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Biomedical subjects

D Williams

Publications and source records attributed to D Williams.

At least 343 records · Page 19Linked to original sources

Hemodynamic alterations in venous blood flow produced by external pneumatic compression.

Venous stasis associated with prolonged bed rest can enhance the risk of deep venous thrombosis (DVT). Pneumatic compression of the lower extremities can reduce this risk by preventing venous stasis. When selecting a method of leg compression for their patients, physicians must chose between two distinctly different types of compression devices. One device applies pressure with a single-chambered sleeve to the below knee region while the other applies pressure in a sequential gradient fashion from the ankle to the thigh. The current prospective study was designed to evaluated the ability of two such devices to increase blood flow in the profunda femoral vein. Venous blood flow velocity, compression time, and vein diameter were measured in nine normal experimental subjects using an Accuson duplex-Doppler before, during and after leg compression. Compression with the single-chambered device produced a significant rise in venous blood flow velocity; however, this could not be maintained and our results indicate a higher average velocity was achieved with the sequential gradient device. The sequential gradient device also moved a greater volume of blood and achieved a higher average blood flow rate. The time between deflation of the sleeve and return of a phasic respiratory signal was greater after compression with the sequential gradient device. These results suggest that sequential gradient compression produces the type of hemodynamic alterations needed to reduce the risk of DVT by achieving a sustained increase in venous blood flow and more completely emptying of the veins in the leg.

Analysis of Variance↗

Isolation of an inhibitor of tumor necrosis factor-alpha-mediated cytotoxicity liberated from chemotaxin-stimulated equine white blood cell populations.

Objectives of this investigation were to extract and isolate protein fractions inhibitory to the cytotoxic properties of tumor necrosis factor-alpha (TNF-alpha). In this context, mixed populations of WBC were harvested from equine blood and were stimulated with a combination of a synthetic chemotactic peptide and a calcium ionophore. Several methods were subsequently applied for the initial preparation of cell-free crude protein extracts, including fractional precipitation with gradient concentrations of ammonium sulfate and preparative-scale isoelectric focusing. In addition, protein fractions were harvested from extracts of concentrated equine urine. Protein extracts of urinary origin were further separated by gel-filtration column chromatography. Identification of protein fractions possessing properties inhibitory to the cytotoxic characteristics of TNF-alpha was facilitated by a tissue culture-based technique for the biological assay of TNF-alpha-mediated cytotoxicity. Purified protein extracts possessed a marked ability to inhibit or neutralize the cytotoxic properties of TNF-alpha, on the basis of survival of murine fibrosarcoma cell populations, compared with appropriate negative and positive reference controls. Relative purity of inhibitors and estimation of approximate molecular weight were established by conventional reducing and nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Equine inhibitory protein fractions from mixed WBC populations, purified in the manner described, had molecular weights of 70,000 to 80,000 and 28,000. An analogous protein fraction of 28 kDa also was isolated from equine concentrated urine. Estimated isoelectric point of TNF-alpha inhibitor protein fractions was between pH of 5.5 and 6.1. These physical characteristics of equine TNF-alpha inhibitor protein fractions were similar to those described for a membrane-associated TNF-alpha receptor protein shed from chemotaxin- and calcium-ionophor-stimulated human WBC populations.

Animals↗

Quantitative determination of non-ionic surfactants in protein samples, using ion-exchange guard columns.

Quantitative determination of Triton X-100 in buffered, organic modifier-containing solutions was performed by use of strong cation- and anion-exchange HPLC guard columns. Recovery was complete for Triton X-100 concentrations of 0.1%, 0.05%, 0.25% and 0.0125% (wt/wt) in 50 mM potassium phosphate buffer (pH 5.0 +/- 0.05, pH 4.0 +/- 0.05, pH 3.0 +/- 0.05 and pH 2.0 +/- 0.05) modified with 30% isopropanol. This procedure can be applied to recovery of other nonionic surfactant systems.

Animals↗

Catheter ablation of the atrioventricular junction using radiofrequency energy and a bilateral cardiac approach.

