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Biomedical subjects

W King

Publications and source records attributed to W King.

At least 19 recordsLinked to original sources
PubMed1996

Evidence for anticipation and association of deletion size with severity in facioscapulohumeral muscular dystrophy. The FSH-DY Group.

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by marked inter- and intrafamilial heterogeneity in its clinical expression. The contribution of genetic factors to this variability is not well characterized. We examined the relationship of phenotype to genotype in a clinically and genetically well-defined FSHD population. Quantitative isometric myometry (QMT) scores, normalized for age, gender, and height, were used to quantify disease severity. We found a significant (r = 0.92, p < 0.004) correlation between disease severity and the size of the 4q35-associated deletion. In addition, when relative disease severity of parent-offspring pairs was compared, the offspring were found to be significantly more severely affected (p = 0.011). This generational effect suggests the presence of anticipation in FSHD and raises the possibility of an underlying dynamic mutation.

Adolescent↗
PubMed1996

The use of sonography in differentiating cervical lymphomatous lymph nodes from cervical metastatic lymph nodes.

Lymphoma and metastases are common causes of cervical lymphadenopathy. Clinical examination alone is unable to differentiate the two. Ultrasound (US) with its high sensitivity and specificity when combined with a find needle aspiration cytology (FNAC) is therefore the ideal initial investigation. We present the spectrum of findings in 19 patients with non Hodgkins lymphoma (NHL), 15 patients with pharyngeal, laryngeal and oesophageal (PLO) carcinomas, 22 patients with oral cavity tumours and 12 patients with infraclavicular carcinomas. The US features found consistently useful in differentiating NHL from other metastases were the distribution of the nodes, distal enhancement and lack of intranodal necrosis. Other US features of abnormal nodes helped identify abnormality but did not help in differentiation.

Adolescent↗
PubMed1995

Myoblast transfer in the treatment of Duchenne's muscular dystrophy.

BACKGROUND: Myoblast transfer has been proposed as a technique to replace dystrophin, the skeletal-muscle protein that is deficient in Duchenne's muscular dystrophy. Donor myoblasts injected into muscles of affected patients can fuse with host muscle fibers, thus contributing their nuclei, which are potentially capable of replacing deficient gene products. Previous controlled trials involving a single transfer of myoblasts have been unsuccessful. METHODS: We injected donor muscle cells once a month for six months to the biceps brachii muscles of one arm of each of 12 boys with Duchenne's muscular dystrophy. The opposite arms served as sham-injected controls. In each procedure 110 million cells donated by fathers or brothers were transferred. The patients were randomly assigned to receive either cyclosporine or placebo. Strength was measured by quantitative isometric muscle testing. Six months after the final myoblast transfer, the presence of dystrophin was assessed with the use of peptide antibodies specific to the deleted exons of the dystrophin gene. RESULTS: There was no significant difference in muscle strength between arms injected with myoblasts and sham-injected arms. In one patient, 10.3 percent of muscle fibers expressed donor-derived dystrophin after myoblast transfer. Three other patients also had a low level of donor dystrophin (< 1 percent); eight had none. CONCLUSIONS: Myoblasts transferred once a month for six months failed to improve strength in patients with Duchenne's muscular dystrophy. The value of exon-specific peptide antibodies in the interpretation of myoblast-transfer results was demonstrated in a patient with Duchenne's muscular dystrophy who had a high percentage of donor-derived dystrophin. Specific variables affecting the efficiency of myoblast transfer need to be identified in order to improve upon this technique.

Antibodies↗
PubMed1995

Outcome and cost at a children's hospital following resuscitation for out-of-hospital cardiopulmonary arrest.

