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Biomedical subjects

M McPherson

Publications and source records attributed to M McPherson.

At least 19 recordsLinked to original sources
PubMed2005

Severe hemolytic anemia due to auto anti-N.

Auto anti-N is infrequently encountered and, in most reported cases, does not cause clinical hemolysis. This case reports an auto anti-N associated with severe hemolytic anemia (Hb=2.7 g/dL) in a 6-year-old Caucasian girl with a history of vomiting, fever, and abdominal pain. Upon admission, she was found to have a metabolic acidosis, secondary to her severe anemia, with abnormal liver function tests. As in three other case reports, the autoimmune hemolytic anemia resolved, with disappearance of the auto anti-N, after corticosteroid therapy.

Acute Disease↗
PubMed2001

S-nitrosoglutathione increases cystic fibrosis transmembrane regulator maturation.

Endogenous S-nitrosoglutathione (GSNO) is known to increase the expression of certain proteins at concentrations present in the normal human airway. We hypothesized that GSNO would increase expression and maturation of the cystic fibrosis transmembrane conductance regulator (CFTR). Cells expressing DeltaF508 and wild type CFTR were exposed to GSNO and analyzed for expression and maturation by Western blot analysis. Physiologically relevant concentrations of GSNO resulted in dose- and time-dependent increases in expression. The GSNO-induced increases were eliminated by cycloheximide, suggesting a posttranscriptional effect. Unlike proteasome inhibitors, GSNO resulted in an increase CFTR maturation. The GSNO effect could be reversed by dithiothreitol and inhibited by acivicin, a gamma glutamyl transpeptidase inhibitor. These observations suggest that GSNO leads to maturation of mutated DeltaF508 CFTR, a process associated with restoration of CFTR function. Because endogenous levels of GSNO are low in the cystic fibrosis (CF) airway, these results raise the possibility that GSNO replacement therapy could be an effective treatment for CF.

Animals↗
PubMed2001

Venlafaxine in the treatment of premenstrual dysphoric disorder.

OBJECTIVE: To evaluate the efficacy and safety of venlafaxine, a new-generation antidepressant that selectively inhibits serotonin and norepinephrine reuptake, in the treatment of premenstrual dysphoric disorder (PMDD). METHOD: We conducted a randomized, double-blind, placebo-controlled, parallel-group, flexible-dose trial. After three screening cycles, including a single-blind placebo cycle, 164 women were randomly assigned to double-blind treatment with venlafaxine (50-200 mg/day) or placebo for four menstrual cycles. Primary outcome measures were the total premenstrual symptom scores as assessed by a daily symptom report (DSR) and the Hamilton Rating Scale for Depression. RESULTS: Venlafaxine was significantly more effective than placebo in reducing PMDD symptoms as assessed by DSR scores (P <.001 for last observation carried forward and observed analyses). Sixty percent of venlafaxine versus 35% of placebo subjects improved >50% (P =.003). Forty-three percent of venlafaxine subjects versus 25% of placebo subjects experienced symptom remission, defined as reduction of DSR scores to the postmenstrual level (P =.034). Venlafaxine treatment was significantly better than placebo for all statistically derived DSR factors (mood, function, pain, and physical symptoms). Improvement was relatively swift, with approximately 80% symptom reduction in the first treatment cycle. Mean venlafaxine doses ranged from 50 mg/day in the first treatment cycle to 130 mg/day in the fourth treatment cycle. Adverse events such as nausea, insomnia, and dizziness were mild and transient. CONCLUSIONS: Venlafaxine is significantly more efficacious than placebo for PMDD treatment. Response to treatment can occur in the first treatment cycle, and venlafaxine is well tolerated. Further studies are needed to evaluate the potential of intermittent (luteal phase) dosing for this cyclic disorder and the efficacy of long-term maintenance treatment with venlafaxine.

Adult↗
PubMed2000

Climbing simulated vegetation to heights of ungulate hosts by larvae of Dermacentor albipictus (Acari: Ixodidae).