Radiofrequency current catheter ablation was used successfully to create complete atrioventricular (AV) block in 60 of 61 patients (98%) with drug refractory supraventricular tachyarrhythmias. The remaining patient developed Mobitz I AV block and is clinically improved (clinical efficacy 100%). In 54 patients (89%), complete AV block was achieved using a right-sided approach. Patients aged > 60 years needed significantly fewer right-sided radiofrequency applications to produce complete AV block (5.3 +/- 5.3 vs 11.1 +/- 10.0; p = 0.009). In 6 of 7 patients with unsuccessful right-sided ablation, a left ventricular approach was used. In each case, 1 to 4 additional radiofrequency applications produced complete AV block. Patients with unsuccessful right-sided ablation were generally younger than those with successful ablation (50 +/- 16 vs 64 +/- 11; p = 0.007). It is concluded that catheter ablation using radiofrequency current is an extremely effective means of producing complete AV block. Older patients appear to be more susceptible to right-sided radiofrequency approaches. Left ventricular ablation easily produces complete AV block in patients refractory to right-sided attempts.

Adult↗

Interleukin-11 promotes accessory cell-dependent B-cell differentiation in humans.

Interleukin-11 (IL-11) is a recently described stromal-derived cytokine that supports the growth of an IL-6-dependent murine plasmacytoma line in the presence of antibody to IL-6 and appears to act in a manner similar to IL-6 on hematopoietic stem cells. Because IL-6 is known to promote differentiation of normal human B cells, the role of IL-11 on B-cell differentiation in vitro was characterized. IL-11 does not result in significantly increased DNA synthesis or Ig secretion by purified B cells alone or B cells cultured with Staphylococcus Cowan I, a T-cell-independent B-cell mitogen. In contrast, purified B cells cultured in the presence of pokeweed mitogen (PWM), irradiated T cells, and monocytes show increased DNA synthesis at day 3 and increased IgG and IgM secretion at day 7 of culture; addition of IL-11 further augments Ig secretion without change in DNA synthesis, an effect that can only be partially blocked by monoclonal antibody to IL-6. Similar experiments confirmed that increased IgG secretion was demonstrable when either IL-11 or IL-6 was added to B cells + CD4+/45RA- T cells + monocytes + PWM; in contrast, Ig secretion was low and equivalent when CD4+/45RA+ T cells were cultured with B cells+monocytes+PWM with or without IL-6 or IL-11. Neither IL-6 nor IL-11 could significantly increase phytohemagglutinin (PHA)-induced DNA synthesis by CD4+/45RA- or CD4+/45RA+ T cells. Although PWM or IL-11 induced IL-6 mRNA expression in both CD4+/45RA- T cells and monocytes, in neither cell did IL-11 increase IL-6 mRNA expression over that noted to PWM alone. These observations support the view that IL-11 promotes differentiation of human B lymphocytes only in the presence of accessory T cells and monocytes and that a minor component of this effect may be through stimulation of IL-6 production by CD4+/45RA- T cells and monocytes.

Actins↗

DNA recognition and binding by the Euplotes telomere protein.

The 51-kDa telomere protein from Euplotes crassus binds to the extreme terminus of macronuclear telomeres, generating a very salt-stable telomeric DNA-protein complex. The protein recognizes both the sequence and the structure of the telomeric DNA. To explore how the telomere protein recognizes and binds telomeric DNA, we have examined the DNA-binding specificity of the purified protein using oligonucleotides that mimic natural and mutant versions of Euplotes telomeres. The protein binds very specifically to the 3' terminus of single-stranded oligonucleotides with the sequence (T4G4) > or = 3 T4G2; even slight modifications to this sequence reduce binding dramatically. The protein does not bind oligonucleotides corresponding to the complementary C4A4 strand of the telomere or to double-stranded C4A4.T4G4-containing sequences. Digestion of the telomere protein with trypsin generates an N-terminal protease-resistant fragment of approximately 35 kDa. This 35-kDa peptide appears to comprise the DNA-binding domain of the telomere protein as it retains most of the DNA-binding characteristics of the native 51-kDa protein. For example, the 35-kDa peptide remains bound to telomeric DNA in 2 M KCl. Additionally, the peptide binds well to single-stranded oligonucleotides that have the same sequence as the T4G4 strand of native telomeres but binds very poorly to mutant telomeric DNA sequences and double-stranded telomeric DNA. Removal of the C-terminal 15 kDa from the telomere protein does diminish the ability of the protein to bind only to the terminus of a telomeric DNA molecule.

