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Biomedical subjects

B J Miller

Publications and source records attributed to B J Miller.

At least 19 recordsLinked to original sources

Life-threatening thrombotic thrombocytopenic purpura (TTP) in a patient with sickle cell-hemoglobin C disease.

We report a patient with hemoglobin sickle cell-hemoglobin C disease who developed the clinical syndrome of thrombotic thrombocytopenic purpura (TTP) during admission for typical acute pain crisis. The potential for multiorgan involvement secondary to vaso-occlusive crisis complicated the diagnosis and overlapped with the patient's clinical presentation of chronic bone pain and hemolytic anemia. Clinical improvement and normalization of laboratory parameters followed rapidly in response to plasma exchange therapy.

Adult↗

Factors affecting the performance of 5' nuclease PCR assays for Listeria monocytogenes detection.

The design and operating parameters affecting the performance of 5' nuclease PCR (TaqMan) assays for the detection of Listeria monocytogenes was investigated. A system previously developed and based on the hlyA gene was used as a model [Appl. Environ. Microbiol. 61 (1995) 3724]. A series of fluorogenic probes labeled with a reporter and a quencher dye was synthesized to explore the effect of probe position and sequence content on the efficiency of probe hydrolysis. In addition, a series of PCR primer pairs that altered the distance between the upstream primer and the interceding probe was examined. The effects of various assay parameters were evaluated by measuring the ratio of the fluorescence intensity of the reporter dye over the quencher dye (deltaRQ). For a given probe sequence, the deltaRQ was typically lower if the 5' terminus was a G residue. Decreasing the probe concentration increased the deltaRQ, although this was at the expense of reproducibility in the assay readout. The distance between the upstream primer and the interceding probe has a significant effect on probe hydrolysis. Reducing the primer-probe distance from, for example, 127 to 4 nt increased the deltaRQ from 2.87 to 5.00. These general rules were used to develop a 5' nuclease PCR (TaqMan) assay with enhanced signal output, providing higher and more reproducible deltaRQ values for L. monocytogenes detection.

Bacterial Toxins↗

Basal cell proliferation in female SKH-1 mice treated with alpha- and beta-hydroxy acids.

Alpha- and beta-hydroxy acids are compounds that have been used extensively in cosmetic and dermatological formulations. Clinical and qualitative effects of alpha- and beta-hydroxy acids have been well characterized, but little is known about their mechanism of action or acute and chronic biochemical effects. In the present study, we examined the acute proliferative effects of glycolic and salicylic acids on cell proliferation in the epidermis of SKH-1 female mice, using BrdU incorporation as a marker of epidermal proliferation. In preliminary experiments, we observed an increase in the rate of proliferation after 3 days of treatment with 10% glycolic acid-containing cream and this was sustained throughout a 6.5-week (treatment 5 days/week) time course compared with untreated control animals. After each treatment with cream containing glycolic acid there was a wave of proliferation that was maximal 12 to 16 h (significant at p < 0.05) after treatment, followed by a subsequent increase in epidermal thickness at 18 to 20 h (significant at p < 0.05). The effects of the concentration and pH level of glycolic acid- and salicylic acid-containing creams on the rate of proliferation and increases in skin thickness in SKH-1 epidermis were also investigated. We observed a dose-dependent increase in epidermal proliferation of animals treated with either glycolic or salicylic acid. A similar time-dependent response was observed in the epidermal thickness in animals treated with salicylic acid, but not with glycolic acid. Differences in pH (3.5 or 4.0) had no significant effect on either epidermal proliferation or skin thickness. The data that we present here should be useful in characterizing not only the beneficial but also the adverse effects that occur following acute or chronic usage of alpha-hydroxy acids.

Animals↗

Outcome of the acute abdomen in patients with previous spinal cord injury.

BACKGROUND: Patients with spinal cord injury (SCI) have always posed difficulties for the diagnosis of an acute abdomen. The aim of the present study was to define this problem retrospectively at Princess Alexandra Hospital and to assess the results of treatment for these patients. METHODS: A retrospective review was conducted of 133 SCI patients admitted with an acute abdomen in the 16 years prior to this analysis at the Spinal Injuries Unit (SIU) of Princess Alexandra Hospital. There were 21 patients who conformed to the study criteria. All the patients had sustained traumatic SCI at or above the level of T11, more than 1 month prior to admission. RESULTS: There were 13 male and eight female patients. The time lapse between SCI and the onset of an acute abdomen ranged from 1.5 months to 27 years. The age range was 26-79 years. The majority of patients had C6 injuries (six patients). There were 18 patients with injury levels above T6 and three patients with injuries below this level. The time taken to diagnose the cause of the acute abdomen ranged between I day and 3 months. Investigations were found to be useful in making the diagnoses in 61.9% of cases. There were 14 patients who had surgical interventions. Five patients had surgical complications and there were two deaths in the study. The length of follow up was 1-132 months. The mortality in the study was 9.5%. CONCLUSION: An aggressive approach to the diagnosis and treatment of the acute abdomen in SCI patients with suspicious symptoms is recommended. A high index of suspicion should be maintained in those patients with pre-existing SCI who present with abdominal trauma.

