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Biomedical subjects

E Smith

Publications and source records attributed to E Smith.

At least 271 records · Page 15Linked to original sources

Chronic anaemia, hyperbaric oxygen and tumour radiosensitivity.

Anaemia is an important factor in the response of some human tumours to radiotherapy. The outcome is also influenced by whether the treatment is given in air or high pressure oxygen (HPO). The present study examined the relationship between anaemia and tumour response to radiation given in air or HPO in C3H mice transplanted with a mammary adenocarcinoma using a growth delay assay to assess the radiation response. Chronic anaemia was induced by the use of a low iron diet and was characterized by a significant reduction in host haematocrit and whole blood viscosity. In addition, anaemia was associated with a right shift in the oxyhaemoglobin dissociation curve and an increase in the volume doubling time of the tumour; but there was no change in the concentration of 2,3-diphosphoglycerate in the red cells. Radiation studies with these anaemic mice demonstrated that the tumour radiosensitivity was decreased when treatment was given in air. HPO was successful in overcoming the increased radioresistance associated with anaemia. This result suggested that tumours grown in anaemic mice have a higher hypoxic fraction than those grown in control mice. Changes in host physiology with chronic anaemia may contribute to the benefit seen with HPO but such alterations per se may be inadequate to maintain tumour oxygenation when treatment is given in air.

Adaptation, Physiological↗

The effects of antithyroid drugs on intercellular mediators.

The antithyroid drugs methimazole and propylthiouracil have been shown to affect the function of monocytes and B and T lymphocytes in vitro. The aim of this study was to investigate the mechanism responsible for signalling between these various cell types. Propranolol, a drug known to have no effect on the immune system, was also included as a control against which the effects of the other drugs could be monitored. Peripheral blood lymphocytes from control subjects were stimulated with phytohemagglutinin in the presence or absence of antithyroid drugs. Propranolol was found significantly to inhibit beta 2 microglobulin production. In addition it was also found to be a very weak scavenger of free oxygen radicals. Methimazole significantly increased interleukin 2 levels (p less than 0.01), but had no significant effect on either gamma-interferon or beta 2 microglobulin production. Propylthiouracil also increased interleukin 2 levels (p less than 0.001) and significantly decreased beta 2 microglobulin production (p less than 0.01). Both drugs were found to be scavengers of free O2 radicals. It would appear that IL-2 is involved in intercellular signalling and this process may involve free radicals.

Cell Communication↗

Trends and patterns of opportunistic diseases in Danish AIDS patients 1980-1990.

We analysed the AIDS-defining diseases in all 618 notified AIDS patients in Denmark by June 30, 1990, and looked for trends and associations over time. Pneumocystis carinii pneumonia (PCP) was the most commonly reported disease (47%), and showed some but insignificant changes over time. The number of patients reported with Kaposi's sarcoma (KS) declined significantly from 33% in 1980-84 to 12% in 1990. KS was reported 5 times as often in homosexual men as in all other AIDS patients while esophageal candidiasis was reported in one fifth of the patients and were reported twice as often in women as in homosexual men. Wasting and HIV encephalopathy were 2.5 times more often reported in women than in homosexual men. The overall survival rate was 56% (95% confidence interval: 51-61%) at 1 year and 21% (95% confidence interval: 15-28%) at 3 years. Significantly improved survival over time was observed in patients diagnosed with PCP. Patients reported with KS had a significantly better prognosis than those with PCP. Women in general had a bad prognosis.

Acquired Immunodeficiency Syndrome↗

Transport of magnesium across an isolated preparation of sheep rumen: a comparison of MgCl2, Mg aspartate, Mg pidolate, and Mg-EDTA.

The transport of Mg across an isolated preparation of rumen epithelium of sheep was studied using different Mg salts: MgCl2. Mg aspartate, mg pidolate, and Mg-EDTA. The measurements were made under short circuit conditions in Ussing chambers. The obtained results showed that Mg transport rates did not differ significantly between MgCl2, Mg aspartate, and Mg pidolate. However, Mg-EDTA reduced Mg transport significantly and increased the short circuit current (Isc). It was shown that this increased Isc can be abolished by mucosal addition of Mg or Ca. It is concluded that Mg is transported if it is free and in the ionized form.

Animals↗

Hyperthecosis of the ovaries in a woman with a placental site trophoblastic tumor.

Rapidly increasing testosterone levels were observed in a patient presenting with sudden onset of virilization. Exploratory laparotomy revealed a placental site trophoblastic tumor in the uterus. Wedge biopsies of the ovaries showed extensive luteinization of the ovarian stroma in both ovaries. Concentrations of testosterone, dihydrotestosterone, and androstenedione were markedly increased in the ovarian vein serum, indicating ovaries as the source of these steroids. The serum concentration of hCG was 69 mIU/mL. Pulsatile secretion of LH persisted in spite of elevated hCG levels. Follicle-stimulating hormone levels were low or undetectable. Elevated hCG levels and low FSH levels resulted in a hormonal environment similar to that seen in polycystic ovary disease (high LH to FSH ratio), resulting in extensive stromal luteinization. Decline in hCG levels after removal of the tumor resulted in the return of androgen levels to normal.

