Acute cardiotoxicity of nucleoside analogs FddA and FddI in rats.

The acute cardiotoxic potential of single dosages of FddA (2'-fluoro-2',3'-dideoxyadenosine) and FddI (2'-fluoro-2',3'-dideoxyinosine) was investigated in 6- to 9-week-old rats. Both nucleoside analogs were administered orally at 1000 and 2000 mg/kg and intravenously at 500 or 1000 mg/kg. For comparative purposes, additional groups of rats received 2'-deoxyadenosine or the 2-fluororibose moiety common to both the FddA and FddI molecules. The effects of two adenosine receptor antagonists, caffeine and theophylline, on the cardiotoxicity induced by FddA were also investigated. Deaths occurred within a few hours to a few days in FddA-treated rats given 2000 mg/kg orally or 500 mg/kg intravenously and in FddI-treated rats given 1000 mg/kg intravenously. Microscopic examination of the hearts revealed myocardial degeneration and necrosis for all rats that died and myocardial fibrosis for many survivors. No deaths or cardiac lesions were observed after administration of 2'-deoxyadenosine or the 2-fluororibose moiety. FddA was more cardiotoxic than FddI in rats at equivalent dosages administered either orally or intravenously. Based on the anatomic findings, all deaths were attributed to cardiac lesions. The administration of high, oral dosages of caffeine and theophylline accentuated the acute cardiotoxicity of FddA in rats.

Pituitary oncocytomas: clinical features, characteristics in cell culture, and treatment recommendations.

To determine whether there are significant differences between oncocytomas and pituitary adenomas, we evaluated clinical features, treatment regimens and outcome in 23 males and 9 females (average age 64 years, range 43-81 years) with the histologic diagnosis of pure pituitary oncocytomas (> 95% oncocytes). Symptom duration was six to twelve months in 6 cases (19%) and more than one year in 19 cases (59%). Three patients presented with sudden onset of symptoms, and were found to have hemorrhage within their tumors. Visual loss (69%) and symptoms of hypopituitarism (44%) were the most common presenting complaints. Preoperative endocrine profiles revealed abnormalities in most cases, including pituitary insufficiency in 56% and hyperprolactinemia in 59%. The tumors were typically large at presentation; all but one had suprasellar extension. 28 patients underwent transsphenoidal tumor resections; 4 underwent subfrontal craniotomies. Gross dural invasion was found at surgery in 11 cases. At a mean followup of 31 months (range 2-68 months), recurrent tumor was identified in 4 patients (12.5%). Tumor size, dural invasion, preoperative endocrine profile, and postoperative radiotherapy did not correlate with recurrence. Among seven oncocytomas grown in culture, five demonstrated two distinct cell types consisting of oncocytes and typical adenoma cells, respectively. Oncocytomas often have a different clinical presentation than functional pituitary adenomas.

The sublabial transseptal transsphenoidal approach to sellar and parasellar lesions.

Multiple surgical approaches to the sella turcica have been described. The sublabial transseptal transsphenoidal approach provides a safe, cosmetically acceptable route to the sella with excellent exposure. Since 1976, we have employed this technique for the surgical treatment of pituitary neoplasms and parasellar tumors. The University of Washington experience with the sublabial transseptal transsphenoidal approach to the sella in a series of 253 patients is reported with respect to the otolaryngological aspects of the surgical technique, results, and complications of the procedure. In addition, a literature review of major studies that used this procedure is included, and the reported results and complications are compared to those of the present study.

A review of enzyme immunoassay for detection of antibody to Brucella abortus in cattle.

Enzyme immunoassay has gained wide acceptance for serological diagnosis of bovine brucellosis because of its ability to detect antibody of all isotypes unlike the conventional tests. The indirect enzyme immunoassay, however, presents several parameters that require careful analysis. These parameters include the choice of antigen and antiglobulin-enzyme conjugate reagents for use in the assay, dealing with the large amount of data the semi-automatic or automatic assay can generate and the inter- and intralaboratory standardization and quality control. This review considers the various methods described in the literature and, briefly, how some of the problems have been overcome or how they might be dealt with.

Application of a timing protocol to the reduction of inter-plate variability in the indirect enzyme immunoassay for detection of anti-Brucella antibody.

