Biomedical subjects

W King

Publications and source records attributed to W King.

At least 19 recordsLinked to original sources

PubMed2001

Randomized controlled trial of IVIg in untreated chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVE: To determine the efficacy of IV immunoglobulin (IVIg) given patients with untreated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: A randomized, double-blind, multicenter, investigator-initiated study compared IVIg (Aventis Behring LLC, King of Prussia, PA) with placebo (5% albumin). On days 1, 2, and 21, IVIg (1 g/kg) or placebo was given. The primary outcome measure was the change in muscle strength from baseline to day 42, using the average muscle score (AMS). Secondary outcome measures included change from baseline AMS at days 10 and 21, the Hughes' functional disability scale, forced vital capacity (FVC), and nerve conduction studies (NCS) of four motor nerves (median, ulnar, peroneal, and tibial). RESULTS: The patients (n = 33) were randomized. Of these, 30 (14 women, 16 men, aged 54 +/- 20 years, range 13 to 82) received IVIg and 23 were given placebo (12 women, 11 men, aged 50 +/- 18 years, range 23 to 73). Baseline AMS values of the groups were similar (IVIg 7.06 +/- 1.31 versus placebo 7.28 +/- 1.18, p = 0.53). There were two dropouts in placebo group and one in the IVIg group. Mean AMS improved at day 42 comparing IVIg with placebo (0.63 versus -0.1, p = 0.006). Improved strength was seen by day 10. The placebo group lost strength over this same interval. In the IVIg, 11 subjects improved by the functional disability scale; none worsened. This differed (p = 0.019) from those in the placebo-treated group (two improved, two got worse, remainder unchanged). Forced vital capacity did not improve with IVIg treatment. IVIg improved ulnar motor distal latency (p = 0.005), tibial distal compound muscle amplitude (p = 0.003), and peroneal nerve conduction velocity (p = 0.03). CONCLUSIONS: IVIg improves strength in patients with untreated CIDP by day 10 with continued benefit through day 42; more than one third improve by at least a functional grade on a disability scale. This study provides data supporting IVIg as the initial treatment for CIDP.

Adolescent↗

PubMed2001

Reprogramming of telomerase activity and rebuilding of telomere length in cloned cattle.

Nuclear reprogramming requires the removal of epigenetic modifications imposed on the chromatin during cellular differentiation and division. The mammalian oocyte can reverse these alterations to a state of totipotency, allowing the production of viable cloned offspring from somatic cell nuclei. To determine whether nuclear reprogramming is complete in cloned animals, we assessed the telomerase activity and telomere length status in cloned embryos, fetuses, and newborn offspring derived from somatic cell nuclear transfer. In this report, we show that telomerase activity was significantly (P < 0.05) diminished in bovine fibroblast donor cells compared with embryonic stem-like cells, and surprisingly was 16-fold higher in fetal fibroblasts compared with adult fibroblasts (P < 0.05). Cell passaging and culture periods under serum starvation conditions significantly decreased telomerase activity by approximately 30-50% compared with nontreated early passage cells (P < 0.05). Telomere shortening was observed during in vitro culture of bovine fetal fibroblasts and in very late passages of embryonic stem-like cells. Reprogramming of telomerase activity was apparent by the blastocyst stage of postcloning embryonic development, and telomere lengths were longer (15-23 kb) in cloned fetuses and offspring than the relatively short mean terminal restriction fragment lengths (14-18 kb) observed in adult donor cells. Overall, telomere lengths of cloned fetuses and newborn calves ( approximately 20 kb) were not significantly different from those of age-matched control animals (P > 0.05). These results demonstrate that cloned embryos inherit genomic modifications acquired during the donor nuclei's in vivo and in vitro period but are subsequently reversed during development of the cloned animal.

Animals↗

PubMed2001

Genetic imbalances in pT2 breast cancers of southern Chinese women.

