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Biomedical subjects

M Nelson

Publications and source records attributed to M Nelson.

At least 91 records · Page 5Linked to original sources
PubMed2002

Light, plants, and power for life support on Mars.

Regardless of how well other growing conditions are optimized, crop yields will be limited by the available light up to saturation irradiances. Considering the various factors of clouds on Earth, dust storms on Mars, thickness of atmosphere, and relative orbits, there is roughly 2/3 as much light averaged annually on Mars as on Earth. On Mars, however, crops must be grown under controlled conditions (greenhouse or growth rooms). Because there presently exists no material that can safely be pressurized, insulated, and resist hazards of puncture and deterioration to create life support systems on Mars while allowing for sufficient natural light penetration as well, artificial light will have to be supplied. If high irradiance is provided for long daily photoperiods, the growing area can be reduced by a factor of 3-4 relative to the most efficient irradiance for cereal crops such as wheat and rice, and perhaps for some other crops. Only a small penalty in required energy will be incurred by such optimization. To obtain maximum yields, crops must be chosen that can utilize high irradiances. Factors that increase ability to convert high light into increased productivity include canopy architecture, high-yield index (harvest index), and long-day or day-neutral flowering and tuberization responses. Prototype life support systems such as Bios-3 in Siberia or the Mars on Earth Project need to be undertaken to test and further refine systems and parameters.

Biomass↗
PubMed2002

Preoperative starvation and pulmonary aspiration. New perspectives and guidelines.

The fear of aspiration of gastric contents and its life-threatening consequences in patients(aspiration pneumonitis and respiratory failure), has caused many medical practitioners, particularly anaesthetists, to rigidly follow conservative (i.e. prolonged) preoperative fasting standards. This is the nil per os (NPO) order for clear fluids/liquids and solids overnight or six to eight hours preceding the induction of anaesthesia. This practice neither takes into account the differences in the rate of gastric emptying for solid food (which may exceed six hours) and clear liquids (which is one to two hours), nor the differences in scheduled times of surgery. Long-term prospective studies and retrospective reviews have shown that the incidence of significant clinical aspiration is low: 1.4-6.0 per 100,00 anaesthetics for elective general surgery. Risk factors for pulmonary aspiration include: a high American Society of Anaesthesiologists (ASA) physical status score; emergency surgery; difficult airway management; increased gastric volume and acidity; increased intra-abdominal pressure; gastro-oesophageal reflux; oesophageal disease; head injury with impaired consciousness and extremes of age. Experimental studies and reviews have consistently shown the safety of clear liquid ingestion up to two hours before induction of anaesthesia in healthy patients without risk factors, and the fact that a longer fluid fast does not necessarily offer any added protection against pulmonary aspiration. The conservative pre-operative fasting standard causes discomfort and in some cases, suffering of patients and is therefore unnecessary for patients without risk factor(s). Anecdotal reports at the University Hospital of the West Indies (UHWI) have shown that application of the liberalized guidelines for preoperative fasting and fluid intake has not resulted in increased pulmonary aspiration, morbidity or mortality. Instead it has resulted in decreased irritability, anxiety, thirst and hunger in the peri-operative period. Patients, especially children are more comfortable and the perioperative period is better tolerated. It is therefore time that all medical personnel adopt the liberalized guidelines.

Fasting↗
PubMed2001

Failure of combination therapy with lamivudine and famciclovir following lamivudine monotherapy for hepatitis B virus infection in patients coinfected with human immunodeficiency virus-1.

Individuals coinfected with human immunodeficiency virus 1 (HIV-1) and hepatitis B virus (HBV) often receive treatment with an antiretroviral regimen including lamivudine. Lamivudine monotherapy for HBV may lead to drug-resistant mutations in a significant number of patients. The virological and biochemical responses of 8 patients coinfected with HBV/HIV-1 treated with both lamivudine and famciclovir were studied. Patients exhibiting HBV viral rebound at 1 year were analyzed for the emergence of HBV polymerase mutations. Only 1 patient had no prior exposure to lamivudine. Addition of famciclovir to the treatment regimen resulted in a median fall in HBV DNA level of 0.33 log(10) at 3 months and an overall rise in HBV DNA level of 3 log(10) at 12 months. The only patient in whom durable viral suppression and HBV e antigen seroconversion were noted began receiving lamivudine and famciclovir simultaneously. HBV polymerase gene sequencing identified resistance-associated mutations in 6 of 7 patients with viral rebound. Sequential nucleoside analogue therapy is unlikely to be successful in achieving long-term suppression of HBV replication, and combination therapy should be considered at treatment initiation.

