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Biomedical subjects

A D Smith

Publications and source records attributed to A D Smith.

At least 163 records · Page 9Linked to original sources
PubMed1997

Synergy between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset confirmed Alzheimer's disease.

The allelic frequency of the gene for the K variant of butyrylcholinesterase (BCHE-K) was 0.17 in 74 subjects with late-onset (age > 65 years) histopathologically diagnosed Alzheimer's disease (AD), which was higher than the frequencies in 104 elderly control subjects (0.09), in 14 early-onset cases of confirmed AD (0.07) and in 29 confirmed cases of other dementia (0.10). The association of BCHE-K with late-onset AD was limited to carriers of the epsilon 4 allele of the apolipoprotein E gene (APOE), among whom the presence of BCHE-K gave an odds ratio of confirmed late-onset AD of 6.9 (95% C.I. 1.65-29) in subjects > 65 years and of 12.8 (1.9-86) in subjects > 75 years. In APOE epsilon 4 carriers over 75 years, only 1/22 controls, compared with 10/24 confirmed late-onset AD cases, had BCHE-K. We suggest that BCHE-K, or a nearby gene on chromosome 3, acts in synergy with APOE epsilon 4 as a susceptibility gene for late-onset AD.

Age of Onset↗
PubMed1997

The effects of additional pathology on the cognitive deficit in Alzheimer disease.

The diagnosis of Alzheimer disease (AD) according to current criteria is a combined clinical and pathological exercise. The clinical discrimination of AD from other types of dementia may be complicated when the patient suffers from more than one disease. In particular the concomitant presence of other neurological conditions may significantly influence the severity of cognitive deficit. In this study we analyze the extent of the influence of vascular and other neurodegenerative pathology on the cognitive deficit in a consecutive series of 88 prospectively assessed elderly subjects. We find that, for any given level of cognitive deficit, the densities of either all plaques or neuritic plaques alone in the neocortex are significantly lower in cases of AD mixed with other CNS pathology than in cases of AD with no other CNS pathology. In AD combined with cerebrovascular disease, the total plaque density makes a significant contribution to cognitive deficit, while neurofibrillary tangle (NFT) densities do not. In contrast, in pure AD tangle density is the major determinant of cognitive deficit. Our findings draw attention to the influence of coexisting brain pathologies on the clinical manifestation of dementia in subjects with AD. These findings indicate that pathological diagnostic criteria for AD should take into account such additional pathology in demented subjects. They also improve understanding of the circumstances in which the amyloid component of AD can play a decisive role in precipitating clinical dementia.

Aged↗
PubMed1997

Identification and analysis of expression of human VACM-1, a cullin gene family member located on chromosome 11q22-23.

We have localized the human homolog of the rabbit vasopressin-activated calcium-mobilizing receptor VACM-1 to a region close to the gene for ataxia telangiectasia ATM on chromosome 11q22-23. We have determined the complete amino acid sequence of the human Hs-VACM-1 protein, which is 780 amino acids long. The human and rabbit sequences are highly conserved, differing at only seven amino acids. Northern analysis of the human gene showed expression in a wide range of human tissues. The Hs-VACM-1 gene has homology with the Caenorhabditis elegans gene Ce-cul-5, a member of a family of cullin genes that are involved in cell cycle regulation and that might, when mutated, contribute to tumor progression.

Amino Acid Sequence↗
PubMed1997

Competition of adenine nucleotides for a 1,3-[3H]-dipropyl-8-cyclopentylxanthine binding site in rat vas deferens.

1. The binding of 1,3-[3H]-dipropyl-8-cyclopentylxanthine ([3H]-DPCPX), a specific adenosine A1 receptor antagonist, was examined in rat vas deferens membrane preparations using radioligand binding techniques. 2. 1,3-[3H]-Dipropyl-8-cyclopentylxanthine bound to these preparations with a KD of 1.07 +/- 0.14 nmol/L (n = 6). The density of [3H]-DPCPX binding sites was 133.38 +/- 5.57 fmol/mg protein. 3. Computer analysis indicated that nucleosides competed for [3H]-DPCPX binding at two distinct sites. The rank order of potency at the higher affinity site corresponded to R-phenylisopropyladenosine (R-PIA) > or = 2-chloroadenosine (2-CIADO) > or = cyclopentyladenosine (CPA) > or = N-ethylcarboxamidoadenosine (NECA) > s-phenylisopropyladenosine (s-PIA). Ki values were in the low nmol/L range. The rank order of nucleoside potency at the lower affinity site corresponded to R-PIA > or = CPA > or = NECA > or = 2-CIADO > S-PIA. Ki values were in the low mumol/L range. 4. Nucleotides competed for [3H]-DPCPX binding at a single site only. The rank order of potency at this site corresponded to alpha, beta-methylene ATP > or = beta, gamma-methylene ATP > or = ATP. Ki values were in the high mumol/L range. The site seemed to correspond with one of the two binding sites predicted by nucleoside competition binding. 5. The ATP-regenerating compound myokinase did not significantly change the competition curve for ATP, indicating that the competition for [3H]-DPCPX binding observed in the presence of ATP was due to an effect of ATP per se and not to an action of a degradation product. 6. The results demonstrate that in rat vasa deferentia there exist two distinct binding sites for [3H]-DPCPX. One of these sites binds only nucleosides and may represent an adenosine A1 receptor, as usually defined. The other site binds both nucleosides and nucleotides and may represent an atypical adenosine A1 receptor, an atypical P2 or a P3 purinoceptor.

