 8051-8059.]. In this study, a transgenic mouse model expressing this S267Q mutation was evaluated using similar techniques to determine if these mice are similarly affected. Male transgenic mice displayed increased acoustic startle responses. However, decreases in glycine-stimulated strychnine-sensitive radioactive chloride (36Cl-) uptake were not observed in spinal cord and brainstem synaptoneurosomes from transgenic mice. No changes in habituation or prepulse inhibition of startle responses or spontaneous locomotion in response to taurine were observed as a result of presence of the transgene. Consistent with previous studies using immunoblotting and strychnine binding [Findlay, G.S., Wick, M.J., Mascia, M.P., Wallace, D., Miller, G.W., Harris, R.A., Blednov, Y.A. 2002. Transgenic expression of a mutant glycine receptor decreases alcohol sensitivity of mice. J Pharmacol Exp Ther 300, 526-534.], the glycine-stimulated strychnine-sensitive chloride flux of cortical microsacs in transgenic mice confirmed the ectopic expression of transgenic GlyR. These results support both the idea that transgenic expression of the S267Q mutation produces a less dramatic phenotype as compared to the knock-in mouse model as well as the idea that the in vivo acoustic startle test (as compared to the in vitro chloride flux assay) is particularly sensitive to disruptions in GlyR function.

An evaluation of the urban stormwater pollutant removal efficiency of catch basin inserts.

In a storm sewer system, the catch basin is the interface between surface runoff and the sewer. Responding to the need to improve the quality of stormwater from urban areas and transportation facilities, and spurred by Phase I and II Stormwater Rules from the U.S. Environmental Protection Agency, several companies market catch basin inserts as best management practices for urban water quality management. However, little data have been collected under controlled tests that indicate the pollutant removal efficiency of these inserts when the inflow is near what can be expected to occur in the field. A stormwater simulator was constructed to test inserts under controlled and replicable conditions. The inserts were tested for removal efficiency of total suspended solids (TSS) and total petroleum hydrocarbons (TPH) at an inflow rate of 757 to 814 L/min, with influent pollutant concentrations of 225 mg/L TSS and 30 mg/L TPH. These conditions are similar to stormwater runoff from small commercial sites in the southeastern United States. Results from the tests indicate that at the test flowrate and pollutant concentration, average TSS removal efficiencies ranged from 11 to 42% and, for TPH, the removal efficiency ranged from 10 to 19%.

Diagnosis of gram negative, ventilator associated pneumonia by assaying endotoxin in bronchial lavage fluid.

AIM: To investigate the usefulness of assaying endotoxin in non-directed bronchial lavage fluid (NBL), bronchoscopic bronchoalveolar lavage fluid (BAL), and sera as a means of diagnosing Gram negative, ventilator associated pneumonia. METHODS: Samples from 64 patients were investigated. Fifty nine BALs and 92 NBLs were assayed in total including specimens taken during 28 episodes of clinical ventilator associated pneumonia (VAP). RESULTS: The concentration of endotoxin in BAL from patients with VAP developing within four days of commencing ventilation was significantly higher than in those without VAP (p = 0.015). There was no significant difference in endotoxin concentration in NBL or serum when comparing patients with and without VAP. A BAL endotoxin concentration of 6 EU/ml yielded the optimal operating characteristics (sensitivity, 81%; specificity, 87%; positive predictive value, 67%; negative predictive value, 95%). However, Gram stain of BAL provided the same information as quickly as the endotoxin assay and is considerably cheaper. CONCLUSIONS: Despite its accuracy and rapidity, the BAL endotoxin assay must be shown to alter clinical management and patient outcome to be cost effective.

The diagnosis of ventilator-associated pneumonia using non-bronchoscopic, non-directed lung lavages.