2-Aminopurine↗
PubMed2001

Baboon mesenchymal stem cells can be genetically modified to secrete human erythropoietin in vivo.

Human mesenchymal stem cells (MSCs) are capable of differentiating into multiple mesenchymal lineages including chondrocytes, osteocytes, adipocytes, and marrow stromal cells. Using a nonhuman primate model, we evaluated nonhuman primate MSCs as targets for gene therapy. Baboon MSCs (bMSCs) cultured from bone marrow aspirates appeared as a homogeneous population of spindle-shaped cells. bMSCs were capable of differentiating into adipocytes and osteocytes in vitro and chondrocytes in vivo. bMSCs were genetically modified with a bicistronic vector encoding the human erythropoietin (hEPO) gene and the green fluorescent protein (GFP) gene. Transduction efficiencies ranged from 72 to 99% after incubation of MSCs with retroviral supernatant. Transduced cells produced from 1.83 x 10(5) to 7.12 x 10(5) mIU of hEPO per 10(6) cells per 24 hr in vitro before implantation. To determine the capacity of bMSCs to express hEPO in vivo, transduced bMSCs were injected intramuscularly in NOD/SCID mice. In a separate experiment, transduced bMSCs were loaded into immunoisolatory devices (IIDs) and surgically implanted into either autologous or allogeneic baboon recipients. Human EPO was detected in the serum of NOD/SCID mice for up to 28 days and in the serum of five baboons for between 9 and 137 days. NOD/SCID mice experienced sharp rises in hematocrit after intramuscular injection of hEPO-transduced bMSCs. The baboon that expressed hEPO for 137 days experienced a statistically significant (p < 0.04) rise in its hematocrit. These data demonstrate that nonhuman primate MSCs can be engineered to deliver a secreted and biologically active gene product. Therefore, human MSCs may be an effective target for future human gene therapy trials.

Adult↗
PubMed2001

Cytogenetic instability, predominantly involving chromosome 1, is characteristic of elastofibroma.

Elastofibroma, an unusual pseudotumor composed of excessive collagen and abnormal elastic fibers, has rarely been subjected to cytogenetic analysis. Only two cases have been previously defined, both of which demonstrated nonclonal abnormalities. In the present study, three cases of elastofibroma were cytogenetically analyzed. Abnormalities of the short arm of chromosome 1 were seen in all three cases (either clonally or as the most frequently involved region among nonclonal aberrations). In addition, a translocation involving chromosomes 8 and 12 was detected as a clonal rearrangement in one of the three cases. The observation of clonal abnormalities in elastofibroma suggests that this lesion may represent a neoplastic rather than a reactive process.

Aged↗
PubMed2001

Receptor activator of NF-kappa B and osteoprotegerin expression by human microvascular endothelial cells, regulation by inflammatory cytokines, and role in human osteoclastogenesis.

The receptor activator of NF-kappaB (RANKL) is the essential signal required for full osteoclast (OC) development, activation, and survival. RANKL is highly expressed in areas of trabecular bone remodeling and inflammatory bone loss, is increased on marrow stromal cells or osteoblasts by osteotropic hormones or cytokines, and is neutralized by osteoprotegerin (OPG), a soluble decoy receptor also crucial for preventing arterial calcification. Vascular endothelial cells (VEC) are critically involved in bone development and remodeling and influence OC recruitment, formation, and activity. Although OCs develop and function in close association with bone VEC and sinusoids, signals mediating their interactions are not well known. Here, we show for the first time that human microvascular endothelial cells (HMVEC) express transcripts for both RANKL and OPG; inflammatory cytokines tumor necrosis factor-alpha and interleukin-1alpha elevate RANKL and OPG expression 5-40-fold in HMVEC (with an early OPG peak that declines as RANKL rises), and RANKL protein increases on the surface of tumor necrosis factor-alpha-activated HMVEC. Cytokine-activated HMVEC promoted the formation, fusion, and bone resorption of OCs formed in co-cultures with circulating human monocytic precursors via a RANKL-mediated mechanism fully antagonized by exogenous OPG. Furthermore, paraffin sections of human osteoporotic fractured bone exhibited increased RANKL immunostaining in vivo on VEC located near resorbing OCs in regions undergoing active bone turnover. Therefore, cytokine-activated VEC may contribute to inflammatory-mediated bone loss via regulated production of RANKL and OPG. VEC-derived OPG may also serve as an autocrine signal to inhibit blood vessel calcification.