OBJECTIVE: To determine the outcome and cost for children resuscitated following out-of-hospital cardiopulmonary arrest. DESIGN: Retrospective case series. SETTING: An organized prehospital emergency medical system within Birmingham, Ala, in a county with 150,493 children under the age of 15 years. PATIENTS: Sixty-three pediatric victims of out-of-hospital cardiopulmonary arrest of any cause presenting to the emergency department of a children's hospital. INTERVENTION: Standard resuscitative techniques were performed for all patients until resuscitative efforts were discontinued in the hospital emergency department or successful resuscitation was achieved. MAIN OUTCOME MEASURES: Successful resuscitation, survival to hospital discharge, neurological outcome, final disposition, and cost of hospital care. RESULTS: Of 63 children with out-of-hospital cardiopulmonary arrest treated in the emergency department of a children's hospital, 60 were pulseless and apneic on arrival, 18 (28.6%) were successfully resuscitated and admitted to the intensive care unit, and six (9.5%) were discharged from the hospital. Five of the survivors had severe neurological deficits and one appeared normal. On follow-up, two patients had died (1 month and 7 months after discharge), three were in a vegetative state, and one was normal. The normal patient had successful defibrillation prior to arrival at the emergency department. The average inpatient charge was $10,667 per patient for those who died and $100,000 for those discharged. CONCLUSIONS: Aggressive treatment does not lead to intact survival for victims of out-of-hospital cardiopulmonary arrest who present to the pediatric emergency department with a preterminal rhythm and absence of spontaneous circulation. Resuscitation efforts in the emergency department are commonly successful but lead to death or severe neurological sequelae at discharge with extremely high cost of care.

Adolescent↗
PubMed1995

The application of ultrasound criteria for malignancy in differentiating tuberculous cervical adenitis from metastatic nasopharyngeal carcinoma.

Tuberculous adenitis and metastatic nodes from Nasopharyngeal carcinoma may have a similar clinical presentation. Clinical examination and laboratory tests alone are unable to differentiate the two. However, ultrasound is a useful initial investigation in differentiating these two conditions. We present ultrasound appearances in 33 patients with proven tuberculous cervical adenitis and 32 patients with proven metastatic nasopharyngeal carcinoma. The ultrasound features we found useful were the distribution of the nodes, cystic change, matting and surrounding soft tissue oedema. The size, shape and internal architecture of the nodes, previously described criteria in differentiating benign from malignant nodes, did not help.

Adolescent↗
PubMed1995

Metastatic cervical nodes in papillary carcinoma of the thyroid: ultrasound and histological correlation.

The ultrasound appearances and histological correlation of metastatic cervical lymph nodes in 20 patients with papillary carcinoma of the thyroid are presented. The majority of the malignant nodes were homogeneous (81.2%), hyperechoic (87.5%) compared to adjacent sternomastoid muscle and 68.7% showed peripheral punctate calcification on US and histology. Histology revealed that the peripheral echogenic foci seen within the nodes on US correlated with psammoma bodies which are characteristic for papillary carcinomas, highlighting the importance of recognizing peripheral punctate calcification in the cervical nodes as a useful sign for the diagnosis of metastatic papillary carcinoma of the thyroid.

Calcinosis↗
PubMed1995

Human vascular endothelial cells process and present autoantigen to human T cell lines.

The effectiveness of cultured human umbilical vein endothelial cells as accessory cells for T cell activation has been investigated using T cell clones and lines derived from patients with myasthenia gravis which were specific for different epitopes on the alpha subunit of the human acetylcholine receptor. The endothelial cells were induced with IFN-gamma to express HLA-DR and -DQ at high and low levels respectively. They could then efficiently present specific peptides of the alpha subunit to an HLA-DR- and an HLA-DQw5-restricted T cell line. They could also process epitopes for both T cell lines from the full-length recombinant alpha subunit (r1-437) of the human acetylcholine receptor, where the known epitopes are 80 amino acid residues apart. The endothelial presentation of r1-437, but not of the peptides, was sensitive to chloroquine inhibition. Presentation appeared slightly less efficient (by 1.5- to 3.0-fold) with endothelial cells than with presenting cells from peripheral blood. This may reflect differences in accessory signalling since mAb blocking studies suggested that ligands for CD28 provided important accessory signalling by peripheral blood presenting cells while LFA-3 was used by endothelial cells.

Antigen Presentation↗
PubMed1995

Comparison of characteristics of Q beta replicase-amplified assay with competitive PCR assay for Chlamydia trachomatis.

