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Biomedical subjects

F W Smith

Publications and source records attributed to F W Smith.

At least 19 recordsLinked to original sources
PubMed1992

Quadruplex structure of Oxytricha telomeric DNA oligonucleotides.

The telomeres of most eukaryotes contain a repeating G-rich sequence with the consensus d(T/A)1-4G1-8, of which 12-16 bases form a 3' single-strand overhang beyond the telomeric duplex. It has been proposed that these G-rich oligonucleotides associate to form four-stranded structures from one, two or four individual strands and that these structures may be relevant in vivo. The proposed structures contain Hoogsteen base-paired G-quartets, precedent for which has been in the literature for many years. Here we use 1H NMR spectroscopy to study the conformations of the DNA oligonucleotides d(G4T4G4) (Oxy-1.5) and d(G4T4G4T4G4T4G4) (Oxy-3.5) which contain the Oxytricha telomere repeat (T4G4). We find that these molecules fold to form a symmetrical bimolecular and an intramolecular quadruplex, respectively. Both structures have four G-quartets formed from nucleotides that are alternately syn and anti along each strand. This arrangement differs from earlier models in which the strands are alternately all syn or all anti. The T4 loops in Oxy-1.5 are on opposite ends of the quadruplex and loop diagonally across the G-quartet, resulting in adjacent strands being alternately parallel and antiparallel.

Animals↗
PubMed1992

Lyophilized formulations of recombinant tumor necrosis factor.

Recombinant tumor necrosis factor-alpha (TNF), an investigational biological response modifier, is a protein and is susceptible to particulate generation during handling in dilute aqueous solutions. TNF is prone to formation of nonreducible dimers and oligomers during formulation, lyophilization, and storage. The effect of various parameters, such as the pH, protein concentration, and nature of excipients present during lyophilization, on the formation of nonreducible dimers and oligomers was investigated. The results of these studies indicate that these parameters can significantly alter the rate of this reaction. Inclusion of an amorphous buffer and an appropriate amount of a crystallizing sugar (mannitol) combined with a suitable quantity of an amorphous protectant (dextran, sucrose, trehalose, or 2-hydroxypropyl-beta-cyclodextrin) was shown to reduce the formation of these dimeric and oligomeric species during lyophilization. Representative lyophilized formulations of TNF based on selected amorphous excipients were found to be fully bioactive and stable over 9 months.

Biological Assay↗
PubMed1992

Pattern of 2-deoxy-2-[18F]-fluro-D-glucose accumulation in liver tumours: primary, metastatic and after chemotherapy.

Eight patients with liver metastases from adenocarcinoma of the colon or rectum, two with suspected hepatic metastases and one with primary hepatoma were studied with 2-deoxy-2-[18F]-fluro-D-glucose (18F-FDG) using positron emission tomography (PET). In five of the patients with metastatic tumour a second examination was performed four weeks after treatment with recombinant interleukin-2 (rIL2) and fluorouracil (5FU). In all tumours (one primary and eight metastatic) the radioactivity was seen to accumulate in a rim around each tumour with a large central area showing no uptake. In the five cases imaged after treatment with rIL2, the appearance of the tumour uptake was the same as before treatment. In the two cases of suspected but not proven metastases, no abnormal accumulation of 18F-FDG was seen.

Adenocarcinoma↗
PubMed1992

Alzheimer's disease in adults with Down's syndrome: the relationship between regional cerebral blood flow equivalents and dementia.

Twenty adult patients suffering from Down's syndrome (DS) were recruited from hospitals and the community, together with 14 age- and sex-matched controls of normal intelligence. Dementia was diagnosed in patients using a structured psychiatric and physical examination as well as a carer interview and case notes. All patients and controls were imaged using single photon emission computerized tomography with 99mTc-exametazime. Four patients were clinically demented and all of them showed regional cerebral blood flow (rCBF) changes commonly found in patients with Alzheimer's disease, namely bilateral temporo-parietal deficits. These changes were also observed in about half of the patients without clinical evidence of dementia, but in none of the healthy controls. Across the group of patients, temporo-parietal rCBF deficits were associated with evidence of deterioration, but not with advancing age.

Adult↗
PubMed1992

Measurement of blood flow in tibial fracture patients using positron emission tomography.

The quantification of local bone blood flow in man has not previously been possible, despite its importance in the study of normal and pathological bone. We report the use of positron emission tomography, using 15O-labelled water, to measure bone blood flow in patients with closed unilateral fractures of the tibia. We compared fractured and unfractured limbs; alterations in blood flow paralleled those found in animal models. There was increased tibial blood flow at the fracture site as early as 24 hours after fracture, reaching up to 14 times that in the normal limb at two weeks. Blood flow increase was less in displaced than in undisplaced fractures. The muscle to bone ratios of blood flow were similar to those in previous animal work using other techniques. Positron emission tomography will allow study of human bone blood flow in vivo in a wide variety of pathological conditions.

Adult↗
PubMed1992

Neurophysiologic basis of acupuncture.

