Biomedical subjects

J E Martin

Publications and source records attributed to J E Martin.

At least 37 records · Page 2Linked to original sources

PubMed2001

A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome.

Rett syndrome (RTT) is an inherited neurodevelopmental disorder of females that occurs once in 10,000-15,000 births. Affected females develop normally for 6-18 months, but then lose voluntary movements, including speech and hand skills. Most RTT patients are heterozygous for mutations in the X-linked gene MECP2 (refs. 3-12), encoding a protein that binds to methylated sites in genomic DNA and facilitates gene silencing. Previous work with Mecp2-null embryonic stem cells indicated that MeCP2 is essential for mouse embryogenesis. Here we generate mice lacking Mecp2 using Cre-loxP technology. Both Mecp2-null mice and mice in which Mecp2 was deleted in brain showed severe neurological symptoms at approximately six weeks of age. Compensation for absence of MeCP2 in other tissues by MeCP1 (refs. 19,20) was not apparent in genetic or biochemical tests. After several months, heterozygous female mice also showed behavioral symptoms. The overlapping delay before symptom onset in humans and mice, despite their profoundly different rates of development, raises the possibility that stability of brain function, not brain development per se, is compromised by the absence of MeCP2.

Animals↗

PubMed2001

Radiological control for 203Hg radiotracer determinations of mercury inventories at chlor-alkali plants.

20Hg has been used safely to determine mercury inventories in large electrochemical process cells in the chlorine industry by a process of isotopic dilution. Laboratory conversion and processing of irradiated HgO can be done in closed systems with non-detectable releases to work areas or the environment and with exposure to whole body <0.25 mSv (25 mrem) and <3 mSv (300 mrem) to extremities. Personnel exposures during plant operations are controlled to non-detectable levels for whole body exposure and <0.3 mSv (30 mrem) to extremities for the operator; exposures for other plant personnel are non-detectable.

Air Pollution, Radioactive↗

PubMed2001

Mechanical treatment of plantar fasciitis. A prospective study.

A randomized, prospective study was conducted to compare the effectiveness of three individual mechanical modalities in the treatment of plantar fasciitis. Two hundred fifty-five subjects were randomly assigned to one of three treatment groups: custom-made orthoses, over-the-counter arch supports, or tension night splints. Subjects were treated for 3 months, with follow-up visits at 2, 6, and 12 weeks. No statistically significant difference was noted among treatment groups with respect to final outcomes based on first-step pain or pain felt during the day. However, there was a statistically significant difference among the three groups with respect to early patient withdrawal from the study due to continued severe pain, noncompliance, or inability to tolerate the device. Patient compliance was greatest with the use of custom-made orthoses.

Adult↗

PubMed2000

Thermal chain model of electrorheology and magnetorheology.

Steady shear simulations of electrorheology (ER) and magnetorheology (MR) in a uniaxial field are presented. These large scale simulations are three dimensional, and include the effect of Brownian motion. In the absence of thermal fluctuations, the expected shear thinning viscosity is observed and a striped phase is seen to rapidly form in a uniaxial field, with a shear slip zone in each sheet. However, as the influence of Brownian motion increases, the fluid stress decreases, especially at lower Mason numbers, and the striped phase eventually disappears, even when the fluid stress is still high. To account for the uniaxial steady shear data we propose a microscopic chain model of the role played by thermal fluctuations on the rheology of ER and MR fluids that delineates the regimes where an applied field can impact the fluid viscosity, and gives an analytical prediction for the thermal effect.

Journal Article↗

PubMed2000

Economic cost of expanded criteria donors in cadaveric renal transplantation: analysis of Medicare payments.

