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Biomedical subjects

M L Campbell

Publications and source records attributed to M L Campbell.

At least 19 recordsLinked to original sources
PubMed2001

Pharmacologic options for the treatment of obesity.

Past and current drug therapies for weight loss are discussed. More than 50% of Americans can be categorized as overweight or obese. Obesity is associated with increased mortality and with comorbidities such as hypertension, hyperglycemia, dyslipidemia, coronary artery disease, and certain cancers. According to guidelines for identification, evaluation, and treatment of obesity, patients with a body mass index (BMI) of > or = 30 kg/m2 should attempt to lose weight. Patients with a BMI of > or = 25 kg/m2 plus two or more risk factors or patients with an excessive waist circumference plus two or more risk factors should also attempt to lose weight. The initial goal is a 10% weight reduction in six months achieved through lifestyle changes. If lifestyle changes alone are not effective, then drug therapy may be indicated. Pharmacotherapeutic options for obesity have decreased over the past few years. Fenfluramine, dexfenfluramine, and phenylpropanolamine have been withdrawn because of severe adverse effects, leaving only sympathomimetics, sibutramine, and orlistat as anorectics with FDA-approved labeling. Phentermine has been shown to cause a 5-15% weight loss if given daily or intermittently. Compared with sibutramine and orlistat, phentermine is cheaper, and specific formulations allow once-daily administration. However, phentermine is indicated only for short-term treatment, and tolerance often develops. Common adverse effects associated with phentermine are dry mouth, insomnia, increased blood pressure, and constipation. Sibutramine increases norepinephrine and serotonin levels in the CNS and should not be taken with many antidepressants because of the risk of increased norepinephrine and serotonin levels. Its use is also contraindicated in patients with cardiovascular disease. Orlistat is not systemically absorbed; therefore, it does not cause the systemic adverse effects or drug interactions of phentermine and sibutramine. Orlistat has a cholesterol-lowering effect not seen with other diet medications. However, the three-times-daily administration and frequent gastrointestinal effects limit its use. Sibutramine, phentermine, and orlistat have both positive and negative properties. Choosing among the medications will depend on concurrent disease states and medications, ease of administration, and cost.

Anti-Obesity Agents↗
PubMed2001

The synthesis of phosphopeptides.

Phosphorylation and dephosphorylation are key events in protein expression and regulation and in signal transduction. Phosphopeptides are very useful reagents for the study of these processes, and have been used to great advantage in the study of phosphatase substrate specificity, SH2 domain ligand specificity, and protein-protein interactions. Furthermore, the advent of cell-permeable peptide carriers, such as those from the antennapedia homeodomain and the HIV TAT transcription factor, has allowed the study of intracellular events, thus underscoring the utility of these reagents. In this paper we review methods for the synthesis of phosphopeptides with the emphasis on the preparation of phosphoamino acid building blocks.

Amino Acid Sequence↗
PubMed2000

Construction of a BAC contig map of chromosome 16q by two-dimensional overgo hybridization.

We have used sequence-based markers from an integrated YAC STS-content/somatic cell hybrid breakpoint physical map and radiation hybrid maps of human chromosome 16 to construct a new sequence-ready BAC map of the long arm of this chromosome. The integrated physical map was generated previously in our laboratory and contains 1150 STSs, providing a marker on average every 78 kb on the euchromatic arms of chromosome 16. The other two maps used for this effort were the radiation hybrid maps of chromosome 16 from Whitehead Institute and Stanford University. To create large sequenceable targets of this chromosome, we used a systematic approach to screen high-density BAC filters with probes generated from overlapping oligonucleotides (overgos). We first identified all available sequences in the three maps. These include sequences from genes, ESTs, STSs, and cosmid end sequences. We then used BLASTto identify 36-bp unique fragments of DNA for overgo probes. A total of 906 overgos were selected from the long arm of chromosome 16. Hybridizations occurred in three stages: (1) superpool hybridizations against the 12x coverage human BAC library (RPCI-11); (2) two-dimensional hybridizations against rearrayed positive BACs identified in the superpool hybridizations; and (3) pooled tertiary hybridizations for those overgos that had ambiguous positives remaining after the two-dimensional hybridization. For the superpool hybridizations, up to 236 overgos have been pooled in a single hybridization against the 12x BAC library. A total of 5187 positive BACs from chromosome 16q were identified as a result of five superpool hybridizations. These positive clones were rearrayed on membranes and hybridized with 161 two-dimensional subpools of overgos to determine which BAC clones were positive for individual overgos. An additional 46 tertiary hybridizations were required to resolve ambiguous overgo-BAC relationships. Thus, after a total of 212 hybridizations, we have constructed an initial probe-content BAC map of chromosome 16q consisting of 828 overgo markers and 3363 BACs providing >85% coverage of the long arm of this chromosome. The map has been confirmed by the fingerprinting data and BAC end PCR screening.