A simple timing protocol was developed to monitor chromogen conversion in an enzyme immunoassay, performed in microtiter plates, for the detection of antibody to Brucella abortus in bovine serum. Application of this protocol decreased the inter-plate coefficient of variation from 28.6% to 6.8% when optical density (OD) values, subsequent to the reaction of a standard antibody reagent, were compared to a static development time. Substantial reductions in variation were also observed for low titered seropositive and for seronegative control reagents. The timing protocol was based on the mathematical relationship of the OD value at 4 minutes of development to a predetermined target OD value (1.0) for a standard antibody reagent. Application of this relationship to the calculation of a variable, final development time eliminated the need for extensive data manipulation and assay calibration.

Demodectic mange in a tamarin (Saguinus geoffroyi).

A young female tamarin (Saguinus geoffroyi) developed erythema, alopecia, and papule formation on the skin of the limbs, tail, and head. Examination of skin scrapings and a biopsy specimen revealed mites identified as Demodex sp. Histologically the mites were found in hair follicles, and they were associated with focal degenerative and inflammatory changes in the skin. Successful treatment included topical application of 1% ronnel solution and rotenone ointment.

Prolactinomas as part of the multiple endocrine neoplastic syndrome type 1.

The pituitary tumors seen in the multiple endocrine neoplastic syndrome type 1 have generally been considered "nonfunctional." Fewer than 40 persons with hyperprolactinemia as part of the syndrome have been described. A family with the largest number of subjects (six) with prolactinomas in one generation reported to date is described. The variable aggressiveness of this disease, the difficulty in treatment because of multiple prolactinomas or hyperplasia or both, and a case of tumor shrinkage with bromocriptine therapy are also demonstrated in this unique family.

Spinal epidural neoplasia. A 15-year review of the results of surgical therapy.

The outcome following decompressive laminectomy and spinal irradiation has been evaluated in 104 consecutive patients with epidural metastatic neoplasia, using broad criteria for successful outcome. Of patients so treated, 33% were benefited, while 23% became worse. Both tumor histology and the preoperative neurological status were important factors in determining the response to this therapy. The authors review the surgical and radiotherapeutic literature in the treatment of this condition, and conclude that there is no clearly established superiority of laminectomy followed by irradiation over radiotherapy alone. Specific indications for surgery exist if prior histological confirmation of malignancy is lacking, if there is neurological deterioration during radiotherapy, or if there are recurrent symptoms referable to a previously irradiated metastasis. Surgery is also indicated if facilities for prompt administration of radiotherapy are unavailable.

Proliferative retinopathy after treatment of carotid-cavernous fistulas.

The carotid-cavernous fistulas of two young patients were treated by multiple carotid artery ligations. The fistulas persisted, supplied by retrograde flow through the ophthalmic artery. In one patient, neovascularization of the optic disc occurred and, in spite of suspected later spontaneous closure of the fistula, progressed to cause nearly total loss of vision. Spontaneous closure of the fistula also occurred in the other patient, but vitreous hemorrhage due to neovascularization of the retina developed four years later.

Progestogen-related gross and microscopic changes in female Beagles.

Long-term studies of megestrol acetate and chlormadinone acetate in 100 female dogs are in progress. Doses of zero, one, 10 and 25 times the expected human dose of megestrol acetate and 25 times the expected human dose of chlormadinone acetate (on a milligram per kilogram body weight basis) are being given daily. During the first 4 years, eight dogs from each of the five groups were killed. The principal gross findings included enlarged uteri with mucoid material in the lumina, mammary development in dogs given middle and high doses of megestrol acetate and chlormadinone acetate, and thickened gallbladder walls in dogs given high doses of each. Histologic evaluation showed inhibition of ovulation for progestogen-treated dogs and suppression of ovarian follicular development with the high doses. Cystic endometrial hyperplasia was slight in the low-dose dogs and moderate to severe in most of the high-dose dogs; a few also had ulcerative endometritis and pyometra. The mammary glands of dogs given the middle and high doses produced lobules, acini, and secretion exceeding natural metestrus. Slight to marked cystic mucinous hyperplasia occurred in the gallbladders of most dogs given the high doses. Tow high-dose megestrol dogs had clinical signs and microscopic pancreatic, renal, and ocular changes indicative of diabetes mellitus.