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Biomedical subjects

D Matthews

Publications and source records attributed to D Matthews.

At least 37 records · Page 2Linked to original sources

Counterregulation during spontaneous nocturnal hypoglycemia in prepubertal children with type 1 diabetes.

OBJECTIVE: To examine counterregulatory responses during spontaneous nocturnal hypoglycemia in prepubertal children with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 29 prepubertal patients with type 1 diabetes underwent two overnight profiles. Data were analyzed from 16 children (median [range] 8.7 [5.9-12.9] years of age) with a night of hypoglycemia and a nonhypoglycemic night. Children hypoglycemic (< 3.5 mmol/l) on night 1 were given 25% extra carbohydrate as uncooked cornstarch with their usual evening snack on night 2 to avoid hypoglycemia. Glucose, growth hormone, and cortisol were measured every 15 min, catecholamines every 30 min, and glucagon, pancreatic polypeptide, insulin, and ketones every 60 min. A group of 15 healthy control subjects, aged 9.5 (5.6-12.1) years, underwent one overnight profile. RESULTS: Median duration of hypoglycemia was 225 (30-630) min, and glucose nadir was 2.0 (1.2-3.3) mmol/l. Insulin levels were not different on the two nights (P = 0.9, analysis of variance), but children with diabetes had higher insulin levels than normal control subjects between 2300 and 0300, maximal at 0200 (mean +/- SEM 57.4 +/- 5.7 vs. 31.6 +/- 5.0 pmol/l, P = 0.002). Peak epinephrine was higher on the night of hypoglycemia (0.98 [0.52-2.09] nmol/l) versus nonhypoglycemia (0.32 [0.21-0.62] nmol/l), P = 0.001, but norepinephrine (1.29 [1.07-2.64] vs. 1.26 [1.04-1.88] nmol/l, P = 0.5), glucagon (93 [64.2-125.6] vs. 100.5 [54.6-158] ng/l, P = 0.6), pancreatic polypeptide (410.2 [191-643.2] vs. 270.8 [158.2-777.8] ng/l, P = 0.5), and cortisol (513 [300-679] vs. 475 [235-739] nmol/l, P = 0.6) were not different. Glucose threshold for epinephrine release was very low, 1.9 +/- 0.2 mmol/l. There was a short-lived rise in growth hormone from 75-105 min after onset of hypoglycemia, maximal at 90 min (7.8 +/- 1.2 vs. 3.5 +/- 0.9 ng/ml, P = 0.02). CONCLUSIONS: The prolonged nature of nocturnal hypoglycemic episodes may be explained in part by defective counterregulation. The risk of nocturnal hypoglycemia needs to be reduced before intensification of insulin therapy can be contemplated in this age-group.

Blood Glucose↗

Survey of the Free and Conjugated Myricetin and Quercetin Content of Red Wines of Different Geographical Origins.

Gradient reversed-phase HPLC was used to obtain quantitative estimates of the levels of free and conjugated myricetin and quercetin in 65 red wines from Italy, Chile, France, California, Australia, Bulgaria, Spain, Romania, New Zealand, Brazil, Morocco, and Hungary. The concentrations of total flavonols ranged from 4.6 to 41.6 mg L(-1). High total flavonol levels appear to be associated with the use of thick-skinned grape varieties, such as Cabernet Sauvignon, with a high skin:volume ratio, which were left to ripen fully in sunny conditions before harvest and which were extracted efficiently by modern methods of vinification. Some Chilean Cabernet Sauvignon wines contained up to 40 mg of total flavonols L(-1), which was higher than the levels detected in Cabernet Sauvignon from France, California, and Australia. The flavonol content of 1989 and 1990 Cabernet Sauvignon from Bulgaria was <6 mg L(-1). Chilean Cabernet Sauvignon, Merlot, and Pinot Noir all contained consistently higher concentrations of flavonols than their counterparts from different geographical regions.

Journal Article↗

Area-wide diabetes care: the Lanarkshire experience with primary health care teams 1994-1997.

In Lanarkshire (population 560,000) an area-wide diabetes database was introduced and process of care was measured. The number of patients with diabetes identified was 11,621 (prevalence = 2.08). In 1997 50% of the diabetic population were reviewed at least once during the year. Compared to those attending hospital clinics, GP patients were significantly older, female and less likely to be on insulin. During 1994-1997 hospital clinics improved the process of care in nearly all areas, but GP patients were much less likely to have any of the process measures carried out. Initiatives are underway to support general practices, and to improve co-ordination between GP and hospital services.

