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Biomedical subjects

D Lewis

Publications and source records attributed to D Lewis.

At least 253 records · Page 14Linked to original sources

Cicuta toxicosis in cattle: case history and simplified analytical method.

Poisoning of cattle by water hemlock roots is a common occurrence. The experience of our Pathology Branch has been that the roots will be found in the esophageal groove with no obvious signs of root in the rumen. Confirmation of the presence of cicuta poisoning is done by analysis for cicutoxin in either the roots of the plants on which the animals were grazing or on the root material removed from the esophageal groove. This report describes a rapid and simple analysis for cicutoxin, cicutol and related compounds (1).

Animals↗

Suicide by ingestion of 2,4-D: a case history demonstrating the prudence of using GC/MS as an investigative rather than a confirmatory tool.

Suicide by ingestion of herbicides or pesticides is not an uncommon occurrence. Several cases have been reported in recent years (1-14); in all of these cases the case history strongly suggested the specific material in question thus making the analytical work confirmatory in nature. There is a veritable dearth of reported cases of suicide involving the serendipitous discovery of a herbicide or a pesticide, as we were able to discover no such cases in recent years (1-14). We now report a case in which an unsuspected herbicide was detected as a result of using GC/MS as the screening tool for toxicological investigations. Conceivably a considerable number of poisonings by agents other than pharmaceuticals are being missed in investigation into mysterious human deaths or admissions to the emergency department of hospitals where this technique is used only to confirm the presence of poisons detected by a preliminary screen designed for pharmaceuticals.

2,4-Dichlorophenoxyacetic Acid↗

Identification of ecdysone 22-long-chain fatty acyl esters in newly laid eggs of the cattle tick Boophilus microplus.

The five major apolar ecdysone esters present in newly laid eggs of the cattle tick Boophilus microplus have been purified by h.p.l.c. The quantities of the apolar esters present in the eggs were increased by administration of ecdysone to the mature females. G.c.-m.s. analysis, as their methyl esters, of the fatty acids released from the apolar ecdysone derivatives by alkali, coupled with positive-ion fast-atom-bombardment m.s. of the intact ecdysone esters, showed that the compounds consisted of a series of fatty acyl esters of ecdysone. The position of esterification of the ecdysone was established by p.m.r. spectroscopy. The combined data show that the novel apolar derivatives of ecdysone consist of the 22-palmitate, -palmitoleate, -stearate, -oleate, and -linoleate esters respectively. Confirmation was obtained by comparison with synthetic ecdysone 22-palmitate. The significance of the ecdysone fatty acyl esters as a possible source of free hormone during embryogenesis is discussed.

Chromatography, High Pressure Liquid↗

Bone marrow involvement in anaplastic small cell lung cancer. Diagnosis, hematologic features, and prognostic implications.

The hematologic changes and prognostic implications of bone marrow involvement in small cell lung cancer (SCLC) were examined in 133 patients undergoing staging procedures including bone marrow aspiration and trephine biopsy. Bone marrow involvement was found to be present in 27 of 133 (20%) at diagnosis. In most instances bone marrow involvement was associated with the presence of other metastases but in five patients (4%) the bone marrow was the sole site of metastasis. Bone marrow biopsy proved superior (14%) to bone marrow aspiration (5%) in detecting marrow infiltration. Peripheral blood hematologic changes were infrequent even in patients with positive bone marrow biopsy results. Although patients with bone marrow involvement had a shorter median survival (9 weeks) than bone marrow-negative patients (33 weeks) the adverse effect on survival appears to have been mainly due to the presence of concomitant metastases at other sites. Intensive chemotherapy was tolerated to the same degree by bone marrow-positive and bone marrow-negative patients.

Biopsy↗

Anti-S-100 serum blocks long-term potentiation in the hippocampal slice.

S-100 is a calcium-binding, glial protein which has been shown to be involved in behavioral learning and memory tasks. Long-term potentiation (LTP) in the hippocampus is a long-lasting enhancement of synaptic efficacy evoked by repetitive afferent stimulation. When anti-S-100 serum is applied by pressure ejection onto the stratum radiatum of area CA1 of the hippocampal slice, the amplitude of the extracellularly recorded population spike is not affected. However, repetitive stimulation of the afferents during S-100 application failed to produce LTP. At a distant site in the same slice, LTP occurs normally. Preimmune normal rabbit serum had no effect on the development of LTP. It appears that S-100 protein is involved in the establishment of LTP.

Animals↗

Long-term potentiation in the goldfish optic tectum.

Field potential recordings were made in the primary retinal synaptic area, the stratum fibrosum et griseum superficiale (SFGS), of an in vitro goldfish optic tectum preparation. Stimulation of the optic nerve at frequencies of 1 and 5 Hz produced a long-term potentiation (LTP) of the synaptic response which developed gradually. No potentiation was seen with lower or higher frequencies. These results demonstrate a significant LTP with a slow time course and restricted low-frequency dependence.

