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Biomedical subjects

M Hamilton

Publications and source records attributed to M Hamilton.

At least 73 records · Page 4Linked to original sources
PubMed1998

Ha-ras and N-ras regulate MAPK activity by distinct mechanisms in vivo.

The Ras GTPases function as molecular switches, regulating a multiplicity of biological events. However the contribution, if any, of a specific c-Ras isoform (Ha-, N-, or Ki-ras A or B) in the regulation of a given biological or biochemical process, is unknown. Murine C3H1OT1/2 fibroblasts transformed with activated (G12V)Ha-ras or (Q61K)N-ras proliferate in serum-free media and have constitutive MAPK activity. The growth factor antagonist, suramin, inhibited the serum-independent proliferation of Ha-ras transformed fibroblasts, but not the serum-independent proliferation of N-ras transformed cells. The inhibition of cell proliferation was concomitant with the abrogation of the constitutive MAPK activity in the Ha-ras transformed fibroblasts. Analysis of the Ras-signalling complexes in immunoprecipitates from Ha-ras transformed cells revealed that Raf-1 co-immunoprecipitated with endogenous c-N-ras but not (G12V)Ha-ras. Pretreatment with suramin resulted in the loss of Raf-1 from c-N-ras immunoprecipitates. A c-N-ras antisense oligonucleotide, which down-regulated c-N-ras protein levels, abrogated the constitutive MAPK activity and serum-independent proliferation of (G12V)Ha-ras transformed cells. The data suggest that Raf-1 has a higher affinity for N-ras then Ha-ras in vivo, and c-N-ras function is required for the serum-independent proliferation of Ha-ras transformed cells.

Animals↗
PubMed1998

Treatment level progress and time spent in treatment in the prediction of outcomes following drug-free therapeutic community treatment.

UNLABELLED: Previous research has suggested that time spent in treatment is the most important predictor of therapeutic community treatment outcomes. Although level divisions or treatment stages represent the basic structure for segmenting responsibility and authority within traditional therapeutic communities, the relationship of this treatment component to treatment outcome has not previously been investigated. AIM: To test the hypothesis that higher treatment level attainment, more time spent in treatment and additional time spent within a treatment level has a linear association with improvements at outcome. DESIGN: Retrospective quasi-experimental. PARTICIPANTS: Four hundred and twenty-seven ex-residents, stratified according to their highest level of treatment in the Melbourne Odyssey House therapeutic community between 1984 and 1988 were targeted for follow-up and 60% were successfully located and interviewed an average of 5.6 years after their first Odyssey entry. Analysis of official records of methadone treatment, convictions and incarcerations demonstrated no post-treatment differences comparing those interviewed with those not interviewed. MEASUREMENTS: Drug use, criminal involvement and employment. FINDINGS. Although both level attainment and time spent in treatment had a linear relationship to improved outcomes, level attainment was a better predictor of outcomes at treatment exit. An unexpected finding was that those who had spent the median time or longer in particular levels demonstrated worse outcomes on official conviction records and on self-reports of employment compared to those remaining for less than the median time. CONCLUSION: The results suggest that it may be level progress rather than simply time spent in treatment that best explains improved functioning following exit from the therapeutic community.

Adult↗
PubMed1998

Ulcerative colitis has an aggressive course after orthotopic liver transplantation for primary sclerosing cholangitis.

BACKGROUND: The course of inflammatory bowel disease after liver transplantation has been reported as variable with usually no change or improvement, but there may be an increased risk of early colorectal neoplasms. In many centres steroids are often withdrawn early after transplantation and this may affect inflammatory bowel disease activity. AIMS: To evaluate the course of inflammatory bowel disease in primary sclerosing cholangitis transplant patients who were treated without long term steroids. METHODS: Between 1989 and 1996, there were 30 patients transplanted for primary sclerosing cholangitis who survived more than 12 months. Ulcerative colitis was diagnosed in 18 (60%) patients before transplantation; two had previous colectomy. All patients underwent colonoscopy before and after transplantation and were followed for 38 (12-92) months. All received cyclosporin or tacrolimus with or without azathioprine as maintenance immunosuppression. RESULTS: Ulcerative colitis course after transplantation compared with that up to five years before transplantation was the same in eight (50%) and worse in eight (50%) patients. It remained quiescent in eight and worsened in four of the 12 patients with pretransplant quiescent course, whereas it worsened in all four patients with pretransplant active course (p=0.08). New onset ulcerative colitis developed in three (25%) of the 12 patients without inflammatory bowel disease before transplantation. No colorectal cancer has been diagnosed to date. CONCLUSIONS: Preexisting ulcerative colitis often has an aggressive course, while de novo ulcerative colitis may develop in patients transplanted for primary sclerosing cholangitis and treated without long term steroids.

