Single photon emission computed tomography of the thyroid.

Single photon emission computed tomography (SPECT) entails imaging at multiple positions along an arc and computed-assisted reconstruction of transaxial, coronal, and sagittal images. To determine if SPECT imaging of the thyroid augments information provided by planar imaging, both SPECT and pinhole planar scans were performed in 52 patients with thyroid disease. After 123I (n = 45), Tc99m (n = 5), or thallium-201 (n = 2) administration, images were acquired at 30 intervals along a 180 degree arc. Nodules that were hypofunctioning on planar scans (n = 4) were equally well shown on SPECT images. SPECT analysis of 123I uptake by 5 palpable nodules with completely normal 123I planar scans demonstrated the nodular tracer uptake was increased (n = 1), equivalent (n = 3), or decreased (n = 1) in comparison with that of extranodular tissue. In 6 of 12 multinodular goiters, transaxial SPECT images showed tracheal compression, which was confirmed by neck x-ray, flow volume loops, or surgery. A neck phantom study was performed to assess the accuracy of SPECT-determined functional thyroid volume. SPECT-estimated volumes (30-173 mL; n = 11) correlated well with true volumes (r = 0.996; P less than 0.001). Our observations suggest that SPECT is a useful adjunct to planar imaging in 1) estimating functional volume for 131I dosimetry; 2) evaluating the size, extension, and tracheal compression of multinodular goiter; and 3) determining the functional properties of palpable nodules with normal 123I planar pinhole images.

The Xenopus laevis TM-4 gene encodes non-muscle and cardiac tropomyosin isoforms through alternative splicing.

A full-length cDNA clone coding for a 248-amino-acid tropomyosin (TM) was isolated from a Xenopus laevis (Xl) oocyte cDNA library. This TM is very similar to the members of the non-muscle (nm) TM family that includes rat TM-4, human TM30pl and chicken cardiac fibroblast FT-C. An RNase protection assay showed that the corresponding transcript is expressed ubiquitously and revealed the presence of an alternative transcript in adult heart RNA. A full-length cDNA clone was isolated from an adult heart cDNA library using a nm TM-encoding cDNA probe. It encodes a muscle TM homologous to chicken FT-C and the corresponding mRNA is expressed in adult RNA and to a very low level in adult skeletal muscle. The two cDNAs correspond to two alternatively spliced isoforms of TM generated from the Xl TM-4 gene. These data, together with published observations, demonstrated that, in this amphibian, the cardiac muscle TM are synthesized from the TM alpha and TM-4 genes.

Iodine-123 SPECT of the thyroid in multinodular goiter.

Iodine-123 single photon emission computed tomography (SPECT) imaging of the thyroid was performed in two patients with multinodular goiter and swallowing difficulty to provide the functional and anatomic orientation of the goiter in relation to the airway. Transaxial slices showed the retrolaryngeal extension of the enlarged thyroid and the tracheal compression by the goiter in both patients. Sagittal and coronal sections confirmed the posterior extension of the goiter. Tracheal displacement was confirmed by roentgenography of the neck in both patients. Vocal cord paralysis demonstrated by fiberoptic laryngoscope and esophageal compression shown by esophagography were found in a patient with toxic multinodular goiter with coexisting papillary carcinoma of the thyroid. In this patient, both the tracheal compression noted in SPECT imaging and the tracheomalacia suggested by the flow volume loop pattern in pulmonary function test were confirmed at the time of thyroidectomy. Our observation suggests that SPECT imaging of large multinodular goiter may be useful in preoperative delineation of the functional anatomy and the extension of goiter in relation to the airway.

Alternative splicing of Xenopus alphafast-tropomyosin pre-mRNA during development: identification of determining sequences.

The Xenopus alphafast-tropomyosin gene contains in its central part a set of mutually exclusive exons, designated 6A and 6B, which are incorporated into mRNA encoding, respectively, nonmuscle and muscle tropomyosins. In this study, we show that usage of both exons is strictly regulated during development, exon 6A being used in the oocyte and nonmuscle tissues of the embryo, while exon 6B is used in muscle tissues. An approach of transient embryo transgenesis was developed to study the mechanisms involved in the splice site choice during development. We demonstrate that a-tropomyosin minigenes driven by tissue-specific promoters that target gene expression in nonmuscle and muscle tissues recapitulate the splicing pattern of the endogenous gene. A mutational analysis showed that regulation occurred at both exons 6A and 6B in muscle and nonmuscle tissues. In this context, we have identified an element located in the intron downstream of 6A that participates in the recognition of the weak 5' splice site of exon 6A and the repression of exon 6B in nonmuscle cells.

Familial hyperparathyroidism caused by solitary adenomas.

Most cases of familial hyperparathyroidism are due to diffuse chief cell hyperplasia. No documented cases of familial disease associated with single adenomas in which multiple glands have been biopsied have been reported. The family described here had solitary adenomas proven in four members. Biopsy of other glands showed normal parathyroid tissue. Despite careful evaluation, additional endocrinopathies have not been found during a 24-year follow-up.

Rationale for the operative management of substernal goiters.