BACKGROUND: The use of expanded criteria donors (ECDs) in cadaveric renal transplantation is increasing in the US. We assess the economic impact of the use of ECDs to the Medicare end stage renal disease program. METHODS: The United Nations for Organ Sharing renal transplant registry was merged to Medicare claims data for 42,868 cadaveric renal transplants performed between 1991-1996 using USRDS identifiers. Only recipients for whom Medicare was the primary payer were considered, leaving 34,534 transplants. An ECD was defined as (1) age < or =5 or > or =55 years, (2) nonheart-beating donors, donor history of (3) hypertension or (4) diabetes. High-risk recipients (HRR) were age >60 years, or a retransplant. Medicare payments from the pretransplant dialysis period were projected forward to provide a financial "breakeven point" with transplantation. RESULTS: There were 25,600 non-HRR transplants, with 5,718 (22%) using ECDs, and 8,934 HRR transplants, of which 2,200 (25%) used ECDs. The 5-year present value of payments for non-ECD/non-HRR donor/recipient pairings was $121,698 vs. $143,329 for ECD/non-HRR pairings (P<0.0001) and, similarly was $134,185 for non-ECD/HRR pairings vs. $165,716 for ECD/HRR pairings (P<0.0001). The break even point with hemodialysis ranged from 4.4 years for non-ECD/ non-HRR pairings to 13 years for the ECD/HRR combinations but was sensitive to small changes in graft survival. Transplantation was always less expensive than hemodialysis in the long run. CONCLUSIONS: The impact of ECDs on Medicare payments is most pronounced in high-risk recipients. Cadaveric renal transplantation is a cost-saving treatment strategy for the Medicare ESRD program regardless of recipient risk status or the use of ECDs.

Aged↗

PubMed2000

Haploinsufficiency of the transcription factors FOXC1 and FOXC2 results in aberrant ocular development.

Anterior segment developmental disorders, including Axenfeld-Rieger anomaly (ARA), variably associate with harmfully elevated intraocular pressure (IOP), which causes glaucoma. Clinically observed dysgenesis does not correlate with IOP, however, and the etiology of glaucoma development is not understood. The forkhead transcription factor genes Foxc1 (formerly Mf1 ) and Foxc2 (formerly Mfh1 ) are expressed in the mesenchyme from which the ocular drainage structures derive. Mutations in the human homolog of Foxc1, FKHL7, cause dominant anterior segment defects and glaucoma in various families. We show that Foxc1 (+/-)mice have anterior segment abnormalities similar to those reported in human patients. These abnormalities include small or absent Schlemm's canal, aberrantly developed trabecular meshwork, iris hypoplasia, severely eccentric pupils and displaced Schwalbe's line. The penetrance of clinically obvious abnormalities varies with genetic background. In some affected eyes, collagen bundles were half normal diameter, or collagen and elastic tissue were very sparse. Thus, abnormalities in extracellular matrix synthesis or organization may contribute to development of the ocular phenotypes. Despite the abnormalities in ocular drainage structures in Foxc1 (+/-)mice, IOP was normal in almost all mice analyzed, on all genetic backgrounds and at all ages. Similar abnormalities were found in Foxc2 (+/-)mice, but no disease-associated mutations were identified in the human homolog FKHL14 in 32 ARA patients. Foxc1 (+/-)and Foxc2 (+/-)mice are useful models for studying anterior segment development and its anomalies, and may allow identification of genes that interact with Foxc1 and Foxc2 (or FKHL7 and FKHL14 ) to produce a phenotype with elevated IOP and glaucoma.

Animals↗

PubMed2000

Mice, the motor system, and human motor neuron pathology.

Motor neurons are among some of the most unusual cells in the body becaue of their immense size and their role as the critical link between the motor centers of the brain and the muscles. In addition to their intrinsic biological interest, it is vital that we gain a better understanding of these cells and their pathology, since motor neuron degenerative diseases are lethal disorders that affect young and old and are relatively common. For example, one form of spinal muscular atrophy (SMA) is the most common genetic killer of children in the developed world. Amyotrophic lateral sclerosis (ALS), another form of motor neuron degeneration, is the third most common neurodegenerative cause of adult death, after Alzheimer's disease and Parkinson's disease, and is significantly more common than multiple sclerosis (Motor Neurone Disease Association 1998). Currently, approximately 1 in 500 people in England and Wales who die have a form of motor neuron disease (Motor Neurone Disease Association 1998). Each year, 5000 Americans are diagnosed with ALS, and of these, 10% are under 40 years old. Mouse models of motor neuron degeneration are essential for understanding the causes and mechanisms of motor neuron pathology. These mice are yielding important information that will ultimately lead to treatments and potentially cures for these diseases.