While much information has been reported on the genetic alterations in breast cancers of Caucasians, little is known about the Oriental populations where breast cancers currently rank the second most common neoplasm. As a first step toward understanding the underlying genetics changes in this population, we used comparative genomic hybridization (CGH) to the genome-wide analysis of forty pT2 tumors from patients of a racially homogenous population in southern China. A complex pattern of genetic alterations emerged with the commonest chromosomal gains identified on 1q (58%), 8q (55%), 11q13 (25%), 16p (28%), 17q (53%) and 20q (35%), and frequent losses on 8p (38%), 11q (28%), 13q (30%) and 18q (25%). When breast cancers with and without lymph-node metastasis were compared, a higher copy gain of 10p was identified in the node-positive group (P=.036). An overall increase in the average number of genetic aberrations was also identified in the late onset group (>45 years)(P=.042) with a higher incidence of genetic losses noted (P=.035). In particular, losses on 16q were detected in 30% of the late onset patients but none in the early onsets (P=0.049). In this study, we have illustrated the pattern of genetic changes in breast tumors of southern Chinese females. While frequent 1q, 8q, 17q and 20q gains, and common 8p and 13q deletions detected were consistent to those aberrations reported from the Caucasian populations, the difference in genetic changes associated in lymph-node metastasis and age of onset identified should provide the basis for additional investigations into the underlying tumorigenesis in the Oriental population.

Adult↗

PubMed2000

Ab initio calculations on hidden modulators of theta class glutathione transferase activity.

The glutathione transferases decrease the pKa of glutathione, allowing its deprotonation and the formation of the more reactive thiolate anion. The thiolate is maintained in the active site through a weak conventional hydrogen bond first sphere interaction donated by a Tyr hydroxyl in the Alpha, Mu, Pi, and Sigma glutathione transferase classes that can be modified by other second sphere or indirect thiolate contacts. However, the Theta and Delta class isoforms use a Ser hydroxyl for stabilizing the GSH thiolate, and as such, have a different chemical system compared with that of the Tyr possessed by other classes. We have used high level ab initio methods to investigate this interaction by using a simple methanol methanethiol system as a model. The hydrogen bond strength of this initial first sphere interaction was calculated to be less than that of the Tyr interaction. A putative second sphere interaction exists in the Theta and Delta class structures between Cys or Ser-14 and Ser-11 in the mammalian Theta subclass 1 and 2, respectively. The effect of this interaction on the first sphere interaction has also been investigated and found to significantly increase the energy of the bond.

Animals↗

PubMed2000

The role of fluorescence in situ hybridization technologies in molecular diagnostics and disease management.

Large genomic changes, such as aneuploidy, deletions, and other chromosomal rearrangements, have long been associated with pregnancy loss, congenital abnormalities, and malignancy. These genomic changes are quantitative, unambiguous, and fundamental in the transition of normal cells to abnormal ones. Detection of these large genetic changes has an increasingly important role in determining patient diagnosis and care, including therapeutic selection. We have developed two major product platforms that assess genomic changes at various levels of resolution. Fluorescence in situ hybridization (FISH) techniques and the related technology of array-based comparative genomic hybridization (CGH) allow detection of genesized or larger alterations in the genome. FISH is a robust DNA probe technology that can measure both balanced and unbalanced genomic changes on a cell-by-cell basis. In most instances, it is not dependent on metaphase chromosomes, and it is widely used in clinical diagnostics. Array-based CGH has much greater multiplexing capabilities than FISH. This technology has the potential to examine many regions of the genome simultaneously for changes in DNA copy number and identify complex patterns of gains and losses within the genome. In this article, we review several of the current medical applications of FISH and discuss such advanced techniques as CGH and array-based CGH.

Databases, Factual↗

PubMed2000

The development of a multitarget, multicolor fluorescence in situ hybridization assay for the detection of urothelial carcinoma in urine.

The purpose of this study was to develop a multitarget, multicolor fluorescence in situ hybridization (FISH) assay for the detection of urothelial carcinoma (UC) in urine specimens. Urinary cells obtained from voided urine specimens of 21 patients with UC and 9 normal donors were analyzed with nine different centromere enumeration probes and a single locus-specific indicator probe to determine an optimal set of FISH probes for UC detection. The four probes with the greatest sensitivity for UC detection were then labeled with a unique fluorophore and combined into a single probe set. The probes with the greatest combined sensitivity for UC detection were CEP3, CEP7, CEP17, and the 9p21 (P16) LSI. This probe set was used to evaluate urine specimens acquired from 179 patients for prospective testing (46 with biopsy-proven UC). FISH slides were evaluated by scanning the slide for cells with nuclear features suggestive of malignancy and assessing the FISH signal pattern of these cells for polysomy (ie, gains of two or more different chromosomes). A receiver operator characteristic curve revealed that a cutoff of 5 cells with polysomy as the positive criterion for cancer resulted in an overall sensitivity of 84.2% for patients with biopsy-proven UC and a specificity of 91.8% among patients with genitourinary disorders but no evidence of UC. This study demonstrates that a multitarget, multicolor FISH assay containing centromeric probes to chromosomes 3, 7, and 17 and a locus-specific probe to band 9p21 has high sensitivity and specificity for the detection of UC in voided urine specimens.

