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Biomedical subjects

M Allen

Publications and source records attributed to M Allen.

At least 73 records · Page 4Linked to original sources
PubMed1999

Post-positivistic critical multiplism: a beginning dialogue.

Following the recognition that logical positivism was no longer tenable in modern science, post-positivism and its research methodology, critical multiplism, emerged and offered a new way of thinking about science. Though not a panacea, critical multiplism, in which methodological pluralism is advocated, offers a way around the debate of which conception of science is appropriate for nursing and, as such, poses advantages for nursing scientific knowledge development.

Bias↗
PubMed1999

Parent beliefs about infant teething: a survey of Australian parents.

OBJECTIVE: Parents ascribe many infant symptoms to teething, despite little evidence to support such an attribution. We report current parental beliefs about teething and its management in a suburban Australian setting. METHODOLOGY: A written questionnaire was given to all English-speaking parents consecutively attending infant hearing testing sessions in one Melbourne municipality between August and October 1997. Approximately 90% of Victorian infants attend these sessions. RESULTS: Parents of 92 infants (mean age 9.9 months) completed questionnaires (97% response rate). Only one believed that teething causes no problems. Most (70-85%) believed that teething causes fever, pain, irritability, sleep disturbance, mouthing/biting, drooling and red cheeks; 35-55% reported nappy rash, 'sooking', ear pulling, feeding problems, runny nose, loose stools, and infections; and a few (< 15%) reported smelly urine, constipation, colic or convulsions. Symptoms reported for a parent's own infant correlated almost perfectly with symptoms believed to be experienced by infants generally (r = 0.97, P < 0.001). Amount of infant distress when teething correlated with more 'difficult' infant temperament (r = 0.25, P < 0.05), and longer duration of symptoms per tooth correlated with parent distress (r = 0.26, P < 0. 05). Paracetamol (60%) and topical analgesia (55%) were commonly used remedies. Parents diagnose teething more by the presence of 'teething symptoms' (65%) than by palpable (43%) or visible (36%) tooth eruption. CONCLUSION: Teething is a distressing but ill-defined phenomenon reported by almost all parents of young children, and most use some form of medication to manage it. Most symptoms are minor and relate to discomfort rather than physical illness, but a substantial minority still ascribes potentially serious symptoms to teething.

Adult↗
PubMed1999

In vivo binding and antitumor activity of Ch14.18.

The melanoma reactive chimeric 14.18 (ch14.18) antibody can mediate enhanced in vitro lysis of human M-21 melanoma cells. This study analyzes the antitumor effects and the in vivo binding of ch14.18 antibody with M-21 melanoma cells in severe combined immunodeficiency (SCID) mice. Outgrowth of tumors was prevented in 6/6 animals by the simultaneous subcutaneous injection of peripheral blood mononuclear cells (PBMC) [3 x 10(6) cells (2 animals); 10 x 10(6) cells (2 animals); and 30 x 10(6) cells (2 animals)], with 0.5 mg ch14.18, 1,500 U interleukin 2 (IL-2), and 10(6) M-21 cells. In contrast, 7 of 7 control mice that received M-21 cells alone, 7 of 7 mice that received M-21 cells and ch14.18, and 5 of 6 mice that received M-21 cells plus PBMC plus IL-2, grew subcutaneous tumors. The in vivo localization of ch14.18 was then evaluated in an intraperitoneal (i.p.) tumor model, where 0.3 cm melanoma nodules develop within 3 weeks after the i.p. administration of M-21 cells. Flow cytometric and immunohistochemical analysis revealed the GD2 antigen present throughout the tumor nodule. Intraperitoneal administration of 0.01, 0.1, or 1.0 mg of ch14.18 to SCID mice previously engrafted i.p. with M-21 cells resulted in detectable ch14.18 binding to tumor cells in vivo within 10 hours of antibody administration. Ch14.18 penetration was limited to approximately 20 cell layers, demonstrating that ch14.18 has limited access to some cells in large tumor nodules. This study demonstrates that the addition of ch14.18 to IL-2 and human effector cells can result in significant antitumor activity by preventing the establishment of tumor nodules. These results suggest that clinical testing of IL-2 plus ch14.18 might be most effective if used in the setting of microscopic residual disease. Therapies that enhance ch14.18 penetration into tumor nodules should be evaluated with ch14.18 for patients with advanced melanoma.

