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Biomedical subjects

D A Lang

Publications and source records attributed to D A Lang.

At least 19 recordsLinked to original sources
PubMed2000

Crystal structure of pseudomonas aeruginosa lipase in the open conformation. The prototype for family I.1 of bacterial lipases.

The x-ray structure of the lipase from Pseudomonas aeruginosa PAO1 has been determined at 2.54 A resolution. It is the first structure of a member of homology family I.1 of bacterial lipases. The structure shows a variant of the alpha/beta hydrolase fold, with Ser(82), Asp(229), and His(251) as the catalytic triad residues. Compared with the "canonical" alpha/beta hydrolase fold, the first two beta-strands and one alpha-helix (alphaE) are not present. The absence of helix alphaE allows the formation of a stabilizing intramolecular disulfide bridge. The loop containing His(251) is stabilized by an octahedrally coordinated calcium ion. On top of the active site a lid subdomain is in an open conformation, making the catalytic cleft accessible from the solvent region. A triacylglycerol analogue is covalently bound to Ser(82) in the active site, demonstrating the position of the oxyanion hole and of the three pockets that accommodate the sn-1, sn-2, and sn-3 fatty acid chains. The inhibited enzyme can be thought to mimic the structure of the tetrahedral intermediate that occurs during the acylation step of the reaction. Analysis of the binding mode of the inhibitor suggests that the size of the acyl pocket and the size and interactions of the sn-2 binding pocket are the predominant determinants of the regio- and enantio-preference of the enzyme.

Amino Acid Sequence↗
PubMed2000

Outcome from complex neurosurgery: an evidence based approach.

BACKGROUND: The aim of this study was to determine outcome, including quality of life, after surgery for petroclival meningioma using a standard skull base approach and to carry out an evidence based appraisal of the relevant literature. METHOD: Pre- and post-operative data including adverse events were prospectively recorded in 19 patients (15 females, age range 29-63) undergoing a transpetrous approach for a petroclival meningioma. Patients were assessed using the GOS and SF-36 post operatively. FINDINGS: 24 operations were done. 6 patients developed a new permanent neurological deficit and 10 experienced a temporary deficit or exacerbation of existing deficits. At 1 year 15 patients had made a good/moderate recovery, 3 were severely disabled and 1 died--in keeping with other studies. By contrast the SF-36 showed that in all 8 categories of the SF-36 between 39-72% of surviving patients were functioning below the accepted norms. INTERPRETATION: After transpetrous excision of a petroclival meningioma the quality of life for the patient is worse than that indicated in surgeons' reported results. This paper represents an attempt to address the issue of evidence-based medicine and finds that such an approach is not apparent in the medical literature on this pathology. While we argue that methods for measuring outcome should be refined and carers input recognised it does raise certain philosophical considerations. It is the counsel of perfection and if achieved may lead to surgeons operating on fewer patients, more petroclival cases being viewed as inoperable because of the higher morbidity, despite there being an inescapable pathway to surgical intervention.

Adult↗
PubMed2000

Crystallization and preliminary X-ray diffraction analysis of the NAD-dependent non--phosphorylating GAPDH of the hyperthermophilic archaeon Thermoproteus tenax.

Recombinant non-phosphorylating NAD(+)-dependent glyceraldehyde-3-phosphate dehydrogenase (GAPN) of the hyperthermophilic crenarchaeote Thermoproteus tenax has been overexpressed, purified and crystallized using the hanging-drop vapour-diffusion technique. Crystals of different habits were obtained from several precipitant solutions (salts and polyethylene glycols). Preliminary X-ray analysis was performed with crystals grown in ammonium formate, which belonged to the primitive hexagonal space group P622, and had unit-cell parameters a = b = 184.8, c = 133.0 A, gamma = 120 degrees. Assuming a molecular weight of 55 kDa, a Matthews parameter of 3.3 A(3) Da(-1) is calculated assuming two molecules per asymmetric unit. The diffraction limit of these crystals is 2.5 A resolution.

Base Sequence↗
PubMed1999

Efficient expression, purification and crystallisation of two hyperthermostable enzymes of histidine biosynthesis.

Enzymes from hyperthermophiles can be efficiently purified after expression in mesophilic hosts and are well-suited for crystallisation attempts. Two enzymes of histidine biosynthesis from Thermotoga maritima, N'-((5'-phosphoribosyl)-formimino)-5-aminoimidazol-4-carb oxamid ribonucleotide isomerase and the cyclase moiety of imidazoleglycerol phosphate synthase, were overexpressed in Escherichia coli, both in their native and seleno-methionine-labelled forms, purified by heat precipitation of host proteins and crystallised. N'-((5'-phosphoribosyl)-formimino)-5-aminoimidazol-4-carb oxamid ribonucleotide isomerase crystallised in four different forms, all suitable for X-ray structure solution, and the cyclase moiety of imidazoleglycerol phosphate synthase yielded one crystal form that diffracted to atomic resolution. The obtained crystals will enable the determination of the first three-dimensional structures of enzymes from the histidine biosynthetic pathway.

