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Biomedical subjects

M L Turner

Publications and source records attributed to M L Turner.

At least 37 records · Page 2Linked to original sources
PubMed2001

Fetomaternal alloimmune thrombocytopenia.

Thrombocytopenia is the second commonest haematological abnormality in the neonatal period after anaemia due to iatrogenic blood letting. One to four percent of all newborn babies have a platelet count < 150 x 10(9)/l at birth and approximately 20-40% of neonates in intensive care units are affected by neonatal thrombocytopenia. The most common cause of severe neonatal thrombocytopenia is fetomaternal platelet incompatibility and subsequent alloimmunisation. During the last decade recent advances in molecular techniques have led to rapid and efficient methods for diagnosis. Progress in fetal medicine has enabled accurate determination of fetal status, allowing improvements in fetal diagnosis and therapy. Human platelet antigen (HPA)-1a is by far the most frequently involved platelet antigen system in Caucasians accounting for 90% of cases, followed at a much lower frequency by HPA-5b (5-15%) and HPA-3a. The incidence is estimated to be 1 per 2000 to 1 per 5000 live births, but this is low in comparison to the incidence of fetomaternal platelet antigen incompatibility especially for the HPA-1 alloantigen system in the Caucasian population in whom the estimated frequency of HPA-1b1b individuals is 2%. Retrospective and prospective studies have reported that the immunogenetic background is important, and the chance of HPA-1a alloimmunisation is strongly associated with maternal HLA class II DRB3*0101 (DR52a) type. A significant association (p = 0.004) between severe thrombocytopenia and a third trimester antiHPA titre >1:32 has been observed. It is now possible to genotype the fetus or neonate and the parents, which provides confirmation as to which HPA systems are incompatible between the mother and father. Simultaneous genotyping of HPA-1, 2, 3 and 5 can be carried out using the polymerase chain reaction-sequence specific primers (PCR-SSP) protocol, which has been widely used for HLA class II determination. The platelet count may continue to fall during the first 48 h after birth and the risk of intracranial bleeding is highest during this period. The best option is transfusion of specially selected antigen negative compatible donor platelets or if unavailable, maternal washed platelets. Antenatal screening for the most common form of fetomaternal alloimmune thrombocytopenia (FMAIT), due to antiHPA-1a is under consideration, but there is no established method at present. The Scottish National Blood Transfusion Service started a study in August 1999 on 25,000 pregnancies to carry out a cost benefit analysis of routine antenatal screening. The aims of the study are to determine the frequency of HPA-1b homozygosity; monitor antibody titres during pregnancy and confirm correlation of antibody emergence with HLA-DRB3*0101, and finally to access cost effectiveness of routine screening across Scotland. Of 26,509 women screened in three Scottish regions 501 (1.9%) are HPA-1b homozygous and about 9%, of the consented women are antibody positive.

Adult↗
PubMed2001

Variant Creutzfeldt-Jakob disease and blood transfusion.

Variant Creutzfeldt-Jakob disease (vCJD) was first described in the United Kingdom in 1996 and is thought to have been transmitted from cattle infected with bovine spongiform encephalopathy probably via the food chain. Thus far just over 100 definite or probable clinical cases have been described, though the number of people currently infected and the eventual size and geographic distribution of any future clinical epidemic remain uncertain. There is little evidence that sporadic CJD is transmitted by blood transfusion. However, the same cannot necessarily be assumed to apply to the new variant strain of disease in which involvement of peripheral lymphoid tissues has been demonstrated. In the face of uncertainty surrounding the risk of transmission of vCJD by blood products, blood transfusion services in a number of countries have implemented precautionary policies, though whether in the long term these will prove to have been necessary or sufficient remains to be seen.

Animals↗
PubMed2001

Drug-induced lupus associated with COL-3: report of 3 cases.

