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Biomedical subjects

D Lockwood

Publications and source records attributed to D Lockwood.

At least 19 recordsLinked to original sources

Clinical features and diagnosis of 42 travellers with cutaneous leishmaniasis.

BACKGROUND: Leishmania species that occur within different geographical areas may cause different clinical manifestations, virulence and drug sensitivity. Patients/Methods. All patients with a clinical diagnosis of cutaneous leishmaniasis seen at the Hospital for Tropical Diseases from 1997 to 2000 were identified and clinical details recorded onto a database, with emphasis on clinical presentation, risk factors, travel history and laboratory diagnosis. RESULTS: Forty-two patients were identified, 23 of whom had travelled to New World and 19 to Old World countries. Clinical presentation typically consisted of a single nodule with ulceration. In 50% infection was caused by L. (Viannia) braziliensis. PCR was performed in specimens from 34 patients and species identification was possible in 32 cases (sensitivity 94%), the two PCR negative patients had amastigotes demonstrated by histology and culture. Patients were treated with established therapies. Seventy one percent were cured by treatment, 12% had a spontaneous cure, 7% were lost to follow-up and the remaining 10% required a second-line therapy. No relapses were reported during a mean follow-up period of 27 months. CONCLUSIONS: Our study highlights the need for comprehensive investigations and the advantages of PCR in the diagnosis of patients with suspected leishmaniasis in non-endemic regions of the world.

Adolescent↗

The public health response to a case of Lassa fever in London in 2000.

OBJECTIVES: Evaluation of the Department of Health 1996 guidance, the Memorandum on the Management and Control of Viral Haemorrhagic Fevers. METHODS: Description of the public health management in 2000 of the fifth UK patient confirmed to have Lassa fever. RESULTS: Delayed risk categorisation of the patient occurred for a variety of reasons. DH Guidance was followed once infection control advice was sought. Active surveillance of 125 contacts was extremely resource intense, involving over 3000 communications. Self-monitoring by healthcare workers should be considered in future. Advice on use of ribavirin prophylaxis is not included in the Memorandum, nor advice or templates for information sheets for contacts. Information sheets are now available from the Health Protection Agency in the event of future cases. International aspects not adequately addressed include the need for reliable risk assessment to be carried out before patients are medically evacuated from the country of origin, and the steps required to repatriate UK nationals. Effective and efficient communication is required between national and international organisations involved in such incidents. CONCLUSIONS: If guidelines are unclear or impracticable they will not be followed. It is important that lessons are learned and documented and that national guidance be regularly reviewed.

Communicable Disease Control↗

Angiotensinogen genotype, plasma protein and mRNA concentration in isolated systolic hypertension.

Isolated systolic hypertension (ISH) occurs predominantly in the elderly, with a considerable morbidity and mortality. Its etiology is unknown but is likely to involve a significant genetic component. The aim of this study was to examine the angiotensinogen gene in ISH. The M235T and G(- 6)A polymorphisms were genotyped by polymerase chain reaction (PCR) in 86 ISH patients and 120 normotensive controls. Plasma angiotensinogen concentration was determined in 198 subjects by an indirect radioimmunoassay technique. Angiotensinogen mRNA concentration was determined by quantitative competitive reverse transcription (RT)-PCR in subcutaneous adipose tissue from a subset of these patients (n = 8) and controls (n = 6). Both the M235T (p = 0.0015) and G(- 6)A (p = 0.029) polymorphisms were associated with ISH. Plasma angiotensinogen concentration was higher in patients than controls (p < 0.0001), but was not associated with genotype. Angiotensinogen mRNA concentration in adipose tissue from ISH subjects was significantly lower than in adipose tissue from normotensive subjects (p = 0.033). The association of angiotensinogen gene variants with ISH and the elevation of plasma angiotensinogen concentration in these patients suggests a role of the angiotensinogen gene in this form of hypertension. Angiotensinogen gene expression may be altered in ISH, but this requires further examination.

Aged↗

Prenatal diagnosis from cystic hygroma fluid: the value of fluorescence in situ hybridization.