Chromosomes, Bacterial↗
PubMed1999

Secondary health conditions among middle-aged individuals with chronic physical disabilities: implications for unmet needs for services.

Data from the Aging with Disability (AwD) Study are used to examine variations in the types and frequency of secondary conditions experienced by 301 middle-aged individuals living with the effects of three disabling conditions: polio (n = 124), rheumatoid arthritis (RA) (n = 103), and stroke (n = 75). All respondents were randomly selected from a county rehabilitation hospital or a community-based subject pool. Secondary conditions are operationalized as (1) the number of new health problems diagnosed or treated since the onset of the primary disability and (2) the amount of change/decline in basic and instrumental daily activities since a previous reference period in the disability trajectory. Also analyzed are changes in use of assistive devices and unmet needs for services. Differences in secondary conditions are examined within the AwD sample by impairment group and between samples by comparing AwD rates to national estimates for the same cohort. Results reveal significant differences in the types of new health problems reported by persons living with polio, RA, and stroke and document marked disparities, or accelerated aging, between disabled and nondisabled adults. Findings are discussed in terms of the changing health care needs of persons aging with disability and the importance of improving access to preventive services, ongoing rehabilitation, and assistive technology.

Activities of Daily Living↗
PubMed1999

Patient responses during rapid terminal weaning from mechanical ventilation: a prospective study.

OBJECTIVE: To describe and analyze patient responses to rapid terminal weaning from mechanical ventilation. DESIGN: A prospective, descriptive, correlational study. SETTING: An urban, university-affiliated, trauma/emergency hospital. PATIENTS: A convenience sample of 31 adult patients experiencing withdrawal of mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Physiologic (peripheral oxygen saturation, end-tidal CO2, heart rate, and respiratory rate) and comfort (electroencephalogram [EEG], Bizek Agitation Scale, and the COMFORT scale) measures were collected at baseline, during, and after the terminal weaning procedure. Clinical status was measured using the Acute Physiology and Chronic Health Evaluation score, Glasgow Coma Scale, and PaO2/F(IO2). Duration of survival after the wean inversely correlated with illness severity but did not correlate with consciousness, use of analgesia/sedation, or pulmonary function. Respiratory rate and oxygen saturation changed significantly during the wean but not end-tidal CO2. Patients remained comfortable with little or no analgesia/sedation, in a predominantly comatose sample. Subjective measures of comfort strongly correlated with objective data from bispectral analysis of EEG. CONCLUSIONS: Patients with altered consciousness or coma can be kept comfortable during a rapid terminal weaning procedure with morphine and benzodiazepines in low doses. Comfort can be reliably evaluated using subjective scales.

APACHE↗
PubMed1998

Spatial and temporal expression of AP-1 responsive rod photoreceptor genes and bZIP transcription factors during development of the rat retina.