Base Sequence↗
PubMed2001

"Living off the land": resource efficiency of wetland wastewater treatment.

Bioregenerative life support technologies for space application are advantageous if they can be constructed using locally available materials, and rely on renewable energy resources, lessening the need for launch and resupply of materials. These same characteristics are desirable in the global Earth environment because such technologies are more affordable by developing countries, and are more sustainable long-term since they utilize less non-renewable, imported resources. Subsurface flow wetlands (wastewater gardens(TM)) were developed and evaluated for wastewater recycling along the coast of Yucatan. Emergy evaluations, a measure of the environmental and human economic resource utilization, showed that compared to conventional sewage treatment, wetland wastewater treatment systems use far less imported and purchased materials. Wetland systems are also less energy-dependent, lessening dependence on electrical infrastructure, and require simpler maintenance since the system largely relies on the ecological action of microbes and plants for their efficacy. Detailed emergy evaluations showed that wetland systems use only about 15% the purchased emergy of conventional sewage systems, and that renewable resources contribute 60% of total emergy used (excluding the sewage itself) compared to less than 1% use of renewable resources in the high-tech systems. Applied on a larger scale for development in third world countries, wetland systems would require the electrical energy of conventional sewage treatment (package plants), and save of total capital and operating expenses over a 20-year timeframe. In addition, there are numerous secondary benefits from wetland systems including fiber/fodder/food from the wetland plants, creation of ecosystems of high biodiversity with animal habitat value, and aesthestic/landscape enhancement of the community. Wetland wastewater treatment is an exemplar of ecological engineering in that it creates an interface ecosystem to handle byproducts of the human economy, maximizing performance of the both the natural economy and natural ecosystems. Wetland systems accomplish this with far greater resource economy than other sewage treatment approaches, and thus offer benefits for both space and Earth applications.

Conservation of Natural Resources↗
PubMed2001

Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusion.

OBJECTIVE: The human bone marrow contains mesenchymal stem cells capable of differentiating along multiple mesenchymal cell lineages. Using a non-human primate model, we sought to determine whether the systemic infusion of baboon-derived mesenchymal stem cells was associated with toxicity and whether these cells were capable of homing to and persisting within the bone marrow. MATERIALS AND METHODS: Five baboons (Papio anubis) were administered lethal irradiation followed by intravenous autologous hematopoietic progenitor cells combined with either autologous (n = 3) or allogeneic (n = 2) mesenchymal stem cells that had been expanded in culture. In four of these baboons, the mesenchymal stem cells were genetically modified with a retroviral vector encoding either the enhanced green fluorescent protein gene (n = 3) or the human placental alkaline phosphatase gene (n = 1) for tracking purposes. A sixth animal received only intravenous gene marked autologous mesenchymal stem cells but no hematopoietic stem cells or conditioning irradiation. RESULTS: Following culture, baboon mesenchymal stem cells appeared morphologically as a homogeneous population of spindle-shaped cells that were identified by the monoclonal antibodies SH-3 and SH-4. These cells did not express the hematopoietic markers CD34 or CD45. Baboon mesenchymal stem cells isolated from primary culture were capable of differentiating along both adipogenic and osteogenic lineages. There was no acute or chronic toxicity associated with the intravenous infusion of mesenchymal stem cells. In all five recipients of gene marked mesenchymal stem cells, transgene was detected in post-transplant bone marrow biopsies. In two animals receiving autologous mesenchymal stem cells, including the one non-conditioned recipient, transgene could be detected over 1 year following infusion. In one recipient of allogeneic gene marked mesenchymal stem cells, transgene was detected in the bone marrow at 76 days following infusion. CONCLUSION: These data demonstrate that baboon mesenchymal stem cells: 1) are not associated with significant toxicity when administered intravenously, 2) are capable of homing to the bone marrow following intravenous infusion, and 3) have the capacity to establish residence within the bone marrow for an extended duration following systemic administration.

