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K Wells

Publications and source records attributed to K Wells.

At least 19 recordsLinked to original sources
PubMed2005

The pre-immune variable kappa repertoire of swine is selectively generated from certain subfamilies of Vkappa2 and one Jkappa gene.

Combinatorial diversity is highly restricted during formation of the pre-immune heavy chain repertoire of swine, raising the question of whether the same is true for the pre-immune light chain repertoire. Before addressing this question, we first used competitive PCR to show that kappa and lambda light chains in swine are equally expressed in mature B cells similar to the situation in humans but alike that in other studied Ungulates. This justified efforts to examine the repertoire of both light chain types. These studies also revealed that lambda is preferentially expressed at sites of B cells lymphogenesis, perhaps because of the use of a surrogate light chain containing lambda5. Data are presented here on >100 VkappaJkappa-containing transcripts and approximately 180 genomic Vkappa genes to show that >90% of the pre-immune repertoire is generated from three subfamilies of IGKV2 genes and one of five Jkappa segments. The kappa locus contains >or=50 IGKV2 genes belonging to at least five subfamilies and an undetermined but perhaps equal number of IGKV1 genes. The porcine IGKV1 and IGKV2 genes share 87% sequence similarity with their human counterparts and Jkappa1 through Jkappa5 share sequence and organizational homology with those in sheep, horse, human and mouse. Swine have a single Ckappa gene. These findings contrast with those from rodents and primates but are reminiscent of those on the pre-immune heavy chain repertoire of swine in that it is generated using a relatively restricted number of gene segments. These restricted pre-immune repertoires may reflect the minimal exposure of the fetus to maternal factors and environmental antigens. The significance for swine immunology of characterizing the pre-immune repertoire is discussed.

Amino Acid Sequence↗
PubMed2005

[Macrostylophora kinabaluae n. sp. (Insecta: Siphonaptera: Ceratophyllidae), a new flea from Sabah (Borneo, Eastern Malaysia)].

This species, known only by a single male, is described from Mount Kinabalu and thus is recorded from the same area as Macrostylophora borneensis (Jordan, 1926), teste Traub (1972). It is distinguished from its congeneric and characterized by the absence of eriged setae on the thorax and first abdominal tergits, as well as by the shape of terminal segments and the phallosom. Macrostylophora kinabaluae was found to parasitize the Sciurid rodent Callosciurus prevostii that is widespread throughout most areas in the Malaysian subregion.

Animals↗
PubMed2005

Exhaled breath condensate pH assays are not influenced by oral ammonia.

BACKGROUND: Measurement of pH in exhaled breath condensate (EBC) is robust and simple. Acidic source fluid (airway lining fluid) traps bases while volatilising acids, leading to EBC acidification in many lung diseases. Lower airway ammonia is one determinant of airway lining fluid pH, raising the concern that addition of the base ammonia by contamination from the mouth might confound EBC pH assays. METHODS: Three discrete methods were used to limit oral ammonia contamination of EBC collections: endotracheal intubation, oral rinsing, and -40 degrees C condenser temperatures. Separately, ammonia was removed from collected EBC samples by lyophilisation and resuspension. Intraweek and intraday variability of ammonia concentration was determined in 76 subjects, and ammonia and pH from a further 235 samples were graphically compared. Ammonia was assayed spectrophotometrically and pH was assessed after deaeration. RESULTS: Data from 1091 samples are presented. Ammonia was reduced in EBC by all methods. Endotracheal intubation decreased EBC ammonia from a mean (SD) of 619 (124) microM to 80 (24) microM (p<0.001, n=32). Oral rinsing before collection also led to a decline in EBC ammonia from 573 (307) microM to 224 (80) microM (p=0.016, n=7). The colder the condensation temperature used, the less ammonia was trapped in the EBC. Lyophilisation removed 99.4 (1.9)% of ammonia. Most importantly, the pH of EBC never decreased after removal of ammonia by any of these methods. Intraweek and intraday coefficients of variation for ammonia were 64 (27)% and 60 (32)%, which is substantially more variable than EBC pH assays. CONCLUSIONS: Although ammonia and pH appear to correlate in EBC, the oral ammonia concentration is not an important determinant of EBC pH. No precautions need to be taken to exclude oral ammonia when EBC pH is of interest. The low pH and low ammonia found in EBC from patients with lung diseases appear to be independent effects of volatile compounds arising from the airway.