OBJECTIVES: (1)To assess the diagnostic utility of quantitative cultures of non-bronchoscopic lung lavage (NBL) in ventilator-associated pneumonia and evaluate the role of the Bacterial Index; (2) To assess the predictive value of NBL surveillance quantitative cultures in ventilated patients; (3) To evaluate the Clinical Pulmonary Infection Score (CPIS) system in ventilated patients. DESIGN: A prospective comparison of NBL with bronchoscopic bronchoalveolar lavage and protected specimen brush. SETTING: Three intensive care units in academic tertiary care centres. PATIENTS: 145 adults ventilated for 72 h, with and without clinical signs of pneumonia. INTERVENTIONS: Sampling of lower airway secretions by NBL, bronchoalveolar lavage and protected specimen brush. MAIN OUTCOME MEASURES: Diagnostic reliability of quantitative cultures, Bacterial Index and CPIS. RESULTS: 34 episodes of clinical ventilator-associated pneumonia were documented in 32 patients. 9 episodes were confirmed by concordant blood/pleural culture or post-mortem lung examination. Qualitative concordance of the predominant pathogen between sequential NBL: bronchoalveolar lavage and protected specimen brush was 83 %. Sensitivity and specificity of non-directed bronchial lavage at a threshold of 10(4) CFU/ml were 68 % and 70 % respectively (p = 0. 003) and were comparable with the bronchoscopic methods. However, the low positive predictive value of NBL indicates that quantitation in the absence of clinical signs is unlikely to be useful. Bacterial Index did not improve discriminatory power of quantitation compared with bacterial load of predominant organism. Mean CPIS for confirmed pneumonia cases was 8.4 +/- 1.01, significantly higher than for non-pneumonia observations (p = < 0.0001). CONCLUSION: NBL is a simple, safe, cheap, readily-available method of diagnosing ventilator-associated pneumonia with comparable diagnostic accuracy to bronchoscopic techniques. Quantitation of respiratory tract cultures can exclude pneumonia in patients with equivocal clinical signs. The diagnostic threshold should vary depending on the length of ventilation, likelihood of pneumonia and antibiotic administration. The Bacterial Index is a flawed mathematical device that has no contributory role in pneumonia diagnosis. The CPIS has some diagnostic role in selected cohorts of ventilated patients.

Allosteric modulation in spontaneously active mutant gamma-aminobutyric acid(A) receptors [corrected].

Tryptophan substitutions were made in the second transmembrane domain of the gamma-aminobutyric acid(A) (GABA(A)) receptor alpha and beta subunits and the resulting mutant receptors, containing alpha(2)(S270W) and/or beta(1)(S265W), were expressed in Xenopus oocytes. Mutation of either or both subunits resulted in receptors that exhibited enhanced sensitivity to agonist and were spontaneously active in the absence of GABA. The spontaneous activity was blocked by picrotoxin or bicuculline. The enhancement of GABA-induced currents by pentobarbital, by the neurosteroid 5alpha-pregnan-3alpha-ol-20-one, and by the benzodiazepine flunitrazepam was dramatically reduced in the mutant receptors. These results are consistent with the idea that a mutation that promotes gating behavior in a ligand-gated ion channel will also show reduced effects of all positive allosteric modulators in a generalized manner, even when these modulators act at distinct sites on the receptor.

Allosteric modulation in spontaneously active mutant gamma-aminobutyric acidA receptors.

Tryptophan substitutions were made in the second transmembrane domain of the gamma-aminobutyric acid(A) (GABAA) receptor alpha and beta subunits and the resulting mutant receptors, containing alpha2(S270W) and/or beta1 (S265W), were expressed in Xenopus oocytes. Mutation of either or both subunits resulted in receptors that exhibited enhanced sensitivity to agonist and were spontaneously active in the absence of GABA. The spontaneous activity was blocked by picrotoxin or bicuculline. The enhancement of GABA-induced currents by pentobarbital, by the neurosteroid 5alpha-pregnan-3alpha-ol-20-one, and by the benzodiazepine flunitrazepam was dramatically reduced in the mutant receptors. These results are consistent with the idea that a mutation that promotes gating behavior in a ligand-gated ion channel will also show reduced effects of all positive allosteric modulators in a generalized manner, even when these modulators act at distinct sites on the receptor.

Contralateral ventricular dilatation in supratentorial tumors.

The computerized tomographic (CT) scans of 411 patients with supratentorial lateralized tumors were compared with an assessment of their clinical condition. More than one-third of these patients showed dilatation of the contralateral lateral ventricle, which was associated with a lower level of consciousness.

Splenic rupture following cardiopulmonary resuscitation.

Cardiopulmonary resuscitation has improved outcome from cardiac arrest. However complications may occur secondary to the resuscitation efforts. We present a case of intraabdominal haemorrhage, due to traumatic rupture of the spleen and discuss the problems of diagnosing intraabdominal haemorrhage in the post cardiac arrest patient, whose hypotension may be ascribed to myocardial dysfunction.