Alkaline Phosphatase↗
PubMed2001

A systematic review of predictors of maintenance of normotension after withdrawal of antihypertensive drugs.

BACKGROUND: The identification and treatment of hypertension in the general community has contributed to the reduction in strokes and coronary heart disease observed during the past 30 years. However, concerns have arisen that some patients may be receiving unnecessary antihypertensive drug therapy leading to wasted resources and the potential for adverse drug effects. Once therapy has been started, treating physicians have difficulty in selecting patients for withdrawal and have concerns regarding patient safety and their own legal liability. PROCEDURES: This study reviews and consolidates information from published studies to identify known predictors of the successful maintenance of normotension after antihypertensive drug withdrawal. The predictors were identified by determining the proportion of subjects with various baseline characteristics who remained normotensive while off medication for at least 12 months. From these data we have developed a clinical algorithm to help identify patients in whom antihypertensive drug withdrawal might be considered. This may assist primary care physicians in achieving successful withdrawal of antihypertensive therapy among selected hypertensive patients. RESULTS: The most consistent predictors identified were blood pressure (BP) (lower pretreatment, on treatment, and after withdrawal), nature of pharmacotherapy (fewer agents and lower dose), and preparedness to accept dietary intervention (weight and sodium reduction). CONCLUSIONS: On the basis of this information, a trial of withdrawal of antihypertensive medication might be recommended for patients who have mildly elevated, uncomplicated BP that is well controlled on a single agent, and who are motivated and likely to accept lifestyle changes.

Antihypertensive Agents↗
PubMed2001

Genotyping fetal DNA by non-invasive means: extraction from maternal plasma.

BACKGROUND AND OBJECTIVES: Identification of fetal DNA in maternal plasma may allow genetic analysis without the use of invasive techniques. The aim of this study was to extract DNA from maternal plasma, identify fetal material through the presence of SRY or RHD gene sequences and assess the reliability of these results. MATERIALS AND METHODS: A polymerase chain reaction (PCR) method of a commercial kit was used with primers for SRY or exon 10 of the RHD gene sequence. RESULTS: Multiple plasma samples were collected from 60 women who were evaluable for either SRY or RHD, or both, fetally derived DNA sequences. Fetal DNA was present in the plasma throughout the pregnancies and for some hours or days after delivery. CONCLUSION: Fetal DNA can be reliably detected in maternal plasma from early in pregnancy and normally is cleared within days of delivery.

Adult↗
PubMed2001

General practitioner participation in the second Australian National Blood Pressure Study (ANBP2).

1. The second Australian National Blood Pressure Study (ANBP2) is an outcome trial of the treatment of hypertension in the elderly conducted entirely in general practices across Australia. Prior to ANBP2, no study of this size and nature had been undertaken in Australian general practice and the response of General Practitioners (GPs) to becoming involved in long-term cardiovascular research was unknown. 2. Academic departments and Divisions of General Practice were approached to support the project. General Practitioners were approached by letter of invitation and contacted by a regional medical coordinator (RMC) either at a face-to-face meeting or by telephone. 3. At the close of recruitment to ANBP2, 1938 GPs from 950 practices had registered as investigators. Sixty-two Divisions of General Practice were approached to support the study in five mainland Australian states with 39 (63%) participating, although participation by state was highly variable (range: 18-100%). Thirty divisional or promotional dinner meetings were held, with 56% (368/658) of those attending registering as investigators. Of the 8098 GPs sent a letter of invitation to participate in the study, 1357 (17%) expressed interest and eventually enrolled as investigators, ranging from 8% in Queensland to 28% in New South Wales. Ninety-six per cent of GPs who had a personal face-to-face contact (696/724) with the RMC registered in the study. 4. The GP recruitment phase of ANBP2 has been successfully completed. Peer-to-peer recruitment was the most successful strategy; however, success varied between states. General Practitioner recruitment to long-term clinical trials appears to be successful with a multifactorial approach focusing on peer-to-peer recruitment.

Aged↗
PubMed2001

Allergic inflammation enhances bacterial sinusitis in mice.

