Biomedical subjects
Publications and source records attributed to P Martin.
Northern blotting using glyoxal to denature a highly folded mRNA, such as goat alpha S1-Casein E, can lead to the detection of multiple incompletely denatured forms. Formaldehyde appears to be the most suitable agent for Northern blotting due to its effective denaturing capacity and lower toxicity than methylmercuric hydroxide.
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The tremendous success of OLT as a highly effective treatment for patients with end-stage liver disease has resulted in a rapid increase in the number of candidates for the procedure. Refinements in organ preservation, improvements in surgical technique and immunosuppression, and better postoperative management have contributed to improved survival rates. The discrepancy between the paucity of organs and the increasing numbers of potential recipients will continue to worsen until there are extraordinary breakthroughs in providing alternatives to human whole-organ livers, such as xenografts or cultured hepatocyte infusions. For now, the vast majority of patients with life-threatening liver disease are not likely to receive a liver graft. Thus, the issues of patient selection and timing of OLT have become even more relevant. Prompt referral to a transplant center is not only in the patient's best interest, but also it has been shown to be cost-effective. Over the last 30 years, it has become clear that hepatic malignancy, initially a common reason for OLT, should be an indication for transplantation only in highly selected individuals. The role of adjuvant chemotherapy needs to be defined, and proven treatment alternatives need to be developed. New antiviral agents may enable a large group of patients with chronic hepatitis B to be successfully transplanted, placing even greater demands on the already limited supply of donor livers. Hepatitis B appears to be species specific, and it is conceivable that xenotransplantation from a nonsusceptible donor species may confer protection to HBV reinfection, eliminating the problems of an inadequate donor supply. Until novel approaches, including xenotransplantation, gene therapy, or replacement of hepatic function by cultured hepatocyte infusions, become a widespread reality, future allocation policies may highlight outcome as well as urgency as a fundamental variable to determine if transplantation is reasonable. Survival rates have been shown to fall with advancing levels of urgency, resulting in a conflict between equity and efficacy in organ allocation. As waiting lists for liver transplantation continue to grow, it is becoming increasingly apparent that patients must be referred to a transplant center earlier in the course of liver disease.
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The predictability of personality for psychological well-being in centenarians when compared to sexagenarians and octogenarians was investigated. Multiple regressions were computed to examine the separate and joint effects of personality traits and states upon morale. Results indicated that low tension and high extraversion predicted high morale for centenarians. Guilt was the most important personality state predicting morale for the 60s age group, and control variables gender and health were significant for the 80s age group. The assessment of personality traits and states has important implications for working with centenarians and other older adults to maintain or improve their subjective well-being.
Small skin wounds in the chick embryo do not heal by lamellipodial crawling of cells at the wound edge as a skin wound does in the adult, but rather by contraction of an actin purse-string that rapidly assembles in the front row of epidermal cells (Martin, P., and J. Lewis. 1992. Nature (Lond.). 360:179-183). To observe the early time course of actin purse-string assembly and to characterize other cytoskeletal components of the contractile machinery, we have followed the healing of incisional or slash wounds on the dorsum of the chick wing; these wounds take only seconds to create and heal within approximately 6 h. Healing of the epithelium depends on a combination of purse-string contraction and zipper-like closure of the gap between the cut edges of the epithelium. Confocal laser scanning microscope studies show that actin initially aligns into a cable at the wound margin in the basal layer of the epidermis within approximately 2 min of wounding. Coincident with actin cable assembly, we see localization of cadherins into clusters at the wound margin, presumably marking the sites where segments of the cable in adjacent cells are linked via adherens junctions. A few minutes later we also see localization of myosin II at the wound margin, as expected if myosin is being recruited into the cable to generate a contractile force for wound healing. At the time of wounding, cells at the wound edge become transiently leaky, allowing us to load them with reagents that block the function of two small GTPases, Rho and Rac, which recently have been shown to play key roles in reorganiztion of the actin cytoskeleton in tissue-culture cells (Hall, A. 1994. Annu. Rev. Cell Biol. 10:31-54). Loading wound edge epidermal cells with C3 transferase, a bacterial exoenzyme that inactivates endogenous Rho, prevents assembly of an actin cable and causes a failure of healing. No such effects are seen with N17rac, a dominant inhibitory mutant Rac protein. These findings support the view that in this system the actin cable is required for healing-both the purse-string contraction and the zipping up-and that Rho is required for formation of the actin cable.