Aging↗

Breakdowns on the path of chronic illness: opportunities for learning.

An unusual case of calciphylaxis, presenting at the onset of end-stage renal disease and evolving into an extended and arduous hospital stay, is described. The medical approach to this case is addressed briefly, but the main focus of this paper is to describe, in the words of various participants, the events and interactions that occurred and to learn from this description how our management of such cases breaks down. When confronted by difficult circumstances, it is common for us to react emotionally in ways that are automatic and based on our own personal histories and behavior patterns. Such automatic reactions prevent us from seeing and understanding what we really need to know about a given situation and leave us vulnerable to discouragement and internal suffering when clinical events do not go well (A. Nierenberg, personal communication, April 1998). The result is often exasperation with patients and families, as well as emotionally laden interactions that do not forward problem solving. In retrospect, the appearance of such breakdowns is not only predictable in the course of chronic illness, but offers us the opportunity to observe our automatic reactions, to re-evaluate our approach, and to redesign our actions. We have written this review, not to find error or blame, but rather to emphasize that we are learning to view these breakdowns as signals first to step back from our automatic reactions and then to listen and communicate clearly as a means to navigating the best pathway through difficult and discouraging clinical challenges.

Calciphylaxis↗

Pre-surgical CT/FEA for craniofacial distraction: I. Methodology, development, and validation of the cranial finite element model.

Recently, surgeons have begun to treat serious congenital craniofacial deformities including craniosynostoses with mechanical devices that gradually distract the skull. As a prospective means of treatment planning for such complex deformities, FE models derived from routine preoperative CT scans (CT/FEA) would provide ideal patient specific engineering analyses. The purpose of this study was to assess the dimensional and predictive accuracy of the CT/FEA process through the development of a 3D model of a dry human calvarium subjected to two-point distraction ex vivo. Comparative skull measurements revealed that CT/FEA construction error did not exceed 1% for transcranial dimensions, and the thickness error did not exceed 8.66% or 0.31 mm. CT/FEA strain predictions for the central region of the skull, between the distraction posts, were not statistically different from homologous gage values at P < 0.05. Peripherally, however, the strain fields were less well behaved and the FE predictions showed only general qualitative agreement with gage recordings.

Biomechanical Phenomena↗

Presurgical finite element analysis from routine computed tomography studies for craniofacial distraction: II. An engineering prediction model for gradual correction of asymmetric skull deformities.

Finite element analysis from routine computed tomography studies (CT/FEA) allows clinicians to predict the mechanical and anatomic consequences of specific distraction systems before human application. A realistic three-dimensional CT/FEA engineering model of an actual plagiocephalic infant with unicoronal synostosis was developed using 4215 parabolic triangular shell elements and intracranial pressure conditions ranging from 10 to 20 mmHg. The completed finite element analysis model was used to predict the anatomic outcome of multiaxial distraction delivered by hypothetical patterns of rod and node distraction units. The predictions for the various patterns of distraction units were also compared quantitatively with respect to force, stress, strain, and intracranial volume. Best anatomic corrections were achieved with bilateral patterns of distraction units that simultaneously elongated the ipsilateral cranium and shortened the contralateral cranium. Greatest strain levels were experienced within the osteotomy callus, greatest stress levels at the appliance anchorage sites, and the greatest rod force at the ipsilateral lower coronal position.

Biomechanical Phenomena↗

Pharmaceutical regulation in the single European market.

This paper assesses the impact of new EU-wide drug authorisation procedures. The paper examines various attempts to introduce harmonised market authorisation routes for pharmaceuticals including the establishment of the multi-state, concentration, decentralised and centralised procedures. The paper considers the current role of the European Medicines Evaluation Agency and the likelihood that its powers will be increased in the future. Finally, the paper assesses whether EU regulation has created beneficial market conditions for pharmaceutical companies operating in the single European market.

Drug Approval↗

Association of polymorphisms of dopamine D2 receptor (DRD2), and dopamine transporter (DAT1) genes with schizoid/avoidant behaviors (SAB).