Abdomen, Acute↗

Developing your campus and facility for long-term growth.

Many hospitals are experiencing facility capacity constraints that threaten their ability to provide enough care to meet the needs of their communities. Although "make do" solutions are required, taking time to develop a comprehensive long-term plan that addresses strategic priorities and meets future capacity need is critical to an organization's long-term success. Putting the right team in place and taking the right steps leads to the right long-term solution. This article explores the people and steps required for coherent long-term campus and facility development.

Hospital Design and Construction↗

Normal fertilization occurs with eggs lacking the integrin alpha6beta1 and is CD9-dependent.

Previous results, based on inhibition of fertilization by an anti-alpha6 integrin mAb (GoH3), suggest that the alpha6beta1 integrin on mouse eggs functions as the receptor for sperm (Almeida, E.A., A.P. Huovila, A.E. Sutherland, L.E. Stephens, P.G. Calarco, L. M. Shaw, A.M. Mercurio, A. Sonnenberg, P. Primakoff, D.G. Myles, and J.M. White. 1995. Cell. 81:1095-1104). Because the egg surface tetraspanin CD9 is essential for gamete fusion (Kaji, K., S. Oda, T. Shikano, T. Ohnuki, Y. Uematsu, J. Sakagami, N. Tada, S. Miyazaki, and A. Kudo. 2000. Nat. Genet. 24:279-282; Le Naour, F., E. Rubinstein, C. Jasmin, M. Prenant, and C. Boucheix. 2000. Science. 287:319-321; Miyado, K., G. Yamada, S. Yamada, H. Hasuwa, Y. Nakamura, F. Ryu, K. Suzuki, K. Kosai, K. Inoue, A. Ogura, M. Okabe, and E. Mekada. 2000. Science. 287:321-324) and CD9 is known to associate with integrins, recent models of gamete fusion have posited that egg CD9 acts in association with alpha6beta1 in fusion (Chen, M.S., K.S. Tung, S.A. Coonrod, Y. Takahashi, D. Bigler, A. Chang, Y. Yamashita, P.W. Kincade, J.C. Herr, and J.M. White. 1999. Proc. Natl. Acad. Sci. USA. 96:11830-11835; Kaji, K., S. Oda, T. Shikano, T. Ohnuki, Y. Uematsu, J. Sakagami, N. Tada, S. Miyazaki, and A. Kudo. 2000. Nat. Genet. 24:279-282; Le Naour, F., E. Rubinstein, C. Jasmin, M. Prenant, and C. Boucheix. 2000. Science. 287:319-321; Miyado, K., G. Yamada, S. Yamada, H. Hasuwa, Y. Nakamura, F. Ryu, K. Su- zuki, K. Kosai, K. Inoue, A. Ogura, M. Okabe, and E. Mekada. 2000. Science. 287:321-324). Using eggs from cultured ovaries of mice lacking the alpha6 integrin subunit, we found that the fertilization rate, fertilization index, and sperm binding were not impaired compared with wild-type or heterozygous controls. Furthermore, a reexamination of antibody inhibition, using an assay that better simulates in vivo fertilization conditions, revealed no inhibition of fusion by the GoH3 mAb. We also found that an anti-CD9 mAb completely blocks sperm fusion with either wild-type eggs or eggs lacking alpha6beta1. Based on these results, we conclude that the alpha6beta1 integrin is not essential for sperm-egg fusion, and we suggest a new model in which CD9 acts by itself, or interacts with egg protein(s) other than alpha6beta1, to function in sperm-egg fusion.

Animals↗

Metastatic pancreatic adenocarcinoma to the heart diagnosed antemortem.

Pancreatic tumors frequently metastasize widely, though it is rare to diagnose pancreatic cardiac metastases in the antemortem state. We report an unusual case of metastatic pancreatic adenocarcinoma to the right atrium. Transesophageal echocardiography showed that the tumor was attached to the superior aspect of the right atrium, prolapsing through and obstructing the tricuspid valve in diastole and retracting back into the right atrium during systole. The tumor was excised, and histologic examination confirmed the presence of moderately differentiated adenocarcinoma with a papillary architectural pattern and with desmoplastic stroma, features comparable to the original primary pancreatic neoplasm.