BACKGROUND: Although it is not proven, one factor considered important in the development of sinusitis is allergic rhinitis. OBJECTIVE: The purpose of this study was to determine whether ongoing allergic rhinitis enhances the infection and inflammation associated with Streptococcus pneumoniae acute sinus infection. METHODS: BALB/c mice were sensitized to ovalbumin by intraperitoneal injection. After infection of the sinuses by S pneumoniae, either with or without concomitant administration of ovalbumin to induce allergic inflammation, mice were killed at various times and their heads were prepared for histologic evaluation of the sinuses. RESULTS: Mice became allergic to ovalbumin and developed eosinophilia in the sinus and lung cavities in response to ovalbumin administration to each of the respective cavities. In comparison with controls, the mice with ongoing nasal allergic inflammation that were inoculated with S pneumoniae had significantly more bacteria recovered at sacrifice and had significantly more inflammation, as indicated by neutrophil, eosinophil, and mononuclear influx into the sinus mucosa. The percentage of the sinus area occupied by neutrophil clusters was also increased after infection in the allergic mice in comparison with the control mice. CONCLUSION: Our data demonstrate that mice can be sensitized to ovalbumin and develop a localized allergic reaction in the skin, nose, or lung. An ongoing local allergic response augments bacterial infection in these animals. We also demonstrate that allergic sensitization alone, allergen exposure alone, or an allergic response at a distal site, the lung, does not augment the sinus infection.

Animals↗
PubMed2001

Meta-analysis of tympanostomy tube sequelae.

OBJECTIVE: To estimate the incidence of tympanostomy tube sequelae based on systematic review of published case series and randomized studies. DATA SOURCES: English-language MEDLINE search from 1966 through April 1999 with manual reference search of proceedings, articles, reports, and guidelines. STUDY SELECTION: Cohort studies with otitis media as the primary indication for tube placement. DATA EXTRACTION: Two reviewers independently extracted data from 134 articles. DATA SYNTHESIS: Transient otorrhea occurred in 16% of patients in the postoperative period and later in 26%; recurrent otorrhea occurred in 7.4% of patients and chronic otorrhea in 3.8%. Sequelae of indwelling tubes included obstruction (7% of ears), granulation tissue (5%), premature extrusion (3.9%), and medial displacement (0.5%). Sequelae after tube extrusion included tympanosclerosis (32%), focal atrophy (25%), retraction pocket (3.1%), cholesteatoma (0.7%), and perforation (2.2% with short-term tubes, 16.6% with long-term tubes). Meta-analysis showed that long-term tubes increased the relative risk of perforation by 3.5 (95% CI, 1.5 to 7.1) and cholesteatoma by 2.6 (95% CI, 1.5 to 4.4). Similarly, intubation increased the relative risk of tympanosclerosis by 3.5 (95% CI, 2.6 to 4.9) and focal atrophy by 1.7 (95% CI, 1.1 to 2.7) over nonintubated control ears (baseline tympanosclerosis and atrophy rates of 10% and 14%, respectively). CONCLUSIONS: Sequelae of tympanostomy tubes are common but are generally transient (otorrhea) or cosmetic (tympanosclerosis, focal atrophy). Nonetheless, the high incidence suggests a need for ongoing otologic surveillance of all patients with indwelling tubes and for a reasonable time period after tube extrusion. Long-term tubes should be used on a selective and individualized basis.

Atrophy↗
PubMed2001

Metabolic, psychological, and health correlates of dietary restraint in healthy postmenopausal women.

BACKGROUND: Dietary restraint, a term used to describe the intentional control of food intake to prevent weight gain or promote weight loss, is commonly practiced by older adults, but little is known about its effects on physiology and metabolism. METHODS: We therefore compared a wide range of parameters between groups of healthy non-obese postmenopausal women classified psychometrically as unrestrained eaters (body mass index [BMI] 23.8 +/- 0.6 [SEM] kg/m(2), n = 28) or restrained eaters (BMI 24.5 +/- 0.5, n = 39). Measurements were made of reported micronutrient intakes, cardiopulmonary function, hematology, body temperature, skin thickness, bone mass, and immune function; in addition, self-perceived health, mood, and some dimensions of eating behavior were assessed by questionnaire. RESULTS: Macronutrient and micronutrient intakes were not significantly different between restrained and unrestrained eaters reporting energy intake to within 30% of predicted total energy expenditure. Restrained eaters had significantly lower hemoglobin (12.9 +/- 0.1 [SEM] vs 13.2 +/- 0.1 g/dl; p <.05), but values were within the normal range in both groups. In addition, restrained eaters scored significantly higher on the Eating Attitudes Test (p <.01) and drive-for-thinness (p <.001) and maturity fears (p <.05) subscores of the Eating Disorders Inventory, but values were again within the normal range. No other parameter differed significantly between groups. CONCLUSIONS: In this normal-weight population, restrained eating was not associated with detrimental effects in a wide range of physiological, metabolic, and health characteristics. Further work is needed to determine the relevance of these results to the general population.