The dopaminergic system, and in particular the dopamine D2 receptor, has been implicated in reward mechanisms in the brain. Dysfunction of the D2 dopamine receptors leads to aberrant substance-seeking behaviors (ethanol, drugs, tobacco, and food) and other related behaviors (pathological gambling, Tourette's disorder, attention-deficit/hyperactivity disorder). This is the first study supporting a strong association between the dopamine D2 receptor Taq A1 allele with schizoid/avoidant behavior (SAB). Additionally, an albeit weaker association between the 480-bp VNTR 10/10 allele of the dopamine transporter (DAT1) gene with SAB was similarly found.

Adult↗

Intraosseous lipoma of the calcaneus.

We present two patients with pathologically proven intraosseous lipoma of the os calcis. A review of the literature, the radiologic criteria, and the differential diagnosis are provided.

Adult↗

Comparative metabolism and retention of iodine-125, yttrium-90, and indium-111 radioimmunoconjugates by cancer cells.

Radiolabeled antibodies have produced encouraging remissions in patients with chemotherapy-resistant hematological malignancies; however, the selection of therapeutic radionuclides for clinical trials remains controversial. In this study, we compared the internalization, lysosomal targeting, metabolism, and cellular retention of radiolabeled murine and humanized monoclonal antibodies targeting the CD33 antigen (monoclonal antibodies mP67 and hP67, respectively) on myeloid leukemia cell lines (HEL and HL-60) and of anti-carcinoma antibodies (monoclonal antibodies hCTM01 and hA33) targeting breast cancer and colorectal carcinoma cell lines (MCF7 and Colo 205, respectively). Each antibody was labeled with 125I (by the IodoGen method) and with 111In and 90Y using macrocyclic chelation technology. Targeted tumor cells were analyzed for retention and metabolism of radioimmunoconjugates using cellular-radioimmunoassays, Percoll gradient fractionation of cell organelles, SDS-PAGE, and TLC of cell lysates and culture supernatants. Our results suggest that antibodies are routed to lysosomes after endocytosis, where they are proteolytically degraded. [125I]monoiodotyrosine is rapidly excreted from cells after lysosomal catabolism of antibodies radioiodinated by conventional methods, whereas small molecular weight 111In and 90Y catabolites remain trapped in lysosomes. As a consequence of the differential disposition of small molecular weight catabolites, 111In and 90Y conjugates displayed superior retention of radioactivity compared with 125I conjugates when tumor cells were targeted using rapidly internalizing antibody-antigen systems (e.g., hP67 with HEL cells and hCTM01 with MCF7 cells). When tumor cells were targeted using antibody-antigen systems exhibiting slow rates of endocytosis (e.g., hP67 on HL-60 cells and hA33 on Colo 205 cells), little differences in cellular retention of radioactivity was observed, regardless of whether 125I, 111In, or 90Y was used.

Antibodies, Monoclonal↗

Evidence that a locus for familial psoriasis maps to chromosome 4q.

Psoriasis is an inflammatory skin disease that affects 2% of the population. It is characterised by red, scaly skin patches which are usually found on the scalp, elbows and knees, and may be associated with severe arthropathy. The lesions are caused by abnormal keratinocyte proliferation, and infiltration of inflammatory cells into the dermis and epidermis. The usual age of onset of psoriasis is between 15 and 30 years, although it can present at any age. Psoriasis is recognised to have a large genetic component. Twin studies show the concordance in monozygotic twins to be between 65-70%, compared to between 15-20% in dizygotic twins. Family studies estimate the risk to first degree relatives at between 8-23%. However, there are also several environmental factors, including streptococcal infection and stress, that affect the onset and presentation of the disease. The mode of inheritance of psoriasis is unclear. We conducted a genome-wide scan to search for psoriasis susceptibility loci in a single large multiplex family. Parametric linkage analysis indicated that a susceptibility locus for familial psoriasis was located on chromosome 4q. Investigation of this locus in five further multiplex families using both parametric and non-parametric methods gave significant localisation to chromosome 4q. The maximum total pairwise lod score obtained was 3.03 with the microsatellite marker D4S1535 at theta = 0.08. Non-parametric multipoint analysis with GENEHUNTER- demonstrated significant excess allele sharing, with a P value of 0.0026, at the same locus.

Chromosome Mapping↗

Enhancing the role public health nurses play in serving children with special health needs: an interactive videoconference on Public Law 99-457 Part H.

