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Biomedical subjects

M Clay

Publications and source records attributed to M Clay.

At least 19 recordsLinked to original sources

Sexual health innovations in undergraduate medical education.

Recent national and global initiatives have drawn attention to the importance of sexual health to individuals' well-being. These initiatives advocate enhancement of efforts to address this under-represented topic in health professions curricula. University of Massachusetts Medical School (UMMS) has undertaken a comprehensive effort to develop an integrated curriculum in sexual health. The UMMS project draws upon the expertise of a multidisciplinary faculty of clinicians, basic scientists, a medical ethicist, and educators. This article describes the project's genesis and development at UMMS, and reports on three innovations in sexual health education implemented as part of this endeavor.

Curriculum↗

Cryopreservation of cord blood after liquid storage.

BACKGROUND: The processing of cord blood may result in delays prior to RBC depletion and cryopreservation. The overall objective of this investigation is to determine the influence of liquid storage prior to cryopreservation on the post-thaw viability. METHODS: UC blood supplemented with CPD anticoagulant (CB) was obtained from normal donors with informed consent. CB was stored undiluted, or diluted with 1:1 ratio of storage solution STM-sav for up to 72 h. The undiluted control samples were stored at room temperature. CB samples supplemented with STM-sav were stored at 4 degrees C. After completion of the storage protocol, the sample was RBC depleted, frozen, stored, thawed, and assayed for viability. Nucleated cell counts, percentage of CD34+ cells, and frequency of colony formation were determined during liquid storage and after cryopreservation. RESULTS: The post-thaw mononuclear cell recovery and viability of cord blood stored for 72 h was significantly lower than that of cord blood stored for 24 h prior to cryopreservation. This difference was true for cord bloods stored in STM-sav and controls. Dilution of the cord blood with STM-sav improved the frequency of CFU-GM observed. DISCUSSION: Liquid storage of cord blood for 24 h prior to cryopreservation does not adversely influence the post-thaw cell recovery. The use of a storage solution (STM-Sav) enhances the retention of colony-forming capabilities post-thaw. These and other studies provide an important foundation for the development of integrated protocols for cord blood banking.

Antigens, CD34↗

Antidepressant-like actions of an AMPA receptor potentiator (LY392098).

LY392098 is a member of a novel class of biarylpropylsulfonamides that potentiates AMPA receptor-mediated responses both in vitro and in vivo. In this study, the effects of LY392098 were evaluated in two "behavioral despair" models (the forced swim and tail suspension tests) commonly used to identify clinically useful antidepressants. LY392098 reduced immobility in the forced swim test in both rats and mice, with a minimum effective dose of 0.5 mg/kg (i.p.) in both species. LY392098 (0.1-10 mg/kg, i.p.) did not affect motor activity of rats, indicating that the ability of this compound to reduce immobility in the forced swim test is unrelated to a motor stimulant action. LY392098 also reduced immobility in the tail suspension test in a dose-dependent manner, with a minimum effective dose of 5 mg/kg (i.p). A non-competitive AMPA antagonist (LY300168) blocked the activity of LY392098 in the forced swim test, but did not affect imipramine-induced reductions in immobility. Thus, AMPA receptor activation appears to be required for the antidepressant-like effect of LY392098, but not imipramine. These findings indicate that biarylpropylsulfonamides, exemplified by LY392098, may represent a novel class of antidepressants.

Animals↗

One year's experience with a program to facilitate personal and professional development in medical students using reflection groups.

PURPOSE: (1) to integrate sociobehavioral science concepts into the early curriculum through a continuity ambulatory clinical experience in primary care, and (2) to expose students to a learning environment in which self-awareness and emotional development are nurtured in the context of dealing with the stresses of an early clinical experience. METHODS: Second-year students spent half a day twice monthly in a primary care community practice, kept a journal of their experiences, and attended biweekly 60-minute Reflection Groups designed to foster personal awareness and empathic witnessing. Analysis of journal entries and Reflection Group field notes identified stressors occurring during the students' clinical encounters. RESULTS: Three sources of stress are illustrated: the role and responsibility of the physician, death and dying, and racial issues. Reflection Groups provided students with opportunities to identify and describe stressors, to feel less isolated, to begin the process of self-awareness development, and to integrate behavioral and social science concepts into clinical practice. Our program incorporates students' early clinical experience with facilitated opportunities to reflect on the emotional challenges of becoming a physician.

Journal Article↗

Rehabilitation in nursing homes.

Rehabilitation is a key concept in the government's plans to modernize the NHS. Its aim is to restore a person's autonomy, although there are sometimes barriers to making effective rehabilitation a reality, some of which are explored here, along with ways of helping teams in nursing homes to undertake more effective rehabilitation.

Aged↗

Oral health in older people.

