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Biomedical subjects

I Young

Publications and source records attributed to I Young.

100 records · Page 6Linked to original sources

Evidence for a role of calmodulin in regulation of pinealocyte cyclic nucleotides.

In rat pinealocytes, norepinephrine (NE) increases cAMP and cGMP accumulation through a synergistic dual receptor mechanism involving alpha 1- and beta-adrenergic receptors. The available evidence indicates that both increases in intracellular Ca2+ ([Ca2+]i, and activation of protein kinase C are involved in the alpha 1-adrenergic potentiation of beta-adrenergically stimulated cAMP and cGMP responses. In this study, the role of Ca2+ was further investigated using three agents with known anti-calmodulin activities: trifluoperazine, pimozide and W7. It was found that none of these inhibitors had any effects on the isoproterenol (ISO)-stimulated cAMP and cGMP responses. By contrast, all three Ca2+/calmodulin inhibitors reduced the NE-stimulated cAMP and cGMP responses. These results suggested that an alpha 1-adrenergic mediated mechanism was likely sensitive to the inhibitory action of the Ca2+/calmodulin inhibitors. To determine the possible site of action of the inhibitors, an activator of protein kinase C, 4 beta-phorbol 12-myristate 13-acetate (PMA), was used to potentiate the ISO-stimulated cAMP response. The PMA potentiation of ISO-stimulated cAMP response was only inhibited by a high concentration of pimozide, and not by trifluoperazine or W7, suggesting that pimozide may have other actions distinct from those of trifluoperazine or W7. Full potentiation of the cGMP response can be achieved by adding both PMA and a depolarizing concentration of K+. All three calmodulin antagonists were effective in inhibiting the PMA and K+ potentiation of cGMP responses in ISO-stimulated cells. These three compounds were also effective in inhibiting the potentiating effects of [Ca2+]i elevating agents on the beta-adrenergically stimulated cAMP and cGMP responses. The three inhibitors, at the concentrations used in the present study, were found to have no effect on the protein kinase C activity determined in vitro. These results indicated that apart from the protein kinase C pathway, the Ca2+/calmodulin pathway of signal transduction may be of importance in the regulation of pinealocyte cGMP and, to a lesser degree, cAMP responses.

Animals↗

Non-Hodgkin's lymphoma of the thyroid gland occurring after treated Hodgkin's lymphoma.

OBJECTIVE: To present a case report of the occurrence of non-Hodgkin's lymphoma in the thyroid gland of a patient who had previously undergone successful treatment of Hodgkin's lymphoma. METHODS: We describe pertinent historical features and current symptoms and laboratory findings in a 62-year-old man who had had successful treatment of Hodgkin's lymphoma 10 years previously and had been free of disease for a decade. We also review the related medical literature on the course of patients after therapy for Hodgkin's lymphoma. RESULTS: Because of a progressively enlarging anterior neck mass, hoarseness, and difficulty with breathing, a patient sought medical attention. Ten years previously, he had undergone irradiation and splenectomy for treatment of Hodgkin's lymphoma. In the current assessment, fine-needle aspiration and open biopsy yielded the diagnosis of non-Hodgkin's lymphoma, for which the patient received irradiation and chemotherapy. Review of the literature pertaining to diseases after treated Hodgkin's lymphoma, including second cancers, failed to identify any such prior reported case. CONCLUSION: Because the clinical profile of our patient was consistent with primary non-Hodgkin's lymphoma of the thyroid gland developing after radiation-treated Hodgkin's lymphoma, we conclude that this represents the first such reported example.

Journal Article↗

Use of iodine-123 as a diagnostic tracer for neck and whole-body scanning in patients with well-differentiated thyroid cancer.

OBJECTIVE: To determine whether 123 I can be used as a safe and effective alternative tracer to 131 I for imaging remnant tissue and for searching for metastatic lesions of well-differentiated thyroid cancer. METHODS: We studied a series of 16 patients (10 women and 6 men; 29 to 73 years of age) who had well-differentiated thyroid cancer and had undergone thyroidectomy and subsequent radioiodine treatment. Diagnostic 10 mCi (either preablation or postablation) were compared with the 5- to 7-day 131 I posttherapy scans (doses, 75 to 200 mCi). Scans were jointly interpreted by nuclear medicine and endocrinology staff members. RESULTS: Of the 16 patients, 15 had concordant findings between the 123 I diagnostic images and the corresponding 131 I posttherapy scans. Only one patient had additional lesions noted on the posttherapy 131 I scan, which was attributed to the higher dose the patient received during radioiodine treatment (a 6% discordance rate). This discordance, however, would not have changed the patient treatment. No advantage was noted for delayed imaging at 48 hours; the 24-hour images were satisfactory. The 123 I scans were of higher resolution than the 131 I scans. CONCLUSION: Diagnostic 123 I scans are an acceptable alternative to 131 I scanning for whole-body imaging in well-differentiated thyroid cancer and demonstrate adequate imaging of thyroid remnant tissue or metastatic lesions from thyroid carcinoma comparable to the post-therapy scans. 123 I scans also offer greater convenience to patients because they do not have to return for 48- or 72-hour scans. Furthermore, they facilitate earlier institution of therapy by decreasing the interval between diagnostic scanning and radioiodine treatment.