PURPOSE: The promoter region of the rod-specific beta subunit of cGMP PDE (beta-PDE) and opsin genes contains highly conserved cis-acting elements, which include an AP-1 and/or Nrl response element (NRE: An extended AP-1 like sequence). Transactivation of AP-1 or NRE appears necessary to drive expression of these rod-specific genes during adulthood, however, their role during development is relatively unknown. Therefore, we determined the spatial and temporal relationships between rod morphological and functional development, rod-specific gene expression, and expression of the bZIP transcription factors c-fos, junD and Nrl. METHODS: Retinas from 0-45 day old (PN0-45) dark- and light-adapted Long-Evans rats were used. Morphological development was monitored by light and electron microscopy. Whole retinal trypsin-activated cGMP-PDE activity and rhodopsin content were measured biochemically. The expression of opsin, beta-PDE, c-fos, junD and Nrl mRNAs were determined by Northern blot analysis. The cellular localization of Nrl was examined with in situ hybridization. RESULTS: The mRNAs for opsin, beta-PDE and c-fos were observed at PN0-2, while cGMP-PDE activity and rhodopsin were detected first at PN5: coincident with rod outer segment development. The developmental pattern of cGMP-PDE activity and rhodopsin accumulation paralleled the expression of beta-PDE and opsin mRNA and all reached their maximal levels by PN45. Nrl expression, for all three transcripts found in the rat retina, was low on PN2 and reached its maximal level at PN14. The c-fos and Nrl expression preceded beta-PDE and opsin mRNA expression by 1-2 days. Nrl expression was detected first in the distal post-mitotic retina at PN5 and then in all nuclear layers during retinal development. Maximal expression shifted from the ganglion cells to the outer nuclear layer as the neural retina matured. In contrast, junD expression was highest at PN0 and declined to a stable level by PN10. CONCLUSIONS: Colocalization of Nrl and c-Fos suggests that expression of rod-specific genes, which utilize AP-1 or NRE sites in their promoter, could be regulated through the formation of Nrl-Fos dimers. We hypothesize that Nrl and c-Fos play a fundamental role in the initiation and regulation of the rod-specific gene expression in developing and adult rod photoreceptors.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1998

A survey of hantavirus antibody in small-mammal populations in selected United States National Parks.

Hantavirus activity in 39 National Parks in the eastern and central United States was surveyed by testing 1,815 small mammals of 38 species for antibody reactive to Sin Nombre virus. Antibody-positive rodents were found throughout the area sampled, and in most biotic communities. Antibody was detected in 7% of 647 deer mice (Peromyscus maniculatus), 2% of 590 white-footed mice (P. leucopus), 17% of 12 rice rats (Oryzomys palustris), 3% of 31 cotton rats (Sigmodon hispidus), and 33% of 18 western harvest mice (Reithrodontomys megalotis). Antibody was also found in three of six species of voles, and in one of 33 chipmunks (Tamias minimus). Prevalence among Peromyscus was highest in the northeast. Although few cases of hantavirus pulmonary syndrome have been identified from the eastern and central regions, widespread infection in reservoir populations indicates that potential exists for human infection throughout much of the United States.

Animals↗
PubMed1998

Small mammal survival and trapability in mark-recapture monitoring programs for hantavirus.

Following the 1993 hantavirus pulmonary syndrome (HPS) epidemic in the south-western United States, mammalogists and epidemiologists instituted long-term studies to monitor population density and prevalence of infection in rodents which constitute the reservoir for Sin Nombre virus (SNV). In this study, field techniques used in sampling small mammals for SNV infection were evaluated to determine if trapping and handling protocols were having significant effects on future trapability or mortality of animals. We compared rodent mark-recapture control plots, on which all rodents were simply measured, marked, and released on site, with experimental plots on which all animals were anesthetized with methoxyflurane, sampled for blood and saliva, measured, marked, and released. Blood samples were obtained from anesthetized animals on the experimental plots via a retro-orbital sinus puncture using a heparinized capillary tube. Dacron tipped oral swabs were used to collect buccal cells and saliva from the rodent's oral cavity. Field data were collected monthly from August 1994 to August 1996 at two sites in New Mexico (USA). Analyses were based on 3,661 captures of 1,513 individuals representing 21 species from three rodent families (Rodentia: Muridae, Heteromyidae, Sciuridae) and two species of rabbits (Lagomorpha: Leporidae). Overall, for most murid rodents (including five Peromyscus spp., Neotoma albigula, and Onychomys leucogaster) and one rabbit species (Sylvilagus floridanus), the handling/bleeding procedures had no significant effects on recapture rates or mortality. In contrast, several species of heteromyids (Dipodomys ordii and Perognathus flavus), one murid (Reithrodontomys megalotis) and one leporid (S. auduboni) suffered higher mortality rates, and heteromyid kangaroo rats (D. ordii and D. merriami) exhibited lower trapability as a result of the anesthesia and sampling procedures. In view of the overall non-significant influence of the sampling procedures on murid rodents, the anesthesia and blood/saliva sampling protocols described herein appear to be appropriate for hantavirus research, and may serve as a model for environmental monitoring of other zoonotic agents and their reservoirs.