Adult↗

[Production of antibodies with the aid of genetic technology].

During the past decade we have witnessed a rapid development of methods for the production of monoclonal antibodies with predefined specificity. These antibodies are now regularly being used both for diagnostic and therapeutic purposes. The first antibodies thus produced were mainly from cell lines generated by fusion of a mouse B lymphocyte with a given specificity with a mouse myeloma line. Efforts have lately been made also to make cell lines producing human antibodies either by immortalizing human cells or by "humanizing" mouse antibodies. The latter has recently been accomplished by genetic engineering. In these experiments the entire variable region of a mouse antibody or the hypervariable regions only (complementarity determining regions) have been grafted onto human constant region genes thus creating chimeric antibodies. Fragments of antibodies with retained binding properties have also been generated and some of these have been effectively produced in bacteria, allowing large scale production. Bifunctional antibodies have also been created with success and have been applied in different systems. The ease with which antibodies with desired specificities can now be designed and produced will form the beginning of a new era in immunology with a potential that we can not as yet foresee.

Animals↗

Glycoproteins that exhibit extensive size polymorphisms in Dictyostelium discoideum.

Electrophoretic variants which arise from amino acid substitutions, leading to charge differences between proteins are ubiquitous and have been used extensively for genetic analysis. Less well documented are polymorphisms in the size of proteins. Here we report that a group of glycoproteins, which share a common carbohydrate epitope, vary in size in different isolates of the cellular slime mould, Dictyostelium discoideum. One of these proteins, PsA, a developmentally regulated prespore-specific surface glycoprotein, has previously been shown to exist in three size forms due to allelic variation at the pspA locus on linkage group I. In this report, a second glycoprotein, PsB, which is also prespore specific but found inside prespore cells, is studied. PsB maps to linkage group II and exhibits at least four different sizes in the isolates examined. We propose that the size polymorphisms are the product of allelic variation at the pspB locus, due to differences in the number of repeat units.

Alleles↗

Home use of rectal diazepam to prevent status epilepticus in children with convulsive disorders.

Thirty families were taught to administer rectal liquid diazepam to their children to stop a seizure at home. Twelve children had previous prolonged afebrile seizures, and 18 had either prolonged or repeated febrile seizures. During follow-up, 17 of the 30 families administered the rectal diazepam an average of three times per child with no complications. Fifteen of 17 families reported prompt cessation of the seizure, while in two the rectal diazepam was unsuccessful and hospital treatment was needed. We conclude that rectal diazepam is a useful adjunctive home treatment for children at risk for prolonged seizures. Hospitalization is decreased and parental confidence increased. Without our knowledge, twelve families taught others how to give the rectal diazepam, a practice that might be hazardous and should be anticipated.

Administration, Rectal↗

A randomized study of carbamazepine versus no medication after a first unprovoked seizure in childhood.

We randomized 31 children with a 1st afebrile unprovoked seizure to receive carbamazepine (CBZ) or no medication for 1 year or until the time of a 2nd seizure. All seizures had a focal onset or were generalized tonic-clonic. Overall, 2/14 randomized to CBZ and 9/17 with no medication had a recurrent afebrile seizure. Compliance with CBZ was excellent in 12/14, but noncompliance may have contributed to 1 of the recurrences with CBZ. Four discontinued CBZ because of side effects. Two additional children taking CBZ had a febrile seizure. Thus, only 6/14 taking CBZ had a year completely seizure-free with no unacceptable medication side effects. Of those taking no medication, 2 had a febrile recurrence, and 7/17 had a year completely-seizure free. Side effects and febrile recurrences may limit the value of CBZ for some children, although CBZ appears to reduce significantly recurrences after a 1st afebrile seizure.

Carbamazepine↗

TRH pharmacokinetics and nerve stimulation evoked prostatic fluid secretion during TRH infusion in the dog.