Animals↗

PubMed2000

Slow transit constipation: a model of human gut dysmotility. Review of possible aetiologies.

Slow transit constipation is a severe condition of gut dysmotility that predominantly affects young women and may result in surgical intervention. Current medical treatments for STC are often ineffective, and the outcome of surgery is unpredictable. STC was first described almost a century ago. Since this time, progress in improving therapy for this condition has been complicated by a lack of understanding of the aetiology, and great variation in the methods and criteria used for the study of patients with this debilitating disorder. It is difficult to find unequivocal data, and harder still to give a definitive picture of the cause or causes of STC. Here we consider the evidence for various aetiologies of STC, in the light of the physiological and pathological findings.

Adult↗

PubMed2000

Oxygen consumption in the early postinjury period: use of continuous, on-line indirect calorimetry.

OBJECTIVE: To determine the patterns of oxygen consumption (Vo2) using indirect calorimetry (IC) for the first 24 hrs after serious blunt traumatic injury. DESIGN: Prospective, observational study. SETTING: Surgical intensive care unit of a Level 1 trauma center. PATIENTS: Sixty-six mechanically ventilated patients with blunt traumatic injury and Injury Severity Score >15. INTERVENTIONS: IC for 24 hrs postinjury. Patients were resuscitated to standard parameters of perfusion. MEASUREMENTS AND MAIN RESULTS: Mean patient age was 50.1+/-18.7 yrs with a mean Injury Severity Score 30.7+/-11.3). Mean Vo2 for all patients for the 24-hr study period was 168.5+/-29.5 mL/min/m2. The level of Vo2 was not related to Injury Severity Score, the number or combination of organ systems injured, or to the use of vasoactive agents. Patients >65 yrs of age had significantly lower Vo2 (P = .0038) compared with patients < or =50 yrs. Vo2 did not change over time after resuscitation to normal parameters of perfusion. Mean Vo2 was 156.5+/-63.2 mL/min/m2 in patients who developed multiple organ dysfunction, and 172.4+/-33.3 mL/min/m2 in those who did not develop multiple organ dysfunction (p = .16). CONCLUSIONS: Seriously injured patients are hypermetabolic in the early postinjury period. The level of Vo2 is unrelated to injury severity or number of organ systems involved. Elderly patients can be expected to have lower levels of Vo2. Vo2 does not change significantly in response to resuscitation to normal parameters of perfusion. Vo2 measured by IC did not predict the development of multiple organ dysfunction.

Adolescent↗

PubMed2000

Comparison of methods of measurements of oxygen consumption in mechanically ventilated patients with multiple trauma: the Fick method versus indirect calorimetry.

OBJECTIVE: The purpose of this study was to compare the measurements of whole body oxygen consumption determined by the Fick method and by indirect calorimetry in mechanically ventilated patients with multiple trauma. DESIGN: A prospective, correlational, within-subjects design. SETTING: Surgical intensive care unit of a Level I trauma center. PATIENTS: Thirty-eight mechanically ventilated adults with multiple injuries who received a pulmonary artery catheter within 24 hrs of admission to the surgical intensive care unit. MEASUREMENTS AND MAIN RESULTS: After the initial resuscitation, simultaneous measurements of oxygen consumption (V(O2) by the reverse Fick equation and by indirect calorimetry were performed every 6 hrs for 24 hrs in normothermic patients who were at rest for at least 30 mins. At each measurement period, the mean V(O2) values determined by indirect calorimetry were significantly greater than the mean V(O2) values determined by the Fick method (time 1: 172+/-38 vs. 125+/-47 mL/min/m2, p < .0001; time 2: 170+/-31 vs. 130+/-48 mL/min/m2, p < .0001; time 3: 170+/-32 vs. 132+/-53 mL/min/m2, p < .0001; time 4: 169+/-29 vs. 130+/-60 mL/min/m2, p < .0002). By using the Bland and Altman technique, the mean bias was 41+/-3.95 mL/min/m2. Correlation coefficients of VO2 values between methods of measurements were statistically significant (r2 = .32, p = .0001; r2 = .32, p = .0001; r2 = .33, p = .0001; r2 = .18, p = .0001). CONCLUSIONS: Indirect calorimetry should be the preferred standard for measurement of oxygen consumption in severely injured patients.

