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Biomedical subjects

J Fletcher

Publications and source records attributed to J Fletcher.

At least 199 records · Page 11Linked to original sources
PubMed1990

Neutrophil function tests.

The complexity of the neutrophil response to inflammation creates many difficulties for the study of neutrophil function in vitro. The environment in which a neutrophil is placed can have marked effects upon a variety of cellular functions. Quantitative tests of neutrophil function present problems not only with assay design but also in the isolation of cells from peripheral blood without disturbing their normal physiology. It is desirable to isolate neutrophils from other leukocytes because soluble factors released by other cells can influence neutrophil function, and other cells may interfere with functional assays; for example, monocytes will phagocytose opsonized particles and eosinophils contain a potent peroxidase. Attention to physical parameters such as temperature, pH or osmolarity, and rigorous exclusion of endotoxin, permits neutrophils to be isolated in a resting state. Subsequent function tests must be selected with an understanding of normal neutrophil physiology and applied with an awareness of any associated technical problems. The investigation of abnormal neutrophil responses may necessitate the screening of several tests of function; for example, defective neutrophil killing may be the result of abnormal chemotaxis, phagocytosis or degranulation. Which tests are appropriate will depend upon the questions to be answered and on the quantity of cells available for study.

Cell Adhesion↗
PubMed1990

A comparison of in-house and regionalized computerized tomography scanning: clinical impact and cost.

Over a two-year interval, computerized tomography (CT) scans at an urban, 400-bed Department of Veterans Affairs medical center (VAMC) were obtained in three ways. First, an in-house low-efficiency machine was used. Then, scans were done at another area hospital, in effect duplicating some aspects of regionalizing services. Finally, a high-efficiency in-house machine was used. Clinical outcomes and costs of diagnosing 181 bronchogenic cancer patients were compared across the three time periods to identify any differences associated with regionalization of CT services. Patient groups were homogeneous with respect to sociodemographic characteristics, clinical presentation, and severity of disease. The first part of the analysis investigated whether the site of CT scanning affected clinical outcomes. Diagnostic procedures, surgical results, mortality, and length of stay were compared using one-way analysis of variance. Significant differences were found only for conventional tomography and CT utilization rates. While conventional tomography declined across the periods, CT utilization increased, exceeding national trends. The second part of the analysis examined the costs of CT scanning. During the regionalized period, the hospital paid a fixed fee of $519 per scan. Estimated costs of in-house scans were $285 in the low-efficiency and $141 in the high-efficiency periods. Charge-based payments made to the external facility and differences in the volumes of patients scanned internally account for the cost differences. The analysis showed that while regionalized CT scanning did not compromise the quality of care for these VA patients, it was more costly. Results suggest that VA hospital administrators should carefully consider ownership and payment arrangements when comparing regionalized and in-house provision of services.

Aged↗
PubMed1990

Ender rods versus external fixation in the treatment of open tibial fractures.

This is a retrospective nonrandomized study of 66 open tibial fracture patients that compares comparable population treated at one trauma center. The fractures were treated with either Ender rods or external fixation. Of these, 29 fractures were eliminated from the study due to incomparable variables. Thus, the study group consisted of a total of 37 tibial fractures: 20 treated by Ender rods and 17 treated by external fixation. Open tibial fractures treated with Ender rods had a significantly lower number of complications than those treated with external fixation. The group treated with Ender rods also had a significantly lower number of surgical procedures per patient in Grades I and II open tibial fractures. There were no statistical differences regarding weeks to union or hospital days. Ender rods are superior to external fixation removed early in the treatment of Gustilo's Grades I, II, and IIIA open fractures with either stable or unstable fracture configuration (Orthopaedic Trauma Association Grades IA-IC, IIA-IID, and IIIA-IIIC). Perhaps future study will allow sufficient numbers to determine whether Ender rods can be used in Grades IIIB and IIIC open tibial fractures, but there are no data at this time to support this conclusion.

Adult↗
PubMed1990

Adult onset nesidioblastosis: response of glucose, insulin, and secondary peptides to therapy with Sandostatin.