OBJECTIVE: We sought to determine the optimal approach to the prenatal chromosome analysis of cystic hygroma fluid using traditional cytogenetic analysis and fluorescence in situ hybridization. STUDY DESIGN: A retrospective evaluation of our experience with traditional cytogenetic and fluorescence in situ hybridization analysis on cystic hygroma fluid was performed through a systematic review of the Genzyme Genetics database from January 1995 to July 2000. Information on gestational age, sample volume, clinical ultrasound findings (including fetal viability), cytogenetic results, fluorescence in situ hybridization results, and turn-around-time were queried. RESULTS: Eighty-three specimens were included in the investigation. The mean gestational age was 18.1 weeks (range, 13-27 weeks), and the mean sample volume was 20.7 mL (range, 0.1-101 mL). Of the 72 samples in which > 5 mL of cystic hygroma fluid was available, the success rate for cytogenetic analysis was 76% (55/72 samples). In 11 specimens of < or = 5 mL of cystic hygroma fluid, cytogenetic analysis was successful in only 1 case (9%). Fluorescence in situ hybridization was attempted on 23 samples, 18 of which were successful (78%), including 6 of 9 cases of cell culture failure (67%). Both traditional cytogenetic analysis and fluorescence in situ hybridization were performed in 21 instances when a sample of > 5 mL was available. A successful result was obtained by either cytogenetic testing or fluorescence in situ hybridization analysis or both in 19 of 21 of these cases (90%). Samples of > 5 mL from viable fetuses had a higher cytogenetic success rate (80%) and fluorescence in situ hybridization success rate (89%) than samples from fetuses with intrauterine death (38% and 50% cytogenetic and fluorescence in situ hybridization success rates, respectively.) The mean turn-around time was 8.2 days (range, 4-17 days). Results were available in < or = 12 days in 91% of cases. There was a 91% aneuploidy rate identified, with 45,X occurring in 86% of the samples. CONCLUSION: We conclude that the optimal approach for the prenatal diagnosis of chromosome abnormalities from cystic hygroma samples is to perform both traditional cytogenetic studies and interphase prenatal fluorescence in situ hybridization evaluation for the most common aneuploidies that involve chromosomes 13, 18, 21, X, and Y. With this combined approach, our data indicate that, in viable pregnancies with a fluid sample of >5 mL, a 90% diagnostic success rate can be achieved.

Congenital Abnormalities↗

A new enzyme immunoassay for soluble fibrin in plasma, with a high discriminating power for thrombotic disorders.

Fibrin formation is a multistep process initiated by thrombin. At first thrombin converts fibrinogen to fibrin molecules which in vivo form soluble complexes with fibrinogen. Soluble fibrin is considered to be an early biochemical marker for intravascular fibrin formation and impending thrombotic events, such as deep venous thrombosis (DVT), pulmonary embolism (PE) and disseminated intravascular coagulopathy (DIC). A new enzyme immunoassay (EIA) was developed on the basis of a monoclonal antibody directed against a fibrin specific neo-epitope located on the gamma-chain of fibrinogen; gamma-(312-324). In addition, it was possible to prepare a lyophilized reference material of thrombin-generated soluble fibrin, that allowed for full antigen recovery after reconstitution with buffer. Assay conditions, e.g. solid phase-Ig concentration and buffer composition, sample and conjugate dilution, and incubation times were optimised. The present assay was found to be specific (no interference of homologous antigens) and reproducible (intra-assay CV 4-8%, interassay CV 4-9%), and therefore highly suited for measuring soluble fibrin levels in a plasma milieu. The median normal value for soluble fibrin was determined in plasma samples obtained from apparently healthy volunteers (n = 81) and found to be 0.040 microg/ml, with a range (10-90 percentiles) of 0.026-0.059 microg/ml. A retrospective study showed that soluble fibrin levels were highly significantly increased in patients with a confirmed diagnosis of DIC (median 1.042 microg FEU/ml, range 0.160-2.319 microg/ml, n = 21, P<0.0001 vs. normal). PE (median 0.527 microg FEU/ml, range 0.084-1.234 microg/ml, n = 29, P<0.0001 vs normal) and DVT (median 0.126 microg FEU/ml, range 0.059-0.878 microg/ml, n = 36, P<0.0001 vs. normal), as determined by the Mann-Whitney U-Test.

Fibrin↗

A hospital/school science fair mentoring program for middle school students.

The Massachusetts General Hospital (MGH) and the James P. Timilty Middle School established a partnership to enhance science education, promote faculty development, and improve the health status and academic performance of all Timilty students. This article describes one of the Partnership's Science Connection programs, the Science Fair Mentoring Program, designed to enhance middle school science education, inform urban early adolescents about professions in the health field, inspire them to pursue postsecondary study in the health sciences, and prepare them for rigorous academic work in high school. In this program, hospital-based clinical and research staff mentor young adolescent students. The authors describe the planning, implementation, and evaluation of the Science Fair Mentoring Program as an innovative learning experience.

Adolescent↗

Impaired glucose tolerance is normalized by treatment with the thiazolidinedione troglitazone.