Public Law 99-457 Part H supports the development of systems to identify infants and toddlers with special health needs and provide these children the comprehensive care they need. Although public health nurses traditionally provide many of the mandated services. Part H, with its roots in education, presents new terminology, conceptual models, and challenges to public health nurses. An interactive videoconference entitled "Public Health Nurses and Part H: Putting the Pieces Together" was broadcast to 525 public health nurses in 11 states. The program goals were to increase knowledge of Part H among public health nurses and to enhance their role in its implementation. An evaluation was conducted to assess knowledge change and satisfaction with the program format. Results revealed a high degree of satisfaction with distance learning and no difference across sites in knowledge acquisition or participant satisfaction. A need identified through this project is increased interdisciplinary communication among those who serve infants and toddlers with special needs. In an era when financial resources are dwindling, interactive videoconferencing is an innovative and cost-effective method for decreasing the isolation of many public health nurses by offering opportunities for education and networking from their local communities.

Child Health Services↗

Guidelines for developing a nurse practitioner practice.

Nurse practitioners must take an active role in defining and establishing their practices. In many cases, medical and administrative staffs develop the NP job description. As a result, many NPs are finding themselves in unsatisfactory, often task-oriented roles. This problem is largely due to NPs' inexperience in establishing practices and a lack of documentation of current practices. When developing the NP practice within the National Cancer Institute-Medicine Branch, it was apparent that the nursing literature offered no information on how to establish an NP practice. This article presents guidelines for developing an NP practice and is based on information obtained during the developmental stages of the nurse practitioner practice at the National Cancer Institute-Medicine Branch.

Forms and Records Control↗

Periodontal manifestations of systemic diseases and their management.

Periodontal diseases result from the response of the host's periodontal tissue to the bacterial toxins present in dental plaque. Several systemic diseases have been shown to influence the course and severity of periodontal diseases by altering the inflammatory response of the host. This paper focuses on the manifestations and dental management of periodontal diseases when these types of systemic conditions, including diabetes mellitus, hormonal changes of pregnancy and puberty, HIV-associated infection, and various blood dyscrasias, are present.

Bacterial Toxins↗

Unrelated donor marrow transplantation in children.

Eighty-eight children 0.5 to 17 years of age (median, 9 years of age) received an unrelated donor marrow transplant for treatment of chronic myeloid leukemia (CML; n = 16), acute lymphoblastic leukemia (ALL) in first or second remission (n = 15) or more advanced stage (n = 28), acute myeloid leukemia (AML; n = 13), or other hematologic diseases (n = 16) between June 1985 and April 1993. All patients were conditioned with cyclophosphamide and total body irradiation and received a combination of methotrexate and cyclosporine as graft-versus-host disease (GVHD) prophylaxis. Fourty-six patients received transplants from HLA-identical donors and 42 patients received transplants from donors who were minor-mismatched at one HLA-A or B or D/DRB1 locus. The Kaplan-Meier estimates of disease-free survival and relapse were 75% and 0% for patients with CML, 47% and 20% for ALL in first or second remission, 10% and 60% for ALL in relapse or third remission, 46% and 46% for AML in first remission (n = 1) or more advanced disease (n = 12), and 29% and 69% for other diseases. HLA disparity was not significantly associated with lower disease-free survival, but the results suggest more relapses in HLA-matched recipients and there was significantly more transplant-related mortality in mismatched recipients (51% v 24%, P = .04). Most deaths were due to infections associated with acute or chronic GVHD and occurred within the first 2 years after transplantation. Granulocyte engraftment occurred in all evaluable patients. Sixty-three percent of HLA-matched and 57% of HLA-mismatched recipients were discharged home disease-free at a median of 98 and 103 days, respectively, after transplantation (P = not significant [NS]). The incidence of grades II-IV acute GVHD was 83% in HLA-matched and 98% in HLA-mismatched recipients (P = .009). The incidence of chronic GVHD was 60% in HLA-matched and 69% in HLA-mismatched recipients (P = NS). One or multiple late adverse events such as cataracts, osteonecrosis of the hip or knee, restrictive or obstructive pulmonary disease, and hypothyroidism have occurred in 11 of 33 (33%) surviving patients. Immunosuppression was discontinued in 58% of surviving patients, including all 12 patients surviving more than 3.2 years, all of whom have a Lansky or Karnofsky score of 100%. These data show that marrow transplantation from fully or partially HLA-matched unrelated donors can be effective therapy for children with hematologic disorders and that pretransplantation disease status and posttransplantation GVHD remain important factors affecting patient outcome.

Adolescent↗