Oral health is an area which is often overlooked when caring for older people. This article gives guidelines on how to ensure that older people do not suffer discomfort and diseases in the mouth.

Aged↗

Effects of granulocyte-colony-stimulating factor on potential normal granulocyte donors.

BACKGROUND: The use of granulocyte-colony-stimulating factor (G-CSF) to increase the granulocyte count and the yield from leukapheresis in normal donors is leading to renewed interest in granulocyte transfusion. Therefore, it is important to understand the side effects of G-CSF. STUDY DESIGN AND METHODS: We studied the effect of G-CSF on peripheral blood counts and recorded the side effects experienced 24 hours after an injection of G-CSF in normal subjects donating peripheral blood progenitor cells for research. RESULTS: Following administration of G-CSF to 261 donors, the neutrophil count increased to 20.6 to 24.5 x 10(9) per microL depending on the dose of G-CSF. This represented a 6.2 to 7.4-fold increase over the neutrophil count before G-CSF administration. Of all donors, 69 percent experienced one or more side effects. The most common effects were: muscle and bone pain, headache, fatigue, and nausea. There was a relationship between the dose of G-CSF and the likelihood of experiencing a side effect. Most side effects were mild, but about 75 percent of donors took analgesics because of them. CONCLUSIONS: In a granulocyte donation program involving G-CSF stimulation, about two-thirds of donors would experience one or more side effects, but these would usually be mild and well tolerated.

Adolescent↗

Rats with hypothalamic obesity are insensitive to central leptin injections.

Genetically determined obesities, involving leptin- and melanocortin-signaling pathways, have focused attention on the four medial hypothalamic nuclei as primary sources of feeding- and metabolically-based obesity. All four medial cell groups contain leptin receptors. To determine which of these cell groups normally mediates the effects of leptin on food intake and body weight gain, we injected colchicine bilaterally into each nucleus and determined the pathophysiological effects of disruption and responsivity to leptin injected intracerebroventricularly. Intracerebroventricular injections of leptin in sham-lesioned rats decreased food intake during the dark period, but not during the light period. Lesions of the arcuate (ARC), paraventricular (PVN), and ventromedial (VMN) nuclei all resulted in leptin insensitivity; by contrast, lesions of the dorsomedial nuclei (DMN) augmented sensitivity to leptin on feeding and body weight gain. Although rats with ARC and PVN lesions were obese, they were still capable of reducing caloric efficiency over the 5 days of study and increasing uncoupling protein content in interscapular brown adipose tissue. Caloric efficiency and uncoupling protein content were unchanged in rats with VMN and DMN lesions. Finally, the slope of the relationship between leptin and mesenteric white adipose tissue was increased in rats with VMN lesions and abolished in rats with ARC lesions. Thus, lesions of the ARC, PVN, and VMN produced obesity via separate pathways. We conclude that the medial hypothalamic cell groups, each with a different role in energy balance, are all necessary for normal leptin responsiveness.

Animals↗

Characterization of a new alloantigen (SH) on the human neutrophil Fc gamma receptor IIIb.

Polymorphic structures of the neutrophil Fc gamma receptor IIIb (Fc gamma RIIIb) result in alloantibody formation that causes alloimmune neonatal neutropenia and transfusion reactions. Alloantigens located on Fc gamma RIIIb include the antigens NA1 and NA2. In four cases of alloimmune neonatal neutropenia, granulocyte-specific alloantibodies directed against a thus far unknown antigen were detected by granulocyte agglutination and immunofluorescence tests in the maternal sera. By the use of the monoclonal antibody-specific immobilization of granulocyte antigens (MAIGA) assay, the new antigen, termed SH, was located on the Fc gamma RIIIb. Nucleotide sequence analysis of the Fc gamma RIIIb coding region from a SH(+) individual showed a single-base C-->A mutation at position 266, which results in an Ala78Asp amino acid substitution. A family study confirmed that this nucleotide difference is inherited, and corresponds to the SH phenotype. Serologic typing of 309 randomly selected individuals showed an antigen frequency of 5% in the white population. The same frequency was found by genotyping, for which a technique based on polymerase chain reaction (PCR) using sequence-specific primers (PCR-SSP) was developed. Typing of all SH(+) individuals for NA1 and NA2, and PCR-restriction fragment length polymorphism analysis of the NA-specific PCR products from five SH(+) individuals using the SH-specific endonuclease SfaN 1 showed that SH antigen is very probably the result of an additional mutational event in the NA2 form of the Fc gamma RIIIB gene. Immunochemical studies also demonstrated that the SH determinants reside on the 65- to 80-kD NA2 isoform of the Fc gamma RIIIb. Our findings show the existence of an additional polymorphism of the Fc gamma RIIIb, which can result in alloantibody formation causing alloimmune neonatal neutropenia.

