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Biomedical subjects

C Rose

Publications and source records attributed to C Rose.

At least 307 records · Page 17Linked to original sources

Immunization against influenza in humans using an oral enteric-coated killed virus vaccine.

By ingestion of subunit-killed influenza virus vaccine in the form of enteric-coated capsules, local synthesis of secretory IgA (sIgA) antibody was stimulated in human nasal secretions. A fairly equal antibody response initiated by oral and intramuscular administration was demonstrated in the nasal secretions, although a systemic immune response was not elicited from ingestion of the vaccine. If the secretory antibody response resulted from absorption of antigen and transport to the respiratory mucosa, systemic (serum) antibody would be expected. Therefore these findings support the hypothesis that specialized collections of lymphoid cells in the small intestines have IgA precursor cells which circulate and populate distant mucosal sites. A number of studies have suggested that protection against mucosal infection by a variety of respiratory viruses correlates better with the presence and level of sIgA antibody than with serum antibody. The orally administered vaccine was associated with no more side effects than placebo, in contradistinction to the intramuscular route. Thus, the oral method of influenza vaccination could prove to be superior in providing for immunological protection due to equal secretory antibody stimulation, improved convenience and less toxicity.

Administration, Oral↗

Incidence of hypothyroidism following multimodality treatment for advanced squamous cell cancer of the head and neck.

The incidence of chemical hypothyroidism, as manifested by elevated thyroid stimulating hormone (TSH) levels, has been estimated to be as high as 25% after radiation therapy and 45% after radiation therapy and surgery to the neck for treatment of nodal metastases from squamous carcinoma of the head and neck. We prospectively evaluated 43 previously untreated patients seen in the Dana Farber Cancer Institute Interdisciplinary Head and Neck Service who were treated with aggressive combination chemotherapy in addition to standard surgery and/or radiotherapy. All patients were serially monitored for serum TSH, serum T4, and clinical evidence of hypothyroidism. Following cis-platinum, bleomycin, and methotrexate chemotherapy and subsequent surgery and/or radiotherapy, decreased thyroid reserve appeared in 37% of patients at a median follow-up of 9 months. Thirty percent of patients receiving radiotherapy alone and 43% of patients receiving surgery and radiotherapy developed elevated TSH levels. Only one patient developed clinical symptoms. Other patients were asymptomatic despite persistently elevated TSH levels. Abnormalities appeared within the first 4 months after completion of all therapy and were slowly progressive. The addition of combination chemotherapy does not appear to increase the incidence or severity of thyroid dysfunction following radiation therapy and surgery to the neck. In view of the extended survival seen in patients treated with interdisciplinary regimens, we recommend that all patients receiving irradiation to the neck--particularly those patients having neck dissections or total laryngectomies--have routine thyroid function studies performed following the cessation of treatment.

Adolescent↗

Oral route as method for immunizing against mucosal pathogens.

In the past three decades significant strides have been made in attempts at nonparenteral immunization. Appreciation of the importance of secretory immunity led to attempts to stimulate antibody production locally. The vaccines developed against respiratory pathogens as a result of this new knowledge have many practical limitations, such as the need for highly trained personnel, expensive equipment, very cooperative recipients for intranasal or aerosol administration, and a vaccine that is both adequately attenuated, immunogenic, and stable during storage. With recognition of the presence of a common mucosal defense system, new approaches to vaccine development have become possible. Oral immunization, by stimulating GALT, presents a promising approach for protecting many secretory surfaces against a variety of infectious agents. Recently, emphasis has been placed on developing an oral vaccine against S. mutans. McGhee et al. have demonstrated antibody to S. mutans in saliva and tears following oral ingestion of that antigen, without a rise in serum antibody, in both humans and rats. The rats were afforded protection from caries after rechallenge with both the original and cross-reacting serotypes of S. mutans. Similar results have recently been seen with viral antigens. Mice have been shown to have significant protection against influenza infection following oral immunization. And in a pilot study with human volunteers, the secretory antibody response in nasal washes was similar following either oral or parenteral vaccination. Oral immunization may prove to be far superior to parenteral vaccination against a variety of pathogens, because of fewer side effects and greater ease in vaccine preparation and administration.

