Citations

AbstractThe prediction of outcome in the rare Hürthle cell tumor of the thyroid continues to present a problem to surgeons and pathologists. To better clarify the distinctions between benign and malignant tumors, we have measured DNA content by flow cytometry on isolated cell nuclei derived from archival paraffin‐embedded tissue blocks of 125 Hürthle cell tumors operated from 1943 to 1985 at the Mayo Clinic, Rochester, Minnesota, U.S.A. Nuclear DNA ploidy patterns were divided into 3 groups. A DNA normal (diploid) pattern was found in 55% of 75 Hürthle cell adenomas and in 26% of 50 Hürthle cell cancers; a DNA tetraploid/polyploid pattern was found in 11% of benign, and 14% of malignant tumors. An abnormal DNA stemline was detected in 34% of benign and 60% of malignant tumors. Hürthle cell cancer was the histologic diagnosis in 24% of the DNA normal, 47% of the DNA tetraploid/polyploid, and 54% of the DNA aneuploid tumors. None of the patients with adenomas developed tumor recurrence. However, 20% of the euploid and 40% of the aneuploid tumors developed local or distant recurrences. Survival to thyroid cancer death was significantly correlated with DNA ploidy status (p=0.02) but did not correlate with either tumor size or histologic grade. To date, deaths from thyroid cancer have been confined to patients whose tumors were DNA aneuploid. We would conclude that determination of DNA ploidy status may not aid the surgical pathologist in the diagnosis of Hürthle cell cancer. However, when a patient's Hürthle cell cancer is DNA aneuploid, there is significant risk of death from thyroid cancer.

Abstract The ability to differentiate benign from malignant Hürthle cell thyroid neoplasms has provoked considerable controversy. This has significant therapeutic implications, since some have advocated total thyroidectomy for all of these lesions. The principal objectives of this study were: (a) to determine whether the histologic diagnosis of Hürthle cell adenoma could be reliably made, (b) to quantitate the risk of inappropriately labelling a Hürthle cell cancer as an adenoma, and (c) to ascertain whether the type of operative procedure affected the clinical course . We reviewed 272 patients who had undergone thyroid resection for benign Hürthle cell neoplasms at the Mayo Clinic from 1960 to 1980. All pathologic sections were rereviewed. Postoperative follow‐up was available on 233 patients (86%), with a mean of 8.9 years. A minimum of 5 years of follow‐up was obtained on 10% of the patients. Nodules ranged in size from 0.3 to 11 cm; 195 (55%) were 2 cm or larger. Surgical resection was limited to one side in 137 (50%) patients and involved both sides in 135 patients. No total thyroidectomies were performed. Evidence of malignancy—a local recurrence—developed in only 1 patient, and she died of unrelated causes. None of the 272 patients died of thyroid cancer, and none showed evidence of metastases. Our data is in agreement with most published reports, with only 6 (0.9%) of 642 reported patients being diagnosed incorrectly. These tumors can be accurately separated into benign and malignant. Routine total thyroidectomy for Hürthle cell adenomas is not justified .

Unauthorized self-administration of hypoglycemic agents produces a unique clinical situation. Because the symptoms and laboratory findings are consistent with a functioning adenoma of the pancreas, there is a significant hazard of unnecessary surgery. By appropriate laboratory tests, however, the alert physician may be able to justify suspicion that the disorder is self-induced. Accurate diagnosis may be further facilitated by recognizing certain similarities in these patients. Review of published reports and study of three cases newly presented have revealed these characteristics with enough consistency for proposal of a psychiatric syndrome. In hypoglycemia, factitial causation is suggested by the combination of female sex, single status, medical knowledge derived from experience as a diabetic or from vocational or family contacts, and features of the hysterical personality.