Aldose-Ketose Isomerases↗
PubMed1999

The extended transbasal approach: a quantitative anatomical and histological study.

Since its introduction in 1972 the transbasal approach to the anterior fossa and sphenoethmoidal region has undergone a number of modifications. The extended transbasal approach with preservation of olfaction not only improves exposure of the anterior fossa, but also provides access to the clivus as far inferiorly as the foramen magnum. An anatomical study has been undertaken to photographically demonstrate and quantify the varying degrees of exposure that this technique provides. The pituitary stalk was used as an intracranial target. The amount of exposure was compared using a standard subfrontal approach, a transbasal approach and an extended transbasal with preservation of olfaction. In addition, a histological study was carried out to investigate the level to which identifiable olfactory nerves extended into the nasal mucosa. The anatomical study demonstrates the area of the "external window of exposure" can be doubled using a transbasal approach and more than quadrupled using the extended transbasal approach, when gaining access to the pituitary stalk. In addition, the study highlights the exposure of other anatomical areas, such as the medial orbit, the cavernous sinus, the clivus and the vertebrobasilar complex. The histological study establishes that the olfactory nerves extend only 10 mms below the cribriform plate.

Brain↗
PubMed1999

The extended transbasal approach: clinical applications and complications.

OBJECTIVES: To describe in detail key technical aspects of the extended transbasal approach which involves en-bloc mobilisation of the supraorbital rim, the orbital roof and the nasoethmoidal complex. In some patients osteotomies were performed around the cribriform plate with a view to maintaining olfaction. To review 18 patients with deep seated lesions located in the central skull base region (including 6 recurrences) to highlight patient selection, presentation, surgical morbidity and outcome. METHODS: Prospective data recording and clinical chart review. RESULTS: Outcome was assessed at a minimum of 1 year after operation using the Glasgow Outcome Score. Thirteen patients had made a good recovery, 1 was moderately disabled, 2 were severely disabled (both had been severely disabled before operation), and 2 died. By contrast, quality of life assessment indicated that only 7 of the surviving 14 adults had returned to normal levels of activity and perceived health; although 6 of the other 7 patients had resumed their former occupations, their follow up assessments showed a reduced quality of life. Of the 13 patients who had an olfaction preservation procedure, 6 showed appreciation of smell on formal testing. CONCLUSIONS: In patients with progressive and extensive deep seated lesions this technique provides wide exposure in a shallow surgical field. Complication rates although acceptable were significantly higher in patients with intradural lesions. In some selected patients it was possible to preserve olfaction. Specific surgical outcome assessments pointed to satisfactory results, but failed to reflect the degree of patient disability. There is a need for outcome measures that take into account the patient's expectations and which address his quality of life in order to validate the benefits of these procedures.

Adolescent↗
PubMed1999

Outcome after complex neurosurgery: the caregiver's burden is forgotten.

OBJECT: The goals of this study were twofold: 1) to determine outcome, including quality of life, in patients who have undergone surgery for petroclival meningioma in which a standard skull base approach was used; and 2) to assess the impact of the patients' surgical treatment on their caregivers. METHODS: Seventeen patients (13 women and four men ranging in age from 29 to 63 years) who underwent a transpetrosal approach for a petroclival meningioma during a 5-year period were prospectively included in this study. Pre- and postoperative data including adverse events were noted. The patients were assessed at 3, 6, and 12 months postoperatively, and annually thereafter, and they completed a postoperative SF-36 questionnaire. In addition, each patient's caregiver was interviewed to determine the effect of the patient's illness on the caregiver's life and responsibilities. Twenty-two operations were performed. A new permanent neurological deficit developed in five patients and in eight a temporary deficit or exacerbation of existing deficits occurred. Two patients underwent surgery to create a facial-hypoglossal nerve communication; five required a temporary percutaneous gastrostomy and/or tracheostomy; three required a shunt; and one underwent successful squint surgery. At 1 year postoperatively 13 patients had made a good or moderate recovery, three were severely disabled, and one had died--outcomes in keeping with other studies. By contrast, responses to the SF-36 questionnaire showed that, in all eight of its categories, between 43% and 75% of surviving patients were functioning below accepted norms. Fifty-six percent of caregivers experienced a major change in lifestyle and 38% experienced a major change with respect to their work. CONCLUSIONS: After transpetrosal excision of a petroclival meningioma, the quality of life for the patient is worse than that indicated in surgeons' reported results. The impact on the patient's caregiver is profound-a burden perhaps not fully appreciated by the surgeon.

Adult↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1995

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↗