BACKGROUND: Anti-angiogenesis is an exciting new approach to anticancer therapy. COL-3, a tetracycline derivative, is a novel anti-angiogenesis agent with potent preclinical anticancer activity. During the conduct of a phase 1 clinical trial for refractory metastatic cancer at the National Institutes of Health, we observed 3 individuals who developed phototoxicity followed by clinical and laboratory features of drug-induced lupus. OBSERVATIONS: Three of 35 patients treated with COL-3 developed sunburnlike eruptions accompanied by fever and a positive antinuclear antibody titer within 8 to 29 days of starting treatment. Two of 3 had positive antihistone antibody levels and arthralgia. One patient had marked systemic manifestations including pulmonary infiltrates and elevated erythrocyte sedimentation rate remittent for more than 1 year after discontinuing COL-3 treatment. The other 2 patients' symptoms and rash abated within 2 weeks of discontinuing therapy although the serologic markers remained abnormal for the duration of follow-up. CONCLUSIONS: COL-3 is the second tetracycline derivative to be implicated in the development of drug-induced lupus. A sunburnlike eruption immediately preceded or accompanied the systemic and serologic changes in these 3 patients. The rapid onset and the phototoxic appearance of the accompanying eruptions might suggest that damage to the keratinocytes caused the formation of neoantigens to which autoantibodies formed.

Administration, Topical↗
PubMed2000

gamma delta T-cell lymphoma of the skin: a clinical, microscopic, and molecular study.

BACKGROUND: Only a few cases of primary gamma delta cutaneous T-cell lymphoma (CTCL) have been reported. We encountered 3 cases of this rare condition. OBJECTIVES: To characterize gamma delta CTCL by clinical, microscopic, and molecular methods and to investigate the role of Epstein-Barr virus (EBV) infection in its pathogenesis. DESIGN: Patients were evaluated by clinical examination, and biopsy specimens of lesional skin were examined by light microscopy and immunohistochemistry. Polymerase chain reaction amplification for T-cell receptor gamma gene rearrangements and in situ hybridization for EBV were performed on 3 biopsy specimens. SETTING: National Institutes of Health, a tertiary referral center. PATIENTS: Individuals with a clinical and histologic diagnosis of primary gamma delta CTCL. OUTCOME MEASURES: Clinical, light microscopic, and immunohistochemical features, and the presence of T-cell rearrangement and EBV RNA in biopsy specimens. RESULTS: Patients exhibited multiple plaques, tumors, and/or subcutaneous nodules primarily distributed over the extremities. Individuals exhibited an aggressive clinical course with resistance to multiagent chemotherapy and radiation. Microscopic examination revealed epidermotropism in 2 cases, a dermal infiltrate in all 3 cases, and subcutaneous involvement in 1 case. Immunohistochemical studies showed the presence of CD3(+)TCR delta(+) in 3 patients, CD8(+)in 1, and CD4(+), CD20(+), CD56(+), and beta F1(+) in none. All 3 cases exhibited an activated cytotoxic T-cell phenotype positive for T-cell intracellular antigen 1, perforin, and granzyme B. A clonal T-cell receptor gamma chain gene rearrangement was detected in all 3 cases by polymerase chain reaction. In situ hybridization was negative for EBV sequences in all 3 cases. CONCLUSION: gamma delta Cutaneous T-cell lymphomas are EBV-negative lymphomas that express a mature cytotoxic phenotype and have an aggressive clinical behavior. Arch Dermatol. 2000;136:1024-1032

Aged↗
PubMed2000

Plasma exchange as successful treatment of thrombotic thrombocytopenic purpura post autologous bone marrow transplant in a child.

We describe the case of a small child with stage IV neuroblastoma who developed thrombotic thromobocytopenic purpura (TTP) post autologous bone marrow transplant. Pneumococcal sepsis may have been the cause, a previously unreported association in transplant-associated TTP. Despite the child's size (10 kg) and the severity of the disease early intensive treatment with whole blood exchange and subsequently plasma exchange with cryosupernatant proved to be rapidly effective, in contrast to previous reports on its ineffectiveness in this setting.

Body Weight↗
PubMed2000

Quality assurance by a commercial flow cytometry method of leucodepletion of whole blood donations: initial application of universal testing and proposals for a batch-release sampling plan.