Animals↗
PubMed1999

Chronic compartment syndrome affecting the lower limb: MIBI perfusion imaging as an alternative to pressure monitoring: two case reports.

Intracompartmental pressure monitoring remains the primary method of diagnosing chronic compartment syndrome. MIBI perfusion imaging is widely available and offers a radionuclear imaging technique for diagnosing this condition. Although the results are not identical with those from pressure monitoring, MIBI may offer a useful screening test for this condition.

Adult↗
PubMed1999

Sequence analysis of the diabetes-protective human leukocyte antigen-DQB1*0602 allele in unaffected, islet cell antibody-positive first degree relatives and in rare patients with type 1 diabetes.

The human leukocyte antigen (HLA)-DQA1*0102/DQB1*0602/DRB1*1501 (DR2) haplotype confers strong protection from type 1 diabetes. Growing evidence suggests that such protection may be mostly encoded by the DQB1*0602 allele, and we reported that even first degree relatives with islet cell antibodies (ICA) have an extremely low diabetes risk if they carry DQB1*0602. Recently, novel variants of the DQB1*0602 and *0603 alleles were reported in four patients with type 1 diabetes originally typed as DQB1*0602 with conventional techniques. One inference from this observation is that DQB1*0602 may confer absolute protection and may never occur in type 1 diabetes. By this hypothesis, all patients typed as DQB1*0602 positive with conventional techniques should carry one of the above diabetes-permissive variants instead of the protective DQB1*0602. Such variants could also occur in ICA/DQB1*0602-positive relatives, with the implication that their diabetes risk could be significantly higher than previously estimated. We therefore sequenced the DQB1*0602 and DQA1*0102 alleles in all ICA/DQB1*0602-positive relatives (n = 8) previously described and in six rare patients with type 1 diabetes and DQB1*0602. We found that all relatives and patients carry the known DQB1*0602 and DQA1*0102 sequences, and none of them has the mtDNA A3243G mutation associated with late-onset diabetes in ICA-positive individuals. These findings suggest that diabetes-permissive DQB1*0602/3 variants may be very rare. Thus, although the protective effect associated with DQB1*0602 is extremely powerful, it is not absolute. Nonetheless, the development of diabetes in individuals with DQB1*0602 remains extremely unlikely, even in the presence of ICA, as confirmed by our further evaluation of ICA/DQB1*0602-positive relatives, none of whom has yet developed diabetes.

Adult↗
PubMed1999

The academic global virtual concept in clinical cancer research and its application to breast cancer: The Breast Cancer International Research Group.

In contrast to previous decades, the 1990s have witnessed an increase of new agents with significant activity in breast cancer, including chemotherapy, hormone therapy, and, more recently, biologic modifiers. All information appears to confirm that such a trend will persist and even accelerate in the coming decades. Unless clear strategies of development for new drugs are strictly followed, it will become difficult to adequately assess the many new agents with potentially important activity against breast cancer, and patient access may become a limiting key factor. The academic, global virtual concept is calling for the definition of a new relationship between the pharmaceutical industry and clinical researchers. The main aspect is related to the creation of partnerships with an academically controlled global strategy of development for promising new agents, in which the quality and independence of processes (adjuvant setting, for example) are critical. The means are based on the globalization of patient access (worldwide network) and the virtuality of the approach (modern means of communication as well as access to subgroups of patients). The Breast Cancer International Research Group is the first academic global virtual cooperative group in breast cancer and is making contributions in the development of new drugs, such as taxanes, new antiestrogens, and new cytokines.

Academic Medical Centers↗
PubMed1998

A clinical trial of a chest-pain observation unit for patients with unstable angina. Chest Pain Evaluation in the Emergency Room (CHEER) Investigators.

