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Biomedical subjects

M McMullen

Publications and source records attributed to M McMullen.

13 recordsLinked to original sources
PubMed1999

Isolation and transduction of CD34+ cells from small quantities of peripheral blood from HIV-1-infected patients not treated with hemopoietic growth factors.

A proposed hemopoietic stem cell gene therapy for treatment for HIV infection would involve transduction of CD34+ hemopoietic stem cells with vectors encoding anti-HIV constructs. Peripheral blood has proved to be a useful source of these hemopoietic stem cells and this study exploits this finding. Small quantities of peripheral blood were obtained from HIV-negative patients and HIV-positive patients who were and were not receiving hemopoietic growth factors (HGFs). CD34+ cells were obtained from these samples using a simple technique and scored for frequency of colony type. This demonstrated that HIV-negative patients had the highest frequency of colony-forming units (CFUs). HIV-positive patients not treated with HGFs had a lower frequency of CFUs, but the same colony type distribution as HIV-negative patients. HIV-positive patients treated with HGFs had the lowest frequency of CFUs, but their colony type distribution demonstrated that they had responded to treatment. CD34+ cells selected in this way were also transduced with the murine retroviral MFG vector using a technique that demonstrated transduction efficiencies ranging from 2% to 16% (median, 11.5%). This study simplifies the experimental requirements for development of a hemopoietic stem cell gene therapy for HIV infection and offers the possibility that longitudinal studies could be performed on peripheral blood CD34+ cells from HIV-positive or HIV-negative patients without the need for granulocyte colony-stimulating factor mobilization.

Adult↗
PubMed1999

Use of topical steroid therapy in the management of nonnecrotizing anterior scleritis.

BACKGROUND: Nonnecrotizing anterior scleritis may be treated with a variety of therapies, including topical steroid therapy, systemic therapy with nonsteroidal antiinflammatory drugs (NSAIDs) and systemic steroid therapy. This study was carried out to determine the efficacy of topical steroid therapy in treating diffuse and nodular scleritis. METHODS: A phase I/II descriptive study was conducted. Thirty-two consecutive patients with nonnecrotizing anterior scleritis referred to a tertiary care ophthalmology cornea and uveitis practice in Ottawa were enrolled between September 1995 and February 1997. The patients received 1% prednisolone acetate, administered topically every 2 hours for at least 2 weeks. The drug was tapered off thereafter based on the clinical response. A successful treatment outcome was defined as resolution of scleritis without the need for systemic steroid or NSAID therapy by 2 months after initial presentation. RESULTS: The 2-month success rate was 47%. Of the 17 patients in whom treatment failed, 5 (29%) still had some evidence of scleritis at 2 months despite systemic treatment with steroids. There was no difference between the two groups in the rate of first recurrence of scleritis (log-rank test). INTERPRETATION: Although topical steroid therapy failed in over half of the patients, a significant number were spared systemic steroid therapy with its potential side effects. Despite the moderately high failure rate, topical steroid therapy could be considered as first-line treatment for nonnecrotizing anterior scleritis, especially in cases in which the likelihood of complications from systemic steroid or NSAID therapy is high.

Administration, Topical↗
PubMed1998

Assessment and management of the woman with lymphedema after breast cancer.

Lymphedema is a life-long potential complication of breast and axillary node surgery and radiation. The primary care provider plays a key role in the prevention, assessment, and treatment of this potentially debilitating condition. Through ongoing educational reinforcement, the condition may be prevented or minimized.

Breast Neoplasms↗
PubMed1997

Autosomal dominant polycystic kidney disease: pathophysiology and treatment.

Once viewed as a hopelessly incurable disease, autosomal dominant polycystic kidney disease (ADPKD) has been given a great deal of attention as geneticists search for ADPKD genes, and cell biologists are studying and understanding cyst formation. Alterations in cellular growth, secretion, and extracellular matrix all participate in cystogenesis. ADPKD is one of the most common hereditary diseases in the United States and is a frequent cause of chronic renal failure. The disease is a systemic disorder that may affect multiple organ systems. Manifestations of ADPKD in renal and extrarenal systems may be challenging problems in the management of these patients. Although no therapy is available, treatment of the complications is highly effective in most cases in supportive management of the disease.

Humans↗
PubMed1995

Breastfeeding and sertraline: a 24-hour analysis.