Neurofibrillary tangles composed of hyperphosphorylated, aggregated tau are a common pathological feature of tauopathies, including Alzheimer's disease. Abnormal phosphorylation of tau by kinases or phosphatases has been proposed as a pathogenic mechanism in tangle formation. To investigate whether kinase inhibition can reduce tauopathy and the degeneration associated with it in vivo , transgenic mice overexpressing mutant human tau were treated with the glycogen synthase kinase-3 (GSK-3) inhibitor lithium chloride. Treatment resulted in significant inhibition of GSK-3 activity. Lithium administration also resulted in significantly lower levels of phosphorylation at several epitopes of tau known to be hyperphosphorylated in Alzheimer's disease and significantly reduced levels of aggregated, insoluble tau. Administration of a second GSK-3 inhibitor also correlated with reduced insoluble tau levels, supporting the idea that lithium exerts its effect through GSK-3 inhibition. Levels of aggregated tau correlated strongly with degree of axonal degeneration, and lithium-chloride-treated mice showed less degeneration if administration was started during early stages of tangle development. These results support the idea that kinases are involved in tauopathy progression and that kinase inhibitors may be effective therapeutically.

Background and Purpose— The aim of this study was to analyze the distribution patterns of delayed cerebral ischemia after subarachnoid hemorrhage (SAH) and the factors that determine their occurrence. Methods— We analyzed clinical and radiological data of 143 consecutive patients with aneurysmal SAH. Computed tomography scan revision was blinded to clinical information. Superficial infarctions were defined as territorial lesions with cortical involvement. Perioperative infarctions were excluded. Results— Fifty-six patients (39%) had cerebral infarctions. They were unilateral in 34 patients (61%) and involved a single territory in 29 (52%). Location was cortical in 34 patients (61%), deep in 10 (18%), and combined cortical and deep in 12 (21%). Single infarctions were cortical in 23 of 28 cases (79%). Deep territory ischemia was more common with multiple lesions (16/28, 57% versus 6/29 with single lesions, 21%; P <0.01). Single infarctions occurred frequently in the territory of the ruptured aneurysm (22/28 patients; 79%), whereas multiple infarctions were often distant to the site of rupture (21/28 cases, 75%). History of diabetes ( P =0.05), early hydrocephalus ( P =0.05), and requirement of external ventricular drainage ( P =0.02) were associated with the occurrence of multiple infarctions on univariate analysis. On multivariable analysis, this association only remained significant for the requirement of external ventricular drainage. Conclusion— The 2 most common patterns of delayed cerebral ischemia after aneurysmal SAH are single cortical infarction, typically near the ruptured aneurysm, and multiple widespread lesions including subcortical locations and often unrelated to the site of aneurysm rupture. These 2 patterns may represent different pathophysiological mechanisms or different degrees of severity of the same vascular process.

Abstract The present study examines the thesis that pulsatile GH secretion is controlled simultaneously by three principal signals; viz., GHRH, GH-releasing peptide (GHRP, ghrelin), and somatostatin (SS). According to this ensemble notion, no single regulatory peptide acts alone or can be interpreted in isolation. Therefore, to investigate gender-specific control of pulsatile GH secretion, we designed dual-effector stimulation paradigms in eight young men and six women as follows: 1) l-arginine/GHRH (to clamp low SS and high GHRH input); 2) l-arginine/GHRP-2 (to clamp low SS and high GHRP drive); 3) GHRH/GHRP-2 (to clamp high GHRH and high GHRP feedforward); vs. 4) saline (unclamped). Statistical comparisons revealed that: 1) fasting pulsatile GH secretion was 7.6-fold higher in women than men (P &lt; 0.001); 2) l-arginine/GHRH and l-arginine/GHRP-2 evoked, respectively, 4.6- and 2.2-fold greater burst-like GH release in women than men (P &lt; 0.001 and P = 0.015); and 3) GHRH/GHRP-2 elicited comparable GH secretion by gender. In the combined cohorts, estradiol concentrations positively predicted responses to l-arginine/GHRP-2 (r2 = 0.49, P = 0.005), whereas testosterone negatively predicted those to l-arginine/GHRH (r2 = 0.56, P = 0.002). Based upon a simplified biomathematical model of three-peptide control, the current outcomes suggest that women maintain greater GHRH potency, GHRP efficacy, and opposing SS outflow than men. This inference upholds recent clinical precedence and yields valid predictions of sex differences in self-renewable GH pulsatility.