Research has shown that the benefits of acupuncture are truth, not fiction. Acupuncture effects are due to local effects, stimulation of neuroendocrine systems, and modulation of the body's electromagnetic energy. The exact mechanisms activated depend on point selection, type of stimulation, and probably time of day. The effectiveness of the treatment will depend on the disease entity treated and the skill and knowledge of the acupuncturist. Knowledge should include both the fundamental principles of Chinese medicine and the more recent scientific understanding of acupuncture's physiologic basis.

Acupuncture Analgesia↗
PubMed1992

Effect of sodium hyaluronate in collagenase-induced superficial digital flexor tendinitis in horses.

Superficial digital flexor tendinitis was induced in each forelimb of 8 horses by injecting 4,000 U of collagenase into the midmetacarpal region of the tendon. In each horse, each tendon was treated 24 and 96 hours after the collagenase injection with SC injections of sodium hyaluronate (treated limbs) or an equal volume of 0.9% NaCl solution (control limbs). Exercise was restricted for the first 3 weeks of the study, and a controlled exercise program was instituted for the remainder of the study. Horses were evaluated clinically for lameness, tendon swelling, and midmetacarpal limb circumference. Ultrasonographic examinations were performed regularly (11 examinations/horse) throughout the study, and all horses were euthanatized 12 weeks after collagenase injections. Tendons from 4 horses were harvested for biomechanical testing, and samples were obtained from tendons from the remaining 4 horses for biochemical analysis of collagen. Samples were obtained from all tendons for microscopic evaluation. Significant differences between treated and control tendons were not noticed in any of the variables examined in live horses, although trends toward less lameness in treated limbs and toward better healing on ultrasonographic examination in control limbs were recorded. Significant differences were not noticed in biomechanical or biochemical evaluations, and the only significant (P < 0.05) microscopic finding was more severe inflammation in tendons from treated limbs. This study did not reveal significant benefits of treatment with sodium hyaluronate outside a synovial sheath on tendon repair in collagenase-induced tendinitis.

Animals↗
PubMed1992

Acupuncture for cardiovascular disorders.

Experimental studies in animals and clinical studies in humans have demonstrated that acupuncture can exert significant effects on the cardiovascular system and provide effective therapy for a variety of cardiovascular ailments. In veterinary practice, acupuncture should be considered as adjunctive therapy in cases of shock and cardiac arrest. Acupuncture may also be beneficial as adjunctive or sole therapy in the management of congestive heart failure, arrhythmias, and systemic hypertension.

Acupuncture Therapy↗
PubMed1992

The short term effects of oral labetalol in patients with chronic renal disease and hypertension.

This double-blind, controlled, crossover study compared the effects on blood pressure control, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) of labetalol, methyldopa and placebo in patients with chronic renal disease and hypertension. When compared with placebo, BP was significantly lower during treatment with both labetalol and methyldopa (P greater than 0.05) but did not differ significantly between the two active treatment periods; post-exercise heart rates were also significantly lower on labetalol than placebo (P less than 0.05). After treatment with labetalol, ERPF was significantly greater than with the placebo (P less than 0.05) but did not differ significantly between the active treatments. GFR did not differ significantly between the three groups. No significant differences were observed in haematology or liver function test results on labetalol compared with placebo. Labetalol is a safe and effective antihypertensive in patients with hypertension associated with chronic renal disease. In the short term it leads to an increase in ERPF which may be beneficial for such patients.

Administration, Oral↗
PubMed1991

A comparison of the chronic effects of oral xamoterol and enalapril on blood pressure and renal function in mild to moderate heart failure.

1. We compared the effects, after 3 weeks oral therapy, of xamoterol 200 mg twice daily and enalapril 2.5, 5 or 10 mg twice daily on home and clinic blood pressure, glomerular filtration rate (GFR) and renal plasma flow, stroke and minute distances, linear resistance and on plasma renin activity in 19 patients with mild to moderate heart failure in a single-blind randomised crossover study. 2. Enalapril reduced mean home blood pressure by 17/7 mm Hg compared with xamoterol (P less than 0.0001) and by 19/7 mm Hg compared with placebo. Compared with placebo xamoterol had no effect. Enalapril reduced predose blood pressure, compared with xamoterol, on average by 15/5 mm Hg (P = 0.02 systolic, 0.09 diastolic) and by 20/7 mm Hg compared with placebo. At 4 h post-dose the mean differences were: xamoterol-enalapril 13/10 mm Hg (P = 0.01 systolic, 0.0007 diastolic) and placebo-enalapril 23/9 mm Hg. 3. Stroke and minute distances were marginally less 4 h following xamoterol than following enalapril: mean (s.e. mean) values were 9.4 (0.7) vs 10.4 (0.8) cm (P = 0.23) and 699 (51.7) vs 767 (62.1) cm (P = 0.04) respectively. Linear resistance was reduced by enalapril, from the placebo value of 13.2 (1.2) to 11.0 (0.9) mm Hg m-1 and marginally increased by xamoterol, to 14.2 (1.2) mm Hg m-1, the difference between active treatments being statistically significant (P = 0.03). 4. Renal plasma flow, GFR and filtration fraction were not influenced by enalapril or xamoterol therapy. There were no significant correlations between glomerular filtration rate and either blood pressure or stroke distance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1991

Screening for colon malignancy with colonoscopy.