Larvae of winter ticks, Dermacentor albipictus (Packard), ascend vegetation in autumn and form clumps that attach to passing ungulate hosts. We tested the hypothesis that vegetation height determines the height of clumps. During the vegetation-to-ungulate transmission period (early September to mid-November), larvae were released at the base of simulated vegetation (nylon rods 245 cm tall) in outdoor and laboratory trials and in the absence of host cues. Rod height exceeded the height of the tallest ungulate host, which is the moose, Alces alces (L.). Most larvae stopped climbing and formed clumps 50-190 cm above ground, which coincided with torso heights of moose; elk, Cervus elaphus L.; and deer, Odocoileus spp. Rafinesque. More clumps formed in outdoor trials than in laboratory trials and clump heights tended to increase over the course of the experiment, but clump number, size, and height did not correlate with weather conditions. Winter tick larvae appear to determine their height above ground in the absence of external cues, but this mechanism may be modified by external conditions.

Animals↗
PubMed1999

American Academy of Pediatrics. Committee on Children With Disabilities. Care coordination: integrating health and related systems of care for children with special health care needs.

Care coordination is a process that links children with special health care needs and their families to services and resources in a coordinated effort to maximize the potential of the children and provide them with optimal health care. Care coordination often is complicated because there is no single entry point to multiple systems of care, and complex criteria determine the availability of funding and services among public and private payers. Economic and sociocultural barriers to coordination of care exist and affect families and health care professionals. In their important role of providing a medical home for all children, primary care pediatricians have a vital role in the process of care coordination, in concert with the family.

Case Management↗
PubMed1998

Managing STIs identified after testing outside genitourinary medicine departments: one model of care.

OBJECTIVES: To develop a local strategy for managing cases of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) which have been identified in the departments of obstetrics and gynaecology (O&G). METHODS: Weekly notification from the local microbiology laboratory to genitourinary medicine (GUM) departments of all positive CT and GC results generated by tests performed in the two local O&G departments. Direct contact made by GUM departments to index patients identified and "fast track" appointments made. Data recorded for future audit include numbers attending, details of health adviser input, and success of contact tracing. RESULTS: Over 18 months, 294 women were identified and 231 (78%) attended GUM departments; 142 (48%) had received antibiotics before attending GUM departments and of these, 58 (41%) had risked reinfection by an untreated partner and 48 (20%) were found on screening to have a previously undiagnosed genital infection. Over 90% were interviewed by a health adviser. Appropriate follow up was achieved in 87% of index cases. Of the contacts, 194 were treated--150 in the local GUM department. Of these 150 men, 99 (66%) had an identifiable genital infection and 84% of those with CT/non-gonococcal urethritis were asymptomatic. There have been no complaints either formal or informal, by women managed by this system. CONCLUSIONS: GUM clinics are the ideal setting to achieve successful treatment of patients with sexually acquired infections, which must include notification and treatment of their partners if reinfection is to be avoided. For patients with infections diagnosed on other settings, such as O&G, a system of direct notification of results to GUM departments by an agreed protocol can be highly successful. For such a system to work, close cooperation and trust between departments is essential.

Adolescent↗
PubMed1998

An epidemiologic profile of children with special health care needs.

OBJECTIVE: To present an epidemiologic profile of children with special health care needs using a new definition of the population developed by the federal Maternal and Child Health Bureau. METHODS: We operationalized the new definition using the recently released 1994 National Health Interview Survey on Disability. Estimates are based on 30 032 completed interviews for children <18 years old. The overall response rate was 87%. RESULTS: Eighteen percent of US children <18 years old in 1994, or 12.6 million children nationally, had a chronic physical, developmental, behavioral, or emotional condition and required health and related services of a type or amount beyond that required by children generally. This estimate includes children with existing special health care needs but excludes the at-risk population. Prevalence was higher for older children, boys, African-Americans, and children from low-income and single-parent households. Children with existing special health care needs had three times as many bed days and school absence days as other children. An estimated 11% of children with existing special health care needs were uninsured, 6% were without a usual source of health care, 18% were reported as dissatisfied with one or more aspects of care received at their usual source of care, and 13% had one or more unmet health needs in the past year. CONCLUSIONS: A substantial minority of US children were identified as having an existing special health care need using national survey data. Children with existing special health care needs are disproportionately poor and socially disadvantaged. Moreover, many of these children face significant barriers to health care.

Adolescent↗
PubMed1997

Lesion of nigrostriatal neurons by 6-hydroxydopamine induces changes in rat brain glutathione-S-transferase.