Animal Welfare↗
PubMed1998

Integrating technology with compassionate care: withdrawal of ventilation in a conscious patient with apnea.

This case was atypical because the patient was conscious and apneic. The usual responses that indicate a patient's distress during terminal weaning would not have been evident in this patient. Introducing noninvasive monitoring of end-tidal CO2 and SpO2 and using BIS allowed the weaning to progress with confidence that the patient was as comfortable as possible. We think we kept our commitment to HD to honor his wishes by using the most humane method we could devise, and to address his family's needs at the same time.

Aged↗
PubMed1997

Depression and life satisfaction in aging polio survivors versus age-matched controls: relation to postpolio syndrome, family functioning, and attitude toward disability.

OBJECTIVE: To compare depressive symptoms and life satisfaction in aging polio survivors with age-matched controls and to relate these outcomes to scores to psychosocial and disability-related variables. DESIGN: A planned medical, functional, and psychosocial study with multivariate analyses. SETTING: A large, urban rehabilitation center. PARTICIPANTS: A volunteer sample of 121 polio survivors and an age-matched control group of 60 people with similar sociodemographic backgrounds. MAIN OUTCOMES: Depression as measured by the Geriatric Depression Scale and an 11-item life satisfaction scale. RESULTS: The prevalence of depressive disorders was not significantly different in the two groups, although the postpolio group tended to have more symptomatology and an overall depressive disorder prevalence of 28%. Some life satisfaction scale scores were significantly lower in the postpolio group, especially those concerned with health. People with postpolio syndrome scored significantly higher on depression scales and lower on some life satisfaction scales than people with a history of polio but without postpolio syndrome. Several psychosocial variables, most notably family functioning and attitude toward disability, helped to mediate this effect. Among people with significant depression, there was little, evidence of adequate treatment in the community. CONCLUSIONS: Postpolio by itself does not relate to higher depression scores or lower life satisfaction. Postpolio syndrome has some relation to depression, but family functioning and attitude toward disability are more important. There is a need for better community-based psychological services.

Activities of Daily Living↗
PubMed1997

Collection of surgical specimens in total joint arthroplasty. Is routine pathology cost effective?

A retrospective review of 715 consecutive cases of total joint arthroplasty (283 hips, 432 knees), performed for a variety of indications during 1992 and 1993, was undertaken to assess the cost effectiveness of routine pathologic examination. The charts were reviewed for preoperative, operative, and pathologic diagnosis, and any discrepancies in diagnosis were noted. Particular attention was paid to pathologic findings suggestive of neoplasia or rheumatoid arthritis that were not noted in the preoperative or operative diagnoses. Six of the 715 cases fit into this category, but all failed to have any clinical significance. No alteration in patient care resulted from routine pathologic examination. This paper questions the necessity of routinely submitting pathologic specimens in uncomplicated total hip and knee arthroplasty.

Aged↗
PubMed1997

Experience with an end-of-life practice at a university hospital.

OBJECTIVE: To describe a 10-yr experience with an end-of-life practice in a hospital. DESIGN: A nonexperimental, prospective, descriptive design was used to record variables from a convenience sample of patients transferred to the Comprehensive Supportive Care Team. SETTING: Detroit Receiving Hospital is an urban, university-affiliated, Level I trauma/emergency hospital. PATIENTS: Patients who are not expected to survive hospitalization, and for whom a decision has been made to focus care on palliative interventions, are candidates for care by this practice. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient demographics, including the following information: age, gender; diagnoses; illness severity; mortality rate; and disposition. Measures of resource utilization included: referral sources; Therapeutic intervention Scoring System values; bed costs; and length of hospital stay. Satisfactory patient/family care with a measurable reeducation in the use of resources can be achieved in the hospital setting. CONCLUSIONS: A hands-on approach to the care of dying patients by this specialty, palliative care service has provided patients, families, and clinicians with the type of support needed for satisfactory end-of-life care. A summary of our experience may be useful to others.

Adolescent↗