2-Chloroadenosine↗
PubMed1997

Physical restraint of patients in a psychiatric hospital.

Use of physical restraint occurs within British psychiatric hospitals yet there has been little evaluative research on current practice. The present study aims to describe a group of disturbed in-patients who had required physical restraint at some point during the course of their stay in hospital and to classify the reasons for its use. Cases were identified using Case Register data and information obtained from patients' records. In the 48 episodes of physical restraint identified, patients were predominantly schizophrenic (60%), male (67%) and had been restrained because of physical violence to others (44%) or because they were attempting to abscond (31%). Although the majority of patients were compulsorily detained prior to the use of physical restraint, three remained informal. The findings are discussed in the context of the legal justifications for use of restraint. Further research on current practice is required to enable formulation of clear guidelines.

Adult↗
PubMed1997

Serum ferritin: it may guide the diagnosis of the anaemic patient.

Crohn's disease is often complicated by anaemia. Assessment of iron deficiency may be hampered by modification of the serum ferritin concentration because of the associated acute phase response when disease is active. However a ferritin value of < 5 micrograms/L is indicative of iron deficiency, which is rarely found in Crohns disease.

Adult↗
PubMed1997

Carcinoma of the bronchus in the Yorkshire region of England 1976-1990: trends since 1984.

We wished to confirm that, in patients with lung cancer, trends in demography and histology, together with modest improvements in survival, first seen in the 1976-1983 cohorts, continued to 1990. All lung cancer patients resident in Yorkshire are notified to the Cancer Registry, whose database was analysed for this report. A total of 38,275 patients were notified. There was no change in annual notification for males but an increase from 513 to 815 annual notifications in females between 1976 and 1990. Mean age increased by 3 yrs, in males to 67.4 yrs and in females to 67.2 yrs. Histological confirmation rate increased from 43% to 60% (mean age from 60.8 to 64.5 yrs). Annual notifications of adenocarcinoma increased consistently from 108 to 253. Two year surgical survival improved from 37.4 to 44.3%, doubling in subjects aged > or = 70 yrs to 43.8%. Over the 15 year period, there was no improvement in survival aged < 60 yrs, but a significant improvement in the 60-69 and > or = 70 yrs age groups. Analysis of survival by quartiles showed significant improvement at all levels (first interval 20 to 24 days, median 79 to 91 days, third interval 224 to 266 days). The modest improvement in outlook was confirmed, confined to older subjects after 1983, and partially masked by increasing age. Survival after surgery is now independent of age.

Adenocarcinoma↗
PubMed1997

Subclinical slipped capital femoral epiphysis. Relationship to osteoarthrosis of the hip.

We examined the femora of 2665 adult human skeletons from an osteological collection to determine the prevalence of post-slip morphology termed femoral head-tilt deformity by Murray and pistol-grip deformity by Stulberg et al. The hypothesis was that primary osteoarthrosis of the hip is a secondary manifestation of a subclinical developmental disorder of the hip. The prevalence of post-slip morphology was 8 per cent (215 of 2665 skeletons). Severe osteoarthrosis was more prevalent in association with post-slip morphology (116 [38 per cent] of 306 hips) than in the matched controls (seventy-nine [26 per cent] of 306 hips) (p < 0.005). In the skeletons that had unilateral post-slip morphology, severe osteoarthrosis was more prevalent in the involved hips (thirty-one [37 per cent] of eighty-three) than in the contralateral, normal hips (eighteen [22 per cent] of eighty-three) (p < 0.05). Post-slip morphology, which was unrelated to age, was found to be a major risk factor for the development of high-grade osteoarthrosis. We noted evidence of high-grade osteoarthrosis in sixty-three (68 percent) of the ninety-three hips with minimum post-slip morphology in skeletons from individuals who had been fifty-six years old or more at the time of death compared with forty-five (48 percent) of the ninety-three control hips. This difference was significant (p < 0.025) [corrected]. The osteoarthrosis in the hips with post-slip morphology was distinctly characterized by anterior flattening of the acetabulum, cystic degeneration in the anterior metaphyseal-epiphyseal region, and progression to global osteoarthrosis of the hip.

