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Biomedical subjects

D Williams

Publications and source records attributed to D Williams.

At least 19 recordsLinked to original sources

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

Developmental impact of frontal lobe injury in middle childhood.

Executive function of frontal lobe systems, like intelligent behavior, appears to demonstrate two major features: it is adaptive and goal-directed. Disruption of executive function following injury to the frontal lobes in childhood might be predicted to impact the trajectory of normal cognitive, behavioral, and social development. Case studies of two children injured at different ages showed the primary developmental impact to involve the behavioral and social realms. While cognitive development may be suspected to also be considerably influenced, assessment of changes in cognitive abilities by traditional psychometric means was found to be problematic. Psychometric changes were found to occur over a prolonged period of time, emphasizing the importance of documenting observations and chronicling postinjury events.

Brain Injuries

Putative apolipoprotein B-100 in the freshwater turtle Chrysemys picta: effects of estrogen and progesterone.

1. The isolation and purification of a putative apolipoprotein B-100 in the plasma of the freshwater turtle Chrysemys picta is described. 2. The protein was purified through differential ultracentrifugation and subsequent Sepharose 6B column chromatography. 3. The molecular weight of the protein determined by electrophoresis was approximately 350 kDa. 4. An antibody to chicken apolipoprotein B-100 specifically recognizes this 350 kDa protein in Western blots, suggesting its identity with apolipoprotein B-100. 5. An antibody to the putative Chrysemys apolipoprotein B-100-like protein was developed and used in an ELISA to quantitate protein levels in plasma. 6. Acute estrogen treatment increased levels of apolipoprotein B-100 (7.64 +/- 0.79 mg/ml plasma) over that of control animals (5.07 +/- 1.74 mg/ml plasma). 7. In contrast, chronic estrogen treatment reduced apolipoprotein B-100 significantly to 2.94 +/- 0.53 mg/ml plasma (P < 0.05).

Animals

Profits, community role, and hospital closure: an urban and rural analysis.

The number of hospital closures increased substantially after the implementation of Medicare's Prospective Payment System (PPS). This acceleration in closures raised a number of concerns over current payment policies and their impact on access. This paper investigates hospital closures that occurred in 1985 through 1988. A hospital's financial status and mission or community standing were found to be determinants of hospital closure. Closed hospitals are much less likely to be publicly owned but more likely to offer fewer facilities and services, and have fewer cases. This may suggest that the patients directly affected by the closure can be absorbed by other hospitals or other nonhospital providers. Profitability is associated with the Medicare case-mix index and the share of Medicare patients. The findings also suggest that the case mix index may be rewarding some small hospitals in excess of the costs attributable to case-mix. For both urban and rural hospitals, a low share of Medicare patients increased the risk of hospital closure, independently of the relationship between Medicare share and profit. The share of Medicare patients also affected closure indirectly, through its effects on profit. Competition appears to affect the odds of closure through its effects on the number of cases. In addition, hospitals in areas with small or declining population are more at risk than other hospitals in both urban and rural areas.

Costs and Cost Analysis