BACKGROUND: Nearly half of patients hospitalized with unstable angina eventually receive a non-cardiac-related diagnosis, yet 5 percent of patients with myocardial infarction are inappropriately discharged from the emergency department. We evaluated the safety, efficacy, and cost of admission to a chest-pain observation unit (CPU) located in the emergency department for such patients. METHODS: We performed a community-based, prospective, randomized trial of the safety, efficacy, and cost of admission to a CPU as compared with those of regular hospital admission for patients with unstable angina who were considered to be at intermediate risk for cardiovascular events in the short term. A total of 424 eligible patients were randomly assigned to routine hospital admission (a monitored bed under the care of the cardiology service) or admission to the CPU (where patients were cared for according to a strict protocol including aspirin, heparin, continuous ST-segment monitoring, determination of creatine kinase isoenzyme levels, six hours of observation, and a study of cardiac function). The CPU was managed by the emergency department staff. Patients whose test results were negative were discharged, and the others were hospitalized. Primary outcomes (nonfatal myocardial infarction, death, acute congestive heart failure, stroke, or out-of-hospital cardiac arrest) and use of resources were compared between the two groups. RESULTS: The 212 patients in the hospital-admission group had 15 primary events (13 myocardial infarctions and 2 cases of congestive heart failure), and the 212 patients in the CPU group had 7 events (5 myocardial infarctions, 1 death from cardiovascular causes, and 1 case of congestive heart failure). There was no significant difference in the rate of cardiac events between the two groups (odds ratio for the CPU group as compared with the hospital-admission group, 0.50; 95 percent confidence interval, 0.20 to 1.24). No primary events occurred among the 97 patients who were assigned to the CPU and discharged. Resource use during the first six months was greater among patients assigned to hospital admission than among those assigned to the CPU (P<0.01 by the rank-sum test). CONCLUSIONS: A CPU located in the emergency department can be a safe, effective, and cost-saving means of ensuring that patients with unstable angina who are considered to be at intermediate risk of cardiovascular events receive appropriate care.

Adult↗
PubMed1998

Restricted tissue expression pattern of a novel human rasGAP-related gene and its murine ortholog.

The mammalian rasGAPs constitute a group of widely expressed proteins involved in the negative regulation of ras-mediated signaling. In this study we have isolated a novel human gene, RASAL (Ras GTPase-activating-like) and its murine ortholog, MRASAL which are most similar to the GAP1 family of rasGAP proteins, based upon the presence and organization of specific conserved domains. Full-length human and murine mRNA sequences are predicted to encode 804 and 799 amino acid polypeptides, respectively. Sequence analysis of these two proteins revealed the presence of two N-terminal calcium-dependent phospholipid binding C2 domains, a conserved GAP related domain (GRD) and a C-terminal pleckstrin homology (PH) domain. Northern blot and mRNA in situ hybridization analyses indicate that RASAL, in contrast to other mammalian rasGAP proteins, has a limited expression pattern; RASAL is highly expressed in the follicular cells of the thyroid and the adrenal medulla and expressed at lower levels in brain, spinal cord and trachea. Human RASAL has been localized by radiation hybrid mapping to chromosome 12q23-24.

Amino Acid Sequence↗
PubMed1998

Complications of use of intrauterine devices among HIV-1-infected women.

BACKGROUND: A WHO expert group and the International Planned Parenthood Federation recommend against use of intrauterine devices (IUDs) in HIV-1-infected women based on theoretical concerns about pelvic infection and increased blood loss. We investigated whether the risk of complications after IUD insertion is higher in HIV-1-infected women than in non-infected women. METHODS: 649 (156 HIV-1 infected 493 non-infected) women in Nairobi, Kenya, who requested and met local eligibility criteria for insertion of an IUD were enrolled. We gathered information on IUD-related complications, including pelvic inflammatory disease, removals due to infection, pain, or bleeding, expulsions, and pregnancies at 1 and 4 months after insertion. Patients' HIV-1 status was masked from physicians. FINDINGS: Complications were identified in 48 of 615 women (11 [7.6%] HIV-1-infected women, 37 [7.9%] non-infected). Incident pelvic inflammatory disease (two [1.4%] HIV-1 infected, one [0.2%] non-infected) and infection-related complications (any tenderness, removal of IUD for infection or pain; ten [6.9%] HIV-1 infected, 27 [5.7%] non-infected) were also rare and similar in the two groups. Complication rates were similar by CD4 (immune) status. Multivariate analyses suggested no association between HIV-1 infection and increased risks for overall complications (odds ratio 0.8 [95% CI 0.4-1.7]) or infection-related complications (1.0 [0.5-2.3]), adjusted for marital status, study site, previous IUD use, ethnic origin, and frequency of sexual intercourse, but a slight increase cannot be ruled out. INTERPRETATION: Our data suggest that IUDs may be a safe contraceptive method for appropriately selected HIV-1-infected women with continuing access to medical services.