Amino Acid Sequence↗

Synthetic neural modeling applied to a real-world artifact.

We describe the general design, operating principles, and performance of a neurally organized, multiply adaptive device (NOMAD) under control of a nervous system simulated in a computer. The complete system, Darwin IV, is the latest in a series of models based on the theory of neuronal group selection, which postulates that adaptive behavior is the result of selection in somatic time among synaptic populations. The simulated brain of Darwin IV includes visual and motor areas that are connected with NOMAD by telemetry. Under suitable conditions, Darwin IV can be trained to track a light moving in a random path. After such training, it can approach colored blocks and collect them to a home position. Following a series of contacts with such blocks, value signals received through a "snout" that senses conductivity allow it to sort these blocks on the basis of differences in color associated with differences in their conductivity. Darwin IV represents a new approach to synthetic neural modeling (SNM), a technique in which large-scale computer simulations are employed to analyze the interactions among the nervous system, the phenotype, and the environment of a designed organism as behavior develops. Darwin IV retains the advantages of SNM while avoiding the difficulties and pitfalls of attempting to simulate a rich environment in addition to a brain.

Behavior↗

Perceptual asymmetry in texture perception.

A fundamental property of human visual perception is our ability to distinguish between textures. A concerted effort has been made to account for texture segregation in terms of linear spatial filter models and their nonlinear extensions. However, for certain texture pairs the ease of discrimination changes when the role of figure and ground are reversed. This asymmetry poses a problem for both linear and nonlinear models. We have isolated a property of texture perception that can account for this asymmetry in discrimination: subjective closure. This property, which is also responsible for visual illusions, appears to be explainable by early visual processes alone. Our results force a reexamination of the process of human texture segregation and of some recent models that were introduced to explain it.

Humans↗

Dogs that bite.

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Animals↗

An electronic method for measuring joint tenderness in rheumatoid arthritis.

OBJECTIVE: To test the precision of a new electronic method for measuring joint tenderness. METHOD: Joint tenderness was measured in 30 patients with rheumatoid arthritis, using an electronic dolorimeter. The results were compared with joint tenderness counts, which were made according to the American Rheumatism Association (ARA) methods. RESULTS: The intra-observer variability using the electronic method was significantly decreased compared with the conventional ARA joint tenderness counts. CONCLUSION: The electronic method is more efficient for use in clinical trials than is the conventional ARA joint tenderness count.

Arthritis, Rheumatoid↗

Oesophageal reflex responses: abnormalities of the enteric nervous system in patients with oesophageal symptoms.

An intraluminal balloon was used to study the peristaltic reflex, which is mediated by the intrinsic nerves of the oesophagus. Serial balloon distension was performed in nine asymptomatic volunteers and 133 patients with oesophageal symptoms. Eight of the volunteers had a normal response with proximal stimulation and distal inhibition of motility. Only 42 patients (31.6 per cent) had a normal response. The commonest abnormal response (39.1 per cent) was some form of failure of the distal inhibitory reflex. Other patterns of abnormality were an unresponsive oesophagus (15.8 per cent) with no motility change during balloon inflation, or spasm (13.5 per cent) proximal to the balloon. These alterations of secondary peristaltic activity suggest that there are abnormalities of the intrinsic (enteric) nerves of the oesophagus. Different abnormalities were found in patients with similar symptoms. Awareness of this difference might allow a more rational approach to treatment. This hypothesis was tested in a small pilot study treating functional dysphagia with cisapride. Three of nine patients had marked symptomatic improvement within 4 weeks and all three had an unresponsive oesophagus. The remaining six patients, who had failure of distal inhibition or a normal response, did not improve.

Adult↗

Comparison of cervical cytology and the polymerase chain reaction for HPV 16 to identify women with cervical disease in a general practice population.

