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D A Lang

Publications and source records attributed to D A Lang.

At least 37 records · Page 2Linked to original sources

Structural basis of the chiral selectivity of Pseudomonas cepacia lipase.

To investigate the enantioselectivity of Pseudomonas cepacia lipase, inhibition studies were performed with Sc- and Rc-(Rp,Sp)-1,2-dialkylcarbamoylglycero-3-O-p-nitrophenyl alkylphosphonates of different alkyl chain lengths. P. cepacia lipase was most rapidly inactivated by Rc-(Rp,Sp)-1,2-dioctylcarbamoylglycero-3-O-p-nitrophenyl octylphosphonate (Rc-trioctyl) with an inactivation half-time of 75 min, while that for the Sc-(Rp,Sp)-1,2-dioctylcarbamoylglycero-3-O-p-nitrophenyl octyl-phosphonate (Sc-trioctyl) compound was 530 min. X-ray structures were obtained of P. cepacia lipase after reaction with Rc-trioctyl to 0.29-nm resolution at pH 4 and covalently modified with Rc-(Rp,Sp)-1,2-dibutylcarbamoylglycero-3-O-p-nitrophenyl butyl-phosphonate (Rc-tributyl) to 0.175-nm resolution at pH 8.5. The three-dimensional structures reveal that both triacylglycerol analogues had reacted with the active-site Ser87, forming a covalent complex. The bound phosphorus atom shows the same chirality (Sp) in both complexes despite the use of a racemic (Rp,Sp) mixture at the phosphorus atom of the triacylglycerol analogues. In the structure of Rc-tributyl-complexed P. cepacia lipase, the diacylglycerol moiety has been lost due to an aging reaction, and only the butyl phosphonate remains visible in the electron density. In the Rc-trioctyl complex the complete inhibitor is clearly defined; it adopts a bent tuning fork conformation. Unambiguously, four binding pockets for the triacylglycerol could be detected: an oxyanion hole and three pockets which accommodate the sn-1, sn-2, and sn-3 fatty acid chains. Van der Waals' interactions are the main forces that keep the radyl groups of the triacylglycerol analogue in position and, in addition, a hydrogen bond to the carbonyl oxygen of the sn-2 chain contributes to fixing the position of the inhibitor.

Binding Sites↗

Craniofacial access in children.

We have used craniofacial access in 20 children (age range 3/12-14 years) for complex skull base/intracranial pathology over the past 5 years. The majority of the patients had a tumour-7 of the skull base, 5 extensive suprasellar lesions and 3 acoustic neuromas; 4 had an aneurysm or AVM and in 1 there was a congenital problem. This extended application of established adult techniques in a paediatric practice emphasises the fundamental point that the quintessence of good surgical practice is the construction of an operation for the individual patient's pathology. We therefore used transzygomatic, orbital, transoral, transmandibular, petrous, transcondylar, translabyrinthine and transbasal access techniques. Good function and cosmesis with minimal complications were achieved. We have not observed complications with craniofacial growth and the majority of patients were able to return to normal school. The range of approaches used emphasise the importance of a multidisciplinary team with both paediatric and neurosurgical expertise, especially with complex vascular and skull base pathology, in dealing with these difficult problems. The case for specialist referral merits some discussion within the representative bodies of paediatric neurosurgeons.

Adolescent↗

Case of the month: June 1998--2 year old boy with lumbosacral mass.

We report the case of a boy aged 2 years with spina bifida and a lipomyelomeningocele which contained ectopic immature renal tissue. He presented with a swelling over the lumbosacral region, incontinence, and bilateral leg weakness. Histopathologic examination revealed adipose tissue in which a focus of fibrous tissue contained neuroglial elements, striated muscle fibres and clusters of glomeruloid structures surrounded by immature tubules. The differential diagnosis of teratoma and lipomyelomeningocele with nephrogenic rests is discussed with reference to possible pathogenesis.

Child, Preschool↗

Can we define or measure manual skills in surgical training?

Neurosurgery requires manual dexterity. But should tests be devised to assess manual skills as part of a selection process for training or used as a means of determining surgical competence? The paper debates this fundamental question and proposes that manual skills for neurosurgical tasks need to be defined within the overall context of a recognised and fully assessed training programme. The importance of training as a means of transferring competence, part of which is manual skills, is emphasised. In conclusion the paper points out the inadequacy of solely measuring manual skills, were it possible, in assessing neurosurgical competence.

Clinical Competence↗

The effect of orbitozygomatic access for ruptured basilar and related aneurysms on management outcome.