Adult onset nesidioblastosis (AON) is an extremely rare entity associated with hypersecretion of insulin. Previous reports have demonstrated that the somatostatin analog, Sandostatin (SMS), will control the clinical symptoms induced by infantile nesidioblastosis. We hypothesized that insulin, C-peptide, and secondary peptide secretion from AON is provocable. We also hypothesized that SMS would suppress both basal and provoked primary and secondary peptide secretion in AON. To test this hypothesis, in a patient with AON, 13 gut peptide levels were determined at set intervals during provocative testing with a test meal, a calcium infusion, a secretin bolus, and a glucagon bolus. These tests were repeated under the influence of SMS. Insulin, C-peptide, and pancreatic polypeptide (PP) levels were elevated in the basal state. SMS suppressed all three peptides (mean 68%) (p less than 0.05). Basal fasting glucose rose by 65%, and glucose ratios were raised throughout all four tests. Insulin:glucose ratios decreased during SMS therapy. Insulin and PP secretion was increased by all four provocative tests (mean 458% and 665% above baseline, respectively). C-peptide was provoked by three tests (mean 204%). Peptides with normal basal values were also provocable. GRP and glucagon were provoked by secretin stimulation (182%, 186%, respectively). Calcium infusion stimulated CIP release by 372%. SMS suppressed the peak provoked peptide levels in all positive provocation tests (p less than 0.05). Peak provoked insulin values were decreased by 59%, C-peptide by 75%, and PP by 92%. Peak provoked glucagon, CRP, neurotensin, and GIP levels were decreased by 20%, 65%, 51%, and 73%, respectively. The patient has been maintained on SMS (25 micrograms bid) for 1 yr and has shown decreased insulin levels, normal glucose levels, and, at 1 yr, leads an asymptomatic normal life. SMS is able to suppress primary and secondary peptide secretion in both the fasting and provoked state. The long-term efficacy of SMS may be predicted by its ability to suppress primary peptide release during peak provocation.

Aged↗
PubMed1989

Identification of susceptibility loci for insulin-dependent diabetes mellitus by trans-racial gene mapping.

INSULIN-dependent (type I) diabetes mellitus (IDDM) follows an autoimmune destruction of the insulin-producing beta-cells of the pancreas. Family and population studies indicate that predisposition is probably polygenic. At least one susceptibility gene lies within the major histocompatibility complex and is closely linked to the genes encoding the class II antigens, HLA-DR and HLA-DQ (refs 3, 4). Fine mapping of susceptibility genes by linkage analysis in families is not feasible because of infrequent recombination (linkage disequilibrium) between the DR and DQ genes. Recombination events in the past, however, have occurred and generated distinct DR-DQ haplotypes, whose frequencies vary between races. DNA sequencing and oligonucleotide dot-blot analysis of class II genes from two race-specific haplotypes indicate that susceptibility to IDDM is closely linked to the DQA1 locus and suggest that both the DQB1 (ref. 7) and DQA1 genes contribute to disease predisposition.

Chromosome Mapping↗
PubMed1989

Conceiving a fetus for bone marrow donation: an ethical problem in prenatal diagnosis.

We present a family who sought prenatal diagnosis in order to bear a healthy child to serve as an HLA-identical bone marrow donor for their son affected with Wiskott-Aldrich syndrome. They intended to abort HLA-incompatible fetuses who would have been unsuitable bone marrow donors. This case led us to conclude that prenatal diagnosis should not be used to benefit a third party or facilitate the conception or abortion of a fetus for the purpose of generating an organ for transplantation. The limits of parental autonomy and physician responsibility are discussed.

Aborted Fetus↗
PubMed1989

Theileria annulata sporozoite surface antigen expressed in Escherichia coli elicits neutralizing antibody.

Theileria annulata is an economically important protozoan parasite that threatens an estimated 250 million cattle with the disease tropical theileriosis. Development of a defined subunit vaccine is one means of trying to develop control measures against the disease. To this end we have characterized a surface antigen complex of the infective stage (sporozoite), by using a monoclonal antibody that neutralizes sporozoite infectivity in vitro. We have cloned the gene coding for this complex and have demonstrated that a fusion protein expressed from a fragment of this gene elicits strong neutralizing antibodies. Furthermore we provide data on the structure and expression of this gene. In particular we show that the region of the gene, expressed in one clone, codes for a protein segment relatively rich in proline residues. Also we demonstrate that expression of this gene appears to be stage specific, transcripts being present only in the sporoblast and sporozoite stages. The relevance of these findings to the production of a defined subunit vaccine is discussed.

Amino Acid Sequence↗
PubMed1989

The role of hypertension and hypercholesterolemia on aortic sudanophilia and carotid distensibility in rabbits.

These experiments were designed to determine if male New Zealand white rabbits made mildly hypertensive (20-30 mm Hg increase) with bilateral renal artery clips developed more or less sudanophilic lesions than controls, and if the animals responded differently if hypercholesterolemia was produced soon (one week) or late (eight weeks) after the animals were operated on. Both groups received the diet of 2% cholesterol and 6% corn oil for six weeks. We also studied the distensibility of the carotid artery to determine if altered elastic behaviour played a role in lesion development. The experiments showed that the acute hypertensive group developed most lesions (by area), but that the lesions in all groups had the same shape and location. The carotid arteries from the chronic hypertensives were least distensible, and most of the changes appeared to be in the elastance of collagen. The blood pressure actually dropped slightly in the chronic shams after the diet was started. These experiments suggest that, at least, in the rabbit, the duration of the hypertension may determine how the arterial wall responds to hypercholesterolemia. They show that mild hypertension, like hypercholesterolemia, alters the rate at which lesions develop, rather than altering their distribution. The changes do not appear to be related to altered distensibility.

Analysis of Variance↗
PubMed1988

A new approach to the treatment of advanced high-grade non-Hodgkin's lymphoma--intensive two-phase chemotherapy.