Adenocarcinoma↗

Cut or paste? The use of glyceryl trinitrate paste in the treatment of acute and chronic anal fissure.

BACKGROUND: Anal fissure unresponsive to conservative measures such as stool softeners frequently requires surgical intervention. The present study describes the use of glyceryl trinitrate (GTN) in the treatment of acute and chronic anal fissure. METHODS: Eighteen consecutive patients with anal fissure were treated with 0.5% GTN paste in soft white paraffin applied twice daily to the anus. These patients were followed at regular intervals to assess symptom control, rate of healing, adverse effects and recurrence rate. RESULTS: Two patients were lost to follow-up. Twelve of the remaining 16 were cured. Of these, symptomatic relief was obtained for most within 2 days, and for all within 1 week. No patient required cessation of treatment due to adverse effects. Treatment failed in four of 16 patients. Two of these patients subsequently underwent successful surgical procedures, and two patients (while not completely cured) had sufficient symptomatic relief to decide against surgery. CONCLUSIONS: The use of GTN paste in the treatment of acute and chronic anal fissure may be a safe and effective modality that can be considered as first-line treatment for this condition.

Acute Disease↗

Uracil misincorporation, DNA strand breaks, and gene amplification are associated with tumorigenic cell transformation in folate deficient/repleted Chinese hamster ovary cells.

Clinical and experimental evidence has linked nutritional folic acid status to both anti- and procarcinogenic activity. Folate supplementation of normal cells appears to have a protective effect; however, folate supplementation of initiated cells may promote neoplastic progression. Given these considerations, the present series of experiments examines alterations in DNA metabolism and cumulative DNA lesions using an in vitro model of folate deprivation and repletion. DNA repair-deficient CHO-UV5 cells were cultured in Ham's F-12 medium or in custom-prepared Ham's F-12 medium lacking in folic acid, thymidine and hypoxanthine for a period of 18 days without cell passage. The results indicated that progressive folate and nucleotide depletion leads to a significant increase in the ratio of dUTP/dTTP and to the misincorporation of uracil into DNA. These alterations were accompanied by growth inhibition, DNA strand breaks, abasic sites and phenotypic abnormalities. After 14 days in culture, there was significant increase in gene amplification potential in the chronically folate-deficient cells, but no significant increase in anchorage-independent growth or in neoplastic transformation. Acute folate repletion of the deficient cells was used as a proliferative stimulus under conditions of dNTP pool imbalance and multiple lesions in DNA. A further increase in gene amplification was accompanied by anchorage-independent growth and neoplastic cell transformation as evidenced by aggressive tumor growth in Balb/c nu/nu mice. Using a sensitive in vitro model system, these results emphasize the essentiality of folic acid for de novo nucleotide synthesis and the integrity of the DNA. However, the in vivo relevance, especially in terms of tumorigenic potential, is not clear.

Animals↗

The John Graham Extrication Prize: its history and importance.

UNLABELLED: Management of Severe Trauma Coursersef Severe Trauma (EMST) course is unique in providing instructive exposure to techniques used in the extrication of severely injured victims from difficult locations using a role play method. Dr John C. Graham FRACS, vascular surgeon in Lismore, was responsible for the initiation of this concept in 1989. Since this component of the trauma course is not used in the Advanced Trauma Life Support (ATLS) course in the USA, from which the EMST course was derived, the purpose of the present study is to determine the opinions of all EMST course directors as to the value of including an extrication scenario station in the EMST course in its current form in Australia and New Zealand. METHODS: The extrication station as devised by John Graham consists of four 40 min scenarios offered to all 16 participants of an EMST course in groups of four. The participants are required to extricate a moulaged victim from a difficult location within the time available in the most skilful and expeditious manner. A prize is offered for the group performing the task best. A survey of the 45 EMST course directors was undertaken by questionnaire. Replies were anonymous. RESULTS: There was a good response rate of 87%. Ninety-two per cent of responding directors routinely used an extrication station. Two directors used the station occasionally and only one director never used it. The most frequently cited reason for use was that the participants come to appreciate commonly encountered problems in extrication, and how EMST principles are applied in the field. Second, the station allows the use of teamwork. Third, it adds entertainment to the course overall. There was a prize awarded by every course director for the winning group of participants. Ninety per cent of these prizes were named the 'John Graham Extrication Prize'. CONCLUSIONS: The extrication station is considered constructive by the great majority of EMST directors. Both historical and competitive aspects are important since most directors still award a named prize for this station. The extrication station promotes a feeling of cohesion among Faculty and participants on an EMST course. The station is a memorable event for many participants and should be retained as a uniquely Australasian contribution to the course.