BACKGROUND: Despite increasing use of craniofacial access for complex intracranial and skull base pathology, there have been no reports detailing the impact of improved access on clinical outcome. METHODS: Orbitozygomatic access was used in 32 patients with an aneurysm of the basilar bifurcation, superior cerebellar, or posterior cerebral arteries over a 9-year period. RESULTS: Operative mortality was 0%, overall management mortality 9% and management morbidity was 9%. This approach was selected for these patients because of the anatomy of the aneurysm and its relationship to the terminal basilar complex and the dorsum sellae/posterior clinoid process. The flexibility achieved by the access allowed intraoperative use of multiple corridors of access. Morbidity directly attributable to the use of orbitozygomatic access was minimal. CONCLUSIONS: While management outcome after aneurysmal subarachnoid hemorrhage relates directly to the severity of the initial hemorrhage, rather than the surgical approach chosen, in selected patients we recommend the use of this approach as a valuable adjunct to the armamentarium of the vascular neurosurgeon.

Adult↗

The transzygomatic approach: an anatomical study.

The transzygomatic approach has been utilised to facilitate neurosurgical access to the skull base for a number of years. Advocates of the technique claim the additional access gained provides wider exposure of the neurosurgical pathology and improved visualisation of adjacent vital neurovascular structures. The aim of this study was to photographically demonstrate the technique and to highlight the anatomical areas to which access can be improved. A morphological cadaver study was undertaken. Specific intracranial structures in the vicinity of the skull base were targeted and exposure was compared with and without the zygoma in position. This study demonstrates the increase in exposure of the basilar bifurcation (via a transsylvian approach) and the P2 segment of the posterior cerebral artery (via a subtemporal approach) that can be achieved and the improved access to adjacent anatomical compartments. It can be concluded that the transzygomatic approach is a relatively simple technique which can readily increase exposure of the skull base. It also provides simultaneous access to the superior pole of the infratemporal fossa, the pterygopalatine fossa and the orbit.

Basilar Artery↗

The orbitozygomatic infratemporal fossa approach: a quantitative anatomical study.

Using detailed cadaveric dissections this study has demonstrated and quantified the increase in exposure and additional access gained by using the orbitozygomatic infratemporal fossa approach for neurosurgical access. The surgical window of exposure can be increased by up to 300% when this technique is utilised to facilitate access via either a subtemporal (to access the P2 segment of the posterior cerebral artery) or transsylvian (to access the basilar bifurcation) approach. In addition the distance between the surgeon and the operative field can be decreased by approximately 2-3 cm. The orbitozygomatic infratemporal fossa approach is a relatively simple technique which can readily increase neurosurgical exposure of the skull base. It also provides simultaneous access to the infratemporal fossa, pterygopalatine fossa and the orbit.

Craniotomy↗

The transzygomatic approach: a long-term clinical review.

The transzygomatic approach has been utilised to improve access to the skull base, infratemporal fossa and orbit for a number of years. It provides a low anterolateral approach to the skull base, along the floor of the middle fossa. It allows both a transsylvian and subtemporal approach with a reduction in brain retraction and better exposure of adjacent neurovasculature structures. A long term review of 53 patients is presented highlighting outcome at two years post surgery and morbidity of the approach. It is concluded that the technique is versatile and can be used to improve exposure of a variety of anatomical locations. There is minimal long term morbidity attributable to the surgery of access and the majority of patients have had good outcomes.

Adolescent↗

Craniofacial osteotomies for skull base access.

During a five year period 150 craniofacial access osteotomies for skull base access have been performed allowing direct exposure of pathology in difficult anatomical acreas with minimal complications. These approaches have been developed by considering the craniofacial skeleton as a single osteoplastic structure. Bone segments are mobilised and replaced using rigid fixation. In this way osteotomies can be planned which significantly improve access and preserve form and function in the complex region of the skull base.

Adult↗

A multidisciplinary approach to tumours involving the orbit: orbital re-construction, a 3-dimensional concept.

Radical tumour removal in the region of the anterior skull base with involvement of the orbit requires not only good exposure but also acceptable reconstruction with good cosmesis, no visible scars and no injury to the eye. The possible approaches, which should be flexible and adapted to the location and extent of the pathology and the appropriate methods of reconstruction, are illustrated by four patients. The relevant literature is reviewed. Emphasis on the need for a 3-dimensional concept in the reconstruction and the importance of a multi disciplinary team is stressed.

Adult↗

Delayed cerebral ischaemia: the pathological substrate.