Adult↗
PubMed2004

[Three new species of the genus Medwayella Traub, 1972 (Insecta: Siphonaptera: Pygiopsyllidae) from Sabah (eastern Malaysia, Borneo)].

Medwayella traubiana n. sp., M. pfeifferi n. sp. and M. sabahae n. sp. (Pygiopsyllidae) are described from Sabah (north of Borneo island), the first two on Tupaia tana (Scandentia), the last on Sundasciurus lowii (Rodentia). Sex male is only identified, because these fleas have been collected in sympatry, or even in syntopy. Their determination is based on segment IX and aedeagus. If M. traubiana and M. pfeifferi are related to some known species, M. sabahae is clearly distinct from other Medwayella.

Animals↗
PubMed2004

Crystalloid preload versus rapid crystalloid administration after induction of spinal anaesthesia (coload) for elective caesarean section.

Current methods of crystalloid preload administration prior to spinal anaesthesia for elective caesarean section are relatively ineffective in preventing hypotension. This study examined the relevance of the timing of the fluid administered. Fifty women were randomly allocated to receive either 20 ml x kg(-1) of crystalloid solution during 20 minutes prior to induction of spinal anaesthesia (preload), or an equivalent volume by rapid infusion immediately after induction (coload). Significantly more patients in the coload group did not require vasopressor therapy pre-delivery (P=0.047). The coload group required a lower median dose (P=0.03) and a lower median number (P=0.04) of ephedrine doses for the treatment of maternal hypotension pre-delivery. There was no between-group difference in either the total cumulative dose, or in the total number of doses of ephedrine. Neonatal outcomes among the two groups were similar. Rapid crystalloid administration after, rather than over 20 minutes before the induction of spinal anaesthesia for elective caesarean section, may be advantageous in terms of managing maternal blood pressure prior to delivery.

Anesthesia, Obstetrical↗
PubMed2001

Cost-effectiveness of practice-initiated quality improvement for depression: results of a randomized controlled trial.

CONTEXT: Depression is a leading cause of disability worldwide, but treatment rates in primary care are low. OBJECTIVE: To determine the cost-effectiveness from a societal perspective of 2 quality improvement (QI) interventions to improve treatment of depression in primary care and their effects on patient employment. DESIGN: Group-level randomized controlled trial conducted June 1996 to July 1999. SETTING: Forty-six primary care clinics in 6 community-based managed care organizations. PARTICIPANTS: One hundred eighty-one primary care clinicians and 1356 patients with positive screening results for current depression. INTERVENTIONS: Matched practices were randomly assigned to provide usual care (n = 443 patients) or to 1 of 2 QI interventions offering training to practice leaders and nurses, enhanced educational and assessment resources, and either nurses for medication follow-up (QI-meds; n = 424 patients) or trained local psychotherapists (QI-therapy; n = 489). Practices could flexibly implement the interventions, which did not assign type of treatment. MAIN OUTCOME MEASURES: Total health care costs, costs per quality-adjusted life-year (QALY), days with depression burden, and employment over 24 months, compared between usual care and the 2 interventions. RESULTS: Relative to usual care, average health care costs increased $419 (11%) in QI-meds (P =.35) and $485 (13%) in QI-therapy (P =.28); estimated costs per QALY gained were between $15 331 and $36 467 for QI-meds and $9478 and $21 478 for QI-therapy; and patients had 25 (P =.19) and 47 (P =.01) fewer days with depression burden and were employed 17.9 (P =.07) and 20.9 (P =.03) more days during the study period. CONCLUSIONS: Societal cost-effectiveness of practice-initiated QI efforts for depression is comparable with that of accepted medical interventions. The intervention effects on employment may be of particular interest to employers and other stakeholders.

Cost of Illness↗
PubMed2001

The effect of a geriatric education program on emergency nurses.