Australia↗

Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women.

To determine the human folate requirement on the basis of changes in biochemical pathways, we studied the effect of controlled folate intakes on plasma homocysteine and lymphocyte DNA methylation and deoxynucleotide content in healthy postmenopausal women. Eight women (49-63 y of age) were housed in a metabolic unit and fed a low folate diet containing 56 microg/d of folate for 91 d. Folate intake was varied by supplementing 55-460 microg/d of folic acid (pteroylglutamic acid) to the diet to provide total folate intake periods of 5 wk at 56 microg/d, 4 wk at 111 microg/d and 3 wk at 286-516 microg/d. A subclinical folate deficiency with decreased plasma folate was created during the first two periods. This resulted in significantly elevated plasma homocysteine and urinary malondialdehyde, and lymphocyte DNA hypomethylation. The folate depletion also resulted in an increased ratio of dUTP/dTTP in mitogen-stimulated lymphocyte DNA and decreased lymphocyte NAD, changes suggesting misincorporation of uracil into DNA and increased DNA repair activity. The DNA hypomethylation was reversed with 286-516 microg/d of folate repletion, whereas the elevated homocysteine decreased with 516 but not 286 microg/d of folate. The results indicate that marginal folate deficiency may alter DNA composition and that the current RDA of 180 microg/d may not be sufficient to maintain low plasma homocysteine concentrations of some postmenopausal women.

Creatinine↗

Diagnostic failure in colonoscopies for malignant disease.

BACKGROUND: While colonoscopy has become established as more accurate than double contrast barium enema for detecting colonic polyps and cancers, as well as offering the opportunity for therapy, there are occasional instances where colonoscopy is misleading. The present study is to determine what problems occur, with a view to finding a solution. METHODS: The records of the Colorectal Project at the Princess Alexandra Hospital indicate retrospectively that 346 patients have been correctly diagnosed with cancer of the colon and rectum by colonoscopy in the 5 years up to October 1996. During the same time eight patients (2.3%) were recorded at the same hospital as being misdiagnosed by colonoscopy, the lesion being either missed completely or misplaced. RESULTS: In five of these patients there was failure to recognize that the whole colon had not been examined endoscopically, thereby missing a more proximal lesion. In two patients the lesion was missed although the entire colon was examined. In one patient the lesion was discovered but inaccurately sited. Six of these mistakes would have been obviated by the routine use of fluoroscopy to confirm the totality of the colonoscopy and to site any lesions found. The other two cases occurred because of failure to remember that colonic examination during withdrawal should be performed meticulously back as far as the anal canal. Failure to diagnose a colon cancer on the initial colonoscopy led to an average delay of 6 months for definitive care. CONCLUSIONS: It is recommended that fluoroscopy be used routinely during colonoscopy to site accurately any lesions found, and to confirm the completeness of insertion if reliable landmarks, including terminal ileum, are not clearly identified.

Aged↗

Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi's sarcoma: results of a randomized phase III clinical trial.

PURPOSE: Kaposi's sarcoma (KS), the most common neoplasm in patients with AIDS, is a significant clinical problem for which current therapies are frequently unsatisfactory. We conducted a randomized phase III clinical trial to compare the efficacy and toxicities of a new form of therapy, pegylated-liposomal doxorubicin, with standard combination chemotherapy in patients with advanced AIDS-related KS (AIDS-KS). PATIENTS AND METHODS: Two hundred fifty-eight patients with advanced AIDS-KS were randomly assigned to receive either pegylated-liposomal doxorubicin (20 mg/m2) or the combination of doxorubicin (20 mg/m2), bleomycin (10 mg/m2) and vincristine (1 mg) (ABV) every 14 days for six cycles. Standard response criteria, toxicity criteria, and predefined indicators of clinical benefit were examined to evaluate outcomes. RESULTS: Among 133 patients randomized to receive pegylated-liposomal doxorubicin, one achieved a complete clinical response and 60 achieved a partial response for an overall response rate of 45.9% (95% confidence interval [CI], 37% to 54%). Among 125 patients randomized to receive ABV, 31 achieved a partial response (24.8%; 95% confidence interval [CI], 17% to 32%). This difference was statistically significant (P < .001). In addition to objective responses, prospectively defined clinical benefits and toxicity outcomes also favored pegylated-liposomal doxorubicin. CONCLUSION: Pegylated-liposomal doxorubicin is more effective and less toxic than the standard combination chemotherapy regimen ABV for treatment of AIDS-KS.

Acquired Immunodeficiency Syndrome↗