Acetabulum↗
PubMed1997

Percutaneous renal surgery.

Percutaneous renal surgery involves instrumentation of the renal collecting system (renal pelvis and calyces) via direct percutaneous access to diagnose and treat a multitude of urological conditions. This chapter will outline the indications, techniques, complications and results of this relatively new and effective operative approach.

Journal Article↗
PubMed1997

Adenocarcinoma of the cervix: a regional retrospective study.

A retrospective study using data from the Yorkshire Cancer Registry was undertaken to investigate the incidence, characteristics and prognosis of cases of cervical adenocarcinoma in the Yorkshire Region. Three hundred and twenty-six women resident in the Yorkshire Region formed the basis of the study. The overall five year survival for adenocarcinoma of the cervix is 53%. This was influenced by stage, lymph node involvement and differentiation. 37 out of 122 surgically treated patients received inappropriate treatment. There is a need for improved data collection in the treatment of these patients. This lends weight to the argument that cancer of the cervix should be managed in cancer units.

Adenocarcinoma↗
PubMed1997

Massive hemorrhage from renal vein injury during percutaneous renal surgery: endourological management.

PURPOSE: Although minor venous injuries respond to simple maneuvers, major venous injuries pose a significant therapeutic problem and may be under diagnosed. We present our experience with major injury to the renal vein during percutaneous renal surgery. MATERIALS AND METHODS: Four patients had massive hemorrhage during percutaneous renal surgery associated with major injury to the renal vein, and 3 also had renal insufficiency. All 4 patients and 1 additional patient with renal insufficiency and massive hemorrhage from an arteriovenous fistula following percutaneous renal surgery were treated nonoperatively with a selectively positioned and inflated Council balloon catheter. RESULTS: Hemorrhage was controlled and renal function was unaffected in all 5 patients. CONCLUSIONS: Renal vein injuries can be associated with massive hemorrhage. Patients with major vascular injuries from percutaneous renal surgery and concomitant renal insufficiency can be treated without open exploration or angiographic embolization using a Council balloon catheter.

Aged↗
PubMed1997

Open surgical exploration after failed endopyelotomy: a 12-year perspective.

PURPOSE: Factors that have a role in endopyelotomy failure have not been fully elucidated but are believed to include high grade hydronephrosis and the presence of crossing vessels at the ureteropelvic junction. MATERIALS AND METHODS: We retrospectively analyzed the importance of renal function, hydronephrosis, ureteral stents, surgeon experience and crossing vessels in determining the outcome of endopyelotomy. RESULTS: Of 401 percutaneous antegrade endopyelotomies performed at our medical center during the last 12 years 60 failed and 54 of these patients underwent surgical exploration. Patients with high grade hydronephrosis and poor initial renal function were much less likely to have successful endopyelotomy than those with moderate hydronephrosis or good renal function (success rates 50 versus 96 and 54 versus 92%, respectively, p <0.001). The most common findings at exploration included severe extrinsic fibrosis and intrinsic fibrotic stenosis. Obstructing crossing vessels were present in 13 patients explored, suggesting a possible role in causing failure in only 4% of all endopyelotomy patients. CONCLUSIONS: Patients with high grade hydronephrosis and poor initial renal function are much more likely to experience endopyelotomy failure. Crossing vessels appear to have a less significant role in endopyelotomy failure than has been previously suggested.

Adolescent↗
PubMed1997

A multicenter clinical trial investigating the use of a fluoroscopically controlled cutting balloon catheter for the management of ureteral and ureteropelvic junction obstruction.