Wistar rats were lesioned into the nigrostriatal pathway with 6-OHDA. The D-amphetamine-induced circling behavior test was performed to evaluated lesion efficiency. Animals that showed more than 620 turns/90 min were named totally lesioned animals (TLA). The group of rats that performed less than 620 turns/90 min were named partially lesioned animals (PLA). The contents of DA and its catabolites in the striata of these groups, and in the same tissue of the untreated animals, were measured. Moreover, the striatal glutathione-S-transferase (GST) specific activity for all groups was tested, and the kinetics parameters for GST purified from the whole brain were evaluated from other three similar groups. The striatal DA depletion on TLA was greater than in PLA. Striatal GST activity showed a significantly bilateral increase in PLA, whereas TLA exhibited only and ipsilateral augment. There were also differences between groups about the kinetic parameters of the purified brain enzyme. The possible role of GST on the interindividual lesion response difference was analyzed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Molecular recognition of diketide substrates by a beta-ketoacyl-acyl carrier protein synthase domain within a bimodular polyketide synthase.

BACKGROUND: Modular polyketide synthases (PKSs) are large multifunctional proteins that catalyze the biosynthesis of structurally complex bioactive products. The modular organization of PKSs has allowed the application of a combinatorial approach to the synthesis of novel polyketides via the manipulation of these biocatalysts at the genetic level. The inherent specificity of PKSs for their natural substrates, however, may place limits on the spectrum of molecular diversity that can be achieved in polyketide products. With the aim of further understanding PKS specificity, as a route to exploiting PKSs in combinatorial synthesis, we chose to examine the substrate specificity of a single intact domain within a bimodular PKS to investigate its capacity to utilize unnatural substrates. RESULTS: We used a blocked mutant of a bimodular PKS in which formation of the triketide product could occur only via uptake and processing of a synthetic diketide intermediate. By introducing systematic changes in the native diketide structure, by means of the synthesis of unnatural diketide analogs, we have shown that the ketosynthase domain of module 2 (KS2 domain) in 6-deoxyerythronolide B synthase (DEBS) tolerates a broad range of variations in substrate structure, but it strongly discriminates against some others. CONCLUSIONS: Defining the boundaries of substrate recognition within PKS domains is crucial to the rationally engineered biosynthesis of novel polyketide products, many of which could be prepared only with great difficulty, if at all, by direct chemical synthesis or semi-synthesis. Our results suggest that the KS2 domain of DEBS1 has a relatively relaxed specificity that can be exploited for the design and synthesis of medicinally important polyketide products.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗
PubMed1997

Strengthening partnerships between state programs for children with special health care needs and managed care organizations.

The roles and responsibilities of state Title V Programs for Children with Special Health Care Needs (CSHCN) are changing with the rapid expansion of managed care. The authors surveyed Title V CSHCN programs to learn about critical issues and examples of collaboration with managed care organizations in the following areas: (1) defining and identifying children with special health care needs, (2) enrollment assistance and family participation, (3) pediatric provider and service requirements, (4) education and training, (5) quality of care, and (6) pediatric risk-adjusted capitation mechanisms. This article also includes recommendations developed by the federal Maternal and Child Health Bureau's Work Group on Managed Care.

Capitation Fee↗
PubMed1994

High-performance liquid chromatographic determination of norepinephrine, epinephrine and dopamine in human foetal adrenal gland.

The purpose of this work was to characterize the human foetal adrenal gland (HFAG) by studying norepinephrine (NE), epinephrine (E), and dopamine (DA) levels in foetuses with ages ranging from 10 to 18 weeks, as a source of chromaffin cells for basic and clinical research, in the treatment of Parkinson's disease. The HFAGs were obtained from ten abortions with foetal ages ranging from 10-12 (n = 7) to 13-18 (n = 3) weeks. For the simultaneous detection of NE, E, and DA a high-performance liquid chromatographic (HPLC) procedure with electrochemical detection was employed. The concentrations found (ng/mg wet weight) were 24.24 +/- 7.06 for NE, 3.56 +/- 2.97 for E and 0.45 +/- 0.27 for DA at 10-12 weeks and 14.91 +/- 9.94 for NE, 8.18 +/- 8.79 for E and 0.16 +/- 0.05 for DA at 13-18 weeks. The DA:E ratio present in HFAG between 10 and 12 weeks was 100 times higher than that reported by other authors in adult adrenal medulla.

Adrenal Glands↗
PubMed1994

The prevention of cell adhesion and the cell-to-cell spread of HIV-1 in vitro by the alpha-glucosidase 1 inhibitor, 6-O-butanoyl castanospermine (MDL 28574).