Adult↗

Molecular characterization of antigenic polymorphisms (Ond(a) and Mart(a)) of the beta 2 family recognized by human leukocyte alloantisera.

We show that the previously described alloantisera Ond and Mart, which recognize the alloantigens Ond(a) and Mart(a), react with polymorphic variants of alpha L and alpha M subunits of the beta 2 integrin family (CD11a and CD11b molecules). This was shown by testing the alloantisera in a monoclonal antibody-specific immobilization of leukocyte antigens, immunoprecipitation, and immunofluorescence assay against cells from normal donors and from patients with leukocyte adhesion deficiency (beta 2 intergrin deficient). To elucidate the molecular basis of the Ond(a) and Mart(a) alloantigens, RNA was isolated from mononuclear leukocytes derived from individuals of known serologic phenotype. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to amplify the entire coding region of the alpha L and alpha M mRNAs. The Ond(a) antigen was found to be due to a G2466C substitution in the DNA coding for the alpha L subunit, which predicts an Arg766Thr amino-acid polymorphism. The Mart(a) antigen was also found to be due to a single nucleotide substitution (G302A) in the DNA coding for the alpha M subunit, which predicts an Arg61His amino acid polymorphism. Using allele-specific restriction enzyme analysis, the association between point mutations and phenotypes was confirmed. The localization of these alloantigens on integrin molecules further illustrates the polymorphic nature of this class of proteins. Whether the polymorphisms influence the adhesive capacity of the leukocyte integrins remains to be investigated.

Alleles↗

Granulocyte transfusions: efficacy in treating fungal infections in neutropenic patients following bone marrow transplantation.

BACKGROUND: A retrospective study was conducted to evaluate the efficacy of granulocyte transfusions in neutropenic patients with fungal infections following bone marrow transplantation. STUDY DESIGN AND METHODS: Systemic fungal infection was detected in 87 patients during the first 100 days following bone marrow transplantation; 50 received granulocytes in addition to appropriate antifungal agents. The median age was 17 years in the transfused patients (range, 1.5-57) and 35 years in the nontransfused patients (range, 0.8-50). Granulocyte transfusions were given on a daily to twice-daily basis. To evaluate their responses, patients were categorized by infection type (candidal [n = 38] vs. noncandidal [n = 49]) and site (fungemia alone [n = 30] vs. invasive infection [n = 57]). Resolution of infection was defined as the resolution of signs and symptoms and negative cultures and/or histopathology. RESULTS: No benefit of granulocyte transfusions could be shown in the resolution of infection in patients with either invasive noncandidal infection (29% in the transfused patients vs. 23% in the nontransfused patients, p > 0.1) or candidal sepsis (56% vs. 50%, p > 0.1). Among patients with delayed marrow recovery, no difference was seen in the resolution of infection in the transfused (25.9%) and nontransfused (50%) patients (p > 0.1); nor was any difference between the transfused and nontransfused patients evident in the duration of febrile episode associated with the fungal infection. Granulocyte transfusions were well tolerated, with the only complications being fever in 12 patients (24%), chills in 10 (20%), and respiratory distress in 2 (4%). Despite attempts to stratify by infection type, invasiveness, and marrow recovery, it was not possible to show any benefit of granulocyte transfusions in this group. CONCLUSIONS: It is likely that only through a prospective randomized trial can the question of the efficacy of granulocyte transfusions in treating fungal infections be conclusively answered.

Adolescent↗

Aerosol delivery in neonatal ventilator circuits: a rabbit lung model.

The benefits of inhaled therapy in ventilated neonates are recognized, but the reliability of drug delivery in nebulizer-ventilator circuits is uncertain. We quantified the effect of changing variables. Twenty-three freshly killed rabbits (1.15-1.9 kg) were ventilated via a tracheostomy by a pressure-limited, time-cycled ventilator (Neovent). A radioaerosol of 99Tcm pertechnetate from an Ultravent nebulizer (Mallinkrodt) was fed into the proximal ventilator tubing. Two 3-minute nebulizations at "standard settings" were followed by 2 at altered pressure, frequency, gas flow, I:E ratio, or position of the nebulizer in the circuit. Each nebulization was followed by a 3-minute gamma camera image and total deposited radioactivity was measured in excised lungs and trachea. Images demonstrated good peripheral aerosol deposition. At standard settings, lung deposition averaged 2.8% of the aerosol released. This was decreased markedly by reducing tidal volume (ventilator pressures) and residence time of aerosol (I:E ratio). Reduced gas flow decreased deposition slightly, presumably by increased particle size and marginally reduced tidal volume. Deposition did not change with increased frequency; increased minute ventilation was offset by decreased residence time of the aerosol. We conclude that the Ultravent nebulizer can be used to nebulize drugs in a standard neonatal circuit, although the dose delivered is small. Tidal volume and aerosol residence time are important determinants of aerosol delivery.

Animals↗