Adult↗
PubMed1998

Surface analysis of human plasma fibronectin adsorbed to commercially pure titanium materials.

Protein binding on metallic implant surfaces, such as titanium, is governed by the physico-chemical nature of the metallic surface. Human plasma fibronectin (HPF) is an important matrix glycoprotein that mediates cell and protein attachment to each other or to the extracellular matrix present during wound healing. The objective of this study was to investigate the adsorption of HPF onto polished commercially pure titanium (cpTi) by using atomic force microscopy (AFM) and electron spectroscopy for chemical analysis (ESCA) and to measure the resultant surface contact angle before and after HPF binding. Two types of cpTi disks, one highly polished in our laboratory (HSS) and one commercially prepared (31), were reacted with HPF solutions of varying concentrations (1 microg/mL-10 ng/mL). ESCA survey spectra of samples coated with 1 microg/mL of fibronectin showed an increase in organic nitrogen and carbon compared with uncoated controls. Contact angle measurements of HSS and 31 cpTi disks showed no significant difference in average contact angle (36.3 degrees +/- 3.5 and 39.1 degrees +/- 3.1) despite differences in local root mean square (RMS) surface roughness (4.45 +/- 0.46 nm and 22.37 +/- 4.17 nm) as measured by AFM. Images obtained by AFM showed that 31 specimens were more irregular, with large parallel polishing grooves. Adsorbed HPF appeared in a globular form with an average length of 16.5 +/- 1.0 nm, a height of 2.5 +/- 0.5 nm, and a width of 9.6 +/- 1.2 nm. Fibronectin coating on both HSS and 31 cpTi specimens resulted in a significant increase in hydrophobicity compared to uncoated specimens. These results indicate the significance of HPF on cpTi and may explain how cpTi implants function in situ.

Adsorption↗
PubMed1998

Transabdominal intra-amniotic endoscopic assessment of previable premature rupture of membranes.

OBJECTIVE: Our purpose was to describe the endoscopic characteristics of the site of rupture in vivo in patients with spontaneous premature rupture of membranes. STUDY DESIGN: Patients with preterm premature rupture of membranes between 16 and 26 weeks of gestation, without evidence of intra-amniotic infection, and with a normal karyotype underwent transabdominal endoscopic examination of the amniotic cavity. Subsequently, an amniopatch of a combination of platelets and cryoprecipitate to seal the membrane defect was administered. The study was approved by the Institutional Review Board of St. Joseph's Hospital in Tampa, Florida, and all patients gave written informed consent. RESULTS: Four patients underwent endoscopic examination and amniopatch administration; three had spontaneous preterm premature rupture of membranes, and in the other the membranes ruptured after an early amniocentesis. The location of the site of rupture was over the internal os in the 3 cases with spontaneous preterm premature rupture of membranes. This area was normal in the patient with iatrogenic preterm premature rupture of membranes. The longer the time between preterm premature rupture of membranes and fetoscopy, the larger and less defined was the site of rupture. The amniopatch restored amniotic integrity for a maximum of 72 hours. CONCLUSIONS: This is the first in vivo endoscopic visualization of the site of spontaneous rupture of membranes from within the uterine cavity. The defect is located over the internal cervical os in patients with spontaneous preterm premature rupture of membranes. There appear to be time-related changes in the morphologic characteristics of the site of rupture. Endoscopic visualization of the site of rupture has the potential for improving our understanding of spontaneous preterm premature rupture of membranes and in the development of possible therapeutic alternatives.

Abdomen↗
PubMed1998

Contrasting effects of ultraviolet A1 and ultraviolet B exposure on the induction of tumour necrosis factor-alpha in human skin.