Journal Article↗

Neck and whole-body scanning with 5-mCi dose of (123)I as diagnostic tracer in patients with well-differentiated thyroid cancer.

OBJECTIVE: To determine whether a 5-mCi dose of 123I can be used as an effective radiotracer for assessing the presence of remnant thyroid tissue and for searching for metastatic lesions in patients with well-differentiated thyroid cancer as well as to attempt to ascertain whether a scan performed only at 4 hours is sufficient for accurate diagnosis and might replace the conventional protocol of scanning at both 4 hours and 24 hours. METHODS: We prospectively studied 27 patients who had undergone near-total thyroidectomy and had a documented diagnosis of well-differentiated thyroid carcinoma. Patients underwent scanning after receiving a 5-mCi dose of 123I, at a time when they had discontinued thyroid replacement therapy and had a thyrotropin level in excess of 30 mIU/mL. Whole-body images at 4 hours and 24 hours were obtained and were compared with posttherapy scans obtained 5 to 7 days after administration of 131I. Scans were interpreted by two board-certified nuclear medicine physicians. RESULTS: Of the 27 patients, 2 (7.4%) showed discordance between the 123I scan performed at 24 hours and the posttherapy 131I scan. When 4-hour images after administration of 123I were compared with the posttherapy 131I scans, a discordance rate of 14.8% (4 of 27 patients) was noted. In addition, two of these four patients showed lesions on the 24-hour images that were not seen on the 4-hour images (one with new lung metastatic involvement and the other with a local recurrence in the lower neck area). The prognosis and treatment of these two patients were substantially changed by the result of the 24-hour images. CONCLUSION: On comparison of scans obtained after administration of a 5-mCi dose of 123I with those obtained after 131I therapy, we conclude that 5 mCi of 123I produces images that have excellent quality and resolution and also compare favorably with those obtained after 131I therapy. Furthermore, a decrease in the dose of 123I from 10 mCi to 5 mCi lowered the cost of the study without compromising the diagnostic accuracy or image quality. Finally, use of 24-hour images will occasionally disclose additional areas of radioiodine uptake not detected on the 4-hour scans and is therefore recommended.

Adolescent↗

15-hydroxyeicosatetraenoic acid synthesis from exogenous arachidonate by bronchial mucosa.

Arachidonate metabolism in bronchial mucosa was investigated. Bronchial biopsies from four asthmatics and three non-asthmatic controls were challenged with 300, 465, 650 and 960 mOsm/kg saline in the presence of [3H]arachidonate. Supernatants were analysed by reverse-phase high-performance liquid chromatography. The major arachidonate metabolite was identified as 15-monohydroxyeicosatetraenoic acid (15-HETE), with significantly higher production in biopsies from asthmatics than controls. Statistical analysis of the full model explained 81% of the variation (F = 14.8; df = 6, 21; P less than 0.001). Hyperosmolarity and the presence of sarcoid had no significant effect on 15-HETE synthesis, reducing R2 by only 6%.

Adult↗

The acute hot joint in medical practice.

We have studied patients with acute hot joints presenting to general practice, casualty and inpatient rheumatology services. Their investigation, management and outcome were measured against guidelines. Different spectra of disease were seen in the different health care settings. The guidelines were not adhered to for crystal arthritis, particularly when it affected the first metatarso-phalangeal joints. The guidelines were broadly adhered to and useful for other joints, especially where septic arthritis was considered to be the likely diagnosis. We found no benefit on outcome from adhering to the guidelines. There was a tendency for the outcome to be worse where the guidelines were followed in full, suggesting that more investigations are performed in the more difficult cases. We conclude that drawing up guidelines for patient management is difficult even in an area where there is broad medical agreement.

Acute Disease↗

Acute appendicitis in children in a community hospital: a five year review.

OBJECTIVE: To review appendectomy cases in children at a small community hospital and to compare with experience at larger centers. DESIGN: A five-year retrospective study. SETTING: Bartlett Regional Hospital, Juneau, Alaska. PATIENTS AND METHODS: Records of children age 14 and younger who underwent appendectomy from 1991 through 1996 were reviewed; 79 charts were found. Cases were grouped as simple appendicitis, advanced appendicitis, and appendectomy without appendicitis. Variables considered included: length of symptoms at first contact, time from onset until surgery, presence or absence of classical symptoms, post-operative complications, length of hospital stay. RESULTS AND CONCLUSION: 51 cases (64.6%) of simple appendicitis, 22 cases (27.9%) of advanced disease, and 6 cases (7.6%) of normal appendix occurred. Advanced disease was high (66.7%) in children less than 5, and low (22.7%) in ages 10-14. Parental delay > 48 hours in seeking care was a significant factor in advanced disease, professional delay (time from first exam until surgery) was not. Post-surgical complications occurred in 7 (31.8%) cases of advanced disease and in none of the cases with simple appendicitis. Advanced disease cases had an average hospital stay of 8.59 days (+/-2.92) vs. 3.86 days (+/-1.46) for simple appendicitis. Review of appendicitis in children at this hospital compared favorably with the experience at larger medical centers.

Acute Disease↗