A comparison of the ability of cervical cytology and the polymerase chain reaction (PCR) for human papilloma virus type 16 (HPV 16) to identify women with cervical disease has been performed in a general practice population of 249 women, none of whom were believed to have current cervical disease prior to examination. Within this population, 29 women were found by colposcopy and subsequent histopathology to have evidence of cervical disease [5 with cervical intraepithelial neoplasia (CIN) 3; 8 with CIN 2; and 16 with CIN 1]. The prevalence of HPV 16 in this population was 18.9% (CIN 3, 80%; CIN 2, 50%, CIN 1, 12.5%, normal, 16.8%). Women with severe disease (CIN 2 and CIN 3) had a significantly higher incidence of HPV 16 DNA than those with mild cervical disease (CIN 1) or no cervical abnormality (P = 0.001). There was no significant difference in the ability of either PCR for HPV 16 or cytology to identify women with cervical disease. The combination of screening by cytology and the presence of HPV 16 DNA resulted in the identification of a higher proportion of the women with disease, but this observation did not reach statistical significance. Although the failure to detect disease by the two screening methods was similar, HPV 16 DNA positivity was associated with a higher false-positive rate for disease detection than cytology (P less than 0.03). The PCR assay for detecting HPV 16 in this investigation was shown to have a false-positive rate of 2.4% and a false-negative rate of 10.4%. The prospect of screening women for cervical disease using PCR for HPV 16 is discussed.

Adolescent↗

Identification of an abnormal esophageal clearance response to intraluminal distention in patients with esophagitis.

Esophageal clearance responses were studied by a new technique comprising a miniature electronic strain gauge attached to an inflatable balloon in 30 normal volunteers and 48 patients with gastroesophageal reflux disease. The pressure changes around the balloon and traction forces acting on the balloon were measured during graded balloon distention (0-12 mL of air for 30 seconds each inflation) in the lower and midesophagus. All normal volunteers responded to distention with development of swallow independent contractions above the balloon [65 mm Hg/30 s (range, 45-100 mm Hg/30 s)] together with generation of an aboral traction force [15 g (range, 9-20 g)]. Patients with reflux esophagitis showed a higher distention threshold for initiation of these responses, induced fewer proximal contractions [24 mm Hg/30 s (range, 0-38 mm Hg/30 s); P less than 0.01 vs. normal], and generated weaker traction forces [4 g (range, 0-6 g) at 10 mL P less than 0.01 vs. normal]. Patients with the most severe esophagitis showed greatest impairment of the clearance response (correlation = 0.7, P less than 0.01) and the greatest esophageal residence of refluxed acid (correlation = 0.5, P less than 0.01). These abnormalities appear to be of relevance to the pathophysiology of esophageal reflux disease although it remains to be determined whether they are the cause, or the result, of the esophagitis.

Adolescent↗

The risk of abdominal operations in children with ventriculoperitoneal shunts.

Ventriculoperitoneal (VP) shunts are the operations of choice for patients with hydrocephalus in most pediatric hospitals. Children with VP shunts frequently undergo abdominal operations unrelated to their shunts, which might lead to shunt infections or to malfunctions related to adhesions. Although prophylactic antibiotics are usually used in this setting, there are few data to support their use, or to assess other risks to the shunt from the abdominal procedures. Consequently, we reviewed the records of 37 children with VP shunts who underwent a total of 44 abdominal operations. In 8 cases, the genitourinary (GU) tract was opened (ureteral reimplantation, bladder augmentation, nephrectomy), whereas in 18 patients the gastrointestinal (GI) tract was opened (appendectomy, gastrostomy, small/large bowel resection). In 18 operations neither GI nor GU tract was opened (lysis of adhesions, herniorrhaphy, orchiopexy). Antibiotic coverage was highly variable: 9 received no antibiotics, 9 received antibiotics only postoperatively, 4 were given antibiotics only preoperatively, and in 22 cases antibiotics were given both preoperatively and postoperatively. One shunt that was involved in a periappendiceal abscess was exteriorized and later successfully replaced. In the remaining cases, no episodes of shunt infection or malfunction occurred in 1 to 10 years of follow-up. Likewise, no abdominal cerebrospinal fluid pseudocysts formed as a result of abdominal adhesions. These data demonstrate that children with VP shunts can safely undergo abdominal operations, even when the GI or GU systems are opened, with minimal risk of shunt infection or malfunction. Rigid protocols of prophylactic antibiotics cannot be supported by this series.

Abdomen↗