Assessment of a computerized system for the diagnosis of iron deficiency.

The aim of this study was to develop a computer expert system that could reproduce a pathologist's diagnosis of iron deficiency from the data obtained from blood tests. 275 cases were collected for construction and testing of the expert system. The expert system used a combination of fuzzy set logic and cut-off points from 14 parameters to arrive at one of 5 diagnostic categories graded from "iron deficient" to "no evidence of iron deficiency". The agreement between pathologist and expert system was 0.91 (Spearman rank correlation coefficient) in the learning population; this dropped to 0.79 in the test population. Absolute agreement on diagnostic category was reached in 71% of cases. In no case was there disagreement by more than 3 grades.

Report of a controlled clinical trial comparing automated percutaneous lumbar discectomy and microdiscectomy in the treatment of contained lumbar disc herniation.

STUDY DESIGN: The results of a randomized controlled trial comparing automated percutaneous lumbar discectomy (APLD) with lumbar microdiscectomy for the treatment of small contained lumbar discal herniations are reported. All patients gave full informed consent and were assessed by an independent observer. Seventy-one patients with radiologically confirmed small contained lumbar disc herniations were randomly assigned to undergo either APLD or lumbar microdiscectomy. All patients were formally assessed by the independent assessor using the Macnab outcome classification at 3 weeks, 2 months, and 6 months after the procedure with follow-up being continued for the duration of the study. OBJECTIVE: The objective was to complete the first randomized and blinded study with sufficient numbers to provide a valid statistical evaluation of these procedures. SUMMARY OF BACKGROUND DATA: No previous randomized controlled study comparing these methods has been previously reported. METHODS: Each procedure was performed by the same surgeon using standard techniques. Statistical analysis was by the chi-square method. RESULTS: In the APLD group only 9 of 31 (29%) had satisfactory outcomes as compared to 32 of 40 (80%) for the microdiscectomy group. Of those patients in the APLD group who had an unsatisfactory outcome and who then opted to undergo surgery (20 of 22 patients), the final success rate was only 65%. Thus, the cumulative success rate of the group initially randomized to APLD including those undergoing either APLD alone or APLD and microdiscectomy after unsuccessful APLD was 22 of 31 (71%). CONCLUSION: In this group of patients, APLD is seen to be ineffective in the treatment of contained lumbar disc herniation.

A 10-year follow-up of the outcome of lumbar microdiscectomy.

STUDY DESIGN: A retrospective analysis of the outcome of lumbar microdiscectomy, with independent assessment of outcome. OBJECTIVES: To explore whether the initial positive outcome after microdiscectomy is maintained at long-term follow-up. SUMMARY OF BACKGROUND DATA: Previous reports on long-term outcome after lumbar disc surgery give conflicting messages about whether an initially positive surgical outcome is maintained throughout a 10-year period. This is partly due to differing methods and the failure to include initial outcome, thereby permitting assessment of possible deterioration in the quality of outcome. METHODS: This study presents the initial and long-term outcome after lumbar microdiscectomy, with an independent assessment of outcome. Eighty-eight consecutive patients undergoing lumbar microdiscectomy were identified. Assessment at 10 years after surgery was obtained in 79 (90%) of the cases. The initial outcome was assessed retrospectively by an independent observer at 6 months after surgery using the Macnab classification. The final outcome Macnab classification was completed by postal questionnaire by the patients themselves, who also completed a modified Roland-Morris disability questionnaire. RESULTS: A successful outcome at 6 months was achieved in 91% of the cases. At 10-year follow-up, this result declined slightly to an 83% success rate. However, there was no statistically significant difference between these outcome results. The long-term Macnab classification results correlated well with disability, as measured by the Roland-Morris score. Patient satisfaction with the results of microdiscectomy 10 years later was high. CONCLUSIONS: Lumbar microdiscectomy achieves a high level of initial success, and this positive outcome is maintained at a 10-year follow-up.

Computer-assisted (axial) tomography in the management of subarachnoid haemorrhage.

A prospective trial of the role of routine computer-assisted (axial) tomography of the brain (CT) in the early management of subarachnoid haemorrhage is reported. A correct aetiological diagnosis was made from the CT scan in 76% of patients. Early routine performance of CT frequently provides valuable information in planning management.