Administration, Oral↗

Antiestrogen treatment of postmenopausal women with primary high risk breast cancer.

The role of antiestrogen treatment in high risk postmenopausal patients with primary breast cancer is currently evaluated in a nationwide, prospective randomized trial conducted by the Danish Breast Cancer Cooperative Group. The primary treatment is total mastectomy and radiotherapy. As of February 1, 1982, 720 women were randomized to treatment with tamoxifen (30 mg daily for 1 year) and 691 women were randomized to no further therapy. Life-table analysis after 36 months shows a difference in recurrence rates of 9% (p = 0.19) in favor of the tamoxifen-treated patients. The material has been analyzed with respect to established prognostic factors such as age, degree of anaplasia, tumor size, and number of positive nodes. The rates of recurrent disease are lower in all subsets of patients treated with tamoxifen, but are only statistically significant in patients 50-59 years of age or with 4 or more positive lymph nodes. Regardless of treatment, ER negative patients have a 23% higher recurrence rate than ER positive patients after 18 months of analysis (p = 0.0033); this represents an approximate doubling of risk, and is independent of age, degree of anaplasia, tumor size, or lymph node status. With regard to PgR status, there is 11% higher recurrence rate in the PgR negative than in the PgR positive patients (p = 0.097).

Actuarial Analysis↗

Estrogen and progesterone receptor profile patterns in primary breast cancer.

Estrogen (ER) and progesterone receptor (PgR) analyses have been performed in 884 primary, malignant human breast tumor biopsies. Receptor contents were evaluated with respect to age and menopausal status. The frequency of ER+ tumors was found to be significantly higher in postmenopausal than in pre/perimenopausal women. Age rather than menopausal status was found to be associated with this difference. The significant association with age was found in the post- but not the pre/perimenopausal women. The frequency of PgR+ tumors was found to be significantly lower in the postmenopausal than in the pre/perimenopausal women. Neither age nor menopausal status alone could account for this difference, which appears to be due to a compound effect of the two factors. The distribution of receptor profile patterns is described according to menopausal status. The patterns differ significantly in pre- and postmenopausal women. PgR dominates in the premenopausal tumor while ER dominates in the postmenopausal tumor. This difference is apparent within the subgroup of ER + PgR + patients as well. The current tenets for prediction of recurrent disease utilizing steroid hormone receptor determinations are discussed for the group of ER + PgR + patients.

Adult↗

Mitoxantrone as first line cytotoxic therapy in advanced breast cancer: preliminary results of a phase II study.

Mitoxantrone, 14 mg/m2 repeated every 3 weeks was administered to postmenopausal patients with advanced measurable breast cancer previously untreated with cytotoxic agents. Response was achieved in 16 out of 28 (44%) evaluable patients and in four of the patients (with soft tissue disease) the response was complete. The median duration of response was 10+ months with a range from 4-12+ months. At doses which cause significant hematological toxicity other objective and subjective toxicities were remarkably mild.

Aged↗

Tumoricidal effects of sodium hexachloroiridate on an ascitic tumor in mice.

Sodium hexachloroiridate injected 1 day after i.p. injection of 10(6) mouse ovarian tumor cells prevents the appearance of ascitic tumors in mice. Mice given injections of tumor cells all die at 20 to 30 days after tumor injection. Mice treated with sodium hexachloroiridate after tumor injection either have significant prolongation of life span without ascites or show no evidence of cancer even up to 7 months after tumor injection.

Animals↗

Glycogenolysis induced by serotonin in brain: identification of a new class of receptor.