Ischaemic complications both at the level of the cortex and the hypothalamus are well recognised after an aneurysmal subarachnoid haemorrhage. We have studied histological changes in the cortex (53 patients) and hypothalamus (48 patients) in patients who died after an aneurysmal subarachnoid haemorrhage. Cortical ischaemic lesions were demonstrated in 41 of the 53 patients studied. These changes were more common in patients who had impaired control of systemic blood pressure (p = 0.0004) and in patients who died gradually (p = 0.0003). Hypothalamic lesions were found in 24 of 48 patients studied; 23 of these patients had widespread associated changes in the cerebral cortex. Patients with moderate/severe cortical changes tended to have hypothalamic lesions and it was uncommon for patients with no cortical lesions to have changes in the hypothalamus (p = 0.0007). We believe that these histological changes are due to diffuse microangiopathy which develops slowly after a subarachnoid haemorrhage and affects the cortex and hypothalamus. Because the cortical lesions are widespread we postulate that they may be implicated in the aetiology of the well described psychosocial or cognitive problems in patients who survive a subarachnoid haemorrhage.

Adult↗

Latent autoimmune diabetes mellitus in adults (LADA): the role of antibodies to glutamic acid decarboxylase in diagnosis and prediction of insulin dependency.

Type 1 diabetes mellitus in adults may present in a manner similar to that of Type 2 diabetes but with a late development of insulin dependency. We studied 65 patients who presented with 'adult-onset' diabetes after the age of 30 years. Of these patients, 19 required insulin therapy. The insulin-treated patients were significantly younger, their onset of diabetes was at an earlier age, and their postprandial serum C-peptide levels were lower than those of the non-insulin-treated group. Moreover, the insulin-treated subjects had a higher mean concentration of antibodies to glutamic acid decarboxylase (GAD) (66.8 +/- 10.2 units) than the patients who did not require insulin (9.9 +/- 1.9 units) (p < 0.001) and their frequency of anti-GAD positivity was 73.7% versus 4.3% (p < 0.001). Thus, among patients attending a diabetes clinic, the majority (73.7%) of subjects who presented with diabetes after 30 years of age and who subsequently required therapy with insulin, actually have the islet cell lesion of Type 1 diabetes which progresses at a slower tempo than in children. We conclude that testing for anti-GAD in adult-onset non-obese diabetic patients should be a routine procedure in order to detect latent insulin-dependency at the earliest possible stage, since this assay can assist in the correct classification of diabetes, and more appropriate therapy.

Adult↗

Diffuse brain swelling after head injury: more often malignant in adults than children?

A series of 118 patients with diffuse traumatic brain swelling was studied retrospectively in order to compare the clinical findings in children with those in adults, and to determine the occurrence of neurological deterioration and outcome. The computerized tomography (CT) picture of absent third ventricle and basal cisterns was used to identify the cases. Although this condition has been associated with children, we found the same number of children and adults (59 cases each). Secondary deterioration (decline in consciousness, the development of new focal neurological signs, or an increase in intracranial pressure) occurred in 40% of cases and was more common in adults than children. Features that were significantly associated with deterioration were the presence of prolonged coma (> 1 hour) after the injury, CT signs of diffuse axonal injury or subarachnoid hemorrhage, or a recorded episode of hypotension. A moderate or good recovery at 6 months was achieved by 70 patients (59%), but 45 patients had a poor outcome (severe disability in nine, vegetative state in three, and death in 33) and this was often a consequence of secondary deterioration. In three patients, the outcome was not known. The combination of a severe initial injury, secondary insult, and diffuse swelling is associated with a poor outlook, particularly in adults. The CT appearance of diffuse swelling may develop more readily in children because of the lack of cerebrospinal fluid available for displacement. In children, diffuse swelling may have a relatively benign course unless there is a severe primary injury or a secondary hypotensive insult.

Adolescent↗

The management outcome of patients with a ruptured posterior circulation aneurysm.

From 1979-1986 121 patients with a vertebro basilar aneurysm were admitted to the Institute of Neurological Sciences, Glasgow. Of the 121 patients, 97 presented with a subarachnoid haemorrhage. In these patients the management mortality was 30% and the operative mortality 13%. Sixteen patients rebled and 16 developed delayed ischaemia. The prognosis of a patient with a ruptured vertebro basilar aneurysm admitted to our Institute is similar to that of a patient with aneurysmal subarachnoid haemorrhage from an anterior circulation aneurysm.

Adolescent↗