Adolescent↗
PubMed1998

Smokeless tobacco use by secondary students in a Mexican bordertown.

Of secondary students living in a Mexican bordertown, 67 boys and 45 girls aged 13 to 18 years, 5 boys reported trying chewing tobacco, but none reported current use, and 61 students believed such use could cause cancer. Low prevalence may be related to low exposure to advertising.

Adolescent↗
PubMed1998

The manufacturing process for recombinant factor IX.

Advances in recombinant DNA manufacturing technology have now made possible the production of a highly purified and active recombinant factor IX (rFIX) product. Recombinant factor IX was developed by (1) stable insertion of the genes for both factor IX and PACE-SOL (a truncated, soluble serine protease needed to enhance the capacity of cells to remove the amino-terminal propeptide from rFIX) into Chinese hamster ovary cells; (2) selection of a cell line that was capable of expressing high amounts of active rFIX while growing in bioreactors containing a completely defined culture medium that does not contain blood or plasma products; and (3) inclusion of four independent chromatography steps, none of which require monoclonal antibodies. Furthermore, rFIX has been extensively tested to demonstrate similarity to plasma-derived factor IX and has been shown to be a consistent, high-purity product. For example, a high-specific-activity product (276+/-23 IU/mg) has been consistently produced throughout 65 consecutive batches from five consecutive manufacturing campaigns. Thus, rFIX offers a consistent and high-purity source of factor IX treatment for patients with hemophilia B.

Animals↗
PubMed1997

Chronic stimulation differentially modulates expression of mRNA for dihydropyridine receptor isoforms in rat fast twitch skeletal muscle.

This study examined the effects of low frequency chronic stimulation on expression of the mRNA encoding the two isoforms of the alpha1 subunit of the dihydropyridine receptor (DHPR) calcium channel, a critical component of skeletal muscle excitation-contraction coupling. RNase protection assay was used to determine alteration in isoform expression in 5-day, 9-day and 13-day chronically stimulated rat tibialis anterior muscle, and to compare it with soleus and extensor digitorum longus muscles. Low frequency chronic stimulation was associated not only with a significant decrease in the mRNA level of the skeletal isoform of the DHPR, but also with a significant increase in the mRNA level of the cardiac isoform of the DHPR, the overwhelming majority of which was the adult splice variant. Significant levels of cardiac DHPR mRNA expression were also found in normal adult slow twitch soleus muscle. These findings raise the question of a potential role for the cardiac DHPR in certain adult skeletal muscles.

Alternative Splicing↗
PubMed1997

The effect of exercise intensity on lipid peroxidation.

This study characterizes exercise-induced lipid peroxidation during graded aerobic exercise in seven healthy men and women (36.4 +/- 3 yr). Levels of ethane and pentane in expired breath during cardiopulmonary exercise stress testing were measured at rest, lactic acidosis threshold (LAT), maximal exercise (VO2max), and recovery. Serum malonaldehyde (MDA) levels were measured at rest before exercise and 5 min after maximal exercise. Expired ethane and pentane flux levels were increased above resting levels at LAT, continued to rise at VO2max, then declined during recovery. Serum MDA levels were not significantly different before and after maximal exercise. Substantial exercise-induced lipid peroxidation (by expired ethane and pentane) apparently occurred in healthy individuals at LAT and continued to increase at VO2max, yet rapidly attenuated during post-exercise recovery. These findings indicate that in healthy individuals physical exercise induced lipid peroxidation transiently and that there was a removal of lipid peroxidation byproducts during recovery.

Acidosis, Lactic↗
PubMed1997

Management of ductal carcinoma in situ of the breast--experiences from National Naval Medical Center during last 10 years.

Seventy-one ductal carcinoma in situ (DCIS) patients were reported to the tumor registry at the National Naval Medical Center between 1986 and 1995. This number represents 6.5% of all breast cancer patients. We did not include the patients with microinvasion or infiltrating ductal carcinoma with extensive DCIS in this study. After excluding 16 cases because of inaccessable clinical records, 55 cases of pure DCIS were analyzed. The mean age at presentation was 52.0 years (32 year-old to 74 year-old) and the most common clinical feature was an abnormal mammographic finding (40 cases, 73%). Family history of breast cancer was positive in 14 cases among the 39 cases with DCIS (35.9%) according to the medical records. Total mastectomy was the most common form of treatment for DCIS (19 cases, 34.5%) during this period, followed by modified radical mastectomy, lumpectomy only, lumpectomy with radiation therapy. Three hundred and two axillary lymph nodes were examined but revealed no nodal metastasis. Comedo type DCIS was the most common subtype (21 cases, 38.2%). There were no local recurrences or DCIS related deaths reported to the tumor registry during this period (mean follow-up interval of 51 months).