Serotonin-containing neurones in brain have been proposed to have a role in the control of physiological mechanisms such as sleep, thermoregulation, pain perception and endocrine secretions as well as in the physiopathology of migraine or depressive illness. One difficulty in testing these possibilities lies in the scarcity of pharmacological agents able to interact selectively with the probably multiple classes of serotonin receptors in the central nervous system. Development of such agents would be facilitated by simple in vitro models in which biological responses to serotonin in mammalian brain could be quantified. Thus a serotonin-sensitive adenylate cyclase has been characterized in rat brain, but the response to serotonin is weak in newborn and practically absent in adult animals. In addition, two pharmacologically distinct classes of serotoninergic binding site have been identified using 3H-serotonin and 3H-spiperone as ligands, but their identification as receptors remains to be established. More recently, serotonin has been shown to stimulate phosphorylation of a neuronal protein in slices from the facial motor nucleus, although the receptors mediating this action were not characterized. We now report that serotonin stimulates glycogen hydrolysis in slices of cerebral cortex, that this action is mediated by a novel class of receptors and that tricyclic antidepressants are among the best competitive antagonists of the indolamine.

Adenylyl Cyclases↗

Separation of nucleic acids and chromatin proteins by hydrophobic interaction chromatography.

A procedure by which chromatin proteins (histones and non-histones) can be rapidly separated from nucleic acids by hydrophobic interaction chromatography is described. The procedure is carried out under non-rigorous conditions that must be assumed to induce little irreversible change in the biological properties of most proteins. More than 90% (w/w) of the chromatin proteins can be retained by hydrophobic interaction while nucleic acids pass quantitatively through the columns. By gradient elution of the columns the histones can be divided into fractions containing H1, H2A/H2B and H3/H4, and at the same time a subfractionation of the non-histone proteins is obtained. Protein recovery depends on the type of column used, but exceeds 80% (w/w) with even the most strongly binding hydrophobic matrix investigated.

Animals↗

Comparative misonidazole metabolism in anaerobic bacteria and hypoxic Chinese hamster lung fibroblast (V-79-473) cells.

The metabolism of the radiation sensitizer misonidazole was similar in anaerobic cecal contents and hypoxic Chinese hamster lung fibroblasts (V-79-473). Both systems formed the amino derivative of misonidazole, [1-(2-aminoimidazol-1-yl)-3-methoxypropan-2-ol] (AIM), and urea, as well as a metabolite, (2-hydroxy-3-methoxypropyl)-guanidine (G), which has not been described previously. It appears that the nitro group of misonidazole was reduced to form AIM and that this compound was then hydrolyzed to yield either urea or G, the latter in yields of 25% (tissue culture) to 55% (cecal contents). When tested with the Ames tester strain, both G and AIM were slightly mutagenic only for strain TA 98 and then only in the presence of the system for microsomal activation.

Animals↗

Relationship between occupation of cerebral H1-receptors and sedative properties of antihistamines. Assessment in the case of terfenadine.

Alpha-[4(1,1-Dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1- piperidinebutanol (terfenadine, RMI 9918, Triludan, Teldane, resp.) inhibits the in vitro binding of [3H]mepyramine to H1-receptors in cerebral membranes with an apparent dissociation constant in good agreement with that found for antagonism of histamine-induced contractions of guinea pig ileum. In contrast, administration of terfenadine in therapeutic dosage does not result in the occupation of cerebral H1-receptors in the living mouse, as observed for most H1-antihistamines. A poor access of the drug to cerebral H1-receptors might account for the absence of sedative side effects.

Animals↗

An update on consent law.

Two recent decisions by the Supreme Court of Canada have altered some aspects of the law of consent and clarified others. The decisions have in part cut down the latitude which a physician has in deciding what to tell his patients. The courts have opted for an objective approach which requires the physician to present to the patient all material facts relating to the patient's situation so that the patient may choose what if any investigation or treatment he will have.

Canada↗

Cigarette smoking and duodenal coating with barium.

A review of two hundred and fifty-eight double contrast barium meal examinations was carried out in a single blind study of the relationship between smoking and the ability to visualize gastric and duodenal mucosal detail. A strong correlation was found between poor duodenal visualization and smoking in the period immediately prior to the examination. Patient compliance with a typed instruction sheet forbidding smoking was found to be poor. It may be possible to improve compliance by including, in the written instructions, an explicit statement that smoking shortly before barium meal examination may cause lesions to be missed.

Barium Sulfate↗