In order to study infections due to Chlamydia trachomatis, we have compared semiquantitative PCR and Q beta replicase-amplified assays for detection of this organism. The PCR assay was directed against the C. trachomatis 16S rRNA gene. Quantitation was accomplished by adding known amounts of a plasmid containing a truncated segment of the 16S rRNA gene target to chlamydia-containing samples and then amplifying with a common primer set. The Q beta replicase assay consisted of reversible target capture of C. trachomatis 16S rRNA, which was followed by amplification of an RNA detector probe in the presence of the enzyme Q beta replicase. In a clinical matrix, the lower limit of detection of both the PCR and Q beta replicase assays was five elementary bodies. The Q beta replicase and PCR assays were quantitative over 10,000- and 1,000-fold ranges of organisms, respectively. Analysis of the effects of endocervical matrix on amplification was accomplished by examining 94 endocervical specimens by each technique. Both assays detected five of six culture-confirmed specimens as well as three culture-negative specimens. PCR inhibitors were detected in 13 specimens. The Q beta replicase assay, in contrast, showed no evidence of sample inhibition. The Q beta replicase and PCR assays should allow quantitative investigation of infections due to C. trachomatis. In addition, because it targets highly labile RNA, the Q beta replicase assay may facilitate investigations into the role of active persisting infection in culture-negative inflammatory conditions.

Base Sequence↗
PubMed1995

Detection of Mycobacterium tuberculosis directly from spiked human sputum by Q-beta replicase-amplified assay.

We report on a rapid, sensitive, Q-Beta replicase-amplified nucleic acid hybridization assay for the detection of Mycobacterium tuberculosis directly from spiked human sputum. Specimens were processed by either an N-acetyl-L-cysteine-NaOH or a 2% NaOH digestion-decontamination method and then washed to neutralize the pH of the cell pellet. The washed sputum pellets were heated at 100 degrees C to inactivate the M. tuberculosis organisms. The heat-inactivated samples were mechanically lysed at 5,000 rpm for 6 min in the GENE-TRAK Sample Processing Instrument in the presence of zirconium oxide beads and a buffer containing guanidine thiocyanate. The released nucleic acid was subjected to the GENE-TRAK Q-Beta replicase-amplified, dual-capture assay. The assay sensitivity was 10(3) purified rRNA targets or 1 CFU of M. tuberculosis spiked into M. tuberculosis-negative human sputum. There was a low level of noise because of the limitations of performing a signal amplification assay in an open system. High levels of other mycobacterial rRNA (approximately 10(7) organisms), including rRNAs of Mycobacterium avium and Mycobacterium gordonae, did not interfere with the sensitivity of the assay.

Bacteriological Techniques↗
PubMed1995

Comparison of amplified Q beta replicase and PCR assays for detection of Mycobacterium tuberculosis.

Because of the long time required to isolate Mycobacterium tuberculosis in culture, there is an acute need for simple rapid methods for direct detection of M. tuberculosis from human sputum specimens. We have developed and characterized quantitative manual Q beta replicase and PCR assays for M. tuberculosis. The Q beta replicase assay was based on reversible target capture of M. tuberculosis 23S rRNA followed by amplification of a replicatable detector probe with Q beta replicase. For PCR assays, primers generating a 370-bp amplification product from the IS6110 insertion element were used in combination with a control plasmid containing an internal deletion in the IS6110 amplicon. Serial dilutions of M. tuberculosis were spiked into sputum and subjected to digestion and decontamination with N-acetyl-L-cysteine and NaOH. Assay conditions were optimized for hybridization and sample processing chemistries in order to maximize sample utilization. Following assay optimization, the sensitivities of the Q beta replicase and PCR assays of spiked sputum samples were 0.5 and 5.0 CFU per assay reaction, respectively. The effects of sputum matrix on each assay were examined by testing 20 patient sputum samples which had been cultured for M. tuberculosis. The culture-positive samples included smear-positive and smear-negative samples. The results of the Q beta replicase assay were not inhibited by sputum and were in 100% agreement with those of culture, including detection of 10 culture-positive specimens. However, using an internal control plasmid coamplified with each PCR as an indicator, we detected PCR inhibition in 9 of 20 samples tested. Decreasing the amount of sample assayed in the PCR 24-fold alleviated the inhibitory effects in all but two specimens, one of which was culture positive. The decreased sample utilization also resulted in a false-negative result with a third specimen which was culture positive for M. tuberculosis. Quantitative smear results and QB replicase assay estimates of the number of organisms present in these specimens were in close agreement. The QB replicase assay performed well in comparison with both culture and PCR and should offer a rapid means for detecting and controlling infection due to M. tuberculosis.