Since tamoxifen is efficacious for the prevention of second primary breast neoplasms in humans and has a low reported incidence of acute side effects, several structurally related compounds have been developed for the treatment of breast cancer including toremifene and idoxifene. We have compared the karyotypic alterations that occur after a single per os administration of 35 mg/kg of tamoxifen, toremifene or idoxifene to female Sprague-Dawley rats. One day following treatment, the rats were sacrificed and the hepatocytes isolated and cultured. After 47 h in culture, colcemid was added for 3 h prior to harvest of the hepatocytes for karyotypic evaluation. At least 100 metaphase spreads were examined for each of five rats per treatment. Toremifene resulted in aneuploidy in 50 +/- 7% of the cells examined and idoxifene induced a 57 +/- 4% aneuploidy compared with the 85 +/- 7% level induced by tamoxifen. Since the level of aneuploidy in solvent-treated rats was 3 +/- 3 %, the induction of aneuploidy in at least 50% of the cells from rats treated with tamoxifen, toremifene or idoxifene was highly significant. Analysis of electron micrographs of cultures treated with these antiestrogens demonstrated a range of phenotypes including multipolar spindles in toremifene-treated rats and condensed chromosomes in the presence of an intact nuclear envelope in occasional idoxifene-treated rat hepatocytes. The exclusion of chromosomes from the spindle apparatus and the lagging of some chromosomes on the metaphase plate correlate with the high rate of induction of aneuploidy in the rat liver as determined by karyotypic analysis of hepatocytes from rats treated with these triphenylethylenes.
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Quality of life is one of the effectiveness measures used to assess the impact of medical interventions. This paper describes results of a study on quality of life of depressed patients treated with fluoxetine or tricyclic antidepressants (TCAs) such as amitriptyline and clomipramine. The quality of life of patients was measured using the Short Form (SF-36), a widely accepted and validated questionnaire. Depressed patients (n = 845) were observed using a cross-sectional design. Patients who had been under treatment for at least 1 week (amitriptyline, clomipramine or fluoxetine) and met the DSM-III-R criteria for major depressive disorder were included. Similar sociodemographic profiles were found across treatment groups. However, more patients with a history of depression were found in the TCA vs the fluoxetine group. Compliance was dramatically lower and length of treatment higher for TCA-treated groups. Controlling for confounding variables, the TCA-treated group also scored lower than the fluoxetine-treated one for general health perception, and social and physical functioning. These differences are not explained by symptom severity since Hamilton scores were similar across treatment groups. These results suggest that fluoxetine treatment may be associated with higher levels of social functioning and health perception than usual TCA treatment.
OBJECTIVE: To evaluate the contribution of angiotensin-(1-7) [Ang-(1-7)] and prostaglandins to the acute and long-term antihypertensive actions of captopril in mild-to-moderate essential hypertensive patients. DESIGN AND METHODS: Blood pressure, cardiac rate and the plasma concentrations of angiotensin I (Ang I), angiotensin II (Ang II), Ang-(1-7), prostaglandin E2 and 6-keto prostaglandin F1 alpha (the breakdown product of prostacyclin) were determined in the peripheral venous blood of 24 essential hypertensive subjects before and 3 h after administration of 50 mg captopril. Eleven of 24 patients completed a 6-month treatment period with captopril monotherapy (50 mg twice a day). The hemodynamic and hormonal response produced by a last 50 mg dose of captopril was determined once again in the 11 subjects who maintained blood pressure control with captopril monotherapy for 6 months. RESULTS: The fall in blood pressure produced 3 h after drug intake was comparable for the first and the last 50 mg captopril dose. Although the first response to captopril increased plasma levels of Ang I only, the response to the last dose of the drug (6 months after) caused significantly higher levels of Ang I and Ang-(1-7). Neither acute nor chronic therapy with captopril had a significant effect on plasma concentrations of Ang II. Although plasma levels of prostaglandin E2 and 6-keto prostaglandin F1 alpha were not modified by a first exposure to captopril, the concentrations of 6-keto prostaglandin F1 alpha but not prostaglandin E2 rose significantly in subjects treated with the inhibitor for 6 months. A negative correlation was also demonstrated between diastolic blood pressure and plasma Ang-(1-7) levels in the 11 essential hypertensive subjects in whom blood pressure was controlled with captopril monotherapy. CONCLUSIONS: Inhibition of angiotensin converting enzyme with captopril had a significant effect on blood pressure that was not directly accounted for by a suppression of plasma Ang II levels. Continuous therapy with captopril unmasked a contribution of Ang-(1-7) and prostacyclin to the antihypertensive actions of this drug.