Screening of asymptomatic individuals for colon malignancy has been advocated for the past 20 yr in the hopes of reducing colon cancer mortality. Although sigmoidoscopy is an important element of current screening recommendations, the sensitivity of this test in asymptomatic subjects has never been studied. The purpose of this study was to determine the prevalence and location of polyps and cancers in an asymptomatic population by performing full colonoscopy. We wished to assess the sensitivity of screening flexible sigmoidoscopy to 60 cm by determining how many patients with adenomas or cancer had "index" adenomatous polyps in the distal 60 cm. One hundred five healthy male outpatients, over 50 yr old, with negative examinations for occult blood in stools and no prior history of colon pathology, had full colonoscopy. Careful examination of the distal 60 cm was performed, followed by a full colon examination to the cecum. Forty-three patients (41%) had adenomatous polyps, and only 19 of these patients had an index adenomatous polyp in the distal 60 cm. Therefore, the sensitivity of sigmoidoscopy was 44%. The prevalence of adenomas increased with age. Patients were assigned to one of three groups based on the findings in the distal 60 cm. Group 1 (n = 65) had no polyps in the distal 60 cm, but 18 of these patients (28%) had adenomatous polyps in the proximal colon. Among 21 patients with only hyperplastic polyps in the distal 60 cm (group 2), six patients (29%) had proximal adenomas. In group 3, eight of 19 patients (42%) with adenomas in the distal 60 cm also had proximal adenomatous polyps. We conclude that adenomatous polyps are common in asymptomatic men who have negative tests for fecal occult blood. Sigmoidoscopy to 60 cm had a sensitivity of only 44% in this patient population, suggesting that this is an insensitive test for the detection of patients with adenomatous polyps.

Aged↗
PubMed1990

Imaging inflammation with 99Tcm HMPAO labelled leucocytes.

Labelling leucocytes with 99Tcm using hexamethylpropyleneamine oxime (HMPAO) utilizes the advantages of technetium over indium in imaging inflammation. A retrospective study has been performed on 43 consecutive patients imaged with 99Tcm HMPAO labelled leucocytes in order to assess the reliability of the technique. Particular attention was paid to the different handling characteristics of the 99Tcm HMPAO labelled cells compared with those labelled with indium. It was found that 99Tcm HMPAO labelled leucocytes gave an overall accuracy of 93.2%, a sensitivity of 92.8%, a specificity of 93.3% and a positive predictive value of 86%. 99Tcm HMPAO labelled leucocyte scanning provides a reliable method of imaging inflammation, though errors in interpretation may occur due to the hepato-biliary excretion of activity that occurs with this technique.

Abscess↗
PubMed1990

Multimodal imaging in Alzheimer's disease. The relationship between MRI, SPECT, cognitive and pathological changes.

Patients with a clinical diagnosis of Alzheimer's disease were studied using MRI, SPECT, and psychometric tests. Significant correlations between focal perfusion deficits and focal cognitive deficits were found. Significant correlations between regional relaxation time of white matter and psychometric tests of diffuse and focal categories were also found. Pathological examination confirmed Alzheimer's disease as the only diagnosis.

Aged↗
PubMed1990

Regional cerebral blood flow imaging: a quantitative comparison of technetium-99m-HMPAO SPECT with C15O2 PET.

The aim of this study was to compare technetium-99m-hexamethylpropyleneamineoxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) with regional cerebral blood flow (rCBF) imaging using positron emission tomography (PET). As investigation of dementia is likely to be one of the main uses of routine rCBF imaging, 18 demented patients were imaged with both techniques. The PET data were compared quantitatively with three versions of the SPECT data. These were, first, data normalized to the SPECT cerebellar uptake, second, data linearly corrected using the PET cerebellar value and, finally, data Lassen corrected for washout from the high flow areas. Both the linearly-corrected (r = 0.81) and the Lassen-corrected (r = 0.79) HMPAO SPECT data showed good correlation with the PET rCBF data. The relationship between the normalized HMPAO SPECT data and the PET data was nonlinear. It is not yet possible to obtain rCBF values in absolute units from HMPAO SPECT without knowledge of the true rCBF in one reference region for each patient.

Aged↗
PubMed1989

Tuberculous polyradiculopathy: the value of magnetic resonance imaging of the neck.

A case of tuberculosis of the cervical spine with polyradiculopathy is described. The patient had musculo-skeletal symptoms for 2 years prior to developing a tuberculous pleural effusion. Magnetic resonance imaging in both sagittal and coronal planes accurately delineated the cervical lesion, demonstrating the value of this technique in the investigation of epidural sepsis in the neck.

Cervical Vertebrae↗