Adult↗

PubMed2000

Nurse practitioner, nurse midwife and physician assistant attitudes and care practices related to persons with HIV/AIDS.

Although multiple studies of nurses' attitudes toward people living with HIV/AIDS (PLWAs) can be found in the literature, little is known about the attitudes, beliefs and practices of nurse practitioners (NPs), certified nurse midwives (CNMs), and physician assistants (PAs). A survey including a 21-item AIDS Attitude Scale measuring the constructs of Avoidance and Empathy was sent to 1,291 NPs, CNMs and PAs in Louisiana, Arkansas and Mississippi to describe their attitudes and care practices related to PLWAs. Respondents who were more comfortable treating PLWAs had significantly lower avoidance scores and significantly higher empathy scores than respondents with lower comfort levels in providing care. Greater than 80% of respondents indicated that they would provide health care to HIV-infected individuals. Respondents who referred HIV/AIDS patients for all care did so primarily due to lack of experience with HIV and the availability of more experienced providers. Avoidance and empathy scores were not found to be significantly associated with referral for care. This study suggests that this group of providers has relatively low avoidance and high empathy toward PLWAs and is willing to care for HIV-infected individuals.

Adult↗

PubMed2000

Warfarin resistance due to sulfasalazine.

OBJECTIVE: To report a case of warfarin resistance associated with the use of sulfasalazine. CASE SUMMARY: A 37-year-old white woman on oral anticoagulant therapy with warfarin was being evaluated for complaints of joint pains. Her past medical history consisted of recurrent deep-vein thrombosis, asthma, and ulcerative colitis. Warfarin concentrations had consistently remained within the therapeutic range with dosages of approximately 30 mg per week. In an attempt to treat arthritis, her gastroenterologist replaced 5-aminosalicylic acid (5-ASA) with sulfasalazine 1000 mg four times daily. Subsequent to the medication changes, the international normalized ratio (INR) decreased and remained at subtherapeutic concentrations despite increases in the warfarin dosage. During this period, the patient developed a deep-vein thrombosis in the right popliteal vein. The INR did not return to an acceptable level until six weeks after sulfasalazine was started. The new warfarin dosage was 75 mg per week, a 250% dosage increase. When sulfasalazine was discontinued and 5-ASA reinstituted, the warfarin dosage requirements to achieve therapeutic INRs returned to weekly dosages of approximately 45 mg. DISCUSSION: Sulfonamides have been well documented to enhance the anticoagulant effect of warfarin. This patient developed a new deep-vein thrombosis due to failure in maintaining therapeutic INR levels after the recent introduction of sulfasalazine. We suspect that she developed warfarin resistance secondary to concomitant use of sulfasalazine. This patient demonstrated warfarin resistance as opposed to enhanced anticoagulant effect with sulfasalazine. CONCLUSIONS: Clinicians managing warfarin therapy should exercise caution when sulfasalazine is added to a patient's medical regimen. This case suggests a possible warfarin-sulfasalazine interaction that resulted in warfarin resistance.

Adult↗

PubMed2000

Addition of casein or whey protein to colostrum or a colostrum supplement product on absorption of IgG in neonatal calves.

