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Biomedical subjects

D W King

Publications and source records attributed to D W King.

At least 19 recordsLinked to original sources

Oral colon transit scintigraphy using indium-111 DTPA: variability in healthy subjects.

Oral colon transit scintigraphy using indium-111 diethylene-triamine-pentaacetic acid was performed in 41 healthy subjects (22 females, 19 males) to determine variability with age and sex and to define normal ranges. Repeat studies were performed in 10 females and 9 males to assess intra-subject variability. Females showed slightly but significantly slower colonic transit than men and slightly greater intra-subject variability. There was no correlation between age and colonic transit. The results have implications for the definition of normal ranges.

Adult

Electromyography of the pubococcygeus muscles in patients with obstructed defaecation.

The function of the pubococcygeus muscles during defaecation straining was compared in 10 women with obstructed defaecation and 12 age-matched control subjects. Video-proctography in each patient showed failure to evacuate the rectum and sagging of the pelvic floor during attempted defaecation. Trans-perineal concentric needle electromyography in the puborectalis muscle and transvaginal electromyography in the pubococcygeus muscle was carried out during defaecation straining and during attempted rectal balloon expulsion. Contraction of the pubococcygeus muscle was observed in 10 of the 12 control subjects and in 2 of the 10 patients with obstructed defaecation (P < 0.005). Virtually equal proportions of subjects in each group showed relaxation or contraction of the puborectalis muscle during straining. There was significant perineal descent on straining in the patient group (P = 0.005). This group of patients with obstructed defaecation showed failure of the pubococcygeus muscles to contract, perhaps due to neuropathic weakness of the muscles. The puborectalis muscle did not cause obstructed defaecation in these patients, and the concept of "paradoxical" contraction of this muscle is questioned.

Adult

A model for focal magnetic brain stimulation.

In this study, we describe a magnetic coil designed for focal brain stimulation. We determined the distribution of magnetically induced currents using a multi-concentric spherical cranial computer model. The induced currents were primarily linearly oriented and concentrated below the coil's center. In comparison with large coils, small coils were less efficient but produced a more concentrated current distribution. Variations in conductivity among brain, scalp and skull produced secondary currents that reduced the magnetically induced current. This reduction in magnetically induced current was greater for larger coils.

Algorithms

Comparison of CT- versus MRI-guided, computer-assisted depth electrode implantation.

Fourteen candidates for ablative seizure surgery underwent CT-guided, computer-assisted stereotactic depth electrode implantation and 21 underwent MRI-guided, computer-assisted implantation. A hand-held computer with no graphic capability was used for CT-guided procedures. A computer work station which included a high-resolution color graphics terminal with touchscreen interfacing and software capable of simulating targets and trajectories in single or multiple views was used for MRI-guided procedures. Previous phantom studies done with a 1.5-tesla MR scanner suggested acceptable localization error. Localizing information was obtained in 10 (71.4%) of 14 of the CT-guided implants and in 16 (76.2%) of 21 of MRI-guided cases. In the CT group, 7 (70%) were seizure-free and 8 (80%) were greater than 90% improved at 1 year follow-up. In the MRI group, 8 (80%) were seizure-free and 9 (90%) were greater than 90% improved at latest follow-up.

Computer Graphics

Differential effects of left versus right seizure focus on human hippocampal evoked responses.

Hippocampal evoked potentials were recorded using the P3 tonal oddball paradigm in 30 patients with unilateral temporal lobe seizure focus. Spectral power of the evoked potentials was decreased on the side of seizure focus, but this reduction was much greater when the focus was on the left. The effect of left/right focus does not appear to be due to group differences in age, sex, seizure duration, or operative pathology. Remote or finer left/right structural differences or differential left/right hippocampal processing for the sequential tonal task are possible explanations.

Adolescent

Surgical management of anal incontinence.

The complex nature of the continence mechanism is reflected in the difficulties experienced in the surgical management of patients with faecal incontinence. Apparent anatomical abnormalities may be identified but the functional outcome following surgery may be unsatisfactory. It is therefore important to improve both the selection of patients as well as the surgical procedures themselves. Selection of patients for appropriate treatment should be based on clinical findings as well as anorectal physiology tests. Most patients referred for assessment fall into one of six categories: incontinence with a normal sphincter; minor incontinence due to local anal conditions; direct sphincter injury; neurogenic ("idiopathic") incontinence; rectal prolapse; generalised neurological condition. Minor anal conditions causing incontinence must be carefully identified for appropriate treatment. A large amount of work has been done over the past ten years on the pathophysiology of major incontinence and new surgical procedures have been developed. A common difficulty is deciding whether anterior sphincter attenuation or neurogenic weakness is the dominant lesion causing incontinence; overlapping sphincter repair is indicated for the former and postanal repair for the latter. Anorectal physiology studies can be helpful in differentiating these conditions and are now used routinely in the assessment of patients.

Electromyography

Biosynthesis and partial amino acid sequence of the human NDA4 antigen. An activation antigen common to B and T cell lineages.