OBJECTIVE: In a previous study, emergency nurses gave a high priority to the educational topics of geriatric depression, physical assessment of the elderly, and mental status testing. Our objective was to measure the impact of a 1-day workshop for emergency nurses that addressed these educational needs. METHODS: The workshop consisted of case-based didactic sessions addressing (1) physical assessment of the elderly, (2) delirium, depression, and dementia, and (3) a practical approach to mental status testing in the elderly. The educational program was evaluated using 2 methods: (1) before, and 1 month after, the workshop, participants rated their own practice patterns; and (2) during the course of 2 years, changes in the number of referrals for geriatric assessment and home care from a large emergency department in the study area were monitored. RESULTS: Of 101 ED nurses who attended the 1-day workshop, 51 completed both preworkshop and postworkshop questionnaires (response rate, 50.5%). the most significant self-reported changes in practice 1 month after the workshop were improved screening for depression and altered mental status in older adults (P <.0001 and P <.01, respectively). Other positive changes were noted for inquiring about unplanned weight loss and assistance received at home. A steady increase in the number of referrals for geriatric assessment and home care was noted from the emergency department being monitored. DISCUSSION: Targeted geriatric educational programs can make an impact on the practice of emergency nurses when they are part of an overall, coordinated approach to improving assessment and discharge planning for elderly patients in emergency departments. Mechanisms for reinforcing learning several months after educational events may prove critical to the long-term success of such initiatives.

Aged↗
PubMed2001

Clinical relevance of the primary findings of the MTA: success rates based on severity of ADHD and ODD symptoms at the end of treatment.

OBJECTIVES: To develop a categorical outcome measure related to clinical decisions and to perform secondary analyses to supplement the primary analyses of the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA). METHOD: End-of-treatment status was summarized by averaging the parent and teacher ratings of attention-deficit/hyperactivity disorder and oppositional defiant disorder symptoms on the Swanson, Nolan, and Pelham, version IV (SNAP-IV) scale, and low symptom-severity ("Just a Little") on this continuous measure was set as a clinical cutoff to form a categorical outcome measure reflecting successful treatment. Three orthogonal comparisons of the treatment groups (combined treatment [Comb], medication management [MedMgt], behavioral treatment [Beh], and community comparison [CC]) evaluated hypotheses about the MTA medication algorithm ("Comb + MedMgt versus Beh + CC"), multimodality superiority ("Comb versus MedMgt"), and psychosocial substitution ("Beh versus CC"). RESULTS: The summary of SNAP-IV ratings across sources and domains increased the precision of measurement by 30%. The secondary analyses of group differences in success rates (Comb = 68%; MedMgt = 56%; Beh = 34%; CC = 25%) confirmed the large effect of the MTA medication algorithm and a smaller effect of multimodality superiority, which was now statistically significant (p < .05). The psychosocial substitution effect remained negligible and nonsignificant. CONCLUSION: These secondary analyses confirm the primary findings and clarify clinical decisions about the choice between multimodal and unimodal treatment with medication.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

Impairment and deportment responses to different methylphenidate doses in children with ADHD: the MTA titration trial.

OBJECTIVE: Results of the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA) were analyzed to determine whether a double-blind, placebo-controlled methylphenidate (MPH) titration trial identified the best MPH dose for each child with attention-deficit/hyperactivity disorder (ADHD). METHOD: Children with ADHD assigned to MTA medication treatment groups (n = 289) underwent a controlled 28-day titration protocol that administered different MPH doses (placebo, low, middle, and high) on successive days. RESULTS: A repeated-measures analysis of variance revealed main effects for MPH dose with greater effects on teacher ratings of impairment and deportment (F3 = 100.6, n = 223, p = .0001; effect sizes 0.8-1.3) than on parent ratings of similar endpoints (F3 = 55.61, n = 253, p = .00001; effect sizes 0.4-0.6). Dose did not interact with period, dose order, comorbid diagnosis, site, or treatment group. CONCLUSIONS: The MTA titration protocol validated the efficacy of weekend MPH dosing and established a total daily dose limit of 35 mg of MPH for children weighing less than 25 kg. It replicated previously reported MPH response rates (77%), distribution of best doses (10-50 mg/day) across subjects, effect sizes on impairment and deportment, as well as dose-related adverse events.

Analysis of Variance↗
PubMed2001

Findings from the NIMH Multimodal Treatment Study of ADHD (MTA): implications and applications for primary care providers.