Adult↗
PubMed1997

The alternate recipient list for heart transplantation: does it work?

BACKGROUND: One quarter of patients awaiting heart transplantation die while on the waiting list. This is largely due to the shortage of donor organs. The alternate recipient list was created to establish a means by which patients who would otherwise be turned down for heart transplantation solely because of age over 65 or a need for a third heart transplantation can receive organs considered marginal that may otherwise be wasted. The hope is that these patients may achieve improved survival with these substandard hearts than they would achieve with medical therapy alone. METHODS: Twenty-two patients ages 47 to 71 years (mean 66.7 years) were listed on the alternate recipient list at the University of California at Los Angeles Medical Center from 1991 to 1996. Seventeen patients underwent heart transplantation from the alternate waiting list. The outcome of this group was compared with the outcome of a contemporaneous group of 266 patients ages 18 to 66 years (mean age 52.1 years) from the standard heart transplantation waiting list. RESULTS: The early mortality rate for the patients in the alternate group was 11.8% (2/ 17). Actuarial survival from time of orthotopic heart transplantation at 6 months and 1 year was the same 74.5% at a mean follow-up was 13.4 months. In comparison, the early mortality rate for the patients on the standard list was 5.6% (15/266), and actuarial survival at 6 months and 1 year was 86.8% and 83.1%, respectively (mean follow-up was 30 months). There was no significant difference in early mortality rate or actuarial survival between the two groups. CONCLUSION: The alternate recipient list for heart transplantation is a valid and ethical option for patients who would otherwise be denied heart transplantation. It provides these patients with similar early and medium-term outcomes in comparison to patients on the standard list, and organs that may otherwise be wasted are used.

Adolescent↗
PubMed1997

Confidentiality, disseminated regulation and ethico-legal liabilities in research with hidden populations of illicit drug users.

An assurance of confidentiality is at the core of trusting relationships in outreach, ethnographic research and patient/client encounters. In the past, centralized State health care services have provided assurances of confidentiality to those engaged in health-related research either through common law or by statute. However, unless specific confidentiality legislation is in place, no assurances of confidentiality can now be made to research subjects involved in either longitudinal, interview-based or ethnographic research. The consequences of this situation become more serious given the recent emergence of the use of peer and community outreach. A significant problem with the outreach model is the failure to provide adequate legal and ethical support for those in outreach roles. Additionally, unless research subjects can be granted assurances of confidentiality, they will not engage in research for fear of later prosecution. At this time when outreach models are the modus operandi, the lack of a fundamental commitment to sustain confidentiality may seriously undermine further research. This paper will draw on the experiences of some Australian qualitative research and will review some of the ethical and legal liabilities for research that arise when an assurance of confidentiality cannot be given to those participating in research.

Australia↗
PubMed1996

The consequences of knowing: ethical and legal liabilities in illicit drug research.

Ethnographic research into illicit drug use necessarily involves the researcher being aware of illegal activities. Information about illegal activities is obtained through the establishment of confidential relationships with research participants; however there are legal and ethical obligations on researchers to breach confidential relationships formed in the research environment. The recent suspension of a research project by an Institutional Ethics Committee serves to illustrate some of the processes that form the research process, shape the boundaries to legitimate knowledge and some of the consequences of knowing about illegal activities.

Confidentiality↗
PubMed1996

Service providers' perceptions of substance use self-help groups.

Using a two-stage Delphi procedure, an investigation was carried out into health and welfare professionals' knowledge of and relationship with self-help groups (SHGs). Professionals indicated that they perceived SHGs to be generally helpful for persons with substance use problems. Provision of social support was the most commonly perceived helpful aspect of SHGs, and unsuitability for some clients was the most commonly perceived unhelpful-aspect. Persons motivated to address their problems were those perceived to be most likely to find a SHG useful, with those not so motivated, or who deny their problem, being perceived to be least likely to find a SHG useful. Drug and alcohol user treatment specialists reported greater perceived failure of SHGs to address underlying psychopathology and greater perceived benefit for clients lacking social support. This may be of particular relevance for future attempts to investigate the process of recovery in SHGs.

Humans↗