Ultraviolet B (UVB) irradiation of the skin causes immunosuppression which is relevant to the induction of skin cancer. The mechanism of this immunomodulation is unclear but various regulatory molecules have been implicated, including cis-urocanic acid (cis-UCA) and the cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin 10 (IL-10). Whether ultraviolet A (UVA) induces similar changes has not been investigated fully. We studied the effect of in vivo UVB and long-wave UVA (UVA1) exposure on the induction of TNF-alpha, IL-10 and cis-UCA in human skin. Volunteers were irradiated with three minimal erythema doses (MED) of UVB or UVA1. At different times after irradiation, suction blisters were raised from irradiated and from non-irradiated (control) skin. The TNF-alpha and IL-10 protein concentration, and the percentage of cis-UCA in the blister fluid, were then determined. UVB irradiation of human skin led to a rapid and significant increase in TNF-alpha concentration in suction-blister fluid, with maximal values 6 h after irradiation (n = 6, P < 0.05). In contrast, UVA1 irradiation led to a decrease in TNF-alpha concentration in the suction-blister fluid compared with non-irradiated skin, with the lowest values 6 h after irradiation (n = 6, P < 0.05). Both UVB and UVA1 exposure of the skin induced a slight increase in IL-10 concentration. However, the increase in IL-10 was only significant after UVB irradiation (UVB, n = 6, P < 0.05; UVA, n = 7, P < 0.1). As previously shown, both UVB and UVA1 result in the photo-isomerization of trans-UCA and an increased percentage of cis-UCA was found in the suction-blister fluid. Thus the results show differential effects of UVB and UVA1 irradiation on the induction of immunoregulatory molecules, which may help to explain the variation in immune responses after UVB and UVA1 exposure of human skin.

Adult↗
PubMed1998

Resistance mutations in protease and reverse transcriptase genes of human immunodeficiency virus type 1 isolates from patients with combination antiretroviral therapy failure.

High-density oligonucleotide arrays were used to determine the sequence of the protease (PR) and reverse transcriptase (RT) genes of human immunodeficiency virus type 1 isolates from 35 patients in whom combination therapy that included a protease inhibitor had failed. Isolates had a median of three PR mutations (range, none to six). Three isolates had no known resistance mutations in PR. Twelve isolates (34%) had two or fewer resistance mutations in PR. The most commonly observed PR mutations were L10I, V82A/T/F, and L90M. No mutations were observed at codons 30 or 48. Mutations at RT codons 215 and 184 were observed in the majority of isolates. These data suggest that therapy can fail in some patients with relatively few PR resistance mutations. Clinical failure in the absence of resistance mutations implies inadequate drug exposure due to pharmacologic factors or suboptimal patient adherence to drug therapy.

Anti-HIV Agents↗
PubMed1998

The importance of stabilization as an endpoint in the treatment of metastatic colorectal carcinoma: recent quality of life studies.

Assessment of the effectiveness of new anticancer chemotherapies in clinical trials is usually based on the degree of objective response obtained. Response is usually defined as 'complete', when there is complete disappearance of all detectable tumor, or 'partial', when there is a 50% reduction in the sum of the products of the largest perpendicular diameters of all measurable disease, with no new lesions (Advanced Colorectal Cancer Meta-analysis Project). Both clinicians, concerned with the welfare of their patients, and healthcare administrators, keen to be assured of cost-effectiveness within their restricted budgets, see such response (along with enhanced survival) as a cardinal indicator of efficacy. Response rates are a primary influence on their decision to treat, or to sanction payment for treatment, with a particular medication. There is, however, growing evidence to suggest that stabilization of disease is also an important endpoint in chemotherapy for carcinoma, with important benefits for the patients' quality of life (QoL). We report on recent international studies on the effects of the topoisomerase I inhibitor irinotecan (Campto) as second-line treatment in patients with metastatic colorectal cancer. These confirm the value of stabilization, as well as response, in such patients, not only in bringing QoL benefits, but also in reducing length of hospitalization and hence costs.

Colorectal Neoplasms↗
PubMed1998

High resolution genetic typing of the class II HLA-DRB1 locus using group-specific amplification and SSO-hybridisation in microplates.

The HLA-DRB1 locus is one of the most polymorphic HLA class II loci and rapid and accurate typing of this polymorphism is important both in bone-marrow transplantation, analysis of disease association and in forensic medicine. The allelic variation at DRB1 is characterized by combinations of a limited number of amino-acid motifs, reducing the resolution of a typing strategy based on a single PCR and subsequent analysis of polymorphic motifs. In the present paper we describe a strategy for typing of DRB1 based on eight allele-specific PCRs followed by sandwich hybridization to immobilized probes in a microplate format. The combined approach results in a rapid typing system with very high resolution. Using a rapid DNA extraction protocol, a complete HLA-DRB1 typing can be performed in less than a day.

Alleles↗