Attitude to Health↗
PubMed2001

Distribution of K103N and/or Y181C HIV-1 mutations by exposure to zidovudine and non-nucleoside reverse transcriptase inhibitors.

Our aim was to identify whether zidovudine has a role in the emergence of the K103N resistance mutation in the HIV-1 reverse transcriptase gene on non-nucleoside reverse transcriptase inhibitors (NNRTIs). No difference was found in the exposure to zidovudine or major zidovudine mutations between the resistance patterns K103N-/Y181C+, K103N+/Y181C- and K103N+/ Y181C+, either in group A (patients on nevirapine and previously NNRTI naive) or in group B (on any NNRTI and experience of two or more NNRTIs including nevirapine). Group B patients had the highest prevalence of K103N+/Y181C+. In conclusion, zidovudine seems not to determine the emergence of K103N; however, there appears to be an accumulation of NNRTI resistance mutations with sequential use of NNRTIs.

Anti-HIV Agents↗
PubMed2001

Incidence and risk factors for the development of indinavir-associated renal complications.

OBJECTIVES: To describe the incidence and risk factors for the development of indinavir-associated renal complications (IRC), and subsequent clinical outcome. PATIENTS AND METHODS: This was a retrospective cohort study based on two large HIV centres in London. Eligible patients received indinavir for at least 1 week between 1 December 1995 and 28 February 1999. Development of IRC was ascertained by case-note review. Multivariate logistic regression and Cox Proportional Hazard's model analysis were used to determine independent risk factors for the development of IRC. RESULTS: 781 patients were eligible. Median CD4 count and viral load at indinavir initiation were 117 x 10(6) cells/L and 47 332 copies/mL, respectively. Median indinavir exposure was 53 weeks (IQR: 20-83). Many patients received other potentially nephrotoxic drugs during indinavir treatment: co-trimoxazole (46%), aciclovir (33%) or both (20%). Overall IRC incidence was 7.3% (6.7 per 100 person-years indinavir exposure). Cases presented with loin pain (58%), renal colic (42%) or dysuria (19%). Identified precipitating events (26%) included fluid depletion or altered indinavir regimen. In the majority of cases indinavir therapy was continued and there was no progressive rise in creatinine levels. In the multivariate analysis, for indinavir treatment >74 weeks there was a reduced risk of developing IRC (OR = 0.23, 95% CI 0.09-0.57, P = 0.001). Concomitant aciclovir increased the IRC risk (OR = 1.99, 95% CI 1.14-3.51, P = 0.016). Factors not associated with outcome were age, gender, ethnicity, baseline CD4 count and viral load, concomitant co-trimoxazole, or use of specific antiretrovirals. CONCLUSION: An overall IRC incidence of 7.3% was identified. Concomitant aciclovir doubled the risk of IRC and we therefore recommend careful monitoring when prescribing aciclovir with indinavir. A precipitating event was identified in 26% of IRC cases, many of which could have been avoided.

Adult↗
PubMed2001

Translocation t(1;3)(p36.3;q25) is a nonrandom aberration in epithelioid hemangioendothelioma.

The cytogenetic findings for two epithelioid hemangioendotheliomas are reported. An identical chromosomal translocation involving chromosomes 1 and 3 [t(1;3)(p36.3;q25)] was detected in both cases of epithelioid hemangioendothelioma, possibly representing a characteristic rearrangement for this histopathologic entity. The presence of clonal karyotypic abnormalities supports a neoplastic origin for the epithelioid variant of hemangioendothelioma. Identification of the 1;3 translocation may be useful diagnostically. Should additional studies confirm these data, this could lead to the identification of the gene(s) central to this neoplastic process.

Adult↗