Aneuploidy↗

PubMed2000

Automation of fluorescence in situ hybridization pretreatment: a comparative study of different sample types.

BACKGROUND: In fluorescence in situ hybridization (FISH) applications, the efficiency of probe hybridization is greatly enhanced by treating the cell or tissue preparation with a variety of reagents that make the target permeable while preserving important morphological features. Pretreatment protocols can be very labor intensive, adding cost to the test. The automation of specimen pretreatment eliminates human variation in the procedure through standardization of such variables as treatment times and temperatures. METHODS AND RESULTS: We developed an instrument, the VP 2000 Processor, that can process up to 50 specimens simultaneously under computer control. In this comparative FISH study of matched specimens, one set was processed according to the manual pretreatment protocol and compared with specimens processed by the VP 2000. Processed specimen types included paraffin-embedded breast tissue, uncultured amniocytes, bone marrow, peripheral-blood lymphocytes, and uroepithelial cells recovered from urine. Data show equivalent or brighter and more specific overall signal quality compared with matched manually executed controls. CONCLUSIONS: The automation of sample pretreatment for FISH provides a superior, more consistent level of performance than the manual format.

Amnion↗

PubMed2000

Can clinical parameters predict fractures in acute pediatric wrist injuries?

OBJECTIVE: Fractures around the wrist are common in pediatric patients presenting to the emergency department (ED). This pilot study was aimed at identifying clinical variables that are most likely to be associated with a fracture. METHODS: This was a prospective blinded case series of patients 3-18 years of age presenting with an acute (<3 days) wrist injury, without obvious deformity. A team of five investigators blinded to the eventual radiographic findings evaluated patients. Physical examination variables included range of motion (ROM), site of maximal tenderness, and functional deficit. The latter was determined objectively, by recording any difference in grip strength between the injured and noninjured hands. Diagnostic radiographs were obtained for all patients. Univariate analysis using Wilks' log likelihood ratio test was performed to identify clinical variables associated with confirmed wrist fractures. Sample size was determined based on the ability to detect a difference of 15 degrees in the ROM variables, 20% point differences in grip strength, and 30% proportion differences in categorical variables using a power of 0.8 and a two-tailed of 0.05. RESULTS: The ROMs were not significantly different between the fracture (Fx) and nonfracture (NFx) group. There was significant change in the grip strength between the Fx and NFx groups (t = 3.3, p = 0.0019). Tenderness over the distal radius was also associated with a greater likelihood of a fracture (G(2) = 5.0, p = 0.02). Sensitivity of clinical prediction was found to be 79%, and specificity was 63%. The false-negative rate was 0.21 and the false-positive rate was 0.37, while the positive predictive value was found to be 0.68 and negative predictive value 0.75. CONCLUSIONS: Distal radius point tenderness and a 20% or more decrease in grip strength were predictive of fractures.

Acute Disease↗

PubMed2000

A comparison of cytology and fluorescence in situ hybridization for the detection of urothelial carcinoma.

PURPOSE: We determine the relative sensitivities of cytology and fluorescence in situ hybridization (FISH) for the detection of urothelial carcinoma. MATERIALS AND METHODS: A mixture of fluorescent labeled probes to the centromeres of chromosomes 3, 7 and 17, and band 9p21 (P16/CDKN2A gene) was used to assess urinary cells for chromosomal abnormalities indicative of malignancy. A total of 280 urine specimens from 265 patients, including 150 with a history of urothelial carcinoma and 115 without a history of urothelial carcinoma, were analyzed. FISH analysis was performed without prior knowledge of clinical findings, that is biopsy, cystoscopy and cytology results. A positive result was defined as 5 or more urinary cells with gains of 2 or more chromosomes. RESULTS: A total of 75 biopsies showed urothelial carcinoma at FISH analysis among the 265 patients. The sensitivity of urine cytology for pTa (36 cases), pTis (18) and pT1-pT4 (15) tumors was 47%, 78% and 60%, respectively, for an overall sensitivity of 58%. The sensitivity of FISH for pTa (37 cases), pTis (17) and pT1-pT4 (19) tumors was 65%, 100% and 95%, respectively, for an overall sensitivity of 81%. FISH was significantly more sensitive than cytology for pTis (p = 0.046), pT1-pT4 (p = 0.025), grade 3 (p = 0.003) and all tumors (p = 0.001). The specificity of cytology and FISH among patients without cystoscopic evidence of urothelial carcinoma and no history of urothelial carcinoma was 98% and 96%, respectively (p = 0.564). CONCLUSIONS: The sensitivity of FISH for the detection of urothelial carcinoma is superior to that of cytology, and the specificity of FISH and cytology for urothelial carcinoma are not significantly different. Further prospective studies are required but FISH has the potential to improve significantly the management of urothelial carcinoma.