Animals↗

Haematological and iron-related measurements in active pulmonary tuberculosis.

59 patients with active pulmonary tuberculosis were evaluated in terms of haematological indices, iron-related measurements and markers of inflammation. The variables evaluated included the Hb, mean cell volume (MCV), serum iron, total iron-binding capacity, percentage saturation, serum ferritin, erythrocyte sedimentation rate (ESR) and C-reactive protein. In addition, marrow iron stores were assessed both histologically and chemically. Among the changes noted was a raised S-Ferritin, which appeared in part to be a component of the acute phase response, since it correlated with C-reactive protein concentration (r 0.59, p less than 0.0001). In addition, there was a good correlation between the S-Ferritin and the concentrations of non-haem iron in the marrow, as assessed chemically on trephine biopsies (r 0.78, p less than 0.0001) and histologically on aspirated and biopsy material (rS 0.78, p less than 0.0001 and rS 0.68, p less than 0.0001, respectively). Furthermore, the quantitative relationship between the S-Ferritin and the chemical concentrations of non-haem iron in the marrow was similar to that found previously in a heterogeneous group of subjects without infections. While the present findings confirm that iron is diverted into reticuloendothelial stores in active pulmonary tuberculosis, no evidence was found to suggest that the anaemia which was present in 45 of the 59 patients was secondary to iron-deficient erythropoiesis; the percentage saturations in the 2 groups were 30.3 and 31.1 respectively. In a final analysis, the present findings were compared with previous ones obtained in a group of patients with Hodgkin's disease. The degree of rise in the S-Ferritin for a given marrow non-haem iron concentration was significantly less in the patients with tuberculosis (p less than 0.0001).

Adult↗

Use of orally administered oxidised copper wire particles for copper therapy in cattle.

Oxidised copper wire particles (OCWP) were given per os to cattle as an alternative to subcutaneous copper glycinate injections. OCWP were recovered from the stomachs of cattle slaughtered 3 months after treatment. OCWP (50g) treatment resulted in sustained higher plasma copper concentrations than subcutaneous injections of copper glycinate. OCWP given at high doses (300g) raised liver copper concentrations to 16 mmol/kg without clinical effects. It is concluded that OCWP could be a practical alternative to current injection methods of copper therapy.

Administration, Oral↗

Norwalk like viruses: study of an outbreak.

An outbreak of acute non-bacterial gastroenteritis is reported, during which a ward had to be closed, and stool samples from 15 patients showed a virus structurally similar to the Norwalk agent.

Child, Preschool↗

Early and late changes in sulphydryl group and copper protein concentrations and activities during drug treatment with aurothiomalate and auranofin.

Superoxide dismutase activity (SOD), plasma and lysate thiol concentrations (PSH and LSH), and caeruloplasmin oxidase activity (CP) reflect the underlying reduction-oxidation imbalance associated with rheumatoid arthritis (RA), and are believed to be involved in the protection of the cell against free radical activity. The early and late changes in these parameters have been observed and compared with standard clinical and biochemical assessments of disease activity in 90 patients with active RA, randomly assigned to receive either sodium aurothiomalate, auranofin, or auranofin placebo. An index based on clinical criteria was used to identify patients as responders or non-responders after 24 weeks of therapy. In the first six weeks of treatment a change in SOD activity and LSH concentration in a direction away from controls was followed by a return towards control levels in responders only. This suggests that in RA evidence of clinical improvement induced by gold drugs is preceded by an initial biochemical response in an inflammatory direction. The extracellular parameters PSH and CP did not show the same early response, but PSH levels in responders showed a slower change towards normal values, though at no time were values obtained that might suggest a complete remission. Thus the intracellular parameters appear to reflect an early effect of the drugs on cells which may possibly be of use in predicting the outcome of therapy, whereas the extracellular parameters provide confirmatory evidence for an eventual improvement.

Arthritis, Rheumatoid↗

A three year follow up of patients allocated to placebo, or oral or injectable gold therapy for rheumatoid arthritis.

Ninety patients randomly allocated to receive auranofin, matching placebo, or sodium aurothiomalate have been followed up for three years. Inefficacy led to cessation of treatment in 14 patients receiving auranofin, 27 receiving placebo, and one receiving sodium aurothiomalate. Twenty seven of the patients receiving placebo were reallocated within the study and 16 continued therapy at three years. This group showed similar statistically significant improvement in clinical and laboratory parameters at one, two, and three years to those on an active drug from the outset. Patients who discontinued auranofin because of inefficacy were offered sodium aurothiomalate therapy--eight patients in this group completed three years of treatment on sodium aurothiomalate and showed significant improvement in some but not all parameters. A hand radiograph erosion score showed a deterioration in 80% of patients remaining on auranofin, 75% of those on sodium aurothiomalate, and 80% of the original placebo group who continued an active drug for three years. Although more patients discontinued auranofin over the study period because of inefficacy, no difference could be shown between the degree of improvement in the subgroup who remained on auranofin and those receiving sodium aurothiomalate. No disadvantage in outcome could be shown for patients originally assigned to placebo.