We have used the Becton-Dickinson LeucoCOUNT test to monitor residual leucocytes in whole blood by flow cytometry following leucodepletion filtration. This test was found to be quick, robust and reliable, and allowed measurement of residual leucocytes down to 2.25 x 104 leucocytes per unit, which was found to match approximately the limit of filter proficiency. The results of testing > 1000 units showed a lognormal distribution with means between log(10) 4.864 (0.73 x 105) and log(10) 5.016 (1.04 x 105) leucocytes per unit in the three different homogeneous groups of filtered units studied. The numbers of units with residual leucocytes exceeding the 5 x 106 upper threshold were 1/577, 2/457 and 0/87 in these groups. The filtration processes were validated according to the published BEST working party guidelines and were well within the 99% confidence and 95% tolerance target for the 5 x 106 upper threshold set for the UK. A sampling plan based on British Standard BS 6001 with elimination of outliers by the extreme studentized deviate (Grubbs' test) was evaluated on random samples from these groups and has been adopted locally as a prospective batch-release criterion for release of leucodepleted blood.

Blood Donors↗
PubMed2000

Leucocyte depletion of blood components.

Universal leucocyte depletion has been implemented in the UK and several other European countries as a precautionary measure against the potential risk of transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Leucocyte depletion had previously only been recommended for a relatively small proportion of transfusion recipients based on clinical and experimental evidence showing clinical benefit. However there is now increasing evidence to support its value in preventing transfusion transmission of infectious agents and in reducing some of the adverse immunomodulatory effects of allogeneic transfusion. The financial costs of providing universal leucocyte depletion are substantial, but, if it transpires that leucocyte depletion has a beneficial effect in reducing, for example, postoperative infection rates, then the health economic gains in this patient group alone may largely or wholly offset these financial costs. The experience in the UK and other European countries in terms of these collateral clinical benefits will help other countries, where the risk of variant Creutzfeldt-Jakob disease may not be so great, to decide whether to similarly adopt universal leucocyte depletion.

Erythrocyte Transfusion↗
PubMed2000

Widespread cutaneous vascular papules associated with peripheral blood eosinophilia and prominent inguinal lymphadenopathy.

A new section entitled "Dermatology Grand Rounds at the NIH" appears this month. The idea behind it is to provide a unique look at instructive dermatologic cases being presented at the weekly Dermatology Branch Grand Rounds at the National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland. Patients seen at the NIH Clinical Center (which includes the NIH inpatient wards and outpatient clinics) are indeed unusual. To be evaluated here, they must be referred by an outside physician and must be placed in a research protocol. In other words, by this criterion, all NIH patients are considered research subjects. The diseases studied at the NIH range from the common to the obscure. Similarly, the dermatologic manifestations of these diseases are equally as diverse. Thus the purpose of this new section is to share some of these fascinating cases with the dermatologic community at large, as well as to provide a glimpse of exciting translational research that has relevance to clinical dermatologists. The format will be simple. Cases will be presented as unknowns, including relevant results from the history, physical examination, and histopathologic analyses. This will be done to challenge the clinicopathologic skills of the readers; authors will make every attempt to make the color clinical and pathologic photographs of the highest quality possible to assist readers in making the correct diagnoses. The discussion will be brief, focusing on the key teaching points of each case. These teaching points will vary from cases to case, covering clinical and histologic information, treatment issues, and/or novel laboratory advances with clinical relevance. Authors will emphasize brevity and clarity in all subsections of the case report, which I hope will promote a good learning experience for dermatology residents and busy practitioners alike. This section will initially be published 4 times annually. Finally, because the section is new to the JAAD, I welcome comments and suggestions to improve the quality of the articles.-Andrew Blauvelt, MD Feature Editor

Aged↗
PubMed2000

Gene transfer to primary acute myeloid leukaemia blasts and myeloid leukaemia cell lines.