The utility of the MLC assay as a test of HLA-D region matching and predictor of graft-versus-host disease (GvHD) was evaluated in 435 patients receiving marrow grafts from unrelated donors. Donors and recipients were phenotyped for HLA-A, B and DR antigens by serology, tested in MLC, and retrospectively genotyped for DRB1, B3, B4, B5, DQB1 and DPB1 alleles by PCR/SSOP. Of the 244 HLA-A, B, DR-identical donor-recipient pairs with valuable MLC and DRB1 typing results available, 208 were matched for HLA-A, B and DRB1, while 36 were matched for HLA-A and B and mismatched for a DRB1 allele. Donor anti-recipient relative responses (RR) in MLC, corresponding to the GvHD vector in marrow transplantation, ranged from 7.2 to 100%, with a median of 4.0%. A comparison of reactivity in MLC between pairs matched versus mismatched for DRB1 alleles showed a significant overlap in the distribution of RRs. Using optimally-defined RR cutoffs of 4 and 16%, no correlation between MLC results and risk of developing clinically significant grades III-IV GvHD (p=0.6 and 0.5, respectively) was found when the contribution of DRB1 mismatch was accounted for. Matching for DRB1 alleles, in contrast, was a better predictor of clinically significant GvHD, with DRB1-matched transplant recipients less likely to develop grades III-IV GvHD than DRB1-mismatched recipients (p=0.14). Among the 208 patients and donors matched for DRB1 alleles, the MLC, although reactive (RR > 4.0%) in 45% of cases, did not predict GvHD. Overall, these results underscore the limitations in using the MLC to predict DRB1 matching or risk of clinically significant GvHD among patients receiving unrelated marrow grafts. The availability of DRB1 allele matching by sequence-specific oligonucleotide probes (SSOP) or by direct sequencing provides a method for donor matching that is rapid, precise and superior to the MLC for predicting clinically relevant outcome.
Six cases (3 cats, 3 dogs) of cryptococcosis were cured using combination chemotherapy that included amphotericin B. We developed a simple, practical and inexpensive method of administering amphotericin B as a subcutaneous infusion during the treatment of these patients. For this, the calculated dose of amphotericin B (0.5 to 0.8 mg/kg) was added to 400 mL, for cats, or to 500 mL, for dogs, of 0.45% saline containing 2.5% dextrose. These amounts were given subcutaneously 2 or 3 times weekly over several months, to a total cumulative dose of 8 to 26 mg/kg body weight. Subcutaneous infusions were generally well tolerated by the animals, although concentrations of amphotericin B in excess of 20 mg/L resulted in local irritation. This protocol enabled the administration of larger, and thus more effective, quantities of amphotericin B without producing marked azotaemia.
The exemplars in this article reflect caring contexts and creative nursing solutions to dementia, depression, and addiction, common mental health problems afflicting elderly patients and for which inpatient evaluation and treatment are necessitated. Optimal functioning and quality of life for elderly individuals depend substantially upon both physical and mental capacity. The coexistence of mental and physical illness leads to rapid impairment of functioning and interrupts the individual's zest for living. Although in most cases dementia is irreversible, other treatable comorbid conditions like delirium can exacerbate suffering and decline. Conversely, mental disorders, like depression and addiction, can amplify the negative effects associated with other health conditions, causing excess disability and mortality, and are associated with older individuals having the highest suicide rate of any age group in the United States. Nurses are well positioned to identify mental health problems and humanely treat primary and secondary symptoms associated with these disorders in their elderly patients. A document to guide medical professionals' assessment of mental disorders is now available (Spitzer et al., 1994). Remaining attentive to early identification of high-risk individuals and mobilizing resources in their behalf will substantially contribute to their well-being. There is ample research evidence on the benefits and efficacy of mental health interventions (Lebowitz, 1994). Much of the challenge and hard work for nurses lies in getting to know the patient, grasping what is happening for the individual and determining which treatment interventions will be most effective given the present circumstances surrounding the illness episode (Benner, 1984).
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The purpose of this exploratory study was to examine the factor structure of health orientation. A secondary purpose was to determine differences in the stability and lability of health orientation. The sample consisted of four women in their sixties and four women in their eighties. A replicated, single-subject design was used to assess short-term intraindividual change in health orientation. Participants completed the Health Orientation Scale questionnaire for 100 days, and P-technique factor analysis was used to determine the factor structure of health orientation. These health orientation factors were graphed over time to assess stability and change. Results indicate that health orientation is more complex for participants in their eighties than for those in their sixties; this may represent age-appropriate development. Health orientation factors were found to be more labile or statelike for women in their eighties. These findings may help health care providers understand differences in interest or adherence to health-seeking behavior in the elderly and improve age-appropriate health care for this population.