Centromere↗

PubMed2000

The prevalence of diabetes in the Cree of western James Bay.

Diabetes prevalence and general demographic data for individuals with diabetes were evaluated in the Cree of Moose Factory, Ontario. Individuals with diabetes were identified through a retrospective review of the diabetes registry as well as of outpatient and inpatient records. The crude prevalence of diabetes was 62 (95% confidence interval: 54 72) per 1,000. The direct age-standardized prevalence of diabetes was 103 per 1,000 for the entire population (95% confidence interval: 89 118 per 1,000, standardized to the 1991 Canadian population). The estimated rate of diabetes in the Canadian population is approximately 5%. The average age of individuals with diabetes in the community was 53 years; the average duration of diabetes was 8.2 years. Most of the population with diabetes were female (64 %) and were using anti-hypertensive medications (64%). This study presents diabetes prevalence data for the population of Moose Factory, Ontario, that indicate a higher prevalence than in both the Canadian population and other Cree populations in the region.

Adolescent↗

PubMed1999

Submental metastases from nasopharyngeal carcinoma.

The primary treatment for nasopharyngeal carcinoma is radiotherapy. Despite optimal treatment the incidence of recurrent persistent or recurrent regional disease is significant. It is believed that recurrent regional disease is usually associated with local disease. Recurrent nodal disease commonly involves the subdigastric and upper jugular region and submental involvement is less common. This study includes 25 patients who had palpable submental nodes 2 years or more after radiotherapy. Five of the seven patients with proven malignant submental nodal recurrence of nasopharyngeal carcinoma had no other evidence of disease. Ultrasound accurately identified enlarged nodes and correctly predicted involvement. The ultrasound appearances of these nodes and their impact on management and prognosis is discussed.

Adult↗

PubMed1999

Treatment of a recurrent subdural hematoma using urokinase.

Previous reports describe the intraventricular, subarachnoid, and intraparenchymal use of thrombolytic agents. However, the use of thrombolytic agents in the management of extraaxial hematomas has not been described. Following the evacuation of a subacute subdural hematoma, this 48-year-old woman experienced declining neurologic function due to the reaccumulation of blood in the subdural space. Urokinase was administered via a subdural drain. The patient experienced rapid clinical improvement and radiographic resolution of the recrudescent subdural hematoma. If repeat surgical evacuation of a subdural hematoma is not possible, urokinase may be instilled into the subdural space to enhance drainage of a subdural hematoma.

Female↗

PubMed1999

"The silent killer": chronic acetaminophen toxicity in a toddler.

We report a case fatality from chronic acetaminophen (APAP) toxicity in an 18-month-old toddler, born 14 weeks premature, who had been receiving less than the standard toxic threshold of the pediatric suspension of APAP for 4 days prior to presentation. Furthermore, he had been on prolonged total parenteral nutrition (TPN) as an infant. We hypothesize that TPN-induced hepatic changes may have diminished the patient's hepatic reserve, making him more susceptible to APAP toxicity. We propose that different "therapeutic" APAP dosing may be needed for those with underlying risk factors for hepatotoxicity.

Acetaminophen↗

PubMed1999

Trihalomethanes in public water supplies and adverse birth outcomes.