In 1992, the National Institute of Mental Health and 6 teams of investigators began a multisite clinical trial, the Multimodal Treatment of Attention-Deficit Hyperactivity Disorder (MTA) study. Five hundred seventy-nine children were randomly assigned to either routine community care (CC) or one of three study-delivered treatments, all lasting 14 months. The three MTA treatments-monthly medication management (usually methylphenidate) following weekly titration (MedMgt), intensive behavioral treatment (Beh), and the combination (Comb)-were designed to reflect known best practices within each treatment approach. Children were assessed at four time points in multiple outcome. Results indicated that Comb and MedMgt interventions were substantially superior to Beh and CC interventions for attention-deficit hyperactivity disorder symptoms. For other functioning domains (social skills, academics, parent-child relations, oppositional behavior, anxiety/depression), results suggested slight advantages of Comb over single treatments (MedMgt, Beh) and community care. High quality medication treatment characterized by careful yet adequate dosing, three times daily methylphenidate administration, monthly follow-up visits, and communication with schools conveyed substantial benefits to those children that received it. In contrast to the overall study findings that showed the largest benefits for high quality medication management (regardless of whether given in the MedMgt or Comb group), secondary analyses revealed that Comb had a significant incremental effect over MedMgt (with a small effect size for this comparison) when categorical indicators of excellent response and when composite outcome measures were used. In addition, children with parent-defined comorbid anxiety disorders, particularly those with overlapping disruptive disorder comorbidities, showed preferential benefits to the Beh and Comb interventions. Parental attitudes and disciplinary practices appeared to mediate improved response to the Beh and Comb interventions.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

Plasminogen-binding activity of neuraminidase determines the pathogenicity of influenza A virus.

When expressed in vitro, the neuraminidase (NA) of A/WSN/33 (WSN) virus binds and sequesters plasminogen on the cell surface, leading to enhanced cleavage of the viral hemagglutinin. To obtain direct evidence that the plasminogen-binding activity of the NA enhances the pathogenicity of WSN virus, we generated mutant viruses whose NAs lacked plasminogen-binding activity because of a mutation at the C terminus, from Lys to Arg or Leu. In the presence of trypsin, these mutant viruses replicated similarly to wild-type virus in cell culture. By contrast, in the presence of plasminogen, the mutant viruses failed to undergo multiple cycles of replication while the wild-type virus grew normally. The mutant viruses showed attenuated growth in mice and failed to grow at all in the brain. Furthermore, another mutant WSN virus, possessing an NA with a glycosylation site at position 130 (146 in N2 numbering), leading to the loss of neurovirulence, failed to grow in cell culture in the presence of plasminogen. We conclude that the plasminogen-binding activity of the WSN NA determines its pathogenicity in mice.

Animals↗
PubMed2001

Amino acids responsible for the absolute sialidase activity of the influenza A virus neuraminidase: relationship to growth in the duck intestine.

The 1957 human pandemic strain of influenza A virus contained an avian virus hemagglutinin (HA) and neuraminidase (NA), both of which acquired specificity for the human receptor, N-acetylneuraminic acid linked to galactose of cellular glycoconjugates via an alpha2-6 bond (NeuAcalpha2-6Gal). Although the NA retained considerable specificity for NeuAcalpha2-3Gal, its original substrate in ducks, it lost the ability to support viral growth in the duck intestine, suggesting a growth-restrictive change other than a shift in substrate specificity. To test this possibility, we generated a panel of reassortant viruses that expressed the NA genes of human H2N2 viruses isolated from 1957 to 1968 with all other genes from the avian virus A/duck/Hong Kong/278/78 (H9N2). Only the NA of A/Singapore/1/57 supported efficient viral growth in the intestines of orally inoculated ducks. The growth-supporting capacity of the NA correlated with a high level of enzymatic activity, comparable to that found to be associated with avian virus NAs. The specific activities of the A/Ann Arbor/6/60 and A/England/12/62 NAs, which showed greatly restricted abilities to support viral growth in ducks, were only 8 and 5%, respectively, of the NA specific activity for A/Singapore/1/57. Using chimeric constructs based on A/Singapore/1/57 and A/England/12/62 NAs, we localized the determinants of high specific NA activity to a region containing six amino acid substitutions in A/England/12/62: Ser331-->Arg, Asp339-->Asn, Asn367-->Ser, Ser370-->Leu, Asn400-->Ser, and Pro431-->Glu. Five of these six residues (excluding Asn400) were required and sufficient for the full specific activity of the A/Singapore/1/57 NA. Thus, in addition to a change in substrate specificity, a reduction in high specific activity may be required for the adaptation of avian virus NAs to growth in humans. This change is likely needed to maintain an optimal balance between NA activity and the lower affinity shown by human virus HAs for their cellular receptor.