NDA4, a cell surface protein of molecular mass 46 kDa common to activated peripheral blood B and T cells, plays a unique role in the control of B and T cell maturation. NDA4 inhibits B and T cell activation, as mitogen-stimulated B and T cell blastogenic responses are decreased in the presence of mAb NDA4, the antibody recognizing NDA4. After mitogen-activation, however, the regulatory function of NDA4 changes. Addition of mAb NDA4 to cultures of Staphylococcus aureus Cowan strain A-activated B cells or alloreactive T cell clones stimulates their proliferation. NDA4 epitopes are conserved across primate species lines and are present on transformed cells of neuroectodermal origin. NDA4 is synthesized as a molecular mass 50 kDa precursor and is processed to a mature 46 kDa form within 30 min. The NDA4 Ag also exists as soluble forms of 40 and 42 kDa. The membrane and soluble forms of NDA4 have been purified to homogeneity and sequenced by N-terminal Edman degradation.

Amino Acid Sequence

In vitro studies of the effect of MAb NDA 4 linked to toxin on the proliferation of a human EBV-transformed lymphoblastoid B cell line and of gibbon MLA leukemia cell line.

The rejection of allografts is mediated by cytolytic T cells and antibody-secreting B cells. Selective ablation of these activated cells from peripheral blood lymphocytes may offer a a method of controlling allograft rejection. An immunotoxin was prepared from the monoclonal antibody (mAb) NDA 4, which recognizes a differentiation antigen (NDA 4) common to activated B and T cells. MAb NDA 4 was conjugated to the ribosome-inhibiting protein gelonin via a cleavable disulfide bond provided by a crosslinking reagent. The purified immunotoxin was evaluated for in vitro cytotoxicity on NDA 4 positive T and B cell lines. Conjugation of mAb NDA 4 to gelonin increased the in vitro cytotoxicity by a concentration factor of 1000, compared to gelonin alone. The specificity and saturability of mAb NDA 4 binding, as well as the number of antigenic sites per cell on resting versus activated T lymphocytes, were also evaluated. Resting T cells expressed 400-800 sites per cell. PHA-activated T cells and the MLA T cell leukemia expressed 10,000 to 80,000 sites per cell. Peripheral blood mononuclear cells obtained from allografted baboons in quiescence or undergoing rejection were compared for NDA 4 expression by flow cytometry. Lymphocytes obtained from baboons rejecting a heart allograft expressed NDA 4, whereas transplant recipients in quiescence showed no detectable NDA 4. These results suggest that mAb NDA 4-derived immunotoxins may be valuable for the selective depletion of activated lymphocytes while sparing the resting population.

Animals

Pudendal nerve function in women with symptomatic utero-vaginal prolapse.

Pelvic floor function has been studied in 27 women with symptomatic utero-vaginal prolapse and 15 age-matched control subjects. There was no evidence in the patients on physiological testing of significant denervation of the pelvic floor muscles, with no significant difference in the maximum resting and squeeze anal pressures, the pudendal nerve terminal motor latency or external anal sphincter fibre density on single fibre electromyography between the groups. However, those patients with a small rectocele (less than 2 cm) had a significantly higher fibre density than the group with a large rectocele (p = 0.03) and the control group (p less than 0.001). Six of eight patients with a small rectocele had increased fibre density compared with 3/19 with a large rectocele (p = 0.006) and 2/15 control subjects (p = 0.006). This was independent of age, obstetric factors and the presence of internal rectal prolapse. These findings suggest that patients with symptomatic utero-vaginal prolapse and small rectoceles have pelvic nerve damage, and development of a large rectocele may provide some protection against perineal descent and pudendal neuropathy, although the number of patients in the small rectocele group was small and confirmation from further similar studies is required.

Anal Canal

Computerized seizure detection of complex partial seizures.

In this study, we describe a computerized method that uses 3 quantified EEG features and discriminant analysis to automatically detect seizure EEG. The quantified EEG features were relative amplitude, dominant frequency and rhythmicity. Using EEGs recorded from intracranial electrodes, the seizure detection method was applied to consecutive non-overlapping 2-channel EEG epochs. A seizure detection sensitivity, ranging from 90% to 100%, was associated with a false positive detection rate of 1.5-2.5/h. The performance of the seizure detection method remained stable for EEG recorded over variable time periods.

Discriminant Analysis

The alloantibody response of pregnant women and its suppression by soluble HLA antigens and anti-idiotypic antibodies.

The aim of this study was to investigate the time course of maternal allosensitization to fetal HLA antigens during normal human pregnancy and to explore mechanisms of suppression of anti-HLA alloantibodies. We found that the mother produces antibodies against some but not all of the mismatched HLA antigens of the fetus as early as the 8th week of pregnancy. These antibodies (Ab1), however, are often complexed with soluble HLA alloantigens and become detectable when immune complexes are dissociated. Soluble HLA antigens of fetal origin are present in the maternal circulation throughout the entire pregnancy beginning at 8 weeks. In some women the production of anti-anti-HLA antibodies (Ab2) became evident as early as the first trimester, while in others Ab2 was documented during the second or third trimester. Analysis of antibody specificity showed that some healthy primipara develop antibodies reactive with self HLA antigens. Although the allo- and autoantibody responses appear to be modulated by soluble HLA antigens, cyclic variations in the level of alloantibodies, as well as the mother's selective response to some, but not all, paternal HLA antigens, are best explained by the development of anti-idiotypic antibodies.