BACKGROUND: Few reports exist on the levels of antidepressants in breast milk or on observed behavioral effects, if any, of neonates who are breast-fed. Thus, a dilemma exists for women who would like to breast-feed but require psychotropic medications. METHOD: Analysis of sertraline levels was performed on eight samples of breast milk obtained over a 24-hour period, after 3 weeks of breastfeeding, from a lactating patient taking sertraline and nortriptyline. During this same 24-hour period, two serum samples each were taken from mother and child for analysis of sertraline and nortriptyline levels. After 7 weeks of exclusive breastfeeding, an additional serum sample was obtained from mother and child for analysis of sertraline levels. Drug metabolites were not measured. RESULTS: Breast milk levels of sertraline were lowest 1 hour before the ingestion of sertraline and highest 5 to 9 hours after ingestion of the drug. The infant's serum sertraline and nortriptyline levels were nondetectable. CONCLUSION: These data indicate that sertraline levels in breast milk vary substantially over 24 hours and appear to be lowest within the 2 hours before and 1 hour after ingestion of the medication, with the peak probably occurring between Hours 1 and 9 postingestion. However, the absence of detectable serum sertraline and nortriptyline levels in the infant suggests that if either medication is present in infant serum, its concentration would be extremely low. No abnormal occurrences have been noted in the development of the infant. It would be important in future studies to measure metabolites in addition to medication levels since the former have been associated with untoward events in an infant.

1-Naphthylamine↗
PubMed1993

Erythrocyte adenosine transport. A rapid screening test for cardiovascular drugs.

An erythrocyte (RBC) model based on whole blood was used to investigate the effect of cardiovascular drugs on the uptake of adenosine in vitro. Fresh whole blood obtained from healthy volunteers was allowed to equilibrate with various concentrations (5-1000 microM) of a tested agent. (2-3H)-Adenosine was used as a substrate, and the reaction was terminated after 2 sec of incubation at room temperature by rapid addition of a "Stopping Solution" which was a mixture of erythro-9-(2-hydroxy-3-nonyl)adenine, dipyridamole, and EDTA. The mixture was centrifuged (1760 g, 4 degrees C, 10 min), and the radioactivity of an aliquot of the supernatant was determined by a scintillation counter. The results showed that dipyridamole was the most potent agent tested (IC50 = 0.2 microM). Amongst the calcium antagonists studied, isradipine was most potent, followed by verapamil, clentiazem, diltiazem, and then nifedipine. The racemates of two metabolites of diltiazem, MX and MB, were more potent than the parent drug. The antiarrhythmic agents, amiodarone and sotalol, the two new lipid peroxidation inhibitors, U-74389F and U-78517F, and the anxiolytic agent, alprazolam, were as active as verapamil. The beta-receptor antagonist propranolol and the angiotensin converting enzyme (ACE) inhibitor, enalapril, were practically inactive. In addition, the model was stereoselective such that the S(-)-enantiomer of verapamil was considerably more potent than the R(+)-antipote, whereas d(+)-sotalol was practically inactive compared to racemic sotalol.

Adenosine↗
PubMed1988

The order and orientation of mouse lambda-genes explain lambda-rearrangement patterns.

Mouse lambda-genes are rearranged in specific V lambda-JC lambda associations: V lambda 1 has only been found to rearrange with JC lambda 3 or JC lambda 1, whereas V lambda 2 mainly rearranges with JC lambda 2 and very rarely with JC lambda 1,3. In order to determine the physical basis for these associations we have cloned the respective lambda-genes and large portions of their flanking regions by chromosomal walking in a total of 141 kb of phage and cosmid clones. With the use of unique probes obtained from such clones, the order and orientation of the mouse lambda-gene segments were determined by analyzing patterns of DNA deletion associated with lambda-gene rearrangements in various cell lines. All V and C gene segments were found to be in the same transcriptional orientation, and V2 and V1 were found not to be next to each other, thus supporting the gene order V2-C2-C4-V1-C3-C1.

Animals↗
PubMed1980

Time dependence of unipolar cathodal and anodal strength-interval curves.

Following pacemaker electrode attachment, greater ventricular vulnerability to arrhythmias exists in an acutely ischemic ventricle with a unipolar anodal than cathodal stimulus falling on the T wave, due to the shorter refractory period exhibited by an anodal stimulus. In order to determine the relationship between anodal and cathodal refractory period at various times following endocardial electrode insertion, ventricular strength-interval curves were determined in nine dogs. With stable electrode position, serial measurements were made for a mean duration of 44 days. It was observed that during the first five days, the anodal refractory period was significantly shorter than cathodal, but within 15-20 days this relationship was reversed in all dogs. The longer anodal refractory period was observed up to the end of each study. These results suggest that due to shorter anodal refractory period, greater vulnerability to arrhythmias may occur with an anodal than cathodal stimulus in the initial 15-20 days following electrode insertion.

Animals↗
PubMedDate not supplied

The Australia Commonwealth Rehabilitation Service.

This paper describes the background of the Australian Government's Rehabilitation Service and its role in disability and injury management. The health and other professionals who are employed in the Service and their clients are described. Priority and target groups are also described, as are some of the more recent achievements of the Service. There has been a shift in service delivery from a centralized focus to a community-based focus.

Adolescent↗