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Biomedical subjects

J Kingdom

Publications and source records attributed to J Kingdom.

43 records · Page 3Linked to original sources

Vancomycin toxicity: a prospective study.

A prospective study of 34 patients treated with 39 courses of intravenous vancomycin, was undertaken in order to assess toxicity. Six patients received vancomycin alone and 27 courses were associated with aminoglycoside administration either concurrently or within two weeks of the first dose of vancomycin. Hearing loss was slight and uncommon; patients were unaware of its occurrence. Tinnitus and dizziness was noted by two patients and resolved on withdrawal of vancomycin. Diminution of renal function was seen both during (7%) and after (9%) vancomycin therapy. A striking feature of these patients with renal deterioration was the severity of their underlying disease. No evidence of synergistic toxicity between vancomycin and aminoglycosides was seen.

Adolescent↗

Fetal growth restriction: a workshop report.

Intrauterine growth restriction (IUGR) is associated with significantly increased perinatal morbidity and mortality as well as cardiovascular disease and glucose intolerance in adult life. A number of disorders from genetic to metabolic, vascular, coagulative, autoimmune, as well as infectious, can influence fetal growth by damaging the placenta, leading to IUGR as a result of many possible fetal, placental and maternal disorders. Strict definitions of IUGR and of its severity are needed in order to eventually distinguish among different phenotypes, such as gestational age at onset, degree of growth restriction and presence of hypoxia. This report explores and reviews some of the most recent developments in both clinical and basic research on intrauterine growth restriction, by seeking mechanisms that involve genetic factors, utero-placental nutrient availability and vascular growth factors. New exciting findings on the genomic imprinting defects potentially associated with IUGR, and the placental anomalies associated with the decreased nutrient transport are summarized. Moreover, recent data on angiogenic growth factors as well as new information arising from application of gene chip technologies are discussed.

Adult↗

Hypoxia favours necrotic versus apoptotic shedding of placental syncytiotrophoblast into the maternal circulation.

In the third trimester of normal pregnancy, the mother tolerates daily shedding of several grams of dying placental trophoblast into the maternal circulation. The balance between apoptotic and necrotic shedding is presently unknown. Since pre-eclampsia is characterized by an altered placental oxygenation and increased trophoblast shedding, we investigated the role of oxygen on the balance of apoptotic versus necrotic trophoblast shedding in vitro. We studied human trophoblast turnover in explanted villi from late first and third trimester placentas in low oxygen (2 per cent) and higher oxygen tensions (6 per cent and 18 per cent) for up to 72h. Trophoblast turnover including apoptosis and necrosis were assessed by histology, immunolocalization of Mib-1 (proliferation marker), Bcl-2 (apoptosis inhibitor), activated caspase 3 (apoptosis promoter), cytokeratin 18 neo-epitope formation (M30 antibody), TUNEL test (DNA degradation), and (3)H-cytidine and(3) H-uridine incorporations. Culture in 2 per cent oxygen increased cytotrophoblast proliferation and syncytiotrophoblast shedding by necrosis. The proteins necessary for execution of apoptosis were mostly retained in the cytotrophoblast due to lack of syncytial fusion. Culture in 6 per cent and 18 per cent oxygen reduced cytotrophoblast proliferation. Syncytial fusion occurred and activity of caspase 3 was found in the syncytiotrophoblast; the latter remained intact demonstrating physiologic turnover, including apoptotic shedding. We conclude that severe placental hypoxia favours necrotic rather than apoptotic shedding of syncytial fragments into the maternal circulation. Since uteroplacental ischaemia is a significant risk factor for pre-eclampsia, these findings may explain the link between reduced uteroplacental blood flow and the systemic clinical manifestations of this disease.

Adult↗

Effect of physiologic perfusion-fixation on the morphometrically evaluated dimensions of the term placental cotyledon.

OBJECTIVE: To estimate the in vivo dimensions of the fetal villous tree of the normal term placenta. METHODS: Dual-circuit perfusion-fixation of a cotyledon from eight normal term placentas was performed with random intra-cotyledon tissue sampling. Stereologic methods were used to derive estimates of villous (intermediate and terminal) surface area and volume, and star volume (a measure of villous volume). RESULTS: Villous surface area (mean 20.9 m2 [standard deviation 1.8]), capillary surface area (12.8 m2 [1.5]), villous volume (469 mL [40]), and capillary volume (80 mL [10]) values were all approximately 50% higher than reported previously. Star volume estimates ranged from 480 to 1350 microns 3. CONCLUSION: Tissue perfusion-fixation more accurately reconstructs the in vivo state, resulting in higher reference values than previously thought for the fetal villous tree dimensions. Up to one-quarter of fetoplacental blood volume is likely to be accommodated within the placenta at term.

Birth Weight↗