The effects of the addition of nonimmunoglobulin protein on absorption of immunoglobulin G (IgG) from colostrum or colostrum supplement products were determined in two experiments. In experiment 1, 48 Holstein calves were fed 4 L of pooled maternal colostrum or 4 L of reconstituted colostrum supplement with 0, 200, or 400 g of added whey protein concentrate or casein. In experiment 2, 38 Jersey calves were fed 2 L of pooled maternal colostrum with 100 or 200 g of whey protein concentrate or casein added immediately before feeding. Blood was collected at 24 h of age and plasma IgG concentration, total protein, hematocrit (experiment 1 only), and plasma urea N were determined. In experiment 1, blood samples were also collected at 4, 8, 12, 16, and 20 h to evaluate absorption of IgG and protein and urea N concentrations. The addition of 400 g of casein to colostrum supplement in experiment 1 reduced plasma IgG from 5.66 g/L (0 g of casein addition) to 3.88 g/L, increased plasma urea N at 24 h, and reduced the change in plasma total protein from 0 to 24 h. Hourly plasma IgG concentrations increased with the consumption of colostrum or supplements but increased more rapidly in calves fed whey protein concentrate and more slowly in calves fed casein. The addition of 200 g of casein or whey protein concentrate to colostrum supplements had no effect on plasma IgG concentration at 24 h of age. The addition of 100 or 200 g of casein or whey protein concentrate to maternal colostrum had no effect on plasma urea N, total protein, or plasma IgG in experiment 2. The addition of nonimmunoglobulin protein to colostrum supplements or maternal colostrum did not affect IgG absorption from the intestine of newborn calves unless the amount of total protein exceeded 500 g of protein.

Animals↗

PubMed1999

The kinesin light chain gene: its mapping and exclusion in mouse and human forms of inherited motor neuron degeneration.

The underlying genetic cause is known for only 10-20% of familial motor neuron disease (MND). Thus the genes involved in the aetiology of 80-90% of familial MND remain to be determined, and animal models are powerful tools for undertaking this task. We have mapped a heritable form of motor neuron degeneration in the mouse to a region that has homology to human chromosome 14q32.1-qter. This region contains the kinesin light chain gene (KLC1), which is a candidate for involvement in motor neuron degeneration because of its function in the motor-protein kinesin, and its neuronal expression. To investigate the role of KLC1 in a mouse motor neuron degeneration mutant that we are studying, we have identified mouse Klc1 gene sequences and mapped them with respect to our mutant locus. We have also investigated KLC1 in human patients with familial MND. Based on recombination and the absence of mutations in the coding region of KLC1, this gene can be excluded as a candidate gene in our mouse mutation and, where we have investigated, it is normal in human familial MND.

Animals↗

PubMed1999

The evaluation of the safety and tolerability of two formulations of cyclosporine: neoral and sandimmune. A meta-analysis.

BACKGROUND: Neoral, a microemulsion formulation of cyclosporine, was approved for use in the United States in 1995. Many studies comparing Neoral and Sandimmune have been conducted, and although most state that Neoral is the superior cyclosporine formulation, results have failed to conclusively demonstrate this claim. The aim of this meta-analysis was to compare the safety and efficacy of Neoral and Sandimmune. METHODS: Publications comparing the use of Neoral and Sandimmune were reviewed for demographic variables, adverse events, rejection incidence, graft losses, and serum creatinine. Neoral and Sandimmune were compared in all patients and in the following subgroups: (1) age (adult or pediatric), (2) transplant type (kidney, liver, or heart), (3) indication (de novo or stable), and (4) study design (randomized prospective trials versus nonrandomized, blinded versus open-labeled studies). RESULTS: The rate of graft loss was similar when comparing Neoral and Sandimmune in all analyses. The incidence of rejection was lower in Neoral-treated de novo renal, liver, and cardiac transplants (P<0.05). There were significantly more adverse events in Sandimmune-treated de novo liver transplants than Neoral-treated de novo liver transplants (P<0.00001). When considering only randomized prospective trials, the incidence of rejection was lower in Neoral-treated de novo and stable patients (P<0.05). However, there were more adverse events in Neoral-treated stable patients (P<0.00001). When considering only blinded studies, there were more adverse events in Neoral-treated patients (P<0.05), whereas in open-labeled studies there was no difference in adverse events comparing Neoral and Sandimmune (P=NS). CONCLUSIONS: Considering all published trials, the data seem to indicate that Neoral therapy is preferred because of a lower rejection incidence, with a trend toward less adverse events. However, when limiting the analysis to only randomized prospective trials, and specifically assessing blinded studies, the data become less clear. Neoral use was associated with more adverse events in blinded studies, and Sandimmune use was associated with more adverse events in open-labeled studies. Careful individual consideration must be given in choosing the best possible cyclosporine formulation.