Bacteriological Techniques↗
PubMed1995

Q-beta replicase-amplified assay for detection of Mycobacterium tuberculosis directly from clinical specimens.

We report the results of a study conducted to evaluate the performance of manual Q-Beta replicase-amplified Mycobacterium tuberculosis complex assay compared with that of culture for detecting M. tuberculosis directly from digested sputum pellets. A total of 261 specimens submitted to three tuberculosis testing laboratories were analyzed. Culture and acid-fast bacillus smear results were provided by the tuberculosis testing laboratories. Of these 261 specimens, 34 (13% prevalence rate) were positive for M. tuberculosis by culture. The samples were digested and decontaminated by the testing laboratories by using their standard digestion and decontamination procedures. An aliquot of the digested and decontaminated pellet was sent to GENE-TRAK. The digested and decontaminated pellet was neutralized by washing it with 0.067 M phosphate buffer (pH 6.8), and the bacteria present in the washed pellet were heat inactivated at 100 degrees C for 15 min. The samples were combined with sample processing buffer containing GuSCN and were treated for 6 min in the GENE-TRAK Sample Processing Instrument to release the nucleic acids. The release rRNA was analyzed in a manual Q-Beta replicase assay format which incorporates elements of sandwich hybridization, reversible target capture, and Q-beta replicase signal amplification technologies. In comparison with culture, the overall assay sensitivity and specificity were 97.1 and 96.5%, respectively. The positive predictive value was 80.5%, and the negative predictive value was 99.5%. After analysis of discrepant results, the assay sensitivity and specificity were 97.3 and 97.8, respectively, and the prevalence rate was 14%. The positive predictive value and the negative predictive value were 87.8 and 99.5%, respectively. The Q-Beta replicase assay is rapid sensitive, semiquantitative, and specific for the direct detection of M. tuberculosis from clinical specimens.

Bacteriological Techniques↗
PubMed1995

Ultrasonographic demonstration of normal axillary lymph nodes: a learning curve.

High frequency transducers with near field resolution allow visualization of superficial structures in the axilla, such as the lymph nodes, which could not be visualized with older equipment. We have been able to observe normal axillary nodes in 61.5% of 26 women who had histologic correlation of normal lymph nodes at axillary dissection. We studied 663 women with a clinically palpable breast lump using breast and axillary ultrasonography. They were divided into four groups. The first group consisted of all women who had undergone surgery and had histologic correlation of axillary nodes. The second, third, and fourth groups were made up of three consecutive series of 221 women examined. Women from group one were included in groups two, three, and four. A steep learning curve of 7.1 to 41.9 to 64.7% was observed in the detection of normal axillary nodes, suggesting that these appearances can be recognized easily.

Axilla↗
PubMed1995

Information. Counting what counts.

The NHS changes are highlighting the need for the collection of meaningful data in the community health services, writes Wendy King. She describes how health visitors can help supercede the simplifications of Korner statistics by helping the NHSE's information management group to devise systems which count what really counts.

Community Health Nursing↗
PubMed1994

Plasma levels of gonadal steroids during final oocyte maturation of striped bass, Morone saxatilis L.

Levels of estradiol-17 beta (E2), testosterone (T), 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (DHP), and 17 alpha,20 beta,21-trihydroxy-4-pregnen-3-one (20 beta-S) were measured by radioimmunoassay (RIA) in blood plasma of striped bass undergoing final oocyte maturation (FOM). Females were captured just prior to, or in the early stages of, FOM and induced to complete maturation and ovulation with injected human chorionic gonadotropin, synthetic salmon gonadotropin-releasing hormone analogue (sGnRHa; [D-Arg6-Pro9 NEt]-sGnRH), sGnRHa plus the dopamine receptor antagonist, domperidone (DOM), or OVAPRIM, a commercial preparation of sGnRHa + DOM. Their plasma levels of immunoreactive DHP and 20 beta-S were significantly greater at ovulation relative to the time of hormone injection, whereas the plasma levels of E2 and T were greatest at injection and decreased by ovulation and 24 hr thereafter. Plasma levels of 20 beta-S, but not DHP, were sustained at high levels after ovulation. Fish injected only with DOM did not undergo FOM, its associated changes in plasma steroid levels, or ovulation. In females captured at various natural stages of FOM, plasma levels of 20 beta-S and DHP were low during germinal vesicle migration (GVM), peaked coincident with germinal vesicle breakdown, and then decreased near the time of ovulation. Plasma levels of E2 and T were greatest during GVM and decreased as DHP and 20 beta-S levels increased. Analyses of conjugated versus free plasma steroids showed 64-79% of the various hormones to be in the free fraction. RIA of plasma fractionated by reversed-phase HPLC showed that half of the 20 beta-S immunoreactivity coeluted with 5 beta-pregnan-3 alpha,17,20 beta,21-tetrol, a putative 20 beta-S metabolite with 99.7% cross-reactivity in the 20 beta-S RIA. These results indicate that striped bass follow the typical profile of changing plasma steroid levels seen in other teleosts during FOM, with a clear shift from C18 and C19 steroids to C21 steroids. They suggest that both DHP and 20 beta-S, both potent inducers of striped bass FOM in vitro, may play a role in regulating FOM in this species.