OBJECTIVE: The primary purpose of this study was to assess the effects of 12 weeks of treatment with either troglitazone, an investigational thiazolidinedione that acts as an insulin-action enhancer, or placebo in patients with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A total of 51 subjects with IGT between 24 and 77 years of age were enrolled in this multicenter, double-blind, placebo-controlled, parallel group study (troglitazone, 25 patients; placebo, 26 patients). Patients were randomly assigned to receive either 400 mg troglitazone (every morning [QAM]) or placebo (QAM). The main outcome measure was the oral glucose tolerance test (OGTT) assessing glucose, insulin, and C-peptide levels in the fasting state and every 30 min up to 2 h after ingesting the glucose load. Fasting serum levels of HbA1c, fructosamine, lipids, and blood pressure were also measured. RESULTS: A total of 46 patients completed the study. The glucose, insulin, and C-peptide responses after a glucose load were significantly reduced at 6 and 12 weeks in the troglitazone treatment group. After 6 weeks of treatment, 75% (n = 18) of those taking troglitazone had improved to normal glucose tolerance, whereas only 38% (n = 9) of those of placebo showed improvement (P = 0.008). After 12 weeks of treatment, 80% (n = 16) of the troglitazone treatment group had normalized their glucose tolerance, while only 48% (n = 10) of those on placebo had converted to normal (P = 0.016). Fasting triglyceride levels in the troglitazone treatment group had decreased by 40 mg/dl (0.45 mmol/l) (P = 0.0016). Other lipid measurements, blood pressure, glycosylated hemoglobin, and fructosamine were normal at baseline for both treatment groups and remained normal throughout the study. CONCLUSIONS: The glycemic response after a glucose load is statistically and clinically significantly improved for patients with IGT treated with troglitazone.

Adult↗

The impact of healthcare trends on imaging products and services.

Key factors in healthcare reform--cost, access to care and quality of care--all have implications for diagnostic imaging. Technology is moving rapidly toward being able to provide images quickly, frequently in digital form to radiologists located in other departments or offsite. Film-based imaging still provides the highest resolution currently available and is the most appropriate option for many situations, such as mammography. Hybrid systems that combine film-based capture with electronic image storage and delivery have also been introduced for situations that require simultaneous review by remote clinicians. Healthcare systems will demand equipment that features open architecture and adheres to industry standards. Healthcare providers will form alliances with imaging equipment and consumable suppliers whose products and services offer advantages in quality, productivity and efficiency that lead to an overall decrease in costs.

Cost Control↗

Glycosylation of Asn397 or Asn418 is required for normal insulin receptor biosynthesis and processing.

Two N-linked sites of glycosylation in the insulin receptor were examined for their contribution to insulin binding, tyrosine kinase activity, and receptor biosynthesis. Asn397 and Asn418 were replaced by Gln using site-directed mutagenesis either as single mutations, i.e., Q-397 and Q-418, or as a double mutation in which both sites were removed (Q-D). The mutations were transiently expressed in COS cells and the findings compared with cells that transiently expressed the wild-type human insulin receptor. Q-397 and Q-418 mutant insulin receptors had insulin-binding characteristics similar to the wild-type human insulin receptor, whereas no insulin-binding activity could be detected above the control level in cells transfected with Q-D. Flow cytometry with antibodies against the human insulin receptor indicated the presence of Q-397, Q-418, and wild-type human insulin receptors in the surface of COS cells and failed to demonstrate a Q-D receptor. Insulin-induced autophosphorylation was similar in Q-397, Q-418, and wild-type human insulin receptors as was their ability to phosphorylate an artificial substrate, poly Glu-Tyr (4:1). Our inability to detect Q-D receptors was not caused by a lack of Q-D mRNA. COS cells transfected with Q-D cDNA generated as much Q-D mRNA as the amount of wild-type human insulin receptor mRNA present in cells transfected with wild-type receptor cDNA. Finally, pulse-chase experiments with [35S]Met were able to detect 190,000-M(r) proreceptors and the alpha-subunits for Q-397, Q-418, and wild-type human insulin receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Exchanging sex for crack-cocaine: a comparison of women from rural and urban communities.

Studies of the HIV risks of crack-cocaine using women have focused on those living in the inner city, urban areas of the country. However, reports indicate that the rates of syphilis and HIV infection have shown greater increases in rural areas than in urban ones. This paper reports the findings of a comparative study of 60 female crack-cocaine users, 25 from rural southeast Georgia and 35 from Miami, Florida, to determine their drug using and sexual practices, as well as their knowledge about AIDS and HIV transmission. Their patterns of initial and continuous drug use were similar, as were their sexual practices. However, the Miami women were more likely to have had a greater number of sexual partners than the Georgia women. Both groups were knowledgeable about AIDS and the transmission of HIV, yet all participated in activities that put them at high risk for HIV infection and transmission. Some 12 percent of the 60 respondents reported testing positive for HIV. The study suggests that at least within these populations, there are few differences between rural and urban crack using women in terms of their crack use, sexual practices, and potential for HIV infection and transmission.

Adolescent↗

The role of the family in psychiatric rehabilitation.

This article describes the multiple roles that families can play in the psychiatric rehabilitation process and suggests ways for professionals to collaborate with them. The authors discuss the family's experience of loss and their process of recovery; their caregiving role; their role in supporting other families; their teaching and educational role; their advocacy role; their role as researchers and research subjects; and some suggestions for supporting family roles.

Caregivers↗