During the course of 872 thyroidectomies performed at the University of Michigan Medical Center between 1972 and 1982, 50 patients (5.7%) were found to have substernal goiters, 42 of which were benign and eight malignant (16%). Symptoms included airway compression (22 patients), dysphagia (13 patients), hoarseness (four patients), weight loss (three patients), and thyrotoxicosis (10 patients). Five patients with compression symptoms, four of whom had benign disease, had superior vena cava syndrome. Most patients were elderly (mean age 66 years), were women (3.2 women:1 man), and had long-standing goiters (mean duration 16 years). All but one operation was performed through a cervical incision. There were no intraoperative deaths. Complications were: pneumonia (one patient), wound hematoma (one patient), transient hypocalcemia (two patients), and atrial fibrillation (two patients). This series illustrates five reasons to support operative management. (1) There is no other treatment for long-standing large multinodular goiters. (2) Iodine 131, the alternative to operation for patients with large thyrotoxic goiters, can precipitate acute reactions in the elderly that can result in respiratory distress. (3) A long history of having a large multinodular goiter precluded neither malignancy, hyperfunction, nor complications such as tracheal or esophageal compression. (4) Malignancy occurs in a significant number of these lesions, which are inaccessible to needle biopsy. (5) Nearly all substernal goiters can be removed through a cervical incision. Presence of a substernal goiter is in itself an indication for operation.

Not all "occult" papillary carcinomas are "minimal".

"Occult" papillary carcinomas are characterized as small papillary tumors of less than 1.5 cm in maximum diameter, with or without bulky metastatic deposits in cervical nodes. The primary lesion is usually not palpable, and although the clinical behavior usually follows a benign course, tumors with unfavorable histologic features (invasiveness, multifocality) or extrathyroidal disease or a combination of both may not do so. In this report six cases are presented to illustrate this entity. No patient had a history of irradiation to the head or neck. All had primary lesions smaller than 1.5 cm. None had a palpable nodule or abnormal thyroid scan results, and the diagnosis of thyroid cancer was based on cervical lymph node or lung biopsy specimens, which revealed papillary thyroid cancer. All of the patients underwent total or near-total thyroidectomies and were found to have small, invasive papillary lesions with additional metastases to cervical nodes noted at the time of thyroidectomy. Adjunctive treatment consisted of a 5 mCi iodine-131 scan, ablative iodine-131 therapy, and suppression with L-thyroxine. Although distant metastasis to lung or other organs is uncommon and the mortality rate is low (as in larger papillary cancers), these invasive lesions--despite their small size--have a high propensity for recurrence and should be considered to behave more like encapsulated papillary tumors with extrathyroidal extension than like their small, unencapsulated intrathyroidal counterparts.

Occult hypoadrenalism in critically ill patients.

No clear criteria exist to rule out hypoadrenal shock by cosyntropin (alpha 1-24-corticotropin, a synthetic subunit of adrenocorticotropic hormone) testing in persons who have critical nonadrenal illness. Four patients in the surgical intensive care unit with critical multisystem disease and refractory high cardiac output, low vascular resistance shock had significantly diminished or terminated vasopressor requirements after institution of hydrocortisone sodium succinate infusion in doses simulating physiologic stress response (100 to 300 mg of hydrocortisone per day). In each case, cosyntropin testing revealed serum cortisol levels higher than those usually associated with hypoadrenal shock. Positive response was defined as maintenance of blood pressure with a decrease to less than 25% of baseline pressor requirements within 48 hours of treatment. We hypothesize a syndrome of functional hypoadrenalism in patients with multisystem critical illness and refractory shock responsive to glucocorticoid administration in doses simulating physiologic stress response despite cosyntropin stimulation test results that would rule out hypoadrenalism in a normal person.

Effect of altered volume of distribution on aminoglycoside levels in patients in surgical intensive care.

The apparent volume of distribution (Vd) of aminoglycosides was found to be increased in 100 patients in a surgical intensive care unit who had gram-negative pneumonia or intraabdominal sepsis and acute physiologic scores greater than 12. Following loading or maintenance doses, carefully timed blood samples were collected for measurements of serum concentrations by fluorescence polarization immunoassay. The Vd, determined by linear regression analysis of a one-compartment model using the Sawchuk-Zaske method, was 0.34 +/- 0.121 L/kg and was larger than the normal Vd of 0.20 to 0.25 L/kg, suggesting a 36% to 70% increase in extracellular fluid volume. Since there is a predictable increase in aminoglycoside Vd in the septic surgical patient, a proportionately larger aminoglycoside dosage is required initially to achieve desirable peak serum levels. Close monitoring of blood levels during maintenance dosing is suggested since dynamic changes in renal function and aminoglycoside Vd occur in the critically ill.

Neutrophil intracellular kill following thermal injury. Different bactericidal capability for patients' organisms and laboratory organisms.

Sixteen patients with septic complications of severe thermal injury were studied with respect to neutrophil intracellular-killing power against clinical isolates from the patients themselves and against other laboratory organisms. Simultaneous measurements of neutrophil chemotaxis, helper/suppressor lymphocyte ratios, and serum IgG concentrations were also carried out. Neutrophils from patients who survived had diminished intracellular-killing capacity for their own organisms, but normal capacity for killing laboratory organisms either matched or unmatched with the patients' own isolate's species. In these patients, the chemotactic index, the lymphocyte helper/suppressor ratio, and the serum IgG concentration remained within normal limits. Neutrophils from patients who died failed to kill their own, as well as laboratory, organisms. In these patients, the chemotactic index, lymphocyte helper/suppressor ratio, and IgG concentration were significantly diminished. The biological implications of these findings are noted.