Chemistry, Pharmaceutical↗

PubMed1999

Onset and progression of motor deficits in motor neuron degeneration (mnd) mice are unaltered by the glycine/NMDA receptor antagonist L-701,324 or the MAO-B inhibitor R(-)-deprenyl.

NMDA-mediated neurotoxicity and oxidative stress have been implicated in the etiology of a number of degenerative diseases including motor neuron disease. The present study examined the effect of chronic administration of the glycine/NMDA receptor antagonist L-701,324 and the monoamine oxidase B inhibitor (r)-deprenyl on the onset and rate of progression of neurological impairment in the motor neuron degeneration (mnd) mouse, a murine model of neurodegeneration. Neurological assessment of mnd mice revealed an onset of motor deficits at 6 months of age as observed by the loss of hindlimb reflex extension. By 7 months, balance was also markedly impaired as measured by deficits in rotarod performance and ability to remain on balancing beams. At 8 months of age mnd mice exhibited gross abnormalities in walking pattern; animals were unable to flex their hindlimbs and tended to walk in small labored movements. Daily administration of L-701,324 (10 mg/kg p.o.) or r(-)-deprenyl (1 mg/kg p.o.) to mnd mice from 4 to 8 months of age failed to delay the onset of symptoms or slow the rate of deterioration of motor performance. These findings suggest that excessive activation of NMDA receptors may not be involved in the pathological process leading to motor neuron dysfunction in mnd mice and do not suggest a protective effect of deprenyl on motor neurons in these mice.

Animals↗

PubMed1999

Smoking cessation following treatment in a smoke-free Navy Alcohol Rehabilitation program.

The purpose of this study was to examine changes in smoking behavior and attitudes following treatment in the smoke-free Navy Alcohol Rehabilitation program (NARC) and to evaluate changes in staff attitudes toward the smoke-free policy. Consecutive patients (N = 404; 93.8% male) admitted to the NARC between February 1, 1993 and September 30, 1993 were studied, of whom 54.7% were current smokers. Measures included patient surveys administered repeatedly at admission and discharge and at 12 months following the 4-week treatment program. The staff were also administered a survey 2 months before (N = 86) and 6 months after (N = 104) policy implementation. Results indicate that alcohol treatment in a smoke-free environment did not markedly affect the smoking status of patients; the proportion of current smokers at discharge was 54.7%. Significant reductions in cigarettes smoked per day (p < .001) were observed among patients from admission to discharge. However, no statistically significant change in readiness to consider smoking cessation scores was detected. Results indicated no significant change in patient smoking status at 12-month follow-up, although the survey response rate was low (35.1%; N = 142). Six months following implementation of the smoke-free policy, 84.6% of staff indicated that the NARC should remain smoke-free and 84.6% recommended that other alcohol and drug treatment facilities be smoke-free.

Adult↗

PubMed1999

Potent inhibitory ligands of the GRB2 SH2 domain from recombinant peptide libraries.

We cloned and expressed the SH2 domain of human GRB2 as glutathione S-transferase and maltose binding protein fusion proteins. We screened three phagemid-based fd pVIII-protein phage display libraries against SH2 domain fusion proteins. Sequence analysis of the peptide extensions yielded a variety of related peptides. By examining the ability of the phage clones to bind other SH2 domains, we demonstrated that the phage were specific for the SH2 domain of GRB2. Based on the sequence motif identified in the "random" library screening experiment, we also built and screened a phage display library based on a Tyr-X-Asn motif (X5-Tyr-X-Asn-X8). To examine the affinity of the phage derived peptides for GRB2, we set up a radioligand competition binding assay based on immobilized GRB2 and radiolabelled autophosphorylated EGFR ICD as the radioligand. Results obtained with peptide competitors derived from the phage sequences demonstrated that nonphosphotyrosine-containing peptides identified with the phage display technology had an affinity for the receptor similar to tyrosine-phosphorylated peptides derived from the EGFR natural substrate. Interestingly, when the phage display peptides were then phosphorylated on tyrosine, their affinity for GRB2 increased dramatically. We also demonstrated the ability of the peptides to block the binding of the GRB2 SH2 domain to EGFR in a mammalian cell-based binding assay.

Adaptor Proteins, Signal Transducing↗