Antibodies, Anti-Idiotypic

Validity issues in research on Vietnam veteran adjustment.

For 2 decades America's Vietnam veterans have been viewed as presenting special problems, and researchers from various disciplines have attempted to understand the network of cause-and-effect relationships accounting for their psychosocial status. In this article, Cook and Campbell's (1979) framework is used to examine validity issues in Vietnam veteran research. Threats to each of the types of validity (statistical conclusion, internal, construct, and external) are discussed using examples from the literature. To counteract these threats and strengthen future research, 7 recommendations are offered.

Adaptation, Psychological

Soluble HLA antigens, anti-HLA antibodies, and antiidiotypic antibodies in the circulation of renal transplant recipients.

Chronic rejection represents the major threat to long-term survival of organ allografts. It is presumed that this form of rejection is mediated by antibodies against mismatched HLA antigens of the graft. The presence and specificity of anti-HLA-antibodies in posttransplantation sera are, however, difficult to document. We have explored the possibility that anti-HLA antibodies form immune complexes with soluble HLA antigens released from the injured graft and/or that they are blocked by antiidiotypic, anti-anti-HLA-antibodies. Our data demonstrate that the long-term survival of renal allografts is significantly lower in patients who develop anti-HLA-antibodies following transplantation than in patients who do not form antibodies. Following depletion of soluble HLA antigens by magnetic immunoaffinity, we could identify anti-HLA-antibodies in 57% of the sera obtained from patients undergoing chronic rejection of kidney allografts, compared with 41% prior to antigen depletion. In patients tolerating the graft for 4 years or more, the corresponding frequencies of antibody-positive sera was 2% and 5% prior and following depletion of HLA antigens. The presence of HLA antigen/anti-HLA-antibody immune complexes in patients' sera was positively associated with chronic humoral rejection (P less than 0.0001). Patients who tolerated the graft in spite of having developed antibodies against one of its mismatched HLA antigens show specific antiidiotypic (anti-anti-HLA-antibodies). Such antiidiotypic antibodies were not found in sera from patients with chronic rejection (P = 0.005). This indicates that antiidiotypic antibodies may delay the progression of chronic humoral rejection.

Antibodies, Anti-Idiotypic

The role of anti-HLA antibodies in heart transplantation.

The major threat to long-term survival of heart allograft recipients is the development of graft atherosclerosis, which seems to be a manifestation of chronic rejection. To assess the role of anti-HLA antibodies in heart allograft rejection we studied 107 patients and compared the survival of recipients who formed anti-HLA antibodies with the survival of recipients who developed no antibodies. At 4 years the actuarial survival was 90% in the nonproducer group and 38% in antibody-producers (P = 0.038). We further explored the possibility that HLA antigens from the injured graft are released into the circulation and can be found in the serum either free or complexed with anti-HLA antibodies. This hypothesis was confirmed by the finding that the frequency of sera containing soluble HLA antigens from the graft or immune complexes of HLA alloantigens with anti-HLA antibodies was significantly higher in patients who rejected compared with patients with successful heart allografts (P less than 0.05). Following depletion of soluble HLA antigens, anti-HLA antibodies became detectable in 53% and 74% sera obtained during the first and second year posttransplantation, respectively, from patients undergoing chronic rejection. Long-term survivors showed a significantly lower (P less than 0.001) frequency of anti-HLA antibodies in sera depleted of HLA antigens. Lastly, studies of anti-anti-HLA-A2 and A3 antibodies in recipient sera suggest that quiescence is maintained by antiidiotypic antibodies.

Antigen-Antibody Complex

Comparative cognitive effects of carbamazepine and phenytoin in healthy adults.

We investigated neuropsychological effects of carbamazepine and phenytoin in 21 healthy adults using a randomized, double-blind, double-crossover design and treating each subject with each drug for 1 month, separated by a 1-month washout. There were neuropsychological evaluations at baseline, the end of each treatment month, and 1 month after the last treatment phase. Cognitive measures included Symbol Digit Modalities Test, Selective Reminding Test, Complex Figures, Paced Auditory Serial Addition Test, Stroop, Finger Tapping, Grooved Pegboard, Choice Reaction Time, P3 Event-Related Potential, Hopkins Symptom Checklist, and Profile of Mood States (POMS). Compared with nondrug conditions, the anticonvulsants significantly impaired Stroop, Choice Reaction Time, Grooved Pegboard, Hopkins, and POMS. Employing anticonvulsant blood levels as covariates, there were only two significant differences between drugs, one in favor of carbamazepine (ie, Finger Tapping) and one in favor of phenytoin (ie, Stroop). The results suggest that differences in cognitive effects of carbamazepine and phenytoin are not clinically significant.

Adult