The pharmacokinetics of TRH have been determined in man and the rat as well as other species whose serum contains TRH degrading enzymes, TRH pharmacokinetics have not been determined in the dog. This species is unusual in that its serum contains little or no TRH degrading activity. TRH pharmacokinetics were determined from measurements of plasma TRH concentrations during and following a 1-h infusion of TRH, 20 micrograms.kg-1.min-1, into dogs bearing prostatic urethral cannula. During TRH administration prostatic fluid secretion was evoked by hypogastric nerve stimulation and the content of TRH immunoreactive material in prostatic fluid was determined. Prostatic fluid was also collected after hypogastric nerve stimulation in dogs that did not receive TRH infusion. The TRH plasma profile in TRH-infused dogs exhibited two-compartment characteristics with an initial half-time of 10.4 +/- 5.4 (mean +/- SD) min, a terminal half-time of 69.4 +/- 24 min, and a metabolic clearance rate of 7.64 +/- 4.48 ml.min-1.kg-1. These findings suggest that the half-time of TRH is longer, and its metabolic clearance rate is less, in the dog than in humans or rats. TRH administration was not associated with altered nerve induced prostatic fluid secretion. Prostatic fluid samples contained TRH immunoreactive material regardless of whether they were collected after epithelial cell stimulation with pilocarpine, or after hypogastric nerve stimulation. In contrast to previous results with vasoactive intestinal peptide, TRH does not acutely alter prostatic fluid secretion. As has been reported for prostatic tissue extracts, immunoreactive material is present in prostatic fluid and appears to arise from epithelial cells.

Animals↗

Disseminated histoplasmosis in a Danish patient with AIDS.

We present the first case of disseminated histoplasmosis in an AIDS patient in Europe, a 33-year-old Danish homosexual man, and recommend a detailed travel history in HIV-positive patients presenting with fever, weight loss and organomegaly. In Scandinavia disseminated histoplasmosis is rare but should be kept in mind as the disease is a major opportunistic infection in patients with AIDS. Treatment with amphotericin B followed by fluconazole was effective.

Acquired Immunodeficiency Syndrome↗

Adipose reduction by beta,beta'-tetramethyl-substituted hexadecanedioic acid (MEDICA 16).

Treatment of normal rats kept on a balanced laboratory chow diet with beta,beta'-tetramethyl-substituted hexadecanedioic acid (MEDICA 16) (Bar-Tana et al., 1985, J. Biol. Chem, 260, 8404-8410) resulted in an acute reduction in adiposity, which was already established during the first week of treatment and was sustained as long as the drug was administered. Adipose reduction consisted of 30-80 percent decrease in the perirenal, omental, epididymal, parametrial and subcutaneous fat with a concomitant 50 percent decrease in total body neutral lipid mass. The reduction in adiposity was accounted for by a respective decrease in the lipid content of individual adipocytes together with a transient or sustained decrease in the number of adipocytes of selected adipose tissues. The decrease in the lipid content resulted from (a) an extensive hypotriglyceridemia in MEDICA 16-treated rats; (b) inhibition of adipose lipogenesis by MEDICA 16; (c) increased sensitivity to catecholamines-. ACTH- and forskolin-induced lipolysis in MEDICA 16 adipocytes. Adipose reduction by MEDICA 16 was not compromised by a decrease in overall net caloric intake but was accompanied by a 40 percent increase in resting metabolic rate.

Adipose Tissue↗

Survival of a dog with pneumonia caused by Mycobacterium fortuitum.

Pneumonia caused by Mycobacterium fortuitum was diagnosed in the left lung lobes of a 3-year-old male Samoyed. Unilateral pneumonectomy and antibiotic treatment (primarily amoxicillin trihydrate-clavulanate potassium and kanamycin) were associated with resolution of the pneumonia. In dogs, M fortuitum causes pulmonary disease that radiographically resembles bacterial pneumonia. Therefore, M fortuitum infection should be considered in dogs with radiographic signs of bronchopneumonia that worsen despite antibiotic treatment.

Animals↗

Operation Everest II: alterations in the immune system at high altitudes.

We investigated the effects on immune function after progressive hypobaric hypoxia simulating an ascent to 25,000 ft (7620 m) over 4 weeks. Multiple simultaneous in vitro and in vivo immunologic variables were obtained from subjects at sea level, 7500 ft (2286 m), and 25,000 ft during a decompression chamber exposure. Phytohemagglutinin-stimulated thymidine uptake and protein synthesis in mononuclear cells were reduced at extreme altitudes. Mononuclear-cell subset analysis by flow cytometry disclosed an increase in monocytes without changes in B cells or T-cell subsets. Plasma IgM and IgA but not IgG levels were increased at altitudes, whereas pokeweed mitogen-stimulated in vitro IgG, IgA, and IgM secretion was unchanged. During exposure to 25,000 ft, in vitro phytohemagglutinin-stimulated interferon production and natural killer-cell cytotoxicity did not change statistically, but larger intersubject differences occurred. IgA and lysozyme levels (nasal wash) and serum antibodies to nuclear antigens were not influenced by altitude exposure. These results suggest that T-cell activation is blunted during exposure to severe hypoxemia, whereas B-cell function and mucosal immunity are not. Although the mechanism of altered in vitro immune responsiveness after exposure to various environmental stressors has not been elucidated in humans, hypoxia may induce alterations in immune regulation as suggested by in vitro immune assays of effector-cell function.

Adult↗