Animals↗
PubMed1994

Hormonal regulation of final maturation of striped bass oocytes in vitro.

An in vitro culture system was developed to investigate hormonal control of final oocyte maturation (FOM) in striped bass (Morone saxatilis). Isolated ovarian fragments exposed to human chorionic gonadotropin (hCG), dibutyryl cAMP, or forskolin produced significant amounts of 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (DHP) and the oocytes underwent germinal vesicle breakdown (GVBD). Slight increases in 17 alpha,20 beta,21-trihydroxy-4-pregnen-3-one (20 beta-S) production were also observed. Production of testosterone and estradiol-17 beta was relatively high at the beginning of in vitro treatment with hCG but decreased as production of DHP increased and GVBD was initiated. Inhibitors of protein transcription (actinomycin-D), translation (cycloheximide), and steroidogenesis (trilostane) completely blocked hCG-induced DHP and 20 beta-S production and the associated GVBD. FOM, assessed from the progress of GVBD, proceeded in trilostane-treated but not in cycloheximide-treated follicle-enclosed oocytes when DHP or 20 beta-S was added to the cultures. Structure-activity experiments revealed that DHP and 20 beta-S were more potent at inducing GVBD than 14 other structurally similar C21 steroids that were tested. These results demonstrate that FOM in striped bass is induced by gonadotropin-mediated production of a delta 4 steroid through an adenylate-cyclase pathway which requires protein synthesis. DHP and 20 beta-S are implicated as final oocyte maturation-inducing steroid hormones in striped bass.

Animals↗
PubMed1994

Role of ultrasonography in thyroid metastases.

The ultrasound features in eight cases of metastases to the thyroid are reported. The primary tumours were bronchogenic carcinoma (4 cases), breast carcinoma (2 cases), oesophageal carcinoma (1 case) and carcinoma of the stomach (1 case). In this series, none of the metastases were from malignant melanoma or a renal neoplasm. Malignant cervical lymphadenopathy was seen in four cases, and five patients had evidence of disseminated disease.

Breast Neoplasms↗
PubMed1994

Novel, ultrasensitive, Q-beta replicase-amplified hybridization assay for detection of Chlamydia trachomatis.

A sensitive, nonisotopic hybridization assay termed "dual capture" is described. The assay rapidly and specifically detects very low levels of target nucleic acids and organisms. The assay is based on the principles of sandwich hybridization, reversible target capture, and Q-Beta replicase amplification. The assay can be completed in less than 4 h, and in the described model format, it detects Chlamydia trachomatis rRNA or rDNA. Up to 96 samples can be analyzed simultaneously. The assay employs two types of probes: a test-specific capture probe, which mediates the cycling of the target probe complex on and off derivatized magnetic beads, and a replicatable RNA detector molecule containing a sequence complementary to and adjacent to the capture probe site on the target. Following reversible target capture, detection of the signal is accomplished by replication of the detector molecule by Q-Beta replicase in the presence of propidium iodide. A specific assay signal can be detected from as few as 1,000 molecules above the background. In a limited study of 94 urogenital samples the assay detected five of the six culture-positive samples and did not detect the C. trachomatis target in 85 of the 88 culture-negative samples.

Base Sequence↗