PURPOSE: We assessed the efficacy of a fluoroscopically controlled cutting balloon catheter for the treatment of ureteropelvic junction and ureteral strictures. MATERIALS AND METHODS: A multicenter trial was performed that included 66 endopyelotomies and 49 endoureterotomies. To our knowledge this study represents the largest number of patients with ureteropelvic junction obstruction and ureteral strictures tested with this device to date. RESULTS: With a mean followup of 7.8 months (range 1 to 17.9) the patency rate was 77% for endopyelotomy, with 72% of the primary and 100% of the secondary ureteropelvic junction obstructions remaining patent. The endoureterotomy patients were followed for an average of 8.7 months (range 1.2 to 17.0), with a patency rate of 55%. CONCLUSIONS: A cutting balloon endoscopic incision is effective in the majority of cases, with patency rates for endopyelotomies and endoureterotomies that mirror current endourological reports using other, albeit more time intensive and more invasive, incisional techniques.

Adolescent↗
PubMed1997

Characteristics of in-patients transferred to a locked ward in a Scottish psychiatric hospital.

OBJECTIVE: To identify and characterise in-patients transferred from open wards to the locked facility (IPCU) of a psychiatric teaching hospital, and to classify reasons for transfer. DESIGN: Retrospective case note study using the Lothian Psychiatric Case Register. A reason for transfer classification was devised. SETTING: Intensive Psychiatric Care Unit (IPCU) of the Royal Edinburgh Hospital. SUBJECTS: All in-patients transferred from other wards of the Royal Edinburgh Hospital to the IPCU during one year. RESULTS: Over one year there were 131 transfer episodes involving 97 patients. Ninety-eight per cent of episodes could be allocated to one of six categories of reason for transfer, with physical violence to others being commonest (30%). Patients' mean age was 31 years. There was a predominance of schizophrenics (51%) and males (66%). In 20% of transfers, patients were not detained under mental health legislation. Associations emerged between schizophrenia and physical violence, hypomania/mania and generally disruptive behaviour, personality disorder and self harm. In half of all transfers the patient had already been an in-patient for at least 1 month. Fifty-seven per cent of patients were transferred more than once over the preceding five years. Most (90%) transfers originated from acute wards, and patients stayed in the IPCU less than two weeks (70%) before returning to the open wards (23% less than 24 hours). CONCLUSIONS: Local locked wards deal with a range of disturbed behaviour and can be an important component in the spectrum of secure provision. Further evaluative research is required.

Adolescent↗
PubMed1997

Protein engineering to create biologically active peptides: recombinant human rhinoviruses that display peptide sequences.

This paper describes the use of human rhinovirus to display peptides corresponding to biologically active sequences. While this system can be used to reconstruct essentially any biologically active sequence for which there is a corresponding ligand that can be used for its selection, we have focused on using this system to display immunogens from dangerous pathogens as a means to develop vaccines. Five mutagenesis approaches are illustrated as ways to generate functionally active moieties. The mutagenesis approaches illustrated can be employed with any of a large number of possible display vectors; however, human rhinovirus might be especially useful in cases where it will be important to derive the benefits of delivery by a live-virus approach. Examples are shown in which reconstruction of immunogens corresponding to the V3 loop of the gp120 glycoprotein of the human immunodeficiency virus type 1 (HIV-1) on the surface of rhinovirus has yielded apparently effective mimics of the HIV-1 immunogens (as measured by their ability to be neutralized by anti-HIV-1 antibodies as well as their ability to elicit the production of antibodies capable of neutralizing HIV-1 in cell culture). This system offers the opportunity to reconstruct functionally important moieties that derive from proteins or pathogens that are either too dangerous or difficult to isolate for use as vaccine preparations themselves.

Amino Acid Sequence↗
PubMed1996

Amygdala input to medial prefrontal cortex (mPFC) in the rat: a light and electron microscope study.

This paper describes the termination pattern and synaptic connectivity of the pathway from the basolateral nucleus of the amygdala (BLA) to the medial prefrontal cortex (mPFC; areas 25, 32, and 24b) of the rat. Discrete injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) were made in the BLA and detailed light microscopical observations made of the distribution of PHA-L labelled fibres and boutons in the mPFC. Labelled fibres were distributed in two tiers: predominantly within deep layer 1/layer 2 and also in layers 5/6. Fibre plexi in layers 2 and 5 were highly varicose. Electron microscopical examination of 120 labelled boutons in area 32 (60 in layer 2 and 60 in layer 5) indicated that 116 (97%) established asymmetrical synaptic contacts with dendritic spines and 4 (3%) were in synaptic contact with small dendritic shafts. No significant differences in target structures were found between layers 2 and 5. The results indicate that BLA input to mPFC in the rat predominantly innervates spine bearing dendrites in layers 2 and 5. This suggests that the neuronal operations of these processes are influenced by direct feedforward excitation from the BLA.

Afferent Pathways↗