Arthritis, Rheumatoid↗

Improvement in men inpatients in an alcoholism rehabilitation unit: a week-by-week comparison.

The Brief Symptom Inventory (BSI), a 53-item psychiatric symptom checklist, was administered to 57 alcoholic inpatients on days 2, 10, 18 and 26 of their 28-day stay in an alcoholism rehabilitation unit at a Veterans Administration hospital. The results of the test show a steady decline in the patients' psychiatric symptomatology from week 1 to week 4 with the most dramatic improvement evidenced between weeks 1 and 2.

Adult↗

Somatostatin, an inhibitor of ACTH secretion, decreases cytosolic free calcium and voltage-dependent calcium current in a pituitary cell line.

Somatostatin is a neurohormone peptide that inhibits a variety of secretory responses in different cell types. We have investigated the effects of somatostatin on calcium current and intracellular free calcium in AtT-20 cells, a pituitary tumor line in which the inhibitory actions of this peptide have been well characterized. At concentrations similar to those that inhibit adrenocorticotropic hormone (ACTH) release, somatostatin and its analogs reduced the levels of intracellular free calcium (as measured by the Quin-2 technique). Nifedipine and other blockers of voltage-dependent calcium channels also reduced cytosolic calcium levels. The effects of somatostatin and nifedipine were not additive, suggesting that somatostatin might inhibit calcium channels. Experiments using the whole-cell patch-clamp technique showed that somatostatin reduces voltage-dependent calcium current. The effects of somatostatin on cytosolic calcium and calcium current appear to be independent of its ability to reduce secretagogue-stimulated cAMP accumulation in these cells. We propose that the somatostatin-induced decrease in cytosolic calcium concentrations and the voltage-dependent calcium current are one of the mechanisms by which somatostatin suppresses ACTH release in AtT-20 cells.

Adrenocorticotropic Hormone↗

Chromosome 3q21 abnormalities associated with hyperactive thrombopoiesis in acute blastic transformation of chronic myeloid leukemia.

Two patients with acute blastic transformation of chronic myeloid leukemia (CML) associated with strikingly elevated platelet counts showed abnormalities of chromosome 3q in addition to the standard Philadelphia (Ph1) chromosome translocation. The first patient had an inversion of chromosome 3 (q21q26) cytologically identical to an inversion 3 previously reported in de novo acute megakaryoblastic leukemia, and the second patient showed a translocation between chromosome 3q and the chromosome 9 homologue not involved in the Ph1 translocation, [t(3;9)(q21;q34)]. Previous studies had incriminated either 3q21 or 3q26 as the locus for a regulatory thrombopoietic gene, but the current study suggests that 3q21 is the relevant site.

Adult↗

Specific dicyclohexylcarbodiimide inhibition of the E-P + H2O equilibrium E + Pi reaction and ATP equilibrium Pi exchange in sarcoplasmic reticulum adenosinetriphosphatase.

Treatment of sarcoplasmic reticulum adenosinetriphosphatase (ATPase) with N,N'-dicyclohexylcarbodiimide is known to produce total inhibition of calcium binding and enzyme activity. However, we now find that treatment with lower reagent:protein ratios produces selective inhibition of hydrolytic Pi cleavage, enzyme phosphorylation with Pi, and ATP in equilibrium Pi exchange, while calcium binding and enzyme phosphorylation with ATP remain largely unaffected. This specific inhibition is attributed to derivatization of residues which are normally involved in acid-base-assisted catalysis of the hydrolytic reaction and its reversal, but are not involved in calcium binding or in the mechanism of phosphoryl transfer from ATP to the enzyme. This specific inhibition is prevented by the presence of micromolar calcium during the incubation with the inhibitor, evidently through an allosteric effect of calcium binding on the catalytic site. We also find that the initial adducts formed between ATPase residues and N,N'-dicyclo[14C]carbodiimide undergo further degradation with release of radioactive product into the medium, while the protein residues remain inactivated probably by linkage with neighboring residues. Therefore, the stoichiometry of radioactive labeling underestimates the actual number of inactivated residues.

Adenosine Triphosphatases↗

Spontaneous lymphocyte activity in rheumatoid arthritis in a longitudinal study in relation to gold therapy.

Spontaneous lymphocyte activity has been measured over 24 weeks in rheumatoid arthritis patients who were receiving placebo, auranofin or gold sodium thiomalate (GST). The results suggest a relationship between a fall in lymphocyte activity and clinical improvement on GST. They also show that the patients with most active disease, as determined by the ESR, had normal levels of lymphocyte activity. We suggest that peripheral lymphocyte activity is secondary to immunological stimulation in the joint capsule, and is not directly related to disease activity. We conclude that spontaneous activity is probably an epiphenomenon and not related directly to disease activity or to disease prognosis.

Arthritis, Rheumatoid↗