The transfer of genes encoding co-stimulatory molecules and/or cytokines to leukaemia cells in order to create autologous tumour vaccines represents a potential immunotherapeutic strategy for treating acute myeloid leukaemia (AML). One of the essential requirements for this strategy if it is to be applicable in a clinical setting is a high efficiency of gene transfer to primary human AML blasts. Using green fluorescent protein (GFP) as a reporter gene, we have systematically evaluated a variety of physical, chemical and viral vector-based gene transfection systems in order to determine which gave the highest gene transfer efficiency to myeloid leukaemia cell lines and primary AML blasts. Transfection efficiency was low for all the physical and chemical transfection methods tested. Retroviral vector-based infection gave a high efficiency of gene transduction in two of the four leukaemia cell lines (KG1a and U937), but was low in primary AML blasts. An adenoviral vector gave a high transduction efficiency in all of the leukaemia cell lines with the exception of the HL60. In primary AML blasts, derived from 19 patients, gene transduction efficiency was variable, ranging from 1.1% to 67.1% (mean 12.1%). Following culture in cytokines GM-CSF/IL-4/CD40L, which induced differentiation of AML blasts to dendritic-like cells, transduction efficiency was increased between two- and eightfold in 6 out of the 15 cases that underwent differentiation.

Adenoviridae↗
PubMed2000

Microcystic adnexal carcinoma associated with primary immunodeficiency, recurrent diffuse herpes simplex virus infection, and cutaneous T-cell lymphoma.

Cutaneous microcystic adnexal carcinoma (MAC) is a rare and poorly understood tumor that predominantly occurs in the head and neck. MAC usually affects people in their fourth and fifth decades. Some patients have had a history of radiation. We present a case of MAC occurring in the left antecubital fossa of an 18-year-old white woman with an unusual immunodeficiency syndrome. The patient also developed a squamous cell carcinoma, a cutaneous T-cell malignancy, and a perigastric leiomyoma. A congenital infection of herpes simplex virus (HSV) persisted throughout her life. The association of HSV infection with MAC and squamous cell carcinoma and that of peripheral T-cell lymphoma with Epstein-Barr virus is discussed in relation to her immunodeficiency.

Adolescent↗
PubMed1999

Birt-Hogg-Dubé syndrome: a novel marker of kidney neoplasia.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is a dominantly inherited predisposition for development of fibrofolliculomas, trichodiscomas, and acrochordons. Concurrent internal tumors, such as colonic polyps and renal carcinoma, have been described in patients with BHD. OBJECTIVE: To evaluate kindreds with familial renal tumors for cutaneous manifestations of BHD. DESIGN: One hundred fifty-two patients from 49 families underwent complete oral and skin examination. Skin lesions were identified by their clinical appearance, and the diagnosis was confirmed by results of histologic examination. Individuals underwent screening for familial renal neoplasms. SETTING: A tertiary referral research hospital. PATIENTS: Individuals with familial renal tumors and their asymptomatic at-risk relatives. MAIN OUTCOME MEASURE: We determined whether any form of renal cancer is associated BHD. RESULTS: We identified 3 extended kindreds in whom renal neoplasms and BHD appeared to segregate together. Two kindreds had renal oncocytomas and a third had a variant of papillary renal cell carcinoma. Thirteen patients exhibited BHD. Seven individuals, including a set of identical twins, had renal neoplasms and BHD. An additional 4 patients (3 deceased and not examined) in these families had renal neoplasms but not BHD. Birt-Hogg-Dubé syndrome without renal neoplasms was present in 6 individuals. Thirteen patients with fibrofolliculomas and trichodiscomas presented clinically with multiple smooth skin-colored to grayish-white papules located on the face, auricles, neck, and upper trunk. Oral papules were present in 9 of 28 and achrochordons in 11 of 28 patients. Features of BHD not previously appreciated included deforming lipomas in 5, collagenomas in 4, and pulmonary cysts in 4 of 28 patients. Families with BHD did not display germline mutations in the von Hippel-Lindau gene or in the tyrosine kinase domain of the MET proto-oncogene. CONCLUSIONS: Birt-Hogg-Dubé syndrome may be associated with familial renal tumors. Birt-Hogg-Dubé and renal tumors segregate together in an autosomal dominant fashion. Patients with BHD and their relatives are at risk for development of renal tumors. Therefore, patients with BHD and their relatives should undergo abdominal computed tomography and renal ultrasound screening for renal tumors.

Adult↗