The intercellular adhesion molecule (ICAM-1, CD54) and its counter receptor, the integrin leukocyte function associated antigen 1 (LFA-1, CD11a/CD18), have important roles in the immune response. These include guiding leukocytes to sites of inflammation (Issekutz and Issekutz, 1992), enhancement of antigen presentation (Moy and Brian, 1992) and potentiation of cytotoxic cell function (Umehara et al., 1992; Sanchez-Madrid et al., 1982). In addition to these activities LFA-1 and ICAM-1 are implicated in the cell-to-cell transmission of human immunodeficiency virus (HIV-1) since antibodies to CD18, CD54 or synthetic peptide analogs of ICAM-1 antagonise the formation of virus-induced syncytia (Fecondo et al., 1993; Gruber et al., 1991; Hildreth and Orentas, 1989; Valentin et al., 1990). The alpha-glucosidase 1 inhibitor 6-O-butanoyl castanospermine (MDL 28574) has antiviral activity for HIV which is manifested by a decrease in syncytia as well as the production of virus with altered gp120 and a reduced infectivity (Taylor et al., 1991). Previously, it has been shown that the alpha-glucose 1 inhibitor (MDL 28574) treatment of human leukocytes in vitro or mouse lymphocytes in vivo affects the detection of LFA-1 but not domain 1 of CD4 nor several other CD markers (Bridges et al., submitted for publication). Here, we demonstrate that pre-treatment of HIV-permissive CD4+ cells with MDL 28574 substantially reduces their capacity to bind with cells chronically infected with HIV-1 which results in reduced virus production.(ABSTRACT TRUNCATED AT 250 WORDS)

CD4-Positive T-Lymphocytes↗
PubMed1993

Test of an instrument to measure function-related quality of life in patients with ulcerative colitis.

An instrument for measuring function-related quality of life (QOL) in patients with ulcerative colitis was tested for validity, reliability, and responsiveness, using concepts and statistical methods easily understandable for pharmaceutical researchers. For this 8-week study, 374 patients were randomised and received placebo or oral mesalazine (mesalamine) at 1g, 2g, or 4g daily. A 10cm visual analogue scale and patient diaries were used to measure the 12 QOL parameters at baseline and study termination. Physician's Global Assessment was measured at end-point and used to assess change in the disease state of each patient. Analysis of covariance was used to test the construct validity, reliability and responsiveness of the instrument. Construct validity (p less than or equal to 0.0001), reliability (p greater than 0.05), and responsiveness (p less than or equal to 0.0001) were established for all 12 parameters of the instrument. We conclude that the instrument demonstrated precision in measuring function-related QOL in patients with active ulcerative colitis. Furthermore, content validity was maximised by combining disease-specific and general questions in the instrument.

Adult↗
PubMed1992

High incidence of significant urinary ascorbic acid concentrations in a west coast population--implications for routine urinalysis.

Examination of 4379 routine urinalysis specimens with dipsticks sensitive to ascorbic acid showed that 22.8% were positive specimens. The mean urinary vitamin C concentration in this population was 2120 mumol/L. There was a high rate of false-negative dipstick results for hemoglobin in patients with vitamin C in the urine. The highest false-negative rates were observed in urine samples containing less than 50 erythrocytes per high-power field. In further experiments when volunteers consumed supplemental oral USP vitamin C at doses of 100, 250, 500, and 1000 mg or vitamin C-containing fruit juices, even the lowest doses of oral vitamin C or juice resulted in sufficient urinary vitamin C to produce false-negative dipstick results in hemoglobin and glucose testing. To prevent potentially dangerous false-negative results, screening urinalysis protocols relying only on dipstick testing should include a check for urinary vitamin C or use a dipstick that is not subject to vitamin C interference.

Ascorbic Acid↗
PubMed1991

National agenda for children with special health needs. Social policy for the 1990s through the 21st century.

The evolution in medical technology for children with special health care needs has been accompanied by an evolution in concepts of care. Broadened diagnostic categories, comprehensive concern for the whole child, and coordinated services that are family-centered and community-based have become part of the national agenda. During the 1980s this agenda was advanced both by congressional action and by joint activities of the U.S. Public Health Service and the private sector. Much remains to be accomplished. Increased parent participation and activism, an integral part of the future, will require vigilant nurturing and support.

Child↗