A total of 110 patients with high-grade non-Hodgkin's lymphoma (NHL) not previously treated by chemotherapy or by radiotherapy at more than one site of disease underwent a regimen comprising an intensive 6-week initial, induction phase using vincristine, adriamycin, methotrexate, and prednisolone (VAMP) followed by the non-cross-resistant combination cyclophosphamide, etoposide, and vindesine (EEE). The median age of patients was 54 years, the majority having stage IV disease. The median follow-up was 34 months and all patients have completed treatment. The overall complete remission (CR) rate for all patients was 68%. The initial phase of treatment produced a CR rate of 49%. The full regimen was completed by 87 patients, and of these, 66 (76%) achieved CR. Of those achieving CR, 72% were relapse-free, on an actuarial basis, at 2 years. Overall 2-year survival was 53%, with a median survival of 31 months. The survival of older patients and those with lymphoblastic histology was comparable to that of other groups. The survival prospects of patients with stage IV disease was not as good as that of other patients, with a significant trend to shorter survival in patients with more advanced disease. Toxicity was predictable and manageable for both phases of the regimen, although it was more severe for the initial phase. Dose-limiting toxicities were neutropenia and mucositis. This regimen is active in the treatment of advanced high-grade NHL with acceptable toxicity. These results have encouraged us to continue the study of weekly chemotherapy, which we will compare with standard cyclical chemotherapy in a prospective, randomized trial.

Adolescent↗
PubMed1988

Trans-racial studies implicate HLA-DQ as a component of genetic susceptibility to type 1 (insulin-dependent) diabetes.

Type 1 (insulin-dependent) diabetic patients and control subjects of Afro-Caribbean Negroid racial origin were investigated by serological HLA-DR-typing and restriction fragment length polymorphism analysis using DNA probes corresponding to the DQ alpha, DQ beta and DR beta chain genes. Combined analysis indicated that four DR antigens are positively associated with the condition in Negroid subjects - DR3, 4, 7 and w9. DR3 and 4 are also associated in Caucasians, but the relative risk for DR3 is lower in Negroid subjects. The DR7 association is specific for the Negroid race, and DRw9 is only weakly associated in Caucasoid subjects. Restriction fragment length polymorphism analysis demonstrated a DQ beta restriction pattern in Negroid subjects which is absent from Caucasoid subjects. This pattern was associated with DRw9 and a subset of DR7, and was markedly increased in frequency in diabetic patients compared with control subjects (48.7% vs 10.4%, respectively; p less than 10(-4). In the absence of this pattern, DR7 showed no positive association. DR3 in Negroid subjects was associated with two distinct DQ alpha-DQ beta patterns, only one of which was positively associated with diabetes. A DQ beta pattern, in linkage disequilibrium with different DR antigens in different races, conferred a consistent protective effect against the development of Type 1 diabetes. Trans-racial genetic analysis thus supports a primary role for DQ in susceptibility to Type 1 diabetes.

Black People↗
PubMed1988

Effect of feverfew on phagocytosis and killing of Candida guilliermondii by neutrophils.

The in vitro effect of the herbal remedy feverfew on neutrophil function was examined. It was shown that addition of feverfew extract inhibited phagocytosis of Candida guilliermondii and its overall killing. However, intracellular killing was not affected, suggesting that the apparent defect in total killing merely reflected the failure of uptake. The implications for the in vivo effects of feverfew are discussed.

Candida↗
PubMed1988

Class II HLA DNA polymorphisms in type 1 (insulin-dependent) diabetic patients of north Indian origin.

Genetic associations with Type 1 (insulin-dependent) diabetes may be primary or secondary to linkage disequilibrium. Studies of different racial groups should allow these to be distinguished. We have reported that Type 1 diabetes is associated with HLA-DR3 and -DR4 in subjects of North Indian (Punjab) origin and now present the results of a study of HLA class II DNA polymorphisms in this group and in white caucasoid subjects. DR4 in North Indian Type 1 diabetic patients was associated with DQ beta and DX alpha DNA polymorphisms identical to those found in DR4-positive white caucasoid patients. This DQ beta/DX alpha pattern was increased in frequency in North Indian diabetic patients vs control subjects (33.3% vs 8.5%, p less than 0.001, relative risk = 5.12 (95% confidence limits: 1.96-13.4)). A DQ beta polymorphism with very low relative risk for Type 1 diabetes in white caucasoid subjects was also markedly reduced in North Indian diabetic patients vs control subjects (2.3% vs 24.7%, p less than 0.02, relative risk = 0.10 (95% confidence limits: 0.02-0.46)). This pattern was associated with DR2 in white caucasoid subjects, but with DRw6 in North Indians. A DR3-associated DR beta polymorphism was markedly increased in North Indian diabetic patients vs control subjects (90.2% vs 40.7%, p less than 10(-6), relative risk = 12.1 (95% confidence limits: 4.32-33.9)). The DQ subregion may be a primary site of genetic influence on susceptibility to Type 1 diabetes. Further studies in different racial groups will clarify the HLA associations of Type 1 diabetes.

Diabetes Mellitus, Type 1↗