Amino Acid Substitution↗
PubMed2001

Ethnic disparities in unmet need for alcoholism, drug abuse, and mental health care.

OBJECTIVE: Recent policy has focused on documenting and reducing ethnic disparities in availability and quality of health care. The authors examined differences by ethnic status in unmet need for alcoholism, drug abuse, and mental health treatment. METHOD: Data were from a follow-up survey of adult respondents to a 1996-1997 national survey. Non-Hispanic whites, African Americans, and Hispanics were compared in access to alcoholism and drug abuse treatment and mental health care (primary or specialty), unmet need for care, satisfaction with care, and use of active treatment for alcoholism, drug abuse, and mental health problems in the prior 12 months. RESULTS: A total of 31.9% of whites, 28.1% of African Americans, and 30.1% of Hispanics had some alcoholism, drug abuse, and mental health care, mostly in primary care. Among those with perceived need, compared to whites, African Americans were more likely to have no access to alcoholism, drug abuse, or mental health care (25.4% versus 12.5%), and Hispanics were more likely to have less care than needed or delayed care (22.7% versus 10.7%). Among those with need, whites were more likely than Hispanics or African Americans to be receiving active alcoholism, drug abuse, or mental health treatment (37.6% versus 22.4%-25.0%). CONCLUSIONS: The authors document greater unmet need for alcoholism and drug abuse treatment and mental health care among African American and Hispanics relative to whites. New policies are needed to improve access to and quality of alcoholism, drug abuse, and mental health treatment across diverse populations.

Adult↗
PubMed2001

Improving depression care: barriers, solutions, and research needs.

Potential solutions for barriers to improved organization of care of depressive illness were identified. These included (1) aligning efforts to improve depression care with broader strategies for improving care of other chronic conditions; (2) increasing the availability of depression case management services in primary care; (3) developing registries and reminder systems to ensure active follow-up of depressed patients; (4) achieving agreement on how depression outcomes should be measured to provide outcomes-based performance standards; (5) providing greater support from mental health specialists for management of depressed patients by primary care providers; (6) campaigns to reduce the stigma associated with treatment of depressive illness; (7) increased dissemination of interventions that activate and empower patients managing a depressive illness; (8) redefining the lack of time of primary care providers for high-quality depression care as issues in organization of care and provider training; and (9) development of incentives (organizational or financial) for high-quality depression care. Research needs were identified according to what has been learned to date. Identified research needs included: studies of approaches to organization of case management, research in new populations (e.g., new diagnostic groups, rural populations, the disadvantaged, the elderly, and those with chronic medical illnesses), research on stepped care and relapse prevention strategies, evaluation of the societal benefits of improved depression care, and multisite trials and meta-analytic approaches that can provide adequate statistical power to assess societal benefits of improved care.

Case Management↗
PubMed2001

Desmoplastic melanoma.

Desmoplastic melanoma is an uncommonly encountered variant of malignant melanoma. Three histological subtypes exist: desmoplastic, neurotropic, and neural transforming. Desmoplastic melanoma commonly presents in conjunction with existing melanocytic lesions or as an amelanotic firm nodule. Local recurrences are common. Thirty patients over a 6-year period were treated at our institution for desmoplastic melanoma. All lesions were treated with local excision. Local recurrence occurred in seven patients (23%) and was treated by aggressive re-excision in each instance. Clinical regional metastasis (lymph nodal basins) were detected in two patients (6%). Distant metastasis (lung) developed in two patients (6%). Twenty-three patients (76%) were found to have desmoplastic subtype, whereas five (17%) had neurotropic subtype. Six patients (20%) had associated pigmented melanotic lesions. Average length of follow-up has been 18 months. Overall survival is 96 per cent. Presentations and histologic diagnosis can sometimes be difficult and misleading. Treatment is aggressive local excision with follow-up necessary to detect resectable recurrent lesions.

Adult↗