We conducted a retrospective cohort study to evaluate the relation between the level of total trihalomethanes in drinking water and adverse birth outcomes. The study population comprised women residing in an area with municipal surface water who had a singleton birth in Nova Scotia between January 1, 1988, and December 31, 1995, or a pregnancy termination for a major fetal anomaly. We found little association between trihalomethane level and the outcomes related to fetal weight or gestational age, but we found an elevated relative risk for stillbirths for average trihalomethane levels during pregnancy of 100 microg/liter or greater (adjusted relative risk = 1.66; 95% confidence interval = 1.09-2.52) relative to women exposed to trihalomethane levels of 0-49 microg/liter. We saw little evidence of an elevated prevalence or dose-response pattern for congenital anomalies, with the possible exception of chromosomal abnormalities (adjusted prevalence ratio = 1.38 and 95% confidence interval = 0.73-2.59 for women exposed to trihalomethane levels of 100 microg/liter or greater).

Abnormalities, Drug-Induced↗

PubMed1999

Thyroglossal duct cysts: sonographic appearances in adults.

BACKGROUND AND PURPOSE: Previous reports have suggested that thyroglossal duct cysts (TDCs) appear on sonograms as well-defined cystic masses with thin walls and posterior enhancement. In our experience, however, TDCs have a variable sonographic appearance. We report our findings in 40 patients with TDCs and document the variability of sonographic patterns. METHODS: All patients in whom the diagnosis of TDC was made clinically (by at least two head and neck surgeons) and sonography detected a cystic mass related to the hyoid bone were included in this study. Sonograms of 40 patients with TDCs were reviewed. The features evaluated were the location, internal echogenicity, posterior enhancement, presence of septa, solid component, and fistulous tract. The echo pattern was not compared with the biopsy results. RESULTS: Four patterns of TDCs were identified: anechoic (28%), homogeneously hypoechoic with internal debris (18%), pseudosolid (28%), and heterogeneous (28%). The majority showed posterior enhancement (88%), were midline (63%), and infrahyoid in location (83%). Only half of all TDCs showed a typical thin wall. CONCLUSION: On sonograms, TDCs in adults are not simple cysts, as previously suggested, but have a complex pattern ranging from a typical anechoic to a pseudosolid appearance.

Adult↗

PubMed1999

"No fear" fund raising.

Successfully asking for a major gift requires practice. We only raise major gifts by asking and that requires us to get out there in front of major gift prospects. We must discipline ourselves to do just that. Being a successful major gift fund raiser requires continual practice.

Charities↗

PubMed1998

Cervical lymphadenopathy: sonographic differentiation between tuberculous nodes and nodal metastases from non-head and neck carcinomas.

PURPOSE: Clinical examination alone cannot differentiate between cervical tuberculous lymphadenitis and cervical nodal metastases from non-head and neck (NHN) carcinomas because the distributions of involved lymph nodes are similar. We evaluated the sonographic features of cervical lymph nodes that could be used to differentiate between the 2 categories of nodes. METHODS: We retrospectively reviewed sonograms of abnormal cervical lymph nodes in 47 patients with proven cervical tuberculous lymphadenitis and in 22 patients with proven nodal metastases from NHN carcinomas. RESULTS: Abnormal nodes in tuberculous lymphadenitis and nodal metastases from NHN carcinomas were commonly found in the supraclavicular fossa (15% and 38%, respectively) and the posterior triangle (70% and 41%, respectively). Statistically significant (p < 0.05) features for differential diagnosis were lymph nodes' longest diameter, echogenicity, short-to-long axis ratio, appearance of surrounding soft tissues, and presence of intranodal cystic necrosis, matting, and posterior enhancement. Nodal size, echogenicity, presence of an echogenic hilum, calcification, coagulation necrosis, and sharpness of borders helped in identifying the abnormal lymph nodes. CONCLUSIONS: Sonographic features that helped to differentiate between the 2 categories of nodes were shape, edema of surrounding soft tissue, homogeneity, intranodal cystic necrosis, matting, and posterior enhancement.

Adult↗

PubMed1998

Solitary cystic nodal metastasis from occult papillary carcinoma of the thyroid mimicking a branchial cyst: a potential pitfall.

Thyroid carcinoma presenting as cervical lymph node metastasis with a clinically normal neck indicates an aggressive tumour of the thyroid. When the nodal metastasis is solitary and cystic, with no obvious suspicious thyroid mass on ultrasound (US) it may be mistaken for a branchial cyst. As the management of these two conditions is different, it is important to make a correct pre-